diff --git a/.gitignore b/.gitignore index 80746ff..84db11a 100644 --- a/.gitignore +++ b/.gitignore @@ -142,3 +142,10 @@ scripts/internal/ # Per-oracle pickle snapshots for multi-oracle consolidator (regenerate on demand) examples/walkthroughs/validation/SORT1_rs12740374_multioracle/*.pkl + +# DHS vocabulary download (90 MB, fetched via gdown when needed) +annotations/ + +# Local screenshot sweeps (regenerate via headless Chrome on demand) +screenshots/ +examples/walkthroughs/**/screenshot_*.png diff --git a/README.md b/README.md index b8c4ec5..cfe0406 100644 --- a/README.md +++ b/README.md @@ -213,15 +213,32 @@ After the first install, to upgrade cleanly: ```bash cd chorus && git pull -# Remove oracle envs first (while the chorus CLI is still available): -chorus remove --oracle enformer -# Repeat for each oracle you had installed... +# Remove all oracle envs, weights, and backgrounds in one command: +chorus cleanup --all # Then remove the base env: mamba env remove -n chorus -y ``` Then re-run the Fresh Install steps above. +#### Uninstalling / starting from scratch + +```bash +# Preview what will be deleted (safe — no changes): +chorus cleanup --all --dry-run + +# Remove everything: all oracle envs, downloaded weights, background CDFs, and genomes: +chorus cleanup --all + +# Finer-grained options: +chorus cleanup --oracle enformer # one oracle only (env + weights) +chorus cleanup --oracle all # all oracle envs + weights, keep backgrounds/genomes +chorus cleanup --backgrounds # remove ~/.chorus/backgrounds/*.npz only +chorus cleanup --genomes # remove downloaded reference genomes only +``` + +The base `chorus` environment itself is not removed by `chorus cleanup` — remove it manually with `mamba env remove -n chorus -y` if you want a complete wipe. + #### Setting up oracle environments one-by-one Chorus uses isolated conda environments for each oracle to avoid dependency conflicts between TensorFlow, PyTorch, and JAX models. @@ -258,6 +275,14 @@ chorus health --timeout 300 **Note:** `chorus setup` pre-downloads each oracle's default weights + background CDFs + the `hg38` reference at install time, so subsequent `chorus health` / prediction calls are fast. If you opted out via `--no-weights`, the first prediction will still do a lazy download. +**Slow or unstable connection?** Use `--setup-timeout SECONDS` to cap how long each phase (env build and weight download) is allowed to run before aborting with a clear error: + +```bash +chorus setup --oracle borzoi --setup-timeout 3600 # 1-hour cap per phase +``` + +Default is unlimited. If a phase times out, re-run the same command — mamba and HuggingFace downloads resume from where they left off. + #### Tokens Two tokens are relevant. `chorus setup` surfaces both so they aren't a mid-prediction surprise: @@ -1163,7 +1188,7 @@ For each position, the layer-appropriate window-sum is added to the track's rese At each of the same ~31,500 positions, **32 random bins** from the full output window are added to the perbin reservoir. This captures the per-bin (not per-window) distribution at the track's native resolution (1 bp for ATAC/CAGE/RNA/PRO-CAP/splice; 128 bp for ChIP-Histone/TF in AlphaGenome). -The per-bin CDFs are used by `perbin_floor_rescale_batch` to rescale raw IGV bin values onto a uniform `[0, 1.5]` display scale where `1.0` always corresponds to the top-1% genome-wide bin value for that track. This makes overlaid tracks visually comparable across cell types. +The per-bin CDFs are used by the unified `chorus.analysis._igv_report.rescale_for_display` helper (which all four track-rendering paths — IGV, matplotlib, CoolBox, notebooks — share) to rescale raw bin values onto a uniform `[0, 3.0]` display scale where `1.0` corresponds to the top-1% genome-wide bin value for that track and `3.0` is a hard cap. Signed layers (Borzoi RNA, Sei, LentiMPRA) use the symmetric variant `signed_floor_rescale_batch`, mapping to `[-3.0, +3.0]` with `±1.0 = p99(|effect|)`. This makes overlaid tracks visually comparable across cell types and across renderers. #### Sample sizes per oracle @@ -1241,7 +1266,8 @@ In the resulting report, every track row gets two extra columns — `Effect %ile | **Effect percentile** (unsigned) | `[0, 1]` | `0.95` = stronger than 95% of ~10K random SNPs in the same track | | **Effect percentile** (signed) | `[-1, 1]` | `+0.95` = strongly above-baseline gain; `-0.95` = strongly above-baseline loss | | **Activity percentile** | `[0, 1]` | `0.95` = reference signal at this site is in the top 5% genome-wide for this track | -| **IGV per-bin display value** | `[0, 1.5]` | `1.0` = top-1% bin value genome-wide for this track; `0` = below the noise floor | +| **Display rescale (unsigned)** | `[0, 3.0]` | `1.0` = top-1% bin value genome-wide; `3.0` = hard cap (3× p99); `0` = below the layer floor (p90 / p95 / p85 depending on layer) | +| **Display rescale (signed layers)** | `[-3.0, +3.0]` | `±1.0` = p99 of `|effect|` genome-wide; symmetric so repressive (negative) signals stay visible. Used by Borzoi RNA, Sei, LentiMPRA. | **Sanity-check rule of thumb:** a *biologically interesting* variant typically shows **effect percentile > 0.95** AND **activity percentile > 0.5** in the same track — i.e. an unusually large effect at a site that already has real regulatory activity. diff --git a/audits/2026-05-08_post_pr79_merge_audit.md b/audits/2026-05-08_post_pr79_merge_audit.md new file mode 100644 index 0000000..4fe7058 --- /dev/null +++ b/audits/2026-05-08_post_pr79_merge_audit.md @@ -0,0 +1,160 @@ +# Post-PR-#79 merge audit — handoff for Lorenzo + +**Date:** 2026-05-08 +**Branch:** `fix/post-v040-followups` (commits `0c2b8e6` + `b2cb4e8` on top of merge `63df601`) +**Auditor:** Luca + Claude (Opus 4.7, 1M context) +**Scope:** verify the merged code (Lorenzo's PR #79 + our local "unify track-rescale" follow-ups) is ready to merge into `main`. + +--- + +## TL;DR + +✅ **376 tests pass** (warm-state pytest after fresh CDF swap). +✅ **All 18 walkthrough HTMLs render** with peaks visible — programmatic IGV inspection found 0 issues. +✅ **Default-call behaviour is unified**: IGV, matplotlib, CoolBox, and notebooks all produce CDF-rescaled output with no extra params (same `1.0 = p99` semantics, same `3.0` cap). +✅ **README + walkthroughs README + NORMALIZATION_GUIDE + VISUALIZATION_GUIDE re-read**; 2 P1 stale-claim fixes applied (display range `1.5 → 3.0`). +✅ **README links audited** (51 targets) — all resolve. (Two Zenodo URLs return HTTP 403 to scripted HEAD but are valid via API/browser.) +✅ **Branch pushed** to `origin/fix/post-v040-followups`. + +~~🟡 **One deferred item**: the local DHS-augmented ChromBPNet CDF +was missing the 744 BPNet/CHIP tracks; needed a rebuild + HF upload.~~ +✅ **Closed 2026-05-09**: the GPU-machine agent rebuilt the 744 CHIP +rows with DHS augmentation on ml007 (~6 h, 2× A100); the local 42 +ATAC/DNASE rows were spliced in on this Mac; resulting **uniform +786-track DHS-augmented NPZ** (sha +`526beb2ce8310f6fdb331f766eac55ce3262b67f1a43416532d8bad8f83183eb`) +uploaded to `huggingface.co/datasets/lucapinello/chorus-backgrounds`. +See `audits/2026-05-09_dhs_chrombpnet_full_rebuild.md` for the +sub-audit. After the upload, all 786 tracks have uniform sampling +(`effect_counts=18672`, `summary_counts=34004`, +`perbin_counts=1088128`). + +--- + +## What changed in this branch (vs `origin/main`) + +``` +b2cb4e8 chore(examples): regenerate SORT1 chrombpnet + multi-oracle artefacts +0c2b8e6 feat(viz): unify track-rescale across IGV / matplotlib / CoolBox / notebooks +63df601 Merge Lorenzo's PR #79 into fix/post-v040-followups +965d0dd Added updated multioracle examples (Lorenzo) +fc38632 fix: support mixed-resolution tracks… (Lorenzo) +9151338 fix: genome concurrent decompression race + stale ChromBPNet health probe +fecf407 feat: add chorus cleanup command +0e4fb6a feat: add --setup-timeout to chorus setup +85b12ca fix: CHIP strand suffix mismatch in normalization + alphagenome_pt CDF alias +``` + +### Lorenzo's PR #79 (kept as-is) + +| Change | File | Notes | +|---|---|---| +| `_match_track_id` / `_find_matching_cdf` (perbin → summary → effect fallback) | `normalization.py` | LegNet uses `summary_cdfs` for IGV rescale via the fallback | +| `_calculate_track_bin_size` per-oracle dispatch | `_igv_report.py` | chrombpnet `bin=20`, legnet `bin=resolution`, others `window/3000` | +| `aggregation_method` param on `_downsample_to_features` | `_igv_report.py` | mean / max | +| `windowFunction: "max"` IGV WIG hint for high-res oracles | `_igv_report.py`, `multi_oracle_report.py` | Browser-side aggregation | +| `(per-track norm)` LegNet panel-label suffix | `multi_oracle_report.py` | Tells users the values aren't directly comparable | +| `get_max_output_size()` widens multi-oracle region to ~1 Mb | `regenerate_multioracle.py` | | +| New `t_start = variant_pos - (actual_bp_in_array // 2)` IGV formula | `_igv_report.py` | Identical to our parallel local fix | + +### Our local follow-ups (one squashed feat commit) + +| Change | File | Why | +|---|---|---| +| Single unified helper `rescale_for_display(values, layer, normalizer, oracle_name, assay_id) → (out, cfg)` | `_igv_report.py` | Single source of truth — IGV, matplotlib, CoolBox, notebooks all use it | +| `apply_floor_rescale` returns 4-tuple `(rescaled, ref, alt, signed)` | `_igv_report.py` | So callers can pick symmetric vs unsigned scale_cfg | +| `signed_floor_rescale_batch` — symmetric signed rescale to `[-3, +3]` using `p99(|cdf|)` | `normalization.py` | Borzoi RNA / Sei / LentiMPRA repressive effects now visible (were clipped to 0) | +| `is_signed()` fuzzy track-id matching incl. CHIP `:+`/`:-` strand stripping | `normalization.py` | LegNet `LentiMPRA:HepG2` correctly resolves to `HepG2` row → signed guard fires | +| `OraclePrediction.add()` backfills `track.assay_id` from dict key | `core/result.py` | ChromBPNet tracks with `assay_id=None` now usable by CoolBox/matplotlib auto-load | +| CoolBox `get_coolbox_representation(normalize=True)` auto-loads normalizer | `core/result.py` | `pred[i].get_coolbox_representation()` with no args → CDF-rescaled output | +| matplotlib `render_track_figures(normalize=True)` auto-loads | `_track_figure.py` | Same default behaviour | +| `_has_samples` guard moved inside `_find_matching_cdf` | `normalization.py` | Failed-build perbin rows fall through to summary instead of saturating to `max_value` | +| `max_value` default `1.5 → 3.0` in `perbin_floor_rescale_batch` | `normalization.py` | Matches `_DISPLAY_MAX = 3.0`; was silent clip-bug for any caller without explicit `max_value=` | +| `ChromBPNetOracle.predict_sliding(seq)` | `oracles/chrombpnet.py` | Slides 2114-bp model across arbitrary intervals with cigar substitutions preserved → ChromBPNet visible across the full multi-oracle 1 Mb locus | +| `_predict()` auto-routes wide queries to `predict_sliding` | `oracles/chrombpnet.py` | PR #79's wider `genomic_region` was triggering a pre-existing IndexError in `_predict_direct`'s sliding formula | +| `_calculate_track_bin_size` chrombpnet uses `agg="max"` (was `"mean"`) | `_igv_report.py` | PR #79's docstring said "max pooling preserves peaks for ChromBPNet" but code returned `"mean"` — corrected | +| Lower per-layer floors: `chromatin_accessibility 0.95→0.90`, `promoter_activity 0.95→0.85` | `_igv_report.py` | Peak base/shoulder visible alongside peak top | +| Causal-report IGV (`causal._build_causal_igv`) goes through the unified helper | `analysis/causal.py` | Same path as variant + multi-oracle reports | +| matplotlib symmetric y-axis fallback for signed layers (no normalizer) | `_track_figure.py` | Repressive RNA/Sei/MPRA signal stays visible in zoom-in/out PNGs | +| DHS-vocabulary utilities `load_dhs_vocabulary()` / `sample_dhs_positions()` | `utils/annotations.py` | Used by the (deferred) DHS-augmented CDF rebuild | +| Multi-oracle wide-locus wiring uses `predict_sliding` | `scripts/regenerate_multioracle.py` | | +| Test updates: `test_apply_floor_rescale_passthrough` (4-tuple); `test_perbin_none_for_scalar_oracles` (perbin → summary fallback); new `test_rescale_for_display_unified_helper` | `tests/test_analysis.py` | | +| README display-range fixes | `README.md` | `1.5 → 3.0` at lines 1191, 1269 | + +--- + +## Verification matrix + +| Check | Result | Notes | +|---|---|---| +| `pytest -m "not integration"` | ✅ 376 passed, 1 skipped, 5 deselected | After swapping in HF-shipped CDF | +| ChromBPNet single-oracle SORT1 regen | ✅ `+0.318 log2FC, ≥99th, Activity 0.603` | Matches expected biology | +| Multi-oracle SORT1 (chrombpnet/legnet/alphagenome + consolidate) | ✅ all 4 artefacts regenerated | LegNet panel: scale `[-3, +3]`, 20,174 negative + 797 positive features | +| All 18 walkthrough HTMLs IGV-parsed | ✅ 0 issues — every panel has data | One file (batch_scoring) is table-only, no IGV expected | +| README link audit (51 links) | ✅ all resolve | 2 Zenodo URLs return 403 to scripted HEAD; valid via API | +| Doc consistency (README, walkthroughs README, NORMALIZATION_GUIDE, VISUALIZATION_GUIDE) | ✅ 2 P1 stale claims fixed | `[0, 1.5]` display-range references → `[0, 3.0]` | + +### Default-call behaviour (no extra params required) + +| Path | Auto-load mechanism | Verified | +|---|---|---| +| IGV variant report | reads `report._normalizer` | ✅ | +| IGV multi-oracle | reads each `rep._normalizer` | ✅ | +| IGV causal | reads `top_s._variant_report._normalizer` | ✅ | +| matplotlib `render_track_figures(...)` | `normalize=True` → `get_normalizer(first.source_model)` | ✅ | +| CoolBox `track.get_coolbox_representation()` | `normalize=True` → `get_normalizer(self.source_model)` | ✅ | + +Opt-out: `normalize=False` for matplotlib + CoolBox; `igv_raw=True` on the variant report. + +### CDF flow per oracle (Lorenzo's principled-not-hack concern) + +| Oracle | Variant `effect_pctile` | Variant `activity_pctile` | IGV per-bin rescale | Notes | +|---|---|---|---|---| +| ChromBPNet | `effect_cdfs` | `summary_cdfs` | `perbin_cdfs` | All three CDFs read directly via the unified helper | +| LegNet | `effect_cdfs` | `summary_cdfs` | `summary_cdfs` (signed) → symmetric `[-3, +3]` rescale via `signed_floor_rescale_batch` | Was per-track autoscale before; now consistent semantics across oracles | +| AlphaGenome / Enformer / Borzoi | `effect_cdfs` | `summary_cdfs` | `perbin_cdfs` | Lorenzo's fallback never triggers (all three present) | +| Sei | `effect_cdfs` (signed) | `summary_cdfs` | n/a — heatmap, not signal track | | + +No CDF is bypassed; no hardcoded thresholds; the DHS-augmented samples (when present) are still doing work at every CDF read. + +--- + +## Deferred work (post-merge follow-ups) + +1. ~~**DHS-augmented ChromBPNet CDF — rebuild ALL 786 tracks, then + upload to HF.**~~ ✅ **Closed 2026-05-09.** Hybrid build (744 CHIP + rows on ml007 + 42 ATAC/DNASE rows from the local Mac May-7 + rebuild, spliced together on this Mac), uniform 786-track NPZ + live on `lucapinello/chorus-backgrounds`. Sub-audit: + `audits/2026-05-09_dhs_chrombpnet_full_rebuild.md`. + +2. **Doc P2 polish** — surface the unified `rescale_for_display()` helper in `VISUALIZATION_GUIDE.md` (currently only mentioned in `README.md`); add a paragraph explaining that signed layers now use symmetric `[-3, +3]` rescale. + +3. **`scripts/regenerate_examples.py` BCL11A/FTO/SORT1_with_CEBP examples** — Lorenzo's PR commented these out. The HTMLs are still in the repo but the regen script won't refresh them. Decide: re-enable, or remove the stale HTMLs. + +--- + +## How to validate the merge before merging into main + +```bash +# 1. Pull the branch +git fetch origin fix/post-v040-followups +git checkout fix/post-v040-followups + +# 2. Tests (warm — uses your existing envs + cached CDFs) +mamba run -n chorus pytest tests/ -q -m "not integration" +# Expected: 376 passed + +# 3. Regenerate the SORT1 multi-oracle (the canonical demo) +mamba run -n chorus-chrombpnet python scripts/regenerate_multioracle.py --oracle chrombpnet +mamba run -n chorus-legnet python scripts/regenerate_multioracle.py --oracle legnet +mamba run -n chorus-alphagenome python scripts/regenerate_multioracle.py --oracle alphagenome +mamba run -n chorus-alphagenome python scripts/regenerate_multioracle.py --consolidate + +# 4. Open the report — visually verify the IGV panel +open examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_multioracle_report.html +# Look for: chrombpnet panel covers full 1 Mb width (predict_sliding); legnet panel +# shows BOTH positive and negative tails (symmetric signed scale, was clipped to 0). +``` + +— end of audit — diff --git a/audits/2026-05-09_dhs_chrombpnet_full_rebuild.md b/audits/2026-05-09_dhs_chrombpnet_full_rebuild.md new file mode 100644 index 0000000..362ce8d --- /dev/null +++ b/audits/2026-05-09_dhs_chrombpnet_full_rebuild.md @@ -0,0 +1,183 @@ +# DHS-augmented ChromBPNet/BPNet CDF rebuild — 2026-05-09 + +**Branch**: `fix/post-v040-followups` +**Goal**: Rebuild the CHIP rows of the per-track CDF NPZ at +`lucapinello/chorus-backgrounds/chrombpnet_pertrack.npz` with the new +DHS-vocabulary augmentation (commit `5e8c323`) so binding-site sampling +better covers open chromatin. +**Outcome**: ✓ done. New NPZ live on HF, round-trip-verified, ATAC/DNASE +rows preserved. + +## Strategy + +Skipped re-running the 42 ChromBPNet ATAC/DNASE models — those already +have good random-genome sampling (effect_counts ≈ 10K). Only rebuilt the +744 BPNet/CHIP rows where DHS augmentation makes the biggest difference +(TFs bind in open chromatin, random-genome sampling barely hits binding +sites). This saved ~12 h of compute over `--assay all`. + +Implementation: + +1. Backed up production NPZ → `chrombpnet_pertrack.npz.bak.20260509_1409` +2. Sliced production NPZ in-place to keep only the 42 ATAC/DNASE rows + (drops 744 old non-DHS CHIP rows) +3. Ran `--assay CHIP --shard-of 2` variants + baselines +4. `--part merge-shards` appends the 744 new CHIP rows onto the + 42-row base via `PerTrackNormalizer.append_tracks()` +5. Uploaded to HF, round-trip-verified + +## Compute — ml007 alone (2× A100-PCIE-40GB) + +Initially attempted to fan out across ml003 (V100-16GB) + ml007 + ml008 +(A100-80GB) for 6-way sharding. Aborted due to: +- **ml008 busy** with another user's `dna-vqvae` training job on both GPUs + (25 GB on GPU 0 + 94% util on GPU 1). +- **ml003 V100 cuDNN errors** on the 16 GB cards — the BPNet inference + batch was too large for the V100 envelope. +- **Mamba lock contention** on panfs `~/.cache/mamba/proc` when launching + multiple shards in fast succession. +- **CUDA_VISIBLE_DEVICES not honored** — the build script overrides the + shell env at line 206 with `os.environ["CUDA_VISIBLE_DEVICES"] = str(args.gpu)`. + Both shards landed on GPU 0 until I started passing `--gpu 0` / `--gpu 1` + to the script directly. Worth documenting in the script's docstring. + +Final config: `--shard-of 2` on ml007 with `TF_FORCE_GPU_ALLOW_GROWTH=true` +and 30 s stagger between shard launches. + +| Phase | Wall-clock | Per-shard rate | Models | +|---|---|---|---| +| variants (--assay CHIP) | 14:21 → 17:12 = 2h 51min | ~2.17 models/min | 744 (372 × 2) | +| baselines (--assay CHIP) | 17:17 → 20:29 = 3h 12min | ~1.85 models/min | 744 (372 × 2) | +| merge-shards | <1 min | n/a | n/a | +| HF upload | ~10 s | n/a | n/a | +| **Total** | **~6 h** | | **744 successful, 0 failed** | + +Per-model wall on A100: ~28 s for variants, ~33 s for baselines. GPU +utilization steady at 19% — bottleneck is Python overhead (reservoir +sampling, per-model TF graph re-trace), not GPU compute. BPNet models +are tiny (~1-2 MB params) so GPU compute per forward pass is microseconds. + +User's original Metal-class estimate of 6 days serial = 660 s/model; +A100 is **~24× faster**. + +## Final NPZ on HuggingFace + +| Field | Value | +|---|---| +| repo | `lucapinello/chorus-backgrounds` (dataset) | +| path | `chrombpnet_pertrack.npz` | +| HF commit | `47908dcdc36ab13b5cc1edbb1e3aafc0482d4d29` | +| size | 78.5 MB | +| sha256 | `b8f8148453e8285195b77430970a2187ecd8df2d2a2b0074c5a0a68f37cb9906` | +| total rows | 786 (42 ATAC/DNASE + 744 CHIP) | +| effect_cdfs | (786, 10000) | +| summary_cdfs | (786, 10000) | +| perbin_cdfs | (786, 10000) | +| signed_flags | all False (chrombpnet unsigned) | + +### CHIP rows (NEW, DHS-augmented) + +All 744 rows uniformly populated: +- `effect_counts = 18672` (= 10K random + 8.7K DHS, per spec) +- `summary_counts = 34004` (= 29K + 5K DHS, per spec) +- `perbin_counts = 1088128` (~1.09M per spec) +- CDFs monotonic on first-20 spot-check ✓ + +### ATAC/DNASE rows (PRESERVED from v29 production) + +42 rows untouched from the v29 production NPZ: +- `effect_counts = 9609` (~10K random samples, no DHS — original v29 build) +- Sliced cleanly via `(track_id starts with ATAC: or DNASE:)` filter + +## Round-trip verification + +``` +rm ~/.chorus/backgrounds/chrombpnet_pertrack.npz +get_pertrack_normalizer('chrombpnet') +→ Downloaded chrombpnet_pertrack.npz from HuggingFace +→ Loaded per-track CDFs for 'chrombpnet': 786 tracks +sha256 of re-downloaded file: b8f8148453e8285195b77430970a2187ecd8df2d2a2b0074c5a0a68f37cb9906 + == upload sha256 ✓ +``` + +## Lessons / followups for the script + +1. **`--gpu` flag overrides `CUDA_VISIBLE_DEVICES`**. Calling `mamba run` + with `CUDA_VISIBLE_DEVICES=$shard` is misleading — the script clobbers + it at line 206. Either pass `--gpu N` explicitly, or update the script + to honor the env var when set (preferred). +2. **No mid-build resume**. Killed shards lose all reservoir state. Worth + adding incremental saves every N models for long runs (>10 h). +3. **Mamba panfs lock contention** — staggering launches by 30 s is the + workaround. A single-process launcher with internal job queue would + sidestep this. +4. **GPU util is 19% on A100** because BPNet matmul is microseconds + and Python/sampling dominates per-cycle. Larger inference batches + (more variants per forward pass) could close the gap. + +## Scope NOT covered + +- **Stage 6 scorched-earth verification** on this box was deferred — would + wipe the chorus envs on ml007 to retest fresh-install round-trip. User + to confirm separately before this is run. +- ATAC/DNASE rows were NOT re-augmented with DHS. The mixing is defensible + (DHS-aware CHIP + non-DHS ATAC/DNASE) but worth re-evaluating if a + future user wants uniformly-DHS-augmented coverage. + +## Branch state + +- Branch `fix/post-v040-followups` HEAD: `43f0bac` (auto-fetch DHS vocab). +- This audit committed on top. +- Ready to merge into `main` once a chorus reviewer confirms downstream + notebooks still produce sensible CHIP normalization output (regenerate + `validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_chrombpnet_report.html` + and look for the chrombpnet panel showing reasonable percentile spread). + +--- + +## Follow-up — 2026-05-09 (uniform DHS coverage shipped) + +The "ATAC/DNASE rows still v29 non-DHS" caveat above is now closed. +Splice approach (no further model-recompute needed): + +1. The local 42-row DHS-augmented ATAC/DNASE NPZ already on Mac Studio + (`/tmp/dhs_local_backup_2026-05-08.npz`, sha + `896e72f1…b151431`, built 2026-05-07 against `chrombpnet_nobias`, + 18,672 effect samples + 34,004 summary samples per row) was merged + in-place into the 786-row HF NPZ produced this morning, replacing + the v29 ATAC/DNASE rows at their existing track-id positions. +2. Result: uniform 786-track NPZ where every row has + `effect_counts=18672, summary_counts=34004, perbin_counts=1088128`. +3. Uploaded to HuggingFace + (`huggingface.co/datasets/lucapinello/chorus-backgrounds/chrombpnet_pertrack.npz`), + sha256 `526beb2ce8310f6fdb331f766eac55ce3262b67f1a43416532d8bad8f83183eb`, + 78.5 MB. Round-trip-verified. + +### Verification against the uniform NPZ (Mac M3 Ultra) + +| Check | Result | +|---|---| +| `pytest -m "not integration"` | ✅ 376 passed, 1 skipped, 5 deselected (~287 s) | +| Pull NPZ from HF (cold cache) | ✅ sha matches upload | +| All ATAC/DNASE + CHIP `effect_counts` uniform 18672 | ✅ | +| Regenerate SORT1 chrombpnet single-oracle | ✅ Effect=+0.318, %ile=0.96, Activity=0.605 (was ≥99th under v29) — **slight conservative shift expected** because the DHS-augmented effect background contains more high-effect SNPs | +| Regenerate SORT1 multi-oracle (chrombpnet/legnet/alphagenome/consolidate) | ✅ all four artefacts written | +| Programmatic IGV inspection of 18 walkthrough HTMLs | ✅ 0 issues — all panels show data | + +### What "uniform DHS" changes for users + +- **Effect %ile** for ATAC/DNASE tracks at moderate-effect variants + (~0.3 log2FC) drops from "≥99th" to "0.95–0.97". This is the + intended behaviour: the previous random-only background + underestimated how many regulatory-region SNPs have meaningful + effects, which inflated percentiles. Strong variants (>0.5 log2FC) + are still ≥99th. +- **Activity %ile** essentially unchanged (the cCRE-anchored summary + reservoir already covered regulatory regions; adding 5K DHS summits + on top is a small adjustment). +- **Cross-track comparison** is now meaningful — ATAC/DNASE and + ChIP-TF/Histone all use the same sampling regime (10K random + 8.7K + DHS), so a 0.95 effect-percentile means the same thing whether the + track is ATAC or CHIP. + +Branch ready to merge. diff --git a/audits/2026-05-09_scorched_earth_fresh_install.md b/audits/2026-05-09_scorched_earth_fresh_install.md new file mode 100644 index 0000000..a28c0ba --- /dev/null +++ b/audits/2026-05-09_scorched_earth_fresh_install.md @@ -0,0 +1,234 @@ +# Scorched-earth fresh-install audit — 2026-05-09 + +**Branch**: `fix/post-v040-followups` HEAD `0cd9f2f` +**Host**: macOS 15.7.4, Apple M3 Ultra (96 GB), `mamba` from miniforge +**Goal**: Validate the README's documented install path **as a brand-new +user**, with all chorus envs / caches / weights / genome / annotations +wiped before starting. Catch first-run bugs that warm-state pytest +sweeps miss (per CLAUDE.md memory: "v27 caught a P0 that 5 warm audits +missed"). + +This is the audit Lorenzo will see referenced from the PR description. + +## Pre-state (clean slate) + +``` +mamba env list | grep chorus → (empty) +ls ~/.chorus/ → (no such dir) +ls genomes/ annotations/ → (empty) +git status --short → (clean) +git log -1 --oneline → 0cd9f2f docs(audit): close the DHS-CDF deferral... +``` + +Wiped via `chorus cleanup --all` (deletes 7 oracle envs + weights + +backgrounds + genomes), then `mamba env remove -n chorus -y` to drop +the base env too, then `rm -rf ~/.chorus/ annotations/*` for the +residue. `chorus` CLI no longer in PATH from the chorus env (only +the leftover one in miniforge base). + +## Step 1 — README "Install (5 minutes)" + +```bash +git clone https://github.com/pinellolab/chorus.git && cd chorus # already cloned +mamba env create -f environment.yml +mamba activate chorus +python -m pip install -e . +``` + +| Sub-step | Wall-clock | Result | +|---|---|---| +| `mamba env create -f environment.yml` | **1m 52s** | ✓ env built | +| `python -m pip install -e .` | **2s** | ✓ chorus 0.4.0 installed | +| `chorus --version` | < 1s | ✓ `chorus 0.4.0` | + +README claim: "5 minutes". **Actual: ~2 min on M3 Ultra with warm +conda package cache.** Cold conda cache would be slower (network +download dominates). + +## Step 2 — README "Get every oracle, weight, and reference" + +```bash +chorus setup --hf-token +``` + +(README also mentions LDlink token — optional, skipped here.) + +**Wall-clock: 18 min 35 s** — README claim "55–75 min" is +conservative; this Mac with a warm conda package cache + good network +came in well under. Real first-time-on-this-host might be 2–3× slower +to download from conda-forge, but still much less than the README +upper bound. + +Per-oracle phases captured from `logs/fresh_install_setup.log`: + +| Oracle | env build | weights | backgrounds | total | +|---|---|---|---|---| +| alphagenome | 44s | 1m 26s | (incl. genome ~10 min) | 11m 56s | +| alphagenome_pt| 39s | 22s | 0s (404 → alias to alphagenome) ✓ | 1m 0s | +| borzoi | 37s | 15s | 10s | 1m 2s | +| chrombpnet | 33s | 31s | 5s ← **the new uniform-DHS NPZ, 78.5 MB** | 1m 9s | +| enformer | 32s | 24s | 11s | 1m 7s | +| legnet | 30s | 24s | 1s | 0m 55s | +| sei | 31s | 28s | 1s | 1m 0s | +| **TOTAL** | — | — | — | **18m 35s** | + +### chrombpnet NPZ round-trip ✓ + +The big artifact in this audit: the new uniform-DHS-augmented +chrombpnet NPZ uploaded today (sha +`526beb2ce8310f6fdb331f766eac55ce3262b67f1a43416532d8bad8f83183eb`, +78.5 MB). The fresh `chorus setup` auto-pulled it from +`huggingface.co/datasets/lucapinello/chorus-backgrounds`: + +``` +$ shasum -a 256 ~/.chorus/backgrounds/chrombpnet_pertrack.npz +526beb2ce8310f6fdb331f766eac55ce3262b67f1a43416532d8bad8f83183eb +``` + +Matches the upload sha. **First-install round-trip: confirmed.** + +### Disk footprint after setup + +``` +chorus envs: ~11 GB (8 envs) +downloads: 6.4 GB (oracle weights) +~/.chorus: 1.6 GB (CDFs) +~/.cache/huggingface: 8.7 GB (HF download cache + alphagenome weights) +hg38 genome: ~3 GB +``` + +README claim: "~28 GB free disk". Actual: ~32 GB end-state, includes +HF cache duplication. README understates by ~10–15% — defensible if +you assume `~/.cache/huggingface` evictions. + +## Step 3 — README "Your first prediction" (β-globin SNP via Enformer) + +```python +import chorus +from chorus.utils import get_genome + +oracle = chorus.create_oracle( + 'enformer', use_environment=True, + reference_fasta=str(get_genome('hg38')), +) +oracle.load_pretrained_model() + +wt = oracle.predict(('chr11', 5247000, 5248000), ['ENCFF413AHU']) +print(f"WT mean signal: {wt['ENCFF413AHU'].values.mean():.3f}") +# → WT mean signal: 0.468 + +effects = oracle.predict_variant_effect( + 'chr11:5247000-5248000', 'chr11:5247500', + ['C', 'A', 'G', 'T'], ['ENCFF413AHU'], +) +n_alts = len(effects['predictions']) - 1 +print(f"Variant result: scored {n_alts} alt alleles " + f"({list(effects['predictions'].keys())})") +# → Variant result: scored 3 alt alleles (['reference', 'alt_1', 'alt_2', 'alt_3']) +``` + +**Wall-clock**: 49 s end-to-end (model load + prefetch metadata + +WT predict + 3-alt variant scan). Output matches README exactly. + +## Tests (cold) + +``` +mamba run -n chorus pytest tests/ -q -m "not integration" +``` + +**376 passed, 1 skipped, 5 deselected — 5m 39s wall.** Same result as +the warm sweep yesterday. No new failures introduced by the +fresh-install path. + +## End-to-end walkthroughs (cold) + +The canonical SORT1 multi-oracle pipeline, run cold against the +freshly-installed envs: + +``` +mamba run -n chorus-chrombpnet python scripts/regenerate_multioracle.py --oracle chrombpnet +mamba run -n chorus-legnet python scripts/regenerate_multioracle.py --oracle legnet +mamba run -n chorus-alphagenome python scripts/regenerate_multioracle.py --oracle alphagenome +mamba run -n chorus-alphagenome python scripts/regenerate_multioracle.py --consolidate +``` + +**Wall-clock: 6m 52s.** `example_output.md` cross-oracle consensus +table: + +| Layer | chrombpnet | legnet | alphagenome | Agreement | +|---|---|---|---|---| +| Chromatin accessibility (log2FC) | +1.241 · DNASE:HepG2 | — | +1.336 · DNASE:HepG2 | all ↑ | +| Promoter activity (Δ alt−ref) | — | +0.000 · LentiMPRA:HepG2 | — | only ↑ (n=1) | +| TF binding (log2FC) | — | — | +2.777 · CHIP:CEBPA:HepG2 | only ↑ (n=1) | +| Histone modifications (log2FC) | — | — | +1.267 · CHIP:H3K27ac:HepG2 | only ↑ (n=1) | +| TSS activity (log2FC) | — | — | +1.522 · CAGE:HepG2 | only ↑ (n=1) | + +ChromBPNet and AlphaGenome agree on direction (both ↑ chromatin +accessibility), magnitudes within 8% of each other. This is the +expected cell-line-correct result for the rs12740374 SORT1 enhancer +in HepG2. + +### All 18 walkthrough HTMLs IGV-inspected + +``` +walkthrough panels with_data verdict +batch_scoring/batch_sort1_locus_scoring.html - - no-IGV +causal_prioritization/SORT1_locus/...locus_causal_report.html 18 18 OK +discovery/SORT1_cell_type_screen/..._HepG2_report.html 30 30 OK +discovery/SORT1_cell_type_screen/..._MCF_10A_report.html 6 6 OK +discovery/SORT1_cell_type_screen/..._left_lobe_of_liver.html 6 6 OK +sequence_engineering/integration_simulation/... 3 3 OK +sequence_engineering/region_swap/... 4 4 OK +validation/SORT1_rs12740374_multioracle/..._alphagenome.html 5 5 OK +validation/SORT1_rs12740374_multioracle/..._chrombpnet.html 1 1 OK +validation/SORT1_rs12740374_multioracle/..._legnet.html 1 1 OK +validation/SORT1_rs12740374_multioracle/..._multioracle.html 7 7 OK +validation/SORT1_rs12740374_with_CEBP/..._CEBP_validation.html 6 6 OK +validation/TERT_chr5_1295046/..._TERT_alphagenome.html 18 18 OK +variant_analysis/BCL11A_rs1427407/..._BCL11A_alphagenome.html 6 6 OK +variant_analysis/FTO_rs1421085/..._FTO_alphagenome.html 6 6 OK +variant_analysis/SORT1_chrombpnet/..._chrombpnet_report.html 1 1 OK +variant_analysis/SORT1_enformer/..._enformer_report.html 48 48 OK +variant_analysis/SORT1_rs12740374/..._alphagenome.html 6 6 OK + +0 need attention +``` + +## Friction / surprises / fixes + +**(none P0/P1)**. Three minor notes for future doc polish: + +1. **README "5 minutes" install claim** is conservative-ish — actual + ~2 min on this hardware with warm conda cache. No fix needed + (the upper bound is the right one to advertise). +2. **README "55–75 min" setup claim** also conservative — actual + ~19 min here. Variance dominated by network throughput on the + alphagenome weights + hg38 genome. No fix. +3. **README "~28 GB free disk"** slightly optimistic — actual ~32 GB + end-state because the HF cache duplicates the alphagenome + weights. Could clarify "~28 GB plus ~8 GB transient HF cache". + Low priority. + +No P0/P1 install bugs. Every README command worked verbatim. Every +oracle env created cleanly. Every weight + CDF + genome + GENCODE +download succeeded on the first try. + +## Sign-off + +Branch `fix/post-v040-followups` (HEAD `0cd9f2f`) is **safe to merge +into `main`** based on this scorched-earth audit: + +- ✅ Fresh-install path works exactly as documented (Steps 1–3) +- ✅ HF auto-fetch works for the new uniform-DHS chrombpnet NPZ + (sha-verified end-to-end) +- ✅ HF auto-fetch works for the DHS vocabulary + (separate test earlier today) +- ✅ 376 tests pass cold +- ✅ All 18 walkthrough HTMLs render with peaks +- ✅ Multi-oracle SORT1 produces sensible cross-oracle consensus + (chrombpnet + alphagenome agree on direction, magnitudes within 8%) + +Recommended next step: open the merge PR +`fix/post-v040-followups` → `main`, link this audit doc + the two +preceding ones (2026-05-08, 2026-05-09 DHS rebuild), and close +Lorenzo's PR #79 with a comment pointing at our merge commit. diff --git a/chorus/__init__.py b/chorus/__init__.py index 40a8ee9..109305f 100644 --- a/chorus/__init__.py +++ b/chorus/__init__.py @@ -5,7 +5,7 @@ models including Enformer, Borzoi, ChromBPNet, and Sei. """ -__version__ = "0.4.0" +__version__ = "0.5.0" # --------------------------------------------------------------------------- # PATH guard for subprocess tools (bgzip, tabix, samtools) diff --git a/chorus/analysis/_igv_report.py b/chorus/analysis/_igv_report.py index 4f709ec..c60ec8a 100644 --- a/chorus/analysis/_igv_report.py +++ b/chorus/analysis/_igv_report.py @@ -123,11 +123,11 @@ def _ensure_igv_local() -> Path | None: _LAYER_FLOOR_PCTILE = { "tss_activity": 0.95, # CAGE/PRO-CAP — sharp TSS peaks "tf_binding": 0.95, # ChIP-TF — sharp binding peaks - "chromatin_accessibility": 0.95, # DNASE/ATAC — focused peaks + "chromatin_accessibility": 0.90, # DNASE/ATAC — lowered from 0.95 so the peak base/shoulder displays alongside the top "splicing": 0.95, # SPLICE — sharp signals "histone_marks": 0.90, # ChIP-Histone — broad domains "gene_expression": 0.90, # RNA-seq — broad coverage - "promoter_activity": 0.95, + "promoter_activity": 0.85, # LentiMPRA via LegNet — predictions are even sparser than chromatin (most of genome is not a strong promoter); floor at p85 keeps moderately-active promoters visible. Note: LegNet's summary_cdfs is signed, so repressive values still clip to 0; lowering the floor expands only the positive half. "regulatory_classification": 0.95, } _PEAK_PCTILE = 0.99 @@ -137,6 +137,107 @@ def _ensure_igv_local() -> Path | None: # 3x stronger than the genome-wide top 1%. Bins above 3.0 clip but # this is rare for real biology. _DISPLAY_MAX = 3.0 +_HIGH_RES_ORACLES = ["chrombpnet", "legnet"] # for visualization mean vs max pooling + + +def rescale_for_display( + values, + layer: str, + normalizer=None, + oracle_name: str | None = None, + assay_id: str | None = None, +): + """Single-track display rescale. Canonical helper used by every + track-rendering path (IGV WIG, matplotlib PNG, CoolBox, notebooks) + so they share one source of truth for normalization semantics. + + Returns ``(out_values, cfg)`` where ``cfg`` is a dict with: + + - ``rescaled`` (bool): True iff CDF-based rescale was applied. + False means the values were returned unchanged and the caller + should autoscale per-track. + - ``signed`` (bool): True iff the layer is signed (Borzoi RNA, Sei, + LentiMPRA). Signed tracks use symmetric ``[-DISPLAY_MAX, +DISPLAY_MAX]``; + unsigned use ``[0, DISPLAY_MAX]``. + - ``ymin`` / ``ymax`` (float): suggested y-axis limits. Renderers + can use these to set IGV ``min``/``max``, matplotlib ``set_ylim``, + or CoolBox ``MinValue``/``MaxValue``. + - ``floor_pctile`` / ``peak_pctile`` / ``display_max`` (float): the + thresholds used (informational; same for every rendering path). + + All semantics: + - 1.0 (unsigned) or ±1.0 (signed) = genome-wide p99 of |signal| + - DISPLAY_MAX = 3.0 = 3× p99 above the floor (cap) + - 0.0 (unsigned) = below the layer floor (genome-wide noise) + + Pass ``normalizer=None`` to opt out (returns values unchanged with + ``rescaled=False``, ``ymin/ymax`` set to data min/max for autoscale). + """ + import numpy as np + + if normalizer is None or oracle_name is None or assay_id is None: + v = np.asarray(values) + return values, { + "rescaled": False, "signed": False, + "ymin": float(v.min()) if v.size else 0.0, + "ymax": float(v.max()) if v.size else 1.0, + "floor_pctile": None, "peak_pctile": None, + "display_max": _DISPLAY_MAX, + } + + from .normalization import PerTrackNormalizer + if not isinstance(normalizer, PerTrackNormalizer): + v = np.asarray(values) + return values, { + "rescaled": False, "signed": False, + "ymin": float(v.min()) if v.size else 0.0, + "ymax": float(v.max()) if v.size else 1.0, + "floor_pctile": None, "peak_pctile": None, + "display_max": _DISPLAY_MAX, + } + + signed = normalizer.is_signed(oracle_name, assay_id) + if signed: + out = normalizer.signed_floor_rescale_batch( + oracle_name, assay_id, values, + peak_pctile=_PEAK_PCTILE, max_value=_DISPLAY_MAX, + ) + if out is None: + v = np.asarray(values) + return values, { + "rescaled": False, "signed": True, + "ymin": float(v.min()) if v.size else -1.0, + "ymax": float(v.max()) if v.size else 1.0, + "floor_pctile": None, "peak_pctile": _PEAK_PCTILE, + "display_max": _DISPLAY_MAX, + } + return out, { + "rescaled": True, "signed": True, + "ymin": -_DISPLAY_MAX, "ymax": _DISPLAY_MAX, + "floor_pctile": None, "peak_pctile": _PEAK_PCTILE, + "display_max": _DISPLAY_MAX, + } + + floor_p = _LAYER_FLOOR_PCTILE.get(layer, _DEFAULT_FLOOR_PCTILE) + out = normalizer.perbin_floor_rescale_batch( + oracle_name, assay_id, values, + floor_pctile=floor_p, peak_pctile=_PEAK_PCTILE, max_value=_DISPLAY_MAX, + ) + if out is None: + v = np.asarray(values) + return values, { + "rescaled": False, "signed": False, + "ymin": float(v.min()) if v.size else 0.0, + "ymax": float(v.max()) if v.size else 1.0, + "floor_pctile": floor_p, "peak_pctile": _PEAK_PCTILE, + "display_max": _DISPLAY_MAX, + } + return out, { + "rescaled": True, "signed": False, + "ymin": 0.0, "ymax": _DISPLAY_MAX, + "floor_pctile": floor_p, "peak_pctile": _PEAK_PCTILE, + "display_max": _DISPLAY_MAX, + } def apply_floor_rescale( @@ -149,43 +250,71 @@ def apply_floor_rescale( ): """Floor-subtract + rescale a ref/alt value pair using the normalizer. - Returns ``(floor_ok, ref_scaled, alt_scaled)``. When ``floor_ok`` is - ``True`` the returned arrays are mapped to ``[0, _DISPLAY_MAX]`` with - layer-aware thresholds (p95 / p99 for sharp signals, p90 / p99 for - broad histone marks) — 1.0 on the y-axis then corresponds to the - genome-wide p99 peak in that assay, making tracks comparable across - assays *and* across reports. When False, callers should fall back to - raw autoscale. - - This helper is shared by the standard variant-report IGV - (:func:`build_igv_html`) and the causal-report IGV - (:func:`chorus.analysis.causal._build_causal_igv`) so both reports - render the same "scaled-by-default" IGV tracks. + Returns ``(rescaled, ref_out, alt_out, signed)``. + + - ``rescaled=True, signed=False``: unsigned floor-rescale, values map + to ``[0, _DISPLAY_MAX]`` with layer-aware thresholds (p95/p99 for + sharp signals, p90/p99 for broad domains). 1.0 = genome-wide p99 + peak. IGV scale_cfg should be ``{min: 0, max: _DISPLAY_MAX}``. + - ``rescaled=True, signed=True``: signed symmetric rescale, values + map to ``[-_DISPLAY_MAX, +_DISPLAY_MAX]`` using ``p99(|cdf|)`` as + the unit. ±1.0 = genome-wide top-1% absolute effect. IGV + scale_cfg should be ``{min: -_DISPLAY_MAX, max: +_DISPLAY_MAX}``. + - ``rescaled=False``: no normalizer / no CDF / lookup miss. Caller + should fall back to raw autoscale. + + Used by every IGV-rendering path so panels share the same semantics. """ - if normalizer is None or oracle_name is None: - return False, ref_vals, alt_vals - from .normalization import PerTrackNormalizer - if not isinstance(normalizer, PerTrackNormalizer): - return False, ref_vals, alt_vals - floor_p = _LAYER_FLOOR_PCTILE.get(layer, _DEFAULT_FLOOR_PCTILE) - ref_fl = normalizer.perbin_floor_rescale_batch( - oracle_name, assay_id, ref_vals, - floor_pctile=floor_p, - peak_pctile=_PEAK_PCTILE, - max_value=_DISPLAY_MAX, + + # Delegate to the unified single-track rescaler (rescale_for_display) + # so IGV, matplotlib, CoolBox and notebook callers all share the same + # semantics — only the wrapper differs (this one returns a 4-tuple + # for the ref/alt pair instead of (values, cfg)). + ref_out, cfg_ref = rescale_for_display( + ref_vals, layer, normalizer=normalizer, + oracle_name=oracle_name, assay_id=assay_id, ) - if ref_fl is None: - return False, ref_vals, alt_vals - alt_fl = normalizer.perbin_floor_rescale_batch( - oracle_name, assay_id, alt_vals, - floor_pctile=floor_p, - peak_pctile=_PEAK_PCTILE, - max_value=_DISPLAY_MAX, + alt_out, cfg_alt = rescale_for_display( + alt_vals, layer, normalizer=normalizer, + oracle_name=oracle_name, assay_id=assay_id, ) - if alt_fl is None: - return False, ref_vals, alt_vals - return True, ref_fl, alt_fl + # Both ref/alt should have identical scale_cfg (same track, same CDF). + # If either failed to rescale, fall back to passthrough. + if not (cfg_ref["rescaled"] and cfg_alt["rescaled"]): + return False, ref_vals, alt_vals, cfg_ref["signed"] + return True, ref_out, alt_out, cfg_ref["signed"] + +def _calculate_track_bin_size( + resolution: int, + window_bp: int, + source_oracle: str, +) -> tuple[int, str]: + """Calculate appropriate bin size and aggregation method. + + Returns: + (bin_size, aggregation_method) where aggregation is "mean" or "max" + """ + # For chrombpnet or legnet models, apply max pooling + # For any other oracle, apply mean pooling. + # ChromBPNet's 1-bp output produces narrow tall peaks; mean-pooling + # over 20 bp dilutes a single sharp peak with 19 near-zero neighbors, + # then the p95 floor-rescale clips the diluted value below zero — + # the panel ends up 97 % empty. Max-pooling preserves the peak top + # within each 20-bp bin so the panel actually shows the peak shape. + # (PR #79's description says "max pooling preserves peak signals for + # ChromBPNet"; the original code path returned "mean" — taking the + # description as ground truth.) + if source_oracle == "chrombpnet": + bin_size = 20 + return bin_size, "max" + elif source_oracle == "legnet": + return resolution, "max" + + # Fallback: return 3_000 features per bin + num_features = 3_000 + bin_size = window_bp // num_features + return bin_size, "mean" def build_igv_html( ref_pred, @@ -279,30 +408,45 @@ def build_igv_html( layer = classify_track_layer(ref_track) rgb = _LAYER_COLORS.get(layer, "70,130,180") - t_start = ref_track.prediction_interval.reference.start t_res = ref_track.resolution + actual_bp_in_array = len(ref_track.values) * t_res + t_start = variant_pos - (actual_bp_in_array // 2) ref_vals = ref_track.values alt_vals = alt_track.values # Apply layer-aware floor-subtract + rescale when available floor_ok = False + signed_track = False if use_floor: - floor_ok, ref_vals, alt_vals = apply_floor_rescale( + floor_ok, ref_vals, alt_vals, signed_track = apply_floor_rescale( normalizer, oracle_name, assay_id, layer, ref_vals, alt_vals, ) + track_bin_size, agg_method = _calculate_track_bin_size( + t_res, window_bp, first.source_model, + ) + + # Signed tracks have negative values that ``skip_zeros`` would + # incorrectly count as background — disable the threshold drop + # so the repressive half stays in the wig features. ref_features = _downsample_to_features( - ref_vals, variant_chrom, t_start, t_res, bin_size, - skip_zeros=not floor_ok, + ref_vals, variant_chrom, t_start, t_res, track_bin_size, + skip_zeros=not (floor_ok or signed_track), + aggregation_method=agg_method ) alt_features = _downsample_to_features( - alt_vals, variant_chrom, t_start, t_res, bin_size, - skip_zeros=not floor_ok, + alt_vals, variant_chrom, t_start, t_res, track_bin_size, + skip_zeros=not (floor_ok or signed_track), + aggregation_method=agg_method ) group_id = assay_id.replace(":", "_").replace(" ", "_") - if floor_ok: + if floor_ok and signed_track: + # Symmetric signed scale: ±1.0 = genome-wide top-1% |effect|. + scale_cfg = {"min": -_DISPLAY_MAX, "max": _DISPLAY_MAX, "autoscale": False} + name_suffix = "" + elif floor_ok: scale_cfg = {"min": 0, "max": _DISPLAY_MAX, "autoscale": False} name_suffix = "" else: @@ -322,6 +466,7 @@ def build_igv_html( display_name = f"{ref_track.assay_type}:{ref_track.cell_type}" # Merged overlay: ref (grey) + alt (coloured) on same panel + source_model = first.source_model tracks.append({ "name": f"{display_name}{name_suffix}", "type": "merged", @@ -331,6 +476,7 @@ def build_igv_html( "type": "wig", "name": f"{display_name} ref", "color": f"rgb({_REF_COLOR})", + "windowFunction": "max" if source_model in _HIGH_RES_ORACLES else "mean", **scale_cfg, "features": ref_features, }, @@ -338,6 +484,7 @@ def build_igv_html( "type": "wig", "name": f"{display_name} alt", "color": f"rgb({rgb})", + "windowFunction": "max" if source_model in _HIGH_RES_ORACLES else "mean", **scale_cfg, "features": alt_features, }, @@ -408,6 +555,7 @@ def _downsample_to_features( resolution: int, bin_size: int, skip_zeros: bool = True, + aggregation_method: str = "mean" ) -> list[dict]: """Downsample a signal array into IGV wig features. @@ -430,7 +578,11 @@ def _downsample_to_features( for i in range(0, n, bins_per): chunk = vals[i:i + bins_per] - v = float(np.mean(chunk)) + + if aggregation_method == "mean": + v = float(np.mean(chunk)) + else: + v = float(np.max(chunk)) # Skip near-zero bins to reduce JSON size (only for raw data) if skip_zeros and abs(v) < threshold * 0.1: diff --git a/chorus/analysis/_track_figure.py b/chorus/analysis/_track_figure.py index c2d311c..ea4090d 100644 --- a/chorus/analysis/_track_figure.py +++ b/chorus/analysis/_track_figure.py @@ -54,21 +54,22 @@ def render_track_figures( gene_name: Optional[str] = None, zoom_in_bp: int = 2000, dpi: int = 150, + normalizer=None, + oracle_name: Optional[str] = None, + normalize: bool = True, ) -> dict[str, str]: """Render zoom-in and zoom-out track figures as base64-encoded PNGs. - Args: - ref_pred: Reference OraclePrediction. - alt_pred: Alternate OraclePrediction. - variant_chrom: Chromosome. - variant_pos: Variant genomic position. - gene_name: Gene to highlight in annotation. - zoom_in_bp: Window size (bp) for zoom-in figure. - dpi: Output resolution. - - Returns: - Dict with optional keys ``"zoom_in"`` and ``"zoom_out"``, each - a base64-encoded PNG string. + By default (``normalize=True``) the panels are CDF-rescaled to the + canonical 0–3.0 (unsigned) or ±3.0 (signed) scale used by the IGV / + CoolBox / notebook paths, so every renderer shares one source of + truth: ``1.0 = genome-wide p99``. The normalizer is auto-loaded + from ``~/.chorus/backgrounds/`` (or the HuggingFace mirror) using + the first track's ``source_model`` as the oracle name. + + Pass ``normalize=False`` to opt out and get autoscaled raw values + (legacy behaviour). Pass an explicit ``normalizer=`` / + ``oracle_name=`` to override the auto-load. """ from .scorers import classify_track_layer @@ -95,6 +96,19 @@ def render_track_figures( pred_start = first.prediction_interval.reference.start pred_end = first.prediction_interval.reference.end + # Auto-load normalizer + oracle_name from the track's source_model + # so default usage matches the IGV / CoolBox panels without the + # caller having to pass anything. Pass ``normalize=False`` to opt out. + if normalize: + if oracle_name is None: + oracle_name = getattr(first, "source_model", None) + if normalizer is None and oracle_name: + try: + from chorus.analysis.normalization import get_normalizer + normalizer = get_normalizer(oracle_name) + except Exception: + normalizer = None + results = {} # --- Zoom-in figure --- @@ -108,6 +122,8 @@ def render_track_figures( title=f"Zoom-in: local regulatory context ({variant_chrom}:{variant_pos:,})", show_genes=True, dpi=dpi, + normalizer=normalizer, + oracle_name=oracle_name, ) if b64: results["zoom_in"] = b64 @@ -123,6 +139,8 @@ def render_track_figures( show_genes=True, show_exons=True, dpi=dpi, + normalizer=normalizer, + oracle_name=oracle_name, ) if b64: results["zoom_out"] = b64 @@ -132,11 +150,14 @@ def render_track_figures( # Keep old single-figure API for backwards compat def render_track_figure(ref_pred, alt_pred, variant_chrom, variant_pos, - gene_name=None, zoom_bp=2000, dpi=150): + gene_name=None, zoom_bp=2000, dpi=150, + normalizer=None, oracle_name=None, + normalize: bool = True): """Render track figures. Returns the zoom-in PNG (or first available).""" figs = render_track_figures( ref_pred, alt_pred, variant_chrom, variant_pos, gene_name=gene_name, zoom_in_bp=zoom_bp, dpi=dpi, + normalizer=normalizer, oracle_name=oracle_name, normalize=normalize, ) return figs.get("zoom_in", figs.get("zoom_out", "")) @@ -150,6 +171,7 @@ def _render_figure( variant_chrom, variant_pos, gene_name, x_start, x_end, pred_start, pred_end, title="", show_genes=True, show_exons=False, dpi=150, + normalizer=None, oracle_name=None, ) -> str: """Render a multi-panel figure for a subset of tracks.""" import matplotlib @@ -206,6 +228,8 @@ def _render_figure( show_legend=(i == 0), show_exon_shading=(show_exons and exons is not None), exons=exons, + normalizer=normalizer, + oracle_name=oracle_name, ) # Gene annotation panel @@ -244,12 +268,19 @@ def _plot_track_panel( x_start, x_end, variant_pos, assay_id, color, show_legend=False, show_exon_shading=False, exons=None, + normalizer=None, oracle_name=None, ): """Plot a single ref-vs-alt signal panel.""" import matplotlib.ticker as ticker + from .scorers import classify_track_layer, LAYER_CONFIGS + from ._igv_report import rescale_for_display + t_res = ref_track.resolution t_start = ref_track.prediction_interval.reference.start + layer = classify_track_layer(ref_track) + layer_cfg = LAYER_CONFIGS.get(layer) + is_signed = bool(layer_cfg and layer_cfg.signed) # Extract the visible window from the arrays bin_s = max(0, (x_start - t_start) // t_res) @@ -263,6 +294,27 @@ def _plot_track_panel( ref_vals = ref_track.values[bin_s:bin_e].astype(np.float64) alt_vals = alt_track.values[bin_s:bin_e].astype(np.float64) + # Unified rescale (same path IGV/CoolBox/notebooks use). When a + # normalizer is supplied, ref/alt are CDF-rescaled to [0, 3] (unsigned) + # or [-3, +3] (signed) and the y-axis snaps to those limits. Without + # a normalizer we fall through to the legacy autoscale (with the + # signed-layer symmetric y-axis fix below). + rescaled_cfg = None + if normalizer is not None and oracle_name is not None: + ref_resc, cfg_r = rescale_for_display( + ref_vals, layer, normalizer=normalizer, + oracle_name=oracle_name, assay_id=assay_id, + ) + alt_resc, cfg_a = rescale_for_display( + alt_vals, layer, normalizer=normalizer, + oracle_name=oracle_name, assay_id=assay_id, + ) + if cfg_r["rescaled"] and cfg_a["rescaled"]: + ref_vals = np.asarray(ref_resc) + alt_vals = np.asarray(alt_resc) + rescaled_cfg = cfg_r + is_signed = cfg_r["signed"] + # Smooth n = len(ref_vals) if n > 50: @@ -297,9 +349,28 @@ def _plot_track_panel( ax.set_ylabel(assay_id, fontsize=8, fontweight="bold", rotation=0, labelpad=65, ha="right", va="center") - # Y-axis - ymax = max(float(np.max(ref_vals)), float(np.max(alt_vals)), 0.01) * 1.05 - ax.set_ylim(bottom=0, top=ymax) + # Y-axis: when CDF-rescaled, snap to the canonical [0,3] (unsigned) + # or [-3,+3] (signed) range so the panel is comparable to the IGV/ + # CoolBox/notebook renders of the same track. When NOT rescaled + # (no normalizer), fall back to autoscale with the signed-layer + # symmetric range so the negative tail of RNA/Sei/MPRA tracks stays + # visible. + if rescaled_cfg is not None: + ax.set_ylim(bottom=rescaled_cfg["ymin"], top=rescaled_cfg["ymax"]) + if rescaled_cfg["signed"]: + ax.axhline(0, color="#9ca3af", linewidth=0.4, linestyle=":", + alpha=0.6, zorder=1) + elif is_signed: + vmax = max(float(np.max(ref_vals)), float(np.max(alt_vals)), 0.0) + vmin = min(float(np.min(ref_vals)), float(np.min(alt_vals)), 0.0) + span = max(vmax - vmin, 0.01) * 1.05 + center = (vmax + vmin) / 2.0 + ax.set_ylim(bottom=center - span / 2.0, top=center + span / 2.0) + ax.axhline(0, color="#9ca3af", linewidth=0.4, linestyle=":", + alpha=0.6, zorder=1) + else: + ymax = max(float(np.max(ref_vals)), float(np.max(alt_vals)), 0.01) * 1.05 + ax.set_ylim(bottom=0, top=ymax) ax.yaxis.set_major_locator(ticker.MaxNLocator(nbins=3, integer=False)) ax.tick_params(axis="y", labelsize=7, length=2) ax.tick_params(axis="x", labelsize=0, length=0) diff --git a/chorus/analysis/causal.py b/chorus/analysis/causal.py index 7290b42..ba5618d 100644 --- a/chorus/analysis/causal.py +++ b/chorus/analysis/causal.py @@ -984,6 +984,8 @@ def _build_causal_igv(result: CausalResult) -> str: from ._igv_report import ( _DISPLAY_MAX, _REF_COLOR, + _HIGH_RES_ORACLES, + _calculate_track_bin_size, _downsample_to_features, apply_floor_rescale, ) @@ -993,7 +995,6 @@ def _build_causal_igv(result: CausalResult) -> str: pred_start = first_track.prediction_interval.reference.start pred_end = first_track.prediction_interval.reference.end window_bp = pred_end - pred_start - bin_size = max(1, window_bp // 3000) alt_rgb = _TOP_VARIANT_COLORS[vi]["r"] if vi < len(_TOP_VARIANT_COLORS) else "70,130,180" # Route signal tracks through the shared floor-rescale helper @@ -1027,27 +1028,41 @@ def _build_causal_igv(result: CausalResult) -> str: display = track_display.get(aid, aid) layer = classify_track_layer(ref_t) - floor_ok, ref_vals, alt_vals = apply_floor_rescale( + floor_ok, ref_vals, alt_vals, signed_track = apply_floor_rescale( normalizer, oracle_name, aid, layer, ref_t.values, alt_t.values, ) + # Per-oracle bin size + aggregation: high-resolution + # oracles (chrombpnet 1 bp, legnet 200 bp) use max-pooling + # so sharp peaks don't get diluted to invisibility when + # zoomed out — see _igv_report._calculate_track_bin_size. + source_model = getattr(ref_t, "source_model", "") or "" + track_bin_size, agg_method = _calculate_track_bin_size( + t_res, window_bp, source_model, + ) + ref_feats = _downsample_to_features( - ref_vals, chrom, t_start, t_res, bin_size, - skip_zeros=not floor_ok, + ref_vals, chrom, t_start, t_res, track_bin_size, + skip_zeros=not (floor_ok or signed_track), + aggregation_method=agg_method, ) alt_feats = _downsample_to_features( - alt_vals, chrom, t_start, t_res, bin_size, - skip_zeros=not floor_ok, + alt_vals, chrom, t_start, t_res, track_bin_size, + skip_zeros=not (floor_ok or signed_track), + aggregation_method=agg_method, ) group_id = f"{aid}_{top_s.variant_id}".replace(":", "_").replace(" ", "_") - if floor_ok: + if floor_ok and signed_track: + scale_cfg = {"min": -_DISPLAY_MAX, "max": _DISPLAY_MAX, "autoscale": False} + elif floor_ok: scale_cfg = {"min": 0, "max": _DISPLAY_MAX, "autoscale": False} else: scale_cfg = {"autoscale": True, "autoscaleGroup": group_id} rank_label = _TOP_VARIANT_COLORS[vi]["label"] if vi < len(_TOP_VARIANT_COLORS) else f"#{vi+1}" + wf = "max" if source_model in _HIGH_RES_ORACLES else "mean" tracks.append({ "name": f"{display} ({rank_label} {top_s.variant_id})", "type": "merged", @@ -1057,6 +1072,7 @@ def _build_causal_igv(result: CausalResult) -> str: "type": "wig", "name": f"{display} ref", "color": f"rgb({_REF_COLOR})", + "windowFunction": wf, **scale_cfg, "features": ref_feats, }, @@ -1064,6 +1080,7 @@ def _build_causal_igv(result: CausalResult) -> str: "type": "wig", "name": f"{display} alt", "color": f"rgb({alt_rgb})", + "windowFunction": wf, **scale_cfg, "features": alt_feats, }, diff --git a/chorus/analysis/multi_oracle_report.py b/chorus/analysis/multi_oracle_report.py index d39a991..70300a7 100644 --- a/chorus/analysis/multi_oracle_report.py +++ b/chorus/analysis/multi_oracle_report.py @@ -364,23 +364,35 @@ def build_unified_igv_html(self) -> str: window_bp = ( ref_t.prediction_interval.reference.end - t_start ) - bin_size = max(1, window_bp // 3000) + + from ._igv_report import ( + _calculate_track_bin_size, + _HIGH_RES_ORACLES + ) + bin_size, agg_method = _calculate_track_bin_size( + t_res, window_bp, ref_t.source_model + ) ref_vals = ref_t.values alt_vals = alt_t.values - floor_ok, ref_vals, alt_vals = apply_floor_rescale( + floor_ok, ref_vals, alt_vals, signed_track = apply_floor_rescale( normalizer, oracle_for_norm, aid, layer, ref_vals, alt_vals, ) ref_features = _downsample_to_features( ref_vals, pred_chrom, t_start, t_res, bin_size, - skip_zeros=not floor_ok, + skip_zeros=not (floor_ok or signed_track), + aggregation_method=agg_method ) alt_features = _downsample_to_features( alt_vals, pred_chrom, t_start, t_res, bin_size, - skip_zeros=not floor_ok, + skip_zeros=not (floor_ok or signed_track), + aggregation_method=agg_method ) - if floor_ok: + if floor_ok and signed_track: + scale_cfg = {"min": -_DISPLAY_MAX, "max": _DISPLAY_MAX, + "autoscale": False} + elif floor_ok: scale_cfg = {"min": 0, "max": _DISPLAY_MAX, "autoscale": False} else: @@ -391,6 +403,12 @@ def build_unified_igv_html(self) -> str: # Prefix track label with oracle name so stacked panels # are identifiable at a glance. panel_label = f"{oracle_name} · {short}" + + if oracle_name == "legnet": + # LentiMPRA uses per-track normalization (no per-bin background distribution). + panel_label = f"{panel_label} (per-track norm)" + + source_model = ref_t.source_model tracks.append({ "name": panel_label, "type": "merged", @@ -400,6 +418,7 @@ def build_unified_igv_html(self) -> str: "type": "wig", "name": f"{panel_label} ref", "color": f"rgb({_REF_COLOR})", + "windowFunction": "max" if source_model in _HIGH_RES_ORACLES else "mean", **scale_cfg, "features": ref_features, }, @@ -407,6 +426,7 @@ def build_unified_igv_html(self) -> str: "type": "wig", "name": f"{panel_label} alt", "color": f"rgb({rgb})", + "windowFunction": "max" if source_model in _HIGH_RES_ORACLES else "mean", **scale_cfg, "features": alt_features, }, diff --git a/chorus/analysis/normalization.py b/chorus/analysis/normalization.py index 5fa1eb3..0ce6007 100644 --- a/chorus/analysis/normalization.py +++ b/chorus/analysis/normalization.py @@ -366,12 +366,19 @@ def has_oracle(self, oracle_name: str) -> bool: return True return self.npz_path(oracle_name).exists() + # Oracles that share an identical CDF with another oracle. + _CDF_ALIASES: dict[str, str] = {"alphagenome_pt": "alphagenome"} + def _ensure_loaded(self, oracle_name: str) -> dict | None: """Lazy-load the NPZ for *oracle_name*. Returns the data dict or None.""" if oracle_name in self._loaded: return self._loaded[oracle_name] path = self.npz_path(oracle_name) if not path.exists(): + # Fall back to a known alias (e.g. alphagenome_pt → alphagenome) + alias = self._CDF_ALIASES.get(oracle_name) + if alias: + return self._ensure_loaded(alias) return None data = np.load(str(path), allow_pickle=False) entry = { @@ -473,6 +480,8 @@ def _lookup( if cdf_matrix is None: return None idx = entry["track_index"].get(track_id) + if idx is None and track_id.endswith((":+", ":-")): + idx = entry["track_index"].get(track_id.rsplit(":", 1)[0]) if idx is None: return None if not self._has_samples(entry, cdf_key, idx): @@ -501,6 +510,8 @@ def _lookup_batch( if cdf_matrix is None: return None idx = entry["track_index"].get(track_id) + if idx is None and track_id.endswith((":+", ":-")): + idx = entry["track_index"].get(track_id.rsplit(":", 1)[0]) if idx is None: return None if not self._has_samples(entry, cdf_key, idx): @@ -550,6 +561,71 @@ def perbin_percentile_batch( ) -> np.ndarray | None: """Map per-bin values to genome-wide percentiles [0, 1] for visualization.""" return self._lookup_batch(oracle_name, track_id, "perbin_cdfs", raw_values, signed=False) + + def _find_matching_cdf(self, entry: dict, idx: int, track_id: str) -> np.ndarray | None: + """Retrieve the CDF array for track at *idx*, falling back through CDF types. + + Tries perbin_cdfs → summary_cdfs → effect_cdfs, returning the first + valid array whose corresponding ``*_counts`` > 0. Skipping CDF + types with zero samples means a track that failed to build at the + per-bin stage but succeeded at summary still gets the summary CDF + (rather than landing on the all-zero perbin row, which would + saturate every display value to ``max_value``). + """ + for cdf_key in ("perbin_cdfs", "summary_cdfs", "effect_cdfs"): + cdf_matrix = entry.get(cdf_key) + if cdf_matrix is None: + continue + + try: + cdf = cdf_matrix[idx] + except (IndexError, TypeError): + continue + + if cdf is None or len(cdf) == 0: + continue + + # Skip CDF types where this track has no background samples + # (counts[idx] == 0 → all-zero CDF row from a failed build). + if not self._has_samples(entry, cdf_key, idx): + continue + + logger.debug(f"Using {cdf_key} for '{track_id}'") + return cdf + + logger.warning(f"No valid CDF found for '{track_id}' (index {idx})") + return None + + def _match_track_id(self, track_id: str, track_index: dict) -> str | None: + """Find *track_id* in *track_index*, trying common alternative formats. + + Returns the matched key, or None if no match is found. + """ + if track_id in track_index: + return track_id + + # Build candidate list from track_id components + parts = track_id.split(":") + candidates = [ + track_id.replace(":", "_"), + track_id.replace("_", ":"), + ] + # CHIP strand suffix: BPNet/CHIP track IDs end in ":+" or ":-" but + # the CDF row is keyed without the strand (e.g. "CHIP:HepG2:CEBPA" + # not "CHIP:HepG2:CEBPA:+"). Strip the suffix so per-strand + # predictions still hit the merged CDF. + if track_id.endswith((":+", ":-")): + candidates.append(track_id.rsplit(":", 1)[0]) + if len(parts) >= 2: + candidates.append(parts[-1]) # Last component only + + for candidate in candidates: + if candidate in track_index: + logger.debug(f"Track ID matched: '{track_id}' → '{candidate}'") + return candidate + + logger.warning(f"Track '{track_id}' not found (candidates: {candidates})") + return None def perbin_floor_rescale_batch( self, @@ -558,7 +634,7 @@ def perbin_floor_rescale_batch( raw_values: np.ndarray, floor_pctile: float = 0.95, peak_pctile: float = 0.99, - max_value: float = 1.5, + max_value: float = 3.0, ) -> np.ndarray | None: """Rescale raw bin values using CDF-derived noise floor and peak threshold. @@ -583,17 +659,29 @@ def perbin_floor_rescale_batch( entry = self._ensure_loaded(oracle_name) if entry is None: return None - cdf_matrix = entry.get("perbin_cdfs") - if cdf_matrix is None: + + # Match track ID with possible alternative formats + track_index = entry.get("track_index", {}) + matched_id = self._match_track_id(track_id, track_index) + if matched_id is None: return None - idx = entry["track_index"].get(track_id) - if idx is None: + + idx = track_index[matched_id] + + # Find appropriate CDF (perbin → summary → effect fallback). + # ``_find_matching_cdf`` skips CDF types with zero samples per + # track, so failed-build perbin rows fall through to summary + # rather than saturating every display bin to ``max_value``. + cdf = self._find_matching_cdf(entry, idx, matched_id) + if cdf is None: return None - cdf = cdf_matrix[idx] + + # Compute thresholds and rescale n = len(cdf) floor = float(cdf[min(int(floor_pctile * n), n - 1)]) peak = float(cdf[min(int(peak_pctile * n), n - 1)]) denom = max(peak - floor, 1e-9) + out = (raw_values.astype(np.float64) - floor) / denom return np.clip(out, 0.0, max_value) @@ -605,10 +693,55 @@ def is_signed(self, oracle_name: str, track_id: str) -> bool: flags = entry.get("signed_flags") if flags is None: return False - idx = entry["track_index"].get(track_id) - if idx is None: + # Use the same fuzzy track-id matching as perbin_floor_rescale_batch + # so callers don't have to know the exact NPZ key (e.g. LegNet + # passes "LentiMPRA:HepG2" but the row is keyed "HepG2"). + track_index = entry.get("track_index", {}) + matched_id = self._match_track_id(track_id, track_index) + if matched_id is None: return False - return bool(flags[idx]) + return bool(flags[track_index[matched_id]]) + + def signed_floor_rescale_batch( + self, + oracle_name: str, + track_id: str, + raw_values: np.ndarray, + peak_pctile: float = 0.99, + max_value: float = 3.0, + ) -> np.ndarray | None: + """Rescale **signed** raw values to ``[-max_value, +max_value]``. + + Uses ``p99(|cdf|)`` as the unit so ``±1.0`` corresponds to the + genome-wide top-1% absolute effect for the track. Both the + positive and negative tails render symmetrically, unlike + :meth:`perbin_floor_rescale_batch` which clips negatives to 0. + + Same CDF-fallback chain as the unsigned version + (perbin → summary → effect via :meth:`_find_matching_cdf`), + so e.g. LegNet (no ``perbin_cdfs``) uses ``summary_cdfs``. + """ + entry = self._ensure_loaded(oracle_name) + if entry is None: + return None + track_index = entry.get("track_index", {}) + matched_id = self._match_track_id(track_id, track_index) + if matched_id is None: + return None + idx = track_index[matched_id] + cdf = self._find_matching_cdf(entry, idx, matched_id) + if cdf is None: + return None + # |cdf|.p99 — the magnitude that defines "1.0" on either side. + # The original CDF is sorted (ascending); for signed values we + # need to compute the abs-percentile from the underlying samples. + abs_cdf = np.sort(np.abs(cdf)) + n = len(abs_cdf) + unit = float(abs_cdf[min(int(peak_pctile * n), n - 1)]) + if unit < 1e-9: + return None + out = raw_values.astype(np.float64) / unit + return np.clip(out, -max_value, max_value) # ------------------------------------------------------------------ # Building / saving @@ -852,6 +985,12 @@ def get_pertrack_normalizer( norm._ensure_loaded(oracle_name) return norm + # alphagenome_pt produces identical predictions to alphagenome (same + # model + weights, different backend), so share the JAX CDF rather + # than requiring a separate upload. + if oracle_name == "alphagenome_pt": + return get_pertrack_normalizer("alphagenome", cache_dir=cache_dir) + return None diff --git a/chorus/cli/_cleanup.py b/chorus/cli/_cleanup.py new file mode 100644 index 0000000..efe6014 --- /dev/null +++ b/chorus/cli/_cleanup.py @@ -0,0 +1,143 @@ +"""chorus cleanup — remove conda envs, downloaded weights, CDFs, and genomes.""" + +from __future__ import annotations + +import shutil +from pathlib import Path +from typing import List, Tuple + +from ..core.globals import CHORUS_DOWNLOADS_DIR, CHORUS_GENOMES_DIR +from ..core.weights_probe import SETUP_MARKER_NAME + +_BACKGROUNDS_DIR = Path.home() / ".chorus" / "backgrounds" + +_ALL_ORACLES = [ + "enformer", "borzoi", "chrombpnet", "sei", "legnet", + "alphagenome", "alphagenome_pt", +] + + +def _dry(msg: str, dry_run: bool) -> None: + prefix = "[DRY RUN] " if dry_run else "" + print(f"{prefix}{msg}") + + +def _remove_path(p: Path, dry_run: bool) -> bool: + """Remove a file or directory tree. Returns True if something was deleted.""" + if not p.exists(): + return False + _dry(f" remove {p}", dry_run) + if not dry_run: + if p.is_dir(): + shutil.rmtree(p) + else: + p.unlink() + return True + + +def _cleanup_oracle( + oracle: str, dry_run: bool, manager +) -> Tuple[int, int]: + """Remove env + weight dir for one oracle. Returns (envs_removed, dirs_removed).""" + envs = 0 + dirs = 0 + + # Conda environment + if manager.environment_exists(oracle): + _dry(f" remove conda env chorus-{oracle}", dry_run) + if not dry_run: + manager.remove_environment(oracle) + envs += 1 + + # Downloaded weights + setup marker + weight_dir = CHORUS_DOWNLOADS_DIR / oracle.lower() + if _remove_path(weight_dir, dry_run): + dirs += 1 + + # Per-oracle background CDF + for pattern in [f"{oracle}_pertrack.npz", f"{oracle}_*.npy"]: + for f in _BACKGROUNDS_DIR.glob(pattern): + _remove_path(f, dry_run) + + return envs, dirs + + +def cleanup_resources(args) -> int: + from ..core.environment import EnvironmentManager + from ..utils.genome import GenomeManager + + manager = EnvironmentManager() + dry_run: bool = args.dry_run + + do_oracle: str | None = getattr(args, "oracle", None) + do_backgrounds: bool = getattr(args, "backgrounds", False) + do_genomes: bool = getattr(args, "genomes", False) + do_all: bool = getattr(args, "all", False) + + if do_all: + do_oracle = "all" + do_backgrounds = True + do_genomes = True + + if not any([do_oracle, do_backgrounds, do_genomes]): + print( + "Nothing to clean up. Specify at least one of:\n" + " --oracle {name|all} conda env + weights\n" + " --backgrounds background CDFs (~/.chorus/backgrounds/)\n" + " --genomes downloaded reference genomes\n" + " --all everything above\n" + "\nAdd --dry-run to preview without deleting." + ) + return 1 + + total_envs = 0 + total_dirs = 0 + total_files = 0 + + # ── Oracle envs + weights ────────────────────────────────────────── + if do_oracle: + oracles: List[str] = _ALL_ORACLES if do_oracle == "all" else [do_oracle] + unknown = [o for o in oracles if o not in _ALL_ORACLES] + if unknown: + print( + f"Unknown oracle(s): {', '.join(unknown)}. " + f"Valid: {', '.join(_ALL_ORACLES)}" + ) + return 1 + + print(f"{'[DRY RUN] ' if dry_run else ''}Cleaning oracle(s): {', '.join(oracles)}") + for oracle in oracles: + e, d = _cleanup_oracle(oracle, dry_run, manager) + total_envs += e + total_dirs += d + + # ── Background CDFs ──────────────────────────────────────────────── + if do_backgrounds and _BACKGROUNDS_DIR.exists(): + print(f"{'[DRY RUN] ' if dry_run else ''}Cleaning backgrounds: {_BACKGROUNDS_DIR}") + for f in sorted(_BACKGROUNDS_DIR.glob("*.npz")) + sorted(_BACKGROUNDS_DIR.glob("*.npy")): + _remove_path(f, dry_run) + total_files += 1 + + # ── Genomes ──────────────────────────────────────────────────────── + if do_genomes: + print(f"{'[DRY RUN] ' if dry_run else ''}Cleaning genomes: {CHORUS_GENOMES_DIR}") + gm = GenomeManager() + for genome_id in gm.list_downloaded_genomes(): + _dry(f" remove genome {genome_id}", dry_run) + if not dry_run: + gm.remove_genome(genome_id) + total_files += 1 + + # ── Summary ──────────────────────────────────────────────────────── + parts = [] + if total_envs: + parts.append(f"{total_envs} environment(s)") + if total_dirs: + parts.append(f"{total_dirs} weight dir(s)") + if total_files: + parts.append(f"{total_files} file(s)") + + verb = "Would remove" if dry_run else "Removed" + summary = f"{verb}: {', '.join(parts)}" if parts else f"{verb}: nothing (already clean)" + print(summary) + return 0 diff --git a/chorus/cli/main.py b/chorus/cli/main.py index 39fca80..85b6eff 100644 --- a/chorus/cli/main.py +++ b/chorus/cli/main.py @@ -82,7 +82,8 @@ def setup_environments(args): if stale.exists(): stale.unlink() - if not manager.create_environment(oracle, force=args.force): + if not manager.create_environment(oracle, force=args.force, + timeout=getattr(args, "setup_timeout", None)): logger.error( f"✗ Failed to build env for {oracle}. " f"Re-run with --force to rebuild, or check the mamba/conda output above." @@ -105,6 +106,7 @@ def setup_environments(args): skip_backgrounds=args.no_backgrounds, skip_genome=args.no_genome, full_chrombpnet=getattr(args, "all_chrombpnet", False), + weights_timeout=getattr(args, "setup_timeout", None), ) if not ok: logger.error(f"✗ Prefetch failed for {oracle}. Details:") @@ -473,6 +475,19 @@ def main(argv: Optional[List[str]] = None): "(~1.8 GB per model on disk)." ), ) + setup_parser.add_argument( + '--setup-timeout', + dest='setup_timeout', + type=int, + default=None, + metavar='SECONDS', + help=( + "Max seconds allowed for each phase (env build and weight " + "download). Default: unlimited. Useful on slow or unstable " + "connections. Set CHORUS_NO_TIMEOUT=1 to disable all timeouts " + "globally." + ), + ) setup_parser.add_argument( '--include-alternative-backends', '--include-experimental', # legacy alias from PR #62 review @@ -596,6 +611,48 @@ def main(argv: Optional[List[str]] = None): from ._backgrounds import register_backgrounds_subcommand bg_parser = register_backgrounds_subcommand(subparsers) + # Cleanup command + from ._cleanup import cleanup_resources + cleanup_parser = subparsers.add_parser( + 'cleanup', + help='Remove conda environments, downloaded weights, CDFs, and genomes', + description=( + "Remove chorus data to free disk space or prepare for a fresh install.\n\n" + "Examples:\n" + " chorus cleanup --oracle enformer # remove one oracle\n" + " chorus cleanup --oracle all # remove all oracle envs + weights\n" + " chorus cleanup --all # everything\n" + " chorus cleanup --all --dry-run # preview without deleting" + ), + formatter_class=argparse.RawDescriptionHelpFormatter, + ) + cleanup_parser.add_argument( + '--oracle', + metavar='NAME', + help='Oracle to clean up (name or "all"). Removes the conda env and downloaded weights.', + ) + cleanup_parser.add_argument( + '--backgrounds', + action='store_true', + help='Remove background CDF files from ~/.chorus/backgrounds/', + ) + cleanup_parser.add_argument( + '--genomes', + action='store_true', + help='Remove downloaded reference genomes', + ) + cleanup_parser.add_argument( + '--all', + action='store_true', + help='Remove everything: all oracle envs, weights, backgrounds, and genomes', + ) + cleanup_parser.add_argument( + '--dry-run', + action='store_true', + help='Print what would be deleted without actually deleting anything', + ) + cleanup_parser.set_defaults(func=cleanup_resources) + # Parse arguments args = parser.parse_args(argv) diff --git a/chorus/core/environment/manager.py b/chorus/core/environment/manager.py index f6380c2..7b82294 100644 --- a/chorus/core/environment/manager.py +++ b/chorus/core/environment/manager.py @@ -214,7 +214,7 @@ def install_chorus_primitive(self, oracle: str) -> bool: raise RuntimeError(f"Execution failed: {result.stderr}") - def create_environment(self, oracle: str, force: bool = False) -> bool: + def create_environment(self, oracle: str, force: bool = False, timeout: int | None = None) -> bool: """ Create a mamba environment for the given oracle. @@ -225,6 +225,8 @@ def create_environment(self, oracle: str, force: bool = False) -> bool: Args: oracle: Name of the oracle force: If True, recreate environment even if it exists + timeout: Max seconds to wait for ``mamba env create``. + None (default) means no limit. Returns: True if successful, False otherwise @@ -304,11 +306,31 @@ def create_environment(self, oracle: str, force: bool = False) -> bool: text=True ) + _timed_out = [] + if timeout is not None: + import threading + def _kill(): + _timed_out.append(True) + process.kill() + timer = threading.Timer(timeout, _kill) + timer.start() + else: + timer = None + # Stream output live for line in process.stdout: print(line, end="") process.wait() + if timer is not None: + timer.cancel() + + if _timed_out: + raise RuntimeError( + f"chorus setup timed out after {timeout}s while building " + f"the {oracle} environment. Re-run with a larger " + f"--setup-timeout value or check your connection." + ) if process.returncode != 0: logger.error(f"Failed to create environment: {process.stderr}") diff --git a/chorus/core/result.py b/chorus/core/result.py index 952936a..6e79423 100644 --- a/chorus/core/result.py +++ b/chorus/core/result.py @@ -315,13 +315,30 @@ def save_as_bedgraph(self, filepath: str, write_header: bool = True): ) track.to_bedgraph(str(filepath), write_header=write_header) - def get_coolbox_representation(self, + def get_coolbox_representation(self, title: str | None = None, - override_params: dict | None = None, - signal_threshold: float | None = None, + override_params: dict | None = None, + signal_threshold: float | None = None, add_xaxis: bool = True, add_highlight: bool = False, - add_vlines: bool = True): + add_vlines: bool = True, + normalizer=None, + oracle_name: str | None = None, + normalize: bool = True): + """Render the track as a CoolBox ``BedGraph`` frame. + + By default (``normalize=True``), values are CDF-rescaled via the + canonical :func:`chorus.analysis._igv_report.rescale_for_display` + helper so this panel uses the **same 0-3.0 / ±3.0 scale and + "1.0 = genome-wide p99" semantics** as the IGV / matplotlib + renderers. The normalizer is auto-loaded from + ``~/.chorus/backgrounds/`` (or the HuggingFace mirror) using + ``self.source_model`` as the oracle name. + + Pass ``normalize=False`` to opt out and get raw autoscaled + values (legacy behaviour). Pass an explicit ``normalizer=`` to + override the auto-load. + """ from coolbox.api import ( BedGraph, TrackHeight, @@ -340,16 +357,50 @@ def get_coolbox_representation(self, if title is None: title = self.assay_id df = self.to_dataframe(use_reference_interval=True) + + # CDF-rescale via the unified helper. Auto-load the per-track + # normalizer from ``~/.chorus/backgrounds/`` (or the HuggingFace + # mirror) using ``self.source_model`` so this panel matches the + # IGV / matplotlib / notebook renders of the same track without + # the caller having to pass anything. Set ``normalize=False`` + # to opt out and get raw autoscaled values. + ymin, ymax = None, None + if normalize: + if oracle_name is None: + oracle_name = getattr(self, "source_model", None) + if normalizer is None and oracle_name: + try: + from chorus.analysis.normalization import get_normalizer + normalizer = get_normalizer(oracle_name) + except Exception: + normalizer = None + if normalizer is not None and oracle_name is not None: + from chorus.analysis._igv_report import rescale_for_display + from chorus.analysis.scorers import classify_track_layer + layer = classify_track_layer(self) + rescaled, cfg = rescale_for_display( + df['value'].to_numpy(), layer, + normalizer=normalizer, oracle_name=oracle_name, + assay_id=self.assay_id, + ) + if cfg["rescaled"]: + df = df.copy() + df['value'] = rescaled + ymin, ymax = cfg["ymin"], cfg["ymax"] + if ymin is None: + ymin = float(min(df['value'].min(), 0)) + ymax = float(df['value'].max()) + coolbox_file = self._storage / self.COOLBOX_FILE_NAME df.to_csv(coolbox_file, sep='\t', index=False, header=False) if signal_threshold is None: - signal_threshold = df['value'].max() + 0.1 - + signal_threshold = ymax + 0.1 + frame = BedGraph(str(coolbox_file), threshold=signal_threshold, threshold_color=coolbox_params['threshold_color']) +\ TrackHeight(coolbox_params['height']) +\ Color(coolbox_params['color']) +\ - MinValue(min(df['value'].min(), 0) ) +\ - MaxValue(df['value'].max()) +\ + MinValue(ymin) +\ + MaxValue(ymax) +\ Title(title) if add_vlines: @@ -560,6 +611,13 @@ def end(self) -> int: def add(self, assay_id: str, track: OraclePredictionTrack): if assay_id in self.tracks: raise Exception(f"The following assay_id already exists: {assay_id}") + # Some oracles (notably ChromBPNet) create the track without an + # explicit assay_id and rely on the OraclePrediction dict key for + # identification. Backfill the field here so downstream code + # (CoolBox auto-rescale, normalization lookups, IGV labels) always + # has a valid assay_id without having to thread the dict key. + if track.assay_id is None: + track.assay_id = assay_id self.tracks[assay_id] = track def __iter__(self): diff --git a/chorus/core/weights_probe.py b/chorus/core/weights_probe.py index 23f81a9..4dd63a0 100644 --- a/chorus/core/weights_probe.py +++ b/chorus/core/weights_probe.py @@ -151,7 +151,10 @@ def _probe_alphagenome_pt() -> Tuple[bool, List[str]]: _ARTIFACT_PROBES: Dict[str, Callable[[], Tuple[bool, List[str]]]] = { "sei": _probe_sei, "legnet": _probe_legnet, - "chrombpnet": _probe_chrombpnet, + # ChromBPNet default path (fold=0, chrombpnet_nobias) downloads to + # the HF hub cache (~/.cache/huggingface/) via the slim mirror, not + # to CHORUS_DOWNLOADS_DIR — same as enformer/borzoi. + "chrombpnet": _probe_library_cached, "alphagenome": _probe_alphagenome, "alphagenome_pt": _probe_alphagenome_pt, "enformer": _probe_library_cached, diff --git a/chorus/oracles/chrombpnet.py b/chorus/oracles/chrombpnet.py index fe2f8fc..a1b6fbf 100644 --- a/chorus/oracles/chrombpnet.py +++ b/chorus/oracles/chrombpnet.py @@ -618,6 +618,17 @@ def _predict(self, seq: str | Tuple[str, int, int] | Interval, assay_ids: List[s else: raise ValueError(f"Unsupported sequence type: {type(seq)}") + # If the caller passes a query wider than the model's input window + # (e.g. PR #79's get_max_output_size makes the multi-oracle region + # ~1 Mb), the legacy `_predict_direct` sliding formula is buggy and + # crashes with an IndexError. Route wide queries through + # `predict_sliding`, which uses the same model.predict_on_batch path + # but with correct stitching. Variant scoring downstream + # (`score_region`) still slices the canonical 501 bp window, so + # the table values are unchanged. + if len(query_interval) > self.sequence_length: + return self.predict_sliding(query_interval, assay_ids) + input_interval = query_interval.extend(self.sequence_length) prediction_interval = query_interval.extend(self.output_size) @@ -683,7 +694,154 @@ def _predict(self, seq: str | Tuple[str, int, int] | Interval, assay_ids: List[s final_prediction.add(track_id, track) return final_prediction - + + def predict_sliding( + self, + seq: "str | Tuple[str, int, int] | Interval", + assay_ids: List[str] = None, + step: int = None, + ) -> OraclePrediction: + """Sliding-window ChromBPNet across a region wider than the model input. + + For an interval longer than ``sequence_length`` (2114 bp), runs the + model at ``step``-spaced centers across the region and stitches the + central ``output_length`` (1000 bp) predictions into a continuous + track. ``step`` defaults to ``output_length`` (non-overlapping + central outputs). + + Returns an :class:`OraclePrediction` whose ``values`` cover exactly + the requested interval at 1 bp resolution, with cigar substitutions + on the input interval preserved (so this works for ref-vs-alt + rendering across a wide locus). + """ + # Resolve to an Interval that supports sequence extraction with cigar + if isinstance(seq, tuple): + chrom, start, end = seq + query_interval = Interval.make(GenomeRef( + chrom=chrom, start=start, end=end, + fasta=self.reference_fasta, + )) + elif isinstance(seq, str): + query_interval = Interval.make(Sequence(sequence=seq)) + elif isinstance(seq, Interval): + query_interval = seq + else: + raise ValueError(f"Unsupported sequence type: {type(seq)}") + + Q = len(query_interval) + if Q <= self.sequence_length: + return self._predict(seq, assay_ids) + + if step is None: + step = self.output_length + if not (0 < step <= self.output_length): + raise ValueError( + f"step must be in (0, output_length={self.output_length}]" + ) + + # Build full sequence over the query (preserves cigar substitutions). + # Then pad with N's on each side so each 2114-bp window has its + # central 1000-bp output landing inside the query. + side_pad = (self.sequence_length - self.output_length) // 2 # 557 + # Number of stride-step windows whose central output covers Q + num_windows = (Q + step - 1) // step + # Total bases needed in the input sequence + needed_len = (num_windows - 1) * step + self.sequence_length + + target_len = max(needed_len, self.sequence_length) + left_pad = side_pad + right_pad = target_len - Q - left_pad + if query_interval.reference.extendible: + stage1 = query_interval.extend(Q + left_pad, how="left") + input_interval = stage1.extend(target_len, how="right") + else: + input_interval = query_interval.extend(target_len, how="both") + full_seq = input_interval.sequence + + import tensorflow as tf + MAPPING = {"A": 0, "C": 1, "G": 2, "T": 3} + N = self.sequence_length + OUT = self.output_length + actual_num_windows = max(1, (len(full_seq) - N) // step + 1) + + all_profiles = [] + BATCH = max(1, getattr(self, "batch_size", 8)) + for batch_start in range(0, actual_num_windows, BATCH): + batch_end = min(batch_start + BATCH, actual_num_windows) + B = batch_end - batch_start + ohe = np.zeros((B, N, 4), dtype=np.float32) + for k in range(B): + offset = (batch_start + k) * step + window = full_seq[offset : offset + N] + for i, base in enumerate(window): + j = MAPPING.get(base.upper()) + if j is not None: + ohe[k, i, j] = 1.0 + ohe_tf = tf.constant(ohe, dtype=tf.float32) + + if self.assay == "CHIP": + profile_bias = np.zeros((B, OUT, 2), dtype=np.float32) + count_bias = np.zeros((B, 1), dtype=np.float32) + preds = self.model.predict_on_batch( + [ohe_tf, profile_bias, count_bias] + ) + else: + preds = self.model.predict_on_batch(ohe_tf) + probs, counts = preds[0], preds[1] + if probs.ndim == 3 and probs.shape[-1] == 2 and self.assay != "CHIP": + probs = probs.sum(axis=-1) + for b in range(B): + p = probs[b] + if p.ndim == 2: + p = p.sum(axis=-1) + norm_p = p - np.mean(p) + sm = np.exp(norm_p) / np.sum(np.exp(norm_p)) + profile = sm * np.exp(counts[b][0]) + all_profiles.append(profile) + + # Stitch central outputs. Window k's central output covers the + # query bases at positions [k*step, k*step + OUT). + out = np.zeros(Q, dtype=np.float64) + weight = np.zeros(Q, dtype=np.float64) + for k, profile in enumerate(all_profiles): + qstart = k * step - left_pad + side_pad + qend = qstart + OUT + qs = max(qstart, 0) + qe = min(qend, Q) + if qe <= qs: + continue + ps = qs - qstart + pe = ps + (qe - qs) + out[qs:qe] += profile[ps:pe] + weight[qs:qe] += 1.0 + weight = np.where(weight == 0, 1.0, weight) + out = out / weight # average overlap (with step=OUT, no overlap → no-op) + + prediction_interval = query_interval + track = OraclePredictionTrack.create( + source_model="chrombpnet", + assay_id=None, + track_id=None, + assay_type=self.assay, + cell_type=self.cell_type, + query_interval=query_interval, + prediction_interval=prediction_interval, + input_interval=input_interval, + resolution=self.bin_size, + values=out, + metadata=None, + preferred_aggregation="mean", + preferred_interpolation="linear_divided", + preferred_scoring_strategy="mean", + ) + track_id = ( + f"{self.assay}:{self.cell_type}" if self.assay != "CHIP" + else f"{self.assay}:{self.cell_type}:{self.tf}:+" + ) + final = OraclePrediction() + final.add(track_id, track) + return final + def _predict_in_environment(self, seq: str, assay_ids: List[str]) -> Tuple[np.ndarray, np.ndarray]: args = { "device": self.device, diff --git a/chorus/utils/annotations.py b/chorus/utils/annotations.py index ededc5e..894fef2 100644 --- a/chorus/utils/annotations.py +++ b/chorus/utils/annotations.py @@ -14,6 +14,7 @@ import os import gzip import logging +import random from pathlib import Path from typing import Optional, Dict, List, Tuple, Union import pandas as pd @@ -715,4 +716,134 @@ def sample_ccre_positions( rng.shuffle(positions) logger.info("Sampled %d positions from %d cCRE categories", len(positions), len(n_per_category)) - return positions \ No newline at end of file + return positions + + +# --------------------------------------------------------------------------- +# Meuleman et al. DHS index (hg38, ~3.6 M peaks) +# --------------------------------------------------------------------------- + +_DHS_VOCAB_CACHE: "pd.DataFrame | None" = None + + +_DHS_VOCAB_HF_REPO = "lucapinello/chorus-backgrounds" +_DHS_VOCAB_HF_FILENAME = "dhs_vocabulary_hg38.txt.gz" +_DHS_VOCAB_SHA256 = "0a4d215026744780ce7f562244e6f46b6387bab9875ca56ad543d30a024c1c48" + + +def load_dhs_vocabulary(dhs_path: "str | None" = None) -> "pd.DataFrame": + """Load the Meuleman et al. DHS Index vocabulary (hg38). + + Columns returned: ``seqname, start, end, identifier, mean_signal, + numsamples, summit, component``. Filtered to autosomes chr1–22. + Cached in process so repeated CDF builds don't re-parse the 90 MB + bgzip every call. + + The file is auto-downloaded from + ``huggingface.co/datasets/lucapinello/chorus-backgrounds`` on first + use (~90 MB, sha256 ``0a4d2150…1c1c48``) and cached at + ``annotations/dhs_vocabulary_hg38.txt.gz`` in the repo root. This + keeps every chorus install (every shard of a multi-GPU CDF rebuild, + every fresh-clone audit) working from byte-identical input — no + manual ``gdown`` step required. + + The original distribution lives at + ``meuleman.org/DHS_Index_and_Vocabulary_hg38_WM20190703.txt.gz``; + our HF mirror is a verbatim copy. + """ + global _DHS_VOCAB_CACHE + if _DHS_VOCAB_CACHE is not None: + return _DHS_VOCAB_CACHE + + if dhs_path is None: + path = Path(CHORUS_ANNOTATIONS_DIR) / "dhs_vocabulary_hg38.txt.gz" + else: + path = Path(dhs_path) + + if not path.exists(): + # Auto-fetch from HuggingFace. Same pattern as per-track NPZ + # downloads — no external Google Drive dependency, no manual + # gdown step needed. + try: + from huggingface_hub import hf_hub_download + except ImportError as exc: + raise FileNotFoundError( + f"DHS vocabulary not found at {path} and huggingface_hub " + f"is not installed. Install it (`pip install huggingface_hub`) " + f"to enable auto-fetch from {_DHS_VOCAB_HF_REPO}, or download " + f"manually with: gdown --id 16wbuNmHnwsek3USWM04nR535vPavNZka " + f"-O {path}." + ) from exc + path.parent.mkdir(parents=True, exist_ok=True) + logger.info( + "DHS vocabulary not cached at %s — downloading from " + "huggingface.co/datasets/%s ...", + path, _DHS_VOCAB_HF_REPO, + ) + downloaded = hf_hub_download( + repo_id=_DHS_VOCAB_HF_REPO, + filename=_DHS_VOCAB_HF_FILENAME, + repo_type="dataset", + local_dir=str(path.parent), + ) + # hf_hub_download usually returns the same path; if not, move it. + dl_path = Path(downloaded) + if dl_path.resolve() != path.resolve() and dl_path.exists(): + dl_path.replace(path) + if not path.exists(): + raise FileNotFoundError( + f"DHS vocabulary download finished but file not found at " + f"{path}. Tried HF mirror {_DHS_VOCAB_HF_REPO}." + ) + logger.info("DHS vocabulary cached at %s", path) + df = pd.read_csv( + path, sep="\t", compression="gzip", low_memory=False, + usecols=["seqname", "start", "end", "identifier", + "mean_signal", "numsamples", "summit", "component"], + ) + valid = {f"chr{i}" for i in range(1, 23)} + df = df[df["seqname"].isin(valid)].copy() + _DHS_VOCAB_CACHE = df + logger.info("Loaded %d DHS peaks across %d components", + len(df), df["component"].nunique()) + return df + + +def sample_dhs_positions( + n: int, + dhs_path: "str | None" = None, + min_numsamples: "int | None" = None, + max_numsamples: "int | None" = None, + min_signal_quantile: "float | None" = None, + max_signal_quantile: "float | None" = None, + seed: int = 42, +) -> "list[tuple[str, int]]": + """Sample (chrom, summit) positions from the Meuleman DHS vocabulary. + + Simple seeded random sampling. Optional filters: + + - ``min_numsamples`` / ``max_numsamples`` constrain cell-type + specificity (1 = highly specific, 733 = ubiquitous). + - ``min_signal_quantile`` / ``max_signal_quantile`` constrain peak + strength via the empirical ``mean_signal`` distribution. + + Returns at most ``n`` positions. + """ + df = load_dhs_vocabulary(dhs_path) + if min_numsamples is not None: + df = df[df["numsamples"] >= min_numsamples] + if max_numsamples is not None: + df = df[df["numsamples"] <= max_numsamples] + if min_signal_quantile is not None: + lo = df["mean_signal"].quantile(min_signal_quantile) + df = df[df["mean_signal"] >= lo] + if max_signal_quantile is not None: + hi = df["mean_signal"].quantile(max_signal_quantile) + df = df[df["mean_signal"] <= hi] + rng = random.Random(seed) + k = min(n, len(df)) + chosen = rng.sample(range(len(df)), k) + return [ + (df.iloc[i]["seqname"], int(df.iloc[i]["summit"])) + for i in chosen + ] \ No newline at end of file diff --git a/chorus/utils/genome.py b/chorus/utils/genome.py index 9770b19..a522fc8 100644 --- a/chorus/utils/genome.py +++ b/chorus/utils/genome.py @@ -132,15 +132,22 @@ def download_genome(self, genome_id: str, force: bool = False) -> bool: logger.info(f"Downloading {genome_id} from {url}...") logger.info("This may take several minutes depending on your connection speed...") download_with_resume(url, gz_path, label=f"{genome_id} genome") - - # Decompress - logger.info(f"Decompressing {genome_id}...") - with gzip.open(gz_path, 'rb') as f_in: - with open(fasta_path, 'wb') as f_out: - shutil.copyfileobj(f_in, f_out) - - # Remove compressed file - gz_path.unlink() + + # Decompress — guard against concurrent runs where another + # process may have already decompressed and deleted the .gz. + if fasta_path.exists(): + gz_path.unlink(missing_ok=True) + elif gz_path.exists(): + logger.info(f"Decompressing {genome_id}...") + with gzip.open(gz_path, 'rb') as f_in: + with open(fasta_path, 'wb') as f_out: + shutil.copyfileobj(f_in, f_out) + gz_path.unlink(missing_ok=True) + else: + raise FileNotFoundError( + f"{gz_path} missing after download and {fasta_path} " + "not present — re-run with --force to retry." + ) # Create FASTA index logger.info(f"Creating FASTA index for {genome_id}...") diff --git a/docs/NORMALIZATION_GUIDE.md b/docs/NORMALIZATION_GUIDE.md index 4a869da..7009cff 100644 --- a/docs/NORMALIZATION_GUIDE.md +++ b/docs/NORMALIZATION_GUIDE.md @@ -637,46 +637,271 @@ prefetch and discovery to work end-to-end. ### Step 4: Write the CDF build script -Create `scripts/build_backgrounds_myoracle.py`. Follow the pattern of -any existing build script. The key structure: +The CDF build is where most of the layer-specific judgment lives. +A new oracle can't reuse an existing build script verbatim because +**what you sample matters more than how you score**. The same model +will produce wildly different percentiles depending on whether your +"baseline" reservoir was drawn from random genome (mostly silent), +ENCODE cCREs (mostly active), DHS summits (open chromatin), +TSSs (transcription start), exons (gene bodies), or splice junctions. +This section is the recipe. + +#### What goes in each CDF + +Each oracle ships **three CDF matrices** (`(n_tracks, n_points)` each) +in a single `{oracle}_pertrack.npz`: + +| CDF | Sampled from | Used for | +|---|---|---| +| `effect_cdfs` | **|effect|** (or signed effect) of ~10–20 K SNPs against the same track | "How unusual is this variant's effect?" → `Effect %ile` column in reports | +| `summary_cdfs` | **window-sum** (or layer-specific aggregate) at ~30–35 K genomic positions | "How active is this site genome-wide?" → `Activity %ile` column | +| `perbin_cdfs` | **individual bin values** at the same baseline positions, dozens of bins per position | IGV / matplotlib / CoolBox display rescale via `rescale_for_display` | + +Each row is a **sorted** array (the empirical CDF). Lookups use binary +search; see [Lookup mechanism](#lookup-mechanism). All three CDFs use the +same baseline position set — you sample the positions once and feed +them into both `summary_cdfs` (window aggregate) and `perbin_cdfs` +(per-bin values within the window). + +Rule of thumb for sample counts: **~20 K samples per track** for +effect, **~30–35 K** for summary, **~1 M total** for perbin (tens of +bins × thousands of positions). Below that you start seeing +visible discreteness in the percentile output. + +#### Reservoir sampling in practice + +For long runs (e.g. 1 M perbin samples × 786 tracks), build the CDF +incrementally using the `ReservoirSampler` pattern from +`scripts/build_backgrounds_chrombpnet.py:ReservoirSampler` — +fixed-capacity uniform sampling so memory stays bounded. The sampler +exposes `to_cdf_matrix(n_points=10000)` which returns the compact +sorted CDF directly. + +#### What to sample, layer by layer + +Helpers used below all live in `chorus.utils.annotations`: +`sample_ccre_positions()`, `sample_dhs_positions()`, +`load_dhs_vocabulary()`, `get_gene_tss()`, `get_gene_exons()`, +`get_screen_ccres()`. All of them are seeded and produce +deterministic outputs. + +**`chromatin_accessibility` (DNASE / ATAC) — sharp, focused peaks.** +Window 501 bp, log2FC, unsigned. + +- **Effect**: ~10 K random genome-wide SNPs (existing) + ~10 K SNPs at + random offsets within ±150 bp of DHS peak summits + (`sample_dhs_positions(10_000, ...)`). Mixing in DHS-anchored SNPs + shifts the interpretation from "unusual among all genomic SNPs" + toward "unusual among SNPs at real regulatory elements" — much more + discriminating for cell-type-specific peaks. See + `scripts/build_backgrounds_chrombpnet.py` `--n-dhs-variants` + for the canonical implementation. +- **Summary / perbin baseline**: ~25 K random + cCRE positions + (`sample_ccre_positions()`) + ~5 K DHS summits + (`sample_dhs_positions(5_000, ...)`). + +**`tf_binding` (ChIP-TF) — sharp binding peaks.** Window 501 bp, +log2FC, unsigned. + +- **Effect**: random SNPs + (optionally) DHS-anchored SNPs as above. + The 744 BPNet/CHIP tracks in the canonical chrombpnet NPZ use the + same random+DHS recipe — TF binding sites overlap heavily with + open chromatin, so DHS sampling is the cheapest "in TF-relevant + regions" enrichment. +- **Summary / perbin baseline**: random + cCRE (`PLS`, `dELS`, `pELS`, + `CA-CTCF`, `CA-TF`) + DHS summits. + +**`histone_marks` (ChIP-Histone) — broad domains.** Window **2001 bp** +(not 501 — histones cover wider regions), log2FC, unsigned. + +- **Effect**: same random + DHS recipe; the wider scoring window + averages over the histone domain. +- **Summary / perbin baseline**: random + cCRE (especially `pELS` + and `dELS`) + DHS summits. + +**`tss_activity` (CAGE / PRO-CAP) — TSS-localized.** Window 501 bp, +log2FC, unsigned. + +- **Effect**: random SNPs is fine — CAGE peaks are sharp, sample + quality dominates over enrichment. +- **Summary / perbin baseline**: random + cCRE **+ explicitly + GENCODE TSSs** (use `get_gene_tss()` over a list of protein-coding + genes, sample ~5–10 K). Without TSSs the summary distribution is + dominated by silent regions and produces inflated "this CAGE site + is active" percentiles. See `build_backgrounds_borzoi.py` and + `build_backgrounds_alphagenome.py` for how the 'CAGE summary + routing' adds TSSs while skipping cCREs. + +**`gene_expression` (RNA-seq) — broad gene bodies; signed effects.** +Window **N/A — exon-based**, logfc, **signed**. + +- **Effect**: random SNPs scored as `mean(prediction[exon_bins])` for + each gene — i.e. for each variant, find the nearest gene's exons, + average the model's per-bin predictions over those exon bins, then + compute the log fold change of that exon-mean vs ref. This is + RNA-specific: gene expression is integrated over exons, not at one + point. See `build_backgrounds_borzoi.py:exon_bins_for_window` for + the exon-mask machinery. +- **Summary / perbin baseline**: gene-body midpoints (use + `get_gene_exons()` per gene, sample midpoint per gene; ~10–15 K + genes). RNA tracks are signed because alleles can repress + transcription — effect/summary CDFs include negative values, so + set `signed_flags[idx] = True` for these tracks. Display rescale + for signed tracks goes through `signed_floor_rescale_batch` + (symmetric `[-3, +3]`) instead of the unsigned floor-rescale. + +**`splicing` (splice site / SPLICE_SITES) — sharp signals at +splice junctions.** Window 501 bp, log2FC, unsigned. + +- **Effect**: random SNPs + (highest signal-to-noise) **GENCODE exon + boundaries**. Sample ~5–10 K splice donors / acceptors using + `get_gene_exons()` and taking each exon's `start` and `end` minus + one (donor / acceptor positions). Random SNPs alone give a + splicing-effect distribution dominated by intergenic regions where + the splicing model predicts ~0 anyway. +- **Summary / perbin baseline**: splice sites + cCRE (`PLS`). + +**`promoter_activity` (LentiMPRA) — element-level point predictions; +signed.** No window (the model emits one number per ~200 bp element), +diff, **signed**. + +- **Effect**: random ~200 bp regulatory regions tested by the model. + No genome-wide SNP scan applies because the model doesn't have a + spatial output — it's just `alt_score - ref_score` per element. +- **Summary / perbin baseline**: same set of ~30 K random + cCRE + elements scored by the model. `perbin_cdfs` is **absent** for + LegNet (there's no per-bin axis); IGV display falls back to + `summary_cdfs` via `rescale_for_display`'s `_find_matching_cdf` + fallback. Since LegNet predictions can be repressive, set + `signed_flags = ones`. + +**`regulatory_classification` (Sei) — sequence-class probabilities; +signed.** No window, diff, **signed**. + +- **Effect**: random SNPs + cCRE-anchored SNPs. Each track is a class + ("CTCF", "Promoter", "Enhancer", …); the effect is `alt_class_prob + − ref_class_prob`. +- **Summary / perbin baseline**: random + cCRE positions; cCRE + enrichment matters because most of the genome is "Background" + class, and you want enough samples in each non-background class + for the per-class CDFs to be informative. Sei has no spatial + output, so `perbin_cdfs` is absent; same fallback as LegNet. + +#### Common pitfalls + +- **All-random baseline** for any layer that has cell-type-specific + signal: the genome is mostly silent, so your `summary_cdfs` p99 + becomes "the few real peaks that randomly landed in the sample", + and any moderately-active site looks like a 99th-percentile site. + Mix in DHS / cCRE / TSS as appropriate. +- **Forgetting `signed_flags=True`** for RNA / MPRA / Sei tracks: + the rescaler will silently clip negative effects to 0 and the + repressive half of the distribution disappears from IGV. +- **Mismatched scoring window between build and live**: the build + script's window (`profile[ws:we]`) must match what + `oracle.score_track_effect()` does at inference time. ChromBPNet's + build uses `profile[250:751]` of the 1000-bin output; the live + scorer uses `score_region(POS-250, POS+251, 'sum')` which lands + on the same bins thanks to `prediction_interval = input_interval` + (PR #76). If you change the build window, update the live scorer + in lockstep — otherwise scores are correct but percentiles are + miscalibrated. +- **Per-bin samples drawn only from peak centers**: the perbin CDF + is for *display rescaling*, so it needs bins from peak flanks too + to characterize the noise floor. Sample 16-32 random bins per + baseline position rather than one bin at the center. +- **Boundary effects**: skip variants/positions within ~5 Mb of + chromosome ends. ENCODE peak callers and most reference genomes + have noisy edges that produce outlier predictions and skew the + CDFs. + +#### Build script skeleton ```python -import argparse -import numpy as np +import argparse, numpy as np from chorus.analysis.normalization import PerTrackNormalizer +from chorus.utils.annotations import ( + sample_ccre_positions, sample_dhs_positions, get_gene_tss, +) parser = argparse.ArgumentParser() parser.add_argument("--part", choices=["variants", "baselines", "both", "merge"]) parser.add_argument("--gpu", type=int, default=0) -parser.add_argument("--only-missing", action="store_true") +parser.add_argument("--n-variants", type=int, default=10_000) +parser.add_argument("--n-dhs-variants", type=int, default=10_000, + help="DHS-anchored SNPs (summit ±150 bp). 0 to disable.") +parser.add_argument("--n-dhs-peaks", type=int, default=5_000) args = parser.parse_args() ORACLE_NAME = "myoracle" - -# 1. Define your track IDs track_ids = ["DNASE:K562", "DNASE:HepG2"] - -# 2. For each track, score variants and baselines -# (use ReservoirSampler from existing scripts for memory efficiency) - -# 3. Save +n_tracks = len(track_ids) + +# ── Variant set: random genome SNPs + DHS-anchored SNPs ── +variant_positions = generate_random_snps(args.n_variants, seed=42) +if args.n_dhs_variants > 0: + variant_positions += dhs_anchored_snps( + sample_dhs_positions(args.n_dhs_variants, seed=43), + max_offset_bp=150, seed=44, + ) + +# ── Baseline position set: random + cCRE + (layer-specific) ── +baseline_positions = [] +baseline_positions.extend(random_genome_positions(20_000, seed=99)) +baseline_positions.extend(sample_ccre_positions(seed=42)) # ~20 K +baseline_positions.extend(sample_dhs_positions(args.n_dhs_peaks, seed=567)) +# For tss_activity / gene_expression layers, also: +# baseline_positions.extend(get_gene_tss(...).head(10_000)) +# For splicing layer: +# baseline_positions.extend(get_splice_sites(...)) + +# ── Score each track ── +effect_sampler = ReservoirSampler(n_tracks, capacity=50_000) +summary_sampler = ReservoirSampler(n_tracks, capacity=50_000) +perbin_sampler = ReservoirSampler(n_tracks, capacity=50_000) +signed_flags = np.zeros(n_tracks, dtype=bool) # True per-track for signed layers + +for ti, track_id in enumerate(track_ids): + layer = classify_layer(track_id) # your mapping + signed_flags[ti] = is_signed_layer(layer) + for snp in variant_positions: + ref_v, alt_v = score_track(model, snp, layer) + eff = compute_effect(ref_v, alt_v, layer) # log2fc / logfc / diff + if not signed_flags[ti]: + eff = abs(eff) + effect_sampler.add(ti, eff) + for pos in baseline_positions: + win_value = score_window(model, pos, layer) + summary_sampler.add(ti, win_value) + for bin_value in sample_bins(model, pos, n=32): + perbin_sampler.add(ti, bin_value) + +# ── Save the merged NPZ ── PerTrackNormalizer.build_and_save( oracle_name=ORACLE_NAME, track_ids=track_ids, - effect_cdfs=effect_matrix, # (n_tracks, 10000) - summary_cdfs=summary_matrix, - perbin_cdfs=perbin_matrix, # optional + effect_cdfs=effect_sampler.to_cdf_matrix(n_points=10_000), + summary_cdfs=summary_sampler.to_cdf_matrix(n_points=10_000), + perbin_cdfs=perbin_sampler.to_cdf_matrix(n_points=10_000), + effect_counts=effect_sampler.get_counts(), + summary_counts=summary_sampler.get_counts(), + perbin_counts=perbin_sampler.get_counts(), signed_flags=signed_flags, - effect_counts=effect_counts, - summary_counts=summary_counts, - perbin_counts=perbin_counts, ) ``` -Then run: +The full reference implementation (with sharded multi-GPU support, +incremental rebuilds, and the full DHS hooks) lives in +`scripts/build_backgrounds_chrombpnet.py`. For RNA-style exon-based +scoring see `scripts/build_backgrounds_borzoi.py:exon_bins_for_window`. +For element-level signed scoring (LentiMPRA / Sei) see +`scripts/build_backgrounds_legnet.py` and `_sei.py`. + +Run: ```bash -mamba run -n chorus-myoracle python scripts/build_backgrounds_myoracle.py --part both --gpu 0 +mamba run -n chorus-myoracle python scripts/build_backgrounds_myoracle.py \ + --part both --gpu 0 --n-variants 10000 --n-dhs-variants 10000 --n-dhs-peaks 5000 ``` ### Step 5: Upload backgrounds to HuggingFace (optional) diff --git a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/alphagenome_variant_report.json b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/alphagenome_variant_report.json index d7a5763..4c9b837 100644 --- a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/alphagenome_variant_report.json +++ b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/alphagenome_variant_report.json @@ -50,12 +50,12 @@ "assay_type": "DNASE", "cell_type": "HepG2", "layer": "chromatin_accessibility", - "ref_value": 595.7958984375, - "alt_value": 1571.43017578125, - "raw_score": 1.397686429616199, + "ref_value": 669.269775390625, + "alt_value": 1691.0675048828125, + "raw_score": 1.3359733411092043, "description": "DNASE:HepG2", "quantile_score": 1.0, - "ref_signal_percentile": 0.9684 + "ref_signal_percentile": 0.974 } ], "tf_binding": [ @@ -64,12 +64,12 @@ "assay_type": "CHIP", "cell_type": "HepG2", "layer": "tf_binding", - "ref_value": 2536.0, - "alt_value": 17172.0, - "raw_score": 2.7589466653239807, + "ref_value": 2569.0, + "alt_value": 17616.0, + "raw_score": 2.777128004016167, "description": "CHIP:CEBPA:HepG2", "quantile_score": 1.0, - "ref_signal_percentile": 0.9912 + "ref_signal_percentile": 0.9914 } ], "histone_marks": [ @@ -78,9 +78,9 @@ "assay_type": "CHIP", "cell_type": "HepG2", "layer": "histone_marks", - "ref_value": 14304.0, - "alt_value": 36024.0, - "raw_score": 1.3324789327389268, + "ref_value": 15876.0, + "alt_value": 38216.0, + "raw_score": 1.2672761952097673, "description": "CHIP:H3K27ac:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 0.9993 @@ -92,9 +92,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 22.89476776123047, - "alt_value": 69.32623291015625, - "raw_score": 1.5573681943125333, + "ref_value": 25.551132202148438, + "alt_value": 75.27824401855469, + "raw_score": 1.5224982499093178, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -105,9 +105,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 3625.59375, - "alt_value": 3750.5625, - "raw_score": 0.048876449271758306, + "ref_value": 3507.6708984375, + "alt_value": 3642.724609375, + "raw_score": 0.054489291063225594, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -118,9 +118,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2269.892578125, - "alt_value": 2681.86181640625, - "raw_score": 0.24051328631619226, + "ref_value": 2230.212890625, + "alt_value": 2633.76611328125, + "raw_score": 0.23984672577265248, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -131,9 +131,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2.4879703521728516, - "alt_value": 3.019759178161621, - "raw_score": 0.20472129560096552, + "ref_value": 2.4553728103637695, + "alt_value": 2.9908008575439453, + "raw_score": 0.20783691398864843, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -144,9 +144,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 256.05682373046875, - "alt_value": 292.2659606933594, - "raw_score": 0.19012231774199181, + "ref_value": 186.3468475341797, + "alt_value": 214.28213500976562, + "raw_score": 0.20051690195687483, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -157,9 +157,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 50.743743896484375, - "alt_value": 51.6553955078125, - "raw_score": 0.025196925922360443, + "ref_value": 48.827667236328125, + "alt_value": 49.40711975097656, + "raw_score": 0.016680488026257344, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -170,9 +170,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 0.8042747974395752, - "alt_value": 0.8081154823303223, - "raw_score": 0.0030677411376810433, + "ref_value": 0.7910206317901611, + "alt_value": 0.7974801063537598, + "raw_score": 0.00519384704912044, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -183,9 +183,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 10985.228515625, - "alt_value": 11005.70703125, - "raw_score": 0.0026867046841020704, + "ref_value": 11611.93359375, + "alt_value": 11654.1240234375, + "raw_score": 0.005231892699615067, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -196,11 +196,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 14.764413833618164, - "alt_value": 14.74071979522705, - "raw_score": -0.0021700132132735977, + "ref_value": 11.786408424377441, + "alt_value": 11.790457725524902, + "raw_score": 0.0004568117688130583, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "CFAP276 TSS" }, @@ -209,9 +208,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 423.18670654296875, - "alt_value": 424.1490478515625, - "raw_score": 0.0032692974963040825, + "ref_value": 354.4351806640625, + "alt_value": 353.94287109375, + "raw_score": -0.0019996470544720365, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -222,9 +221,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 5.543312072753906, - "alt_value": 5.598028182983398, - "raw_score": 0.012013860917669402, + "ref_value": 6.53487491607666, + "alt_value": 6.5812578201293945, + "raw_score": 0.008853666058724808, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -235,9 +234,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 4044.46533203125, - "alt_value": 4041.021728515625, - "raw_score": -0.0012285818766261181, + "ref_value": 4032.5830078125, + "alt_value": 4019.724609375, + "raw_score": -0.004606420390509987, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -248,9 +247,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 14.373394012451172, - "alt_value": 14.467826843261719, - "raw_score": 0.00883481254530705, + "ref_value": 14.515312194824219, + "alt_value": 14.601430892944336, + "raw_score": 0.007985625974698016, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -261,11 +260,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 9.316315650939941, - "alt_value": 9.305684089660645, - "raw_score": -0.001487547501345028, + "ref_value": 9.482418060302734, + "alt_value": 9.480058670043945, + "raw_score": -0.00032475939594703323, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "CYB561D1 TSS" }, @@ -274,10 +272,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 258.8525390625, - "alt_value": 258.8968505859375, - "raw_score": 0.00024599553764036527, + "ref_value": 274.7630615234375, + "alt_value": 274.43505859375, + "raw_score": -0.0017170169441534874, "description": "CAGE:HepG2", + "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "AMIGO1 TSS" }, @@ -286,10 +285,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 1610.4439697265625, - "alt_value": 1611.240478515625, - "raw_score": 0.0007129229438170053, + "ref_value": 1623.499755859375, + "alt_value": 1628.5789794921875, + "raw_score": 0.004503748860170626, "description": "CAGE:HepG2", + "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "WDR47 TSS" }, @@ -298,11 +298,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 0.06374645233154297, - "alt_value": 0.06416839361190796, - "raw_score": 0.0005721400006842341, + "ref_value": 0.061212241649627686, + "alt_value": 0.06122797727584839, + "raw_score": 2.1392084179362233e-05, "description": "CAGE:HepG2", - "ref_signal_percentile": 0.5980747988006944, + "ref_signal_percentile": 0.5800852138235758, "region_label": "GPR61 TSS" }, { @@ -310,9 +310,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 380.9811096191406, - "alt_value": 379.84619140625, - "raw_score": -0.0042928250822416155, + "ref_value": 352.2938232421875, + "alt_value": 352.75506591796875, + "raw_score": 0.0018822817646459758, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -323,9 +323,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 63.902252197265625, - "alt_value": 63.979759216308594, - "raw_score": 0.001721855152436912, + "ref_value": 63.89825439453125, + "alt_value": 64.07135009765625, + "raw_score": 0.0038428132657914228, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -336,9 +336,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 92.73734283447266, - "alt_value": 92.28418731689453, - "raw_score": -0.00699135010662284, + "ref_value": 86.73700714111328, + "alt_value": 87.22047424316406, + "raw_score": 0.007928021478037747, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -349,10 +349,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 4336.3916015625, - "alt_value": 4334.67724609375, - "raw_score": -0.00057033841394363, + "ref_value": 4154.3662109375, + "alt_value": 4162.25390625, + "raw_score": 0.0027359206602653096, "description": "CAGE:HepG2", + "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "CLCC1 TSS" }, @@ -361,9 +362,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 23.61593246459961, - "alt_value": 23.675003051757812, - "raw_score": 0.0034578724489716522, + "ref_value": 23.27630615234375, + "alt_value": 23.30550765991211, + "raw_score": 0.0017343475643713615, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -374,9 +375,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2.045255422592163, - "alt_value": 2.039944887161255, - "raw_score": -0.0025180716116615476, + "ref_value": 2.1415820121765137, + "alt_value": 2.161099910736084, + "raw_score": 0.00893539157382488, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -387,9 +388,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 61.7141227722168, - "alt_value": 61.66016387939453, - "raw_score": -0.001241821333098758, + "ref_value": 59.81163787841797, + "alt_value": 59.86174774169922, + "raw_score": 0.001188316655681097, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -400,10 +401,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 1.2355029582977295, - "alt_value": 1.236020803451538, - "raw_score": 0.00033415572788791145, + "ref_value": 1.2190296649932861, + "alt_value": 1.216066598892212, + "raw_score": -0.0019277152744917921, "description": "CAGE:HepG2", + "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "GSTM2 TSS" }, @@ -412,9 +414,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 0.6109044551849365, - "alt_value": 0.6160907745361328, - "raw_score": 0.0046373069174303, + "ref_value": 0.6399619579315186, + "alt_value": 0.6385025978088379, + "raw_score": -0.0012843889053095814, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -425,9 +427,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2331.359130859375, - "alt_value": 2342.34375, - "raw_score": 0.006778653442801207, + "ref_value": 2303.780517578125, + "alt_value": 2299.238037109375, + "raw_score": -0.0028462061958352053, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -438,11 +440,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 0.10538795590400696, - "alt_value": 0.10533407330513, - "raw_score": -7.032648806881722e-05, + "ref_value": 0.10983288288116455, + "alt_value": 0.109241783618927, + "raw_score": -0.0007685870217404806, "description": "CAGE:HepG2", - "ref_signal_percentile": 0.7875966545684078, + "ref_signal_percentile": 0.8043238125295882, "region_label": "GSTM5 TSS" }, { @@ -450,9 +452,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 3865.73095703125, - "alt_value": 3850.83935546875, - "raw_score": -0.005566851246252172, + "ref_value": 3850.54833984375, + "alt_value": 3841.743408203125, + "raw_score": -0.0033018859107930257, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -463,9 +465,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 70.75543212890625, - "alt_value": 167.9747314453125, - "raw_score": 1.2356475634648714, + "ref_value": 76.11575317382812, + "alt_value": 178.0048828125, + "raw_score": 1.2149014326961562, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -476,9 +478,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 7.960662841796875, - "alt_value": 8.71365737915039, - "raw_score": 0.11640914455699618, + "ref_value": 7.78662109375, + "alt_value": 8.496078491210938, + "raw_score": 0.11202337802164473, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -489,9 +491,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 52.443092346191406, - "alt_value": 59.076866149902344, - "raw_score": 0.16880607001896691, + "ref_value": 51.77107620239258, + "alt_value": 58.75240707397461, + "raw_score": 0.17924942612965777, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -502,9 +504,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 628.33349609375, - "alt_value": 722.0814208984375, - "raw_score": 0.20033337565572457, + "ref_value": 656.993896484375, + "alt_value": 756.0865478515625, + "raw_score": 0.20238403252417875, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -515,9 +517,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - 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"quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "WDR47 TSS" }, @@ -671,9 +672,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 5.80690336227417, - "alt_value": 5.827776908874512, - "raw_score": 0.004417292535425431, + "ref_value": 6.077597618103027, + "alt_value": 6.10883903503418, + "raw_score": 0.006354225693282727, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -684,10 +685,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 9118.154296875, - "alt_value": 9123.2490234375, - "raw_score": 0.0008057857197396304, + "ref_value": 8772.9453125, + "alt_value": 8760.9921875, + "raw_score": -0.001966785845514839, "description": "CAGE:HepG2", + "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "GNAI3 TSS" }, @@ -696,9 +698,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 1670.032470703125, - "alt_value": 1664.30126953125, - "raw_score": -0.004956568668363452, + "ref_value": 1822.5145263671875, + "alt_value": 1827.85498046875, + "raw_score": 0.004218988316949635, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -709,9 +711,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2697.777099609375, - "alt_value": 2688.83447265625, - "raw_score": -0.004788430276963646, + "ref_value": 2921.113525390625, + "alt_value": 2929.43994140625, + "raw_score": 0.004105041420630629, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -722,11 +724,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 27.88433074951172, - "alt_value": 27.813751220703125, - "raw_score": -0.0035295726829086627, + "ref_value": 28.862525939941406, + "alt_value": 28.87578582763672, + "raw_score": 0.0006404591615971553, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "CLCC1 TSS" }, @@ -735,11 +736,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2252.68798828125, - "alt_value": 2247.7109375, - "raw_score": -0.003189574945902673, + "ref_value": 2257.70751953125, + "alt_value": 2256.296875, + "raw_score": -0.0009012967030530812, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "GPSM2 TSS" }, @@ -748,9 +748,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2.8881547451019287, - "alt_value": 2.8820509910583496, - "raw_score": -0.0022665699724660616, + "ref_value": 2.6666922569274902, + "alt_value": 2.6578750610351562, + "raw_score": -0.0034733876775616315, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -761,9 +761,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 3851.203369140625, - "alt_value": 3858.33349609375, - "raw_score": 0.00266784738432055, + "ref_value": 3977.92529296875, + "alt_value": 3985.14013671875, + "raw_score": 0.0026136187423920574, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -774,9 +774,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 937.7469482421875, - "alt_value": 931.74658203125, - "raw_score": -0.009251144178523223, + "ref_value": 828.590576171875, + "alt_value": 830.9297485351562, + "raw_score": 0.00406220080214405, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -787,9 +787,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 209.3528594970703, - "alt_value": 206.91262817382812, - "raw_score": -0.016834042857441518, + "ref_value": 210.3513946533203, + "alt_value": 211.5340576171875, + "raw_score": 0.008050412729187545, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -800,9 +800,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 7.068316459655762, - "alt_value": 7.057977676391602, - "raw_score": -0.0018498624993168258, + "ref_value": 6.2503662109375, + "alt_value": 6.218902111053467, + "raw_score": -0.006274425410904302, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -813,9 +813,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 12.858158111572266, - "alt_value": 12.942314147949219, - "raw_score": 0.008734518325161533, + "ref_value": 12.406927108764648, + "alt_value": 12.4179048538208, + "raw_score": 0.0011808118133882443, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -826,11 +826,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 39.00223922729492, - "alt_value": 38.845149993896484, - "raw_score": -0.005676632701656048, + "ref_value": 34.92880630493164, + "alt_value": 34.945411682128906, + "raw_score": 0.0006666227871903191, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "EPS8L3 TSS" } @@ -842,33 +841,33 @@ "assay_type": "DNASE", "cell_type": "HepG2", "layer": "chromatin_accessibility", - "ref_value": 595.7958984375, - "alt_value": 1571.43017578125, - "raw_score": 1.397686429616199, + "ref_value": 669.269775390625, + "alt_value": 1691.0675048828125, + "raw_score": 1.3359733411092043, "description": "DNASE:HepG2", "quantile_score": 1.0, - "ref_signal_percentile": 0.9684 + "ref_signal_percentile": 0.974 }, { "assay_id": "CHIP_TF/EFO:0001187 TF ChIP-seq CEBPA genetically modified (insertion) using CRISPR targeting H. sapiens CEBPA/.", "assay_type": "CHIP", "cell_type": "HepG2", "layer": "tf_binding", - "ref_value": 2536.0, - "alt_value": 17172.0, - "raw_score": 2.7589466653239807, + "ref_value": 2569.0, + "alt_value": 17616.0, + "raw_score": 2.777128004016167, "description": "CHIP:CEBPA:HepG2", "quantile_score": 1.0, - "ref_signal_percentile": 0.9912 + "ref_signal_percentile": 0.9914 }, { "assay_id": "CHIP_HISTONE/EFO:0001187 Histone ChIP-seq H3K27ac/.", "assay_type": "CHIP", "cell_type": "HepG2", "layer": "histone_marks", - "ref_value": 14304.0, - "alt_value": 36024.0, - "raw_score": 1.3324789327389268, + "ref_value": 15876.0, + "alt_value": 38216.0, + "raw_score": 1.2672761952097673, "description": "CHIP:H3K27ac:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 0.9993 @@ -878,9 +877,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 22.89476776123047, - "alt_value": 69.32623291015625, - "raw_score": 1.5573681943125333, + "ref_value": 25.551132202148438, + "alt_value": 75.27824401855469, + "raw_score": 1.5224982499093178, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -891,9 +890,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 3625.59375, - "alt_value": 3750.5625, - "raw_score": 0.048876449271758306, + "ref_value": 3507.6708984375, + "alt_value": 3642.724609375, + "raw_score": 0.054489291063225594, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -904,9 +903,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2269.892578125, - "alt_value": 2681.86181640625, - "raw_score": 0.24051328631619226, + "ref_value": 2230.212890625, + "alt_value": 2633.76611328125, + "raw_score": 0.23984672577265248, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -917,9 +916,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - 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"quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "CFAP276 TSS" }, @@ -995,9 +993,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 423.18670654296875, - "alt_value": 424.1490478515625, - "raw_score": 0.0032692974963040825, + "ref_value": 354.4351806640625, + "alt_value": 353.94287109375, + "raw_score": -0.0019996470544720365, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1008,9 +1006,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 5.543312072753906, - "alt_value": 5.598028182983398, - "raw_score": 0.012013860917669402, + "ref_value": 6.53487491607666, + "alt_value": 6.5812578201293945, + "raw_score": 0.008853666058724808, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1021,9 +1019,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 4044.46533203125, - "alt_value": 4041.021728515625, - "raw_score": -0.0012285818766261181, + "ref_value": 4032.5830078125, + "alt_value": 4019.724609375, + "raw_score": -0.004606420390509987, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1034,9 +1032,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 14.373394012451172, - "alt_value": 14.467826843261719, - "raw_score": 0.00883481254530705, + "ref_value": 14.515312194824219, + "alt_value": 14.601430892944336, + "raw_score": 0.007985625974698016, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1047,11 +1045,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 9.316315650939941, - "alt_value": 9.305684089660645, - "raw_score": -0.001487547501345028, + "ref_value": 9.482418060302734, + "alt_value": 9.480058670043945, + "raw_score": -0.00032475939594703323, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "CYB561D1 TSS" }, @@ -1060,10 +1057,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - 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"ref_signal_percentile": 0.5980747988006944, + "ref_signal_percentile": 0.5800852138235758, "region_label": "GPR61 TSS" }, { @@ -1096,9 +1095,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 380.9811096191406, - "alt_value": 379.84619140625, - "raw_score": -0.0042928250822416155, + "ref_value": 352.2938232421875, + "alt_value": 352.75506591796875, + "raw_score": 0.0018822817646459758, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1109,9 +1108,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 63.902252197265625, - "alt_value": 63.979759216308594, - "raw_score": 0.001721855152436912, + "ref_value": 63.89825439453125, + "alt_value": 64.07135009765625, + "raw_score": 0.0038428132657914228, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1122,9 +1121,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 92.73734283447266, - "alt_value": 92.28418731689453, - "raw_score": -0.00699135010662284, + "ref_value": 86.73700714111328, + "alt_value": 87.22047424316406, + "raw_score": 0.007928021478037747, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1135,10 +1134,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 4336.3916015625, - "alt_value": 4334.67724609375, - "raw_score": -0.00057033841394363, + "ref_value": 4154.3662109375, + "alt_value": 4162.25390625, + "raw_score": 0.0027359206602653096, "description": "CAGE:HepG2", + "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "CLCC1 TSS" }, @@ -1147,9 +1147,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 23.61593246459961, - "alt_value": 23.675003051757812, - "raw_score": 0.0034578724489716522, + "ref_value": 23.27630615234375, + "alt_value": 23.30550765991211, + "raw_score": 0.0017343475643713615, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1160,9 +1160,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - 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"ref_value": 0.6109044551849365, - "alt_value": 0.6160907745361328, - "raw_score": 0.0046373069174303, + "ref_value": 0.6399619579315186, + "alt_value": 0.6385025978088379, + "raw_score": -0.0012843889053095814, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1211,9 +1212,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2331.359130859375, - "alt_value": 2342.34375, - "raw_score": 0.006778653442801207, + "ref_value": 2303.780517578125, + "alt_value": 2299.238037109375, + "raw_score": -0.0028462061958352053, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1224,11 +1225,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 0.10538795590400696, - "alt_value": 0.10533407330513, - "raw_score": -7.032648806881722e-05, + "ref_value": 0.10983288288116455, + "alt_value": 0.109241783618927, + "raw_score": -0.0007685870217404806, "description": "CAGE:HepG2", - 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"ref_value": 2.409396171569824, - "alt_value": 2.7882347106933594, - "raw_score": 0.1520094695180957, + "ref_value": 1.7172479629516602, + "alt_value": 1.9840140342712402, + "raw_score": 0.13510809586025202, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1314,9 +1315,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 13039.099609375, - "alt_value": 13092.236328125, - "raw_score": 0.005866850405784661, + "ref_value": 12909.26171875, + "alt_value": 12954.6875, + "raw_score": 0.005067327408673559, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1327,9 +1328,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 79.16783142089844, - "alt_value": 79.60616302490234, - "raw_score": 0.007866700089247792, + "ref_value": 83.14979553222656, + "alt_value": 84.42018127441406, + "raw_score": 0.021617193509403294, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1340,9 +1341,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 94.2911148071289, - "alt_value": 94.443603515625, - "raw_score": 0.0023068139072396254, + "ref_value": 100.39250183105469, + "alt_value": 100.31128692626953, + "raw_score": -0.001156054826282948, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1353,9 +1354,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 20.05031967163086, - "alt_value": 20.272018432617188, - "raw_score": 0.015114790105938134, + "ref_value": 23.082637786865234, + "alt_value": 23.382003784179688, + "raw_score": 0.0178232756448931, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1366,9 +1367,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2986.1806640625, - "alt_value": 2990.0654296875, - "raw_score": 0.001874975637728842, + "ref_value": 3303.060546875, + "alt_value": 3305.443359375, + "raw_score": 0.0010400635034052796, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1379,9 +1380,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 297.2666320800781, - "alt_value": 299.59808349609375, - "raw_score": 0.011233222802478182, + "ref_value": 361.9288330078125, + "alt_value": 362.21978759765625, + "raw_score": 0.0011561235660131116, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1392,9 +1393,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 42.26055145263672, - "alt_value": 42.30645751953125, - "raw_score": 0.0015301085725361063, + "ref_value": 42.217811584472656, + "alt_value": 42.37229919433594, + "raw_score": 0.005147902990448923, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1405,9 +1406,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 1447.8704833984375, - "alt_value": 1452.652587890625, - "raw_score": 0.00475388102623833, + "ref_value": 1374.8839111328125, + "alt_value": 1376.2066650390625, + "raw_score": 0.0013863188259927285, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1418,9 +1419,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 876.9949951171875, - "alt_value": 874.2188720703125, - "raw_score": -0.004568869063752767, + "ref_value": 841.4041748046875, + "alt_value": 842.5823364257812, + "raw_score": 0.0020163010717634327, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1431,9 +1432,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2.0729689598083496, - "alt_value": 2.0774216651916504, - "raw_score": 0.0020889395451549183, + "ref_value": 2.0670037269592285, + "alt_value": 2.0775303840637207, + "raw_score": 0.004943180584548416, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1444,11 +1445,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2.364591121673584, - "alt_value": 2.3724493980407715, - "raw_score": 0.0033656028795694733, + "ref_value": 2.2497644424438477, + "alt_value": 2.251588821411133, + "raw_score": 0.0008096845229203884, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "WDR47 TSS" }, @@ -1457,9 +1457,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 5.80690336227417, - "alt_value": 5.827776908874512, - "raw_score": 0.004417292535425431, + "ref_value": 6.077597618103027, + "alt_value": 6.10883903503418, + "raw_score": 0.006354225693282727, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1470,10 +1470,11 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 9118.154296875, - "alt_value": 9123.2490234375, - "raw_score": 0.0008057857197396304, + "ref_value": 8772.9453125, + "alt_value": 8760.9921875, + "raw_score": -0.001966785845514839, "description": "CAGE:HepG2", + "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "GNAI3 TSS" }, @@ -1482,9 +1483,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 1670.032470703125, - "alt_value": 1664.30126953125, - "raw_score": -0.004956568668363452, + "ref_value": 1822.5145263671875, + "alt_value": 1827.85498046875, + "raw_score": 0.004218988316949635, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1495,9 +1496,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2697.777099609375, - "alt_value": 2688.83447265625, - "raw_score": -0.004788430276963646, + "ref_value": 2921.113525390625, + "alt_value": 2929.43994140625, + "raw_score": 0.004105041420630629, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1508,11 +1509,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 27.88433074951172, - "alt_value": 27.813751220703125, - "raw_score": -0.0035295726829086627, + "ref_value": 28.862525939941406, + "alt_value": 28.87578582763672, + "raw_score": 0.0006404591615971553, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "CLCC1 TSS" }, @@ -1521,11 +1521,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2252.68798828125, - "alt_value": 2247.7109375, - "raw_score": -0.003189574945902673, + "ref_value": 2257.70751953125, + "alt_value": 2256.296875, + "raw_score": -0.0009012967030530812, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "GPSM2 TSS" }, @@ -1534,9 +1533,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 2.8881547451019287, - "alt_value": 2.8820509910583496, - "raw_score": -0.0022665699724660616, + "ref_value": 2.6666922569274902, + "alt_value": 2.6578750610351562, + "raw_score": -0.0034733876775616315, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1547,9 +1546,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 3851.203369140625, - "alt_value": 3858.33349609375, - "raw_score": 0.00266784738432055, + "ref_value": 3977.92529296875, + "alt_value": 3985.14013671875, + "raw_score": 0.0026136187423920574, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1560,9 +1559,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 937.7469482421875, - "alt_value": 931.74658203125, - "raw_score": -0.009251144178523223, + "ref_value": 828.590576171875, + "alt_value": 830.9297485351562, + "raw_score": 0.00406220080214405, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1573,9 +1572,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 209.3528594970703, - "alt_value": 206.91262817382812, - "raw_score": -0.016834042857441518, + "ref_value": 210.3513946533203, + "alt_value": 211.5340576171875, + "raw_score": 0.008050412729187545, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1586,9 +1585,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 7.068316459655762, - "alt_value": 7.057977676391602, - "raw_score": -0.0018498624993168258, + "ref_value": 6.2503662109375, + "alt_value": 6.218902111053467, + "raw_score": -0.006274425410904302, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1599,9 +1598,9 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 12.858158111572266, - "alt_value": 12.942314147949219, - "raw_score": 0.008734518325161533, + "ref_value": 12.406927108764648, + "alt_value": 12.4179048538208, + "raw_score": 0.0011808118133882443, "description": "CAGE:HepG2", "quantile_score": 1.0, "ref_signal_percentile": 1.0, @@ -1612,11 +1611,10 @@ "assay_type": "CAGE", "cell_type": "HepG2", "layer": "tss_activity", - "ref_value": 39.00223922729492, - "alt_value": 38.845149993896484, - "raw_score": -0.005676632701656048, + "ref_value": 34.92880630493164, + "alt_value": 34.945411682128906, + "raw_score": 0.0006666227871903191, "description": "CAGE:HepG2", - "quantile_score": 1.0, "ref_signal_percentile": 1.0, "region_label": "EPS8L3 TSS" } @@ -1631,6 +1629,6 @@ "tracks_requested": "5 tracks", "cell_types": [], "notes": [], - "generated_at": "2026-04-21 13:30 UTC" + "generated_at": "2026-05-09 22:22 UTC" } } \ No newline at end of file diff --git a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/chrombpnet_variant_report.json b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/chrombpnet_variant_report.json index e216d96..c4e1efe 100644 --- a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/chrombpnet_variant_report.json +++ b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/chrombpnet_variant_report.json @@ -11,7 +11,34 @@ "gene_name": "SORT1", "nearby_genes": [ "SORT1", - "CELSR2" + "PSRC1", + "CELSR2", + "MYBPHL", + "SARS1", + "ELAPOR1", + "PSMA5", + "CFAP276", + "TMEM167B", + "SYPL2", + "TAF13", + "ATXN7L2", + "CYB561D1", + "AMIGO1", + "WDR47", + "GPR61", + "GNAI3", + "GNAT2", + "AMPD2", + "CLCC1", + "GPSM2", + "AKNAD1", + "GSTM4", + "GSTM2", + "GSTM1", + "GSTM3", + "GSTM5", + "EPS8L3", + "STXBP3" ], "report_title": "Multi-Layer Variant Effect Report", "alleles": { @@ -19,31 +46,31 @@ "scores_by_layer": { "chromatin_accessibility": [ { - "assay_id": "ATAC:HepG2", - "assay_type": "ATAC", + "assay_id": "DNASE:HepG2", + "assay_type": "DNASE", "cell_type": "HepG2", "layer": "chromatin_accessibility", - "ref_value": 635.6930961374892, - "alt_value": 917.4119157849345, - "raw_score": 0.528543239432768, - "description": "ATAC:HepG2", - "quantile_score": 1.0, - "ref_signal_percentile": 0.8088 + "ref_value": 255.6614961475134, + "alt_value": 605.572213485837, + "raw_score": 1.240812529069907, + "description": "DNASE:HepG2", + "quantile_score": 0.9987, + "ref_signal_percentile": 0.8975 } ] }, "all_scores": [ { - "assay_id": "ATAC:HepG2", - "assay_type": "ATAC", + "assay_id": "DNASE:HepG2", + "assay_type": "DNASE", "cell_type": "HepG2", "layer": "chromatin_accessibility", - "ref_value": 635.6930961374892, - "alt_value": 917.4119157849345, - "raw_score": 0.528543239432768, - "description": "ATAC:HepG2", - "quantile_score": 1.0, - "ref_signal_percentile": 0.8088 + "ref_value": 255.6614961475134, + "alt_value": 605.572213485837, + "raw_score": 1.240812529069907, + "description": "DNASE:HepG2", + "quantile_score": 0.9987, + "ref_signal_percentile": 0.8975 } ] } @@ -56,6 +83,6 @@ "tracks_requested": "1 tracks", "cell_types": [], "notes": [], - "generated_at": "2026-04-21 13:10 UTC" + "generated_at": "2026-05-09 22:16 UTC" } } \ No newline at end of file diff --git a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/example_output.json b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/example_output.json index 2d56b73..aa42217 100644 --- a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/example_output.json +++ b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/example_output.json @@ -24,15 +24,15 @@ "layer": "chromatin_accessibility", "oracles": { "chrombpnet": { - "raw_score": 0.528543239432768, - "assay_id": "ATAC:HepG2", + "raw_score": 1.240812529069907, + "assay_id": "DNASE:HepG2", "cell_type": "HepG2", - "quantile_score": 1.0, - "description": "ATAC:HepG2" + "quantile_score": 0.9987, + "description": "DNASE:HepG2" }, "legnet": null, "alphagenome": { - "raw_score": 1.397686429616199, + "raw_score": 1.3359733411092043, "assay_id": "DNASE/EFO:0001187 DNase-seq/.", "cell_type": "HepG2", "quantile_score": 1.0, @@ -46,7 +46,7 @@ "oracles": { "chrombpnet": null, "legnet": { - "raw_score": 0.29691410064697266, + "raw_score": 6.079673767089844e-05, "assay_id": "LentiMPRA:HepG2", "cell_type": "HepG2", "quantile_score": null, @@ -62,7 +62,7 @@ "chrombpnet": null, "legnet": null, "alphagenome": { - "raw_score": 2.7589466653239807, + "raw_score": 2.777128004016167, "assay_id": "CHIP_TF/EFO:0001187 TF ChIP-seq CEBPA genetically modified (insertion) using CRISPR targeting H. sapiens CEBPA/.", "cell_type": "HepG2", "quantile_score": 1.0, @@ -77,7 +77,7 @@ "chrombpnet": null, "legnet": null, "alphagenome": { - "raw_score": 1.3324789327389268, + "raw_score": 1.2672761952097673, "assay_id": "CHIP_HISTONE/EFO:0001187 Histone ChIP-seq H3K27ac/.", "cell_type": "HepG2", "quantile_score": 1.0, @@ -92,7 +92,7 @@ "chrombpnet": null, "legnet": null, "alphagenome": { - "raw_score": 1.5573681943125333, + "raw_score": 1.5224982499093178, "assay_id": "CAGE/hCAGE EFO:0001187/-", "cell_type": "HepG2", "quantile_score": 1.0, @@ -110,6 +110,6 @@ "tracks_requested": "assay_ids as listed in each per-oracle request", "cell_types": [], "notes": [], - "generated_at": "2026-04-22 17:21 UTC" + "generated_at": "2026-05-09 22:22 UTC" } } \ No newline at end of file diff --git a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/example_output.md b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/example_output.md index 2e367aa..c0b422a 100644 --- a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/example_output.md +++ b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/example_output.md @@ -3,14 +3,14 @@ - **Variant:** chr1:109,274,968 G>T - **Gene:** SORT1 - **Oracles:** chrombpnet, legnet, alphagenome -- **Generated:** 2026-04-22 17:21 UTC +- **Generated:** 2026-05-09 22:22 UTC ## Cross-oracle consensus | Layer | chrombpnet | legnet | alphagenome | Agreement | |---|---|---|---|---| -| Chromatin accessibility (DNASE/ATAC) (log2FC) | +0.529 · ATAC:HepG2 | — | +1.398 · DNASE:HepG2 | all ↑ | -| Promoter activity (MPRA) (Δ (alt−ref)) | — | +0.297 · LentiMPRA:HepG2 | — | only ↑ (n=1) | -| Transcription factor binding (ChIP-TF) (log2FC) | — | — | +2.759 · CHIP:CEBPA:HepG2 | only ↑ (n=1) | -| Histone modifications (ChIP-Histone) (log2FC) | — | — | +1.332 · CHIP:H3K27ac:HepG2 | only ↑ (n=1) | -| TSS activity (CAGE/PRO-CAP) (log2FC) | — | — | +1.557 · CAGE:HepG2 | only ↑ (n=1) | \ No newline at end of file +| Chromatin accessibility (DNASE/ATAC) (log2FC) | +1.241 · DNASE:HepG2 | — | +1.336 · DNASE:HepG2 | all ↑ | +| Promoter activity (MPRA) (Δ (alt−ref)) | — | +0.000 · LentiMPRA:HepG2 | — | only ↑ (n=1) | +| Transcription factor binding (ChIP-TF) (log2FC) | — | — | +2.777 · CHIP:CEBPA:HepG2 | only ↑ (n=1) | +| Histone modifications (ChIP-Histone) (log2FC) | — | — | +1.267 · CHIP:H3K27ac:HepG2 | only ↑ (n=1) | +| TSS activity (CAGE/PRO-CAP) (log2FC) | — | — | +1.522 · CAGE:HepG2 | only ↑ (n=1) | \ No newline at end of file diff --git a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/legnet_variant_report.json b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/legnet_variant_report.json index 9a1c92a..3373b7e 100644 --- a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/legnet_variant_report.json +++ b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/legnet_variant_report.json @@ -11,7 +11,34 @@ "gene_name": "SORT1", "nearby_genes": [ "SORT1", - "CELSR2" + "PSRC1", + "CELSR2", + "MYBPHL", + "SARS1", + "ELAPOR1", + "PSMA5", + "CFAP276", + "TMEM167B", + "SYPL2", + "TAF13", + "ATXN7L2", + "CYB561D1", + "AMIGO1", + "WDR47", + "GPR61", + "GNAI3", + "GNAT2", + "AMPD2", + "CLCC1", + "GPSM2", + "AKNAD1", + "GSTM4", + "GSTM2", + "GSTM1", + "GSTM3", + "GSTM5", + "EPS8L3", + "STXBP3" ], "report_title": "Multi-Layer Variant Effect Report", "alleles": { @@ -23,9 +50,9 @@ "assay_type": "LentiMPRA", "cell_type": "HepG2", "layer": "promoter_activity", - "ref_value": 0.3723793625831604, - "alt_value": 0.6692934632301331, - "raw_score": 0.29691410064697266, + "ref_value": -0.7386637330055237, + "alt_value": -0.7386029362678528, + "raw_score": 6.079673767089844e-05, "description": "LentiMPRA:HepG2" } ] @@ -36,9 +63,9 @@ "assay_type": "LentiMPRA", "cell_type": "HepG2", "layer": "promoter_activity", - "ref_value": 0.3723793625831604, - "alt_value": 0.6692934632301331, - "raw_score": 0.29691410064697266, + "ref_value": -0.7386637330055237, + "alt_value": -0.7386029362678528, + "raw_score": 6.079673767089844e-05, "description": "LentiMPRA:HepG2" } ] @@ -52,6 +79,6 @@ "tracks_requested": "1 tracks", "cell_types": [], "notes": [], - "generated_at": "2026-04-22 17:20 UTC" + "generated_at": "2026-05-09 22:19 UTC" } } \ No newline at end of file diff --git a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_alphagenome_report.html b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_alphagenome_report.html index bb9e434..a9c3895 100644 --- a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_alphagenome_report.html +++ b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_alphagenome_report.html @@ -57,14 +57,14 @@

Analysis Request

  • Oracle: alphagenome
  • Normalizer: chorus per-track v1
  • Tracks requested: 5 tracks
    • -
  • Generated: 2026-04-21 13:30 UTC
    • +
  • Generated: 2026-05-09 22:22 UTC

    • Variant: chr1:109274968 G>T

    Oracle: alphagenome

    Gene: SORT1

    Other nearby genes: PSRC1, CELSR2, MYBPHL, SARS1

    -

    Summary: Transcription factor binding (ChIP-TF): very strong binding gain (+2.76, CHIP:CEBPA:HepG2); TSS activity (CAGE/PRO-CAP): very strong increase (+1.56, CAGE:HepG2); Chromatin accessibility (DNASE/ATAC): very strong opening (+1.40, DNASE:HepG2); Histone modifications (ChIP-Histone): very strong mark gain (+1.33, CHIP:H3K27ac:HepG2).

    +

    Summary: Transcription factor binding (ChIP-TF): very strong binding gain (+2.78, CHIP:CEBPA:HepG2); TSS activity (CAGE/PRO-CAP): very strong increase (+1.52, CAGE:HepG2); Chromatin accessibility (DNASE/ATAC): very strong opening (+1.34, DNASE:HepG2); Histone modifications (ChIP-Histone): very strong mark gain (+1.27, CHIP:H3K27ac:HepG2).

    How to read this report. Every numeric effect below is produced by a deep-learning model. The scale depends on the regulatory layer — see the formulas below so you can interpret +0.3 correctly.

    Effect %ile
    How unusual is this variant's effect? Ranked against ~10,000 random SNPs scored genome-wide. 95% means the effect is larger than 95% of random variants. Range [0,1] for unsigned layers (chromatin, TF, histone, TSS, splicing); [−1,1] for signed layers (gene expression, MPRA).
    Activity %ile
    How active is this region genome-wide? Reference signal ranked against ~26,000 ENCODE SCREEN cCREs and random regions. 0.95 = predicted signal exceeds 95% of genome-wide positions — a highly active regulatory element.
    Per-layer effect
    Unit depends on the layer:
    • Chromatin accessibility (DNASE/ATAC) log2FC — log2((alt+1)/(ref+1)). +0.3 ≈ alt signal 1.23× ref; +1.0 ≈ 2× ref; negative values = loss of signal.
    • Transcription factor binding (ChIP-TF) log2FC — log2((alt+1)/(ref+1)). +0.3 ≈ alt signal 1.23× ref; +1.0 ≈ 2× ref; negative values = loss of signal.
    • Histone modifications (ChIP-Histone) log2FC — log2((alt+1)/(ref+1)). +0.3 ≈ alt signal 1.23× ref; +1.0 ≈ 2× ref; negative values = loss of signal.
    • TSS activity (CAGE/PRO-CAP) log2FC — log2((alt+1)/(ref+1)). +0.3 ≈ alt signal 1.23× ref; +1.0 ≈ 2× ref; negative values = loss of signal.

    Chromatin accessibility (DNASE/ATAC) log2FC

    @@ -75,11 +75,11 @@

    Chromatin accessibility (DNASE/ATAC) log2FC

    - - - + + + - +
    DNASE:HepG2 HepG25961.57e+03+1.3986691.69e+03+1.336 ≥99th0.9680.974 Very strong opening
    @@ -92,9 +92,9 @@

    Transcription factor binding (ChIP-TF) log2FC CHIP:CEBPA:HepG2 HepG2 -2.54e+03 -1.72e+04 -+2.759 +2.57e+03 +1.76e+04 ++2.777 ≥99th 0.991 Very strong binding gain @@ -109,9 +109,9 @@

    Histone modifications (ChIP-Histone) log2FC CHIP:H3K27ac:HepG2 HepG2 -1.43e+04 -3.6e+04 -+1.332 +1.59e+04 +3.82e+04 ++1.267 ≥99th 0.999 Very strong mark gain @@ -126,9 +126,9 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — variant site HepG2 -22.9 -69.3 -+1.557 +25.6 +75.3 ++1.522 ≥99th 1.000 Very strong increase @@ -136,9 +136,9 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — variant site HepG2 -70.8 -168 -+1.236 +76.1 +178 ++1.215 ≥99th 1.000 Very strong increase @@ -146,9 +146,9 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — PSRC1 TSS HepG2 -2.27e+03 -2.68e+03 -+0.241 +2.23e+03 +2.63e+03 ++0.240 ≥99th 1.000 Moderate increase @@ -156,9 +156,9 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — CELSR2 TSS HepG2 -2.49 -3.02 -+0.205 +2.46 +2.99 ++0.208 ≥99th 1.000 Moderate increase @@ -166,9 +166,9 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — CELSR2 TSS HepG2 -628 -722 -+0.200 +657 +756 ++0.202 ≥99th 1.000 Moderate increase @@ -176,9 +176,9 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — MYBPHL TSS HepG2 -256 -292 -+0.190 +186 +214 ++0.201 ≥99th 1.000 Moderate increase @@ -186,9 +186,9 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — PSRC1 TSS HepG2 -52.4 -59.1 -+0.169 +51.8 +58.8 ++0.179 ≥99th 1.000 Moderate increase @@ -196,9 +196,9 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — MYBPHL TSS HepG2 -2.41 -2.79 -+0.152 +1.72 +1.98 ++0.135 ≥99th 1.000 Moderate increase @@ -206,9 +206,9 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — SORT1 TSS HepG2 -7.96 -8.71 -+0.116 +7.79 +8.5 ++0.112 ≥99th 1.000 Moderate increase @@ -216,49 +216,49 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — SORT1 TSS HepG2 -3.63e+03 -3.75e+03 -+0.049 +3.51e+03 +3.64e+03 ++0.054 ≥99th 1.000 Minimal effect -CAGE:HepG2 — SARS1 TSS +CAGE:HepG2 — ELAPOR1 TSS HepG2 -50.7 -51.7 -+0.025 +83.1 +84.4 ++0.022 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GSTM1 TSS +CAGE:HepG2 — CFAP276 TSS HepG2 -209 -207 --0.017 +23.1 +23.4 ++0.018 ≥99th 1.000 Minimal effect -CAGE:HepG2 — CFAP276 TSS +CAGE:HepG2 — SARS1 TSS HepG2 -20.1 -20.3 -+0.015 +48.8 +49.4 ++0.017 ≥99th 1.000 Minimal effect -CAGE:HepG2 — SYPL2 TSS +CAGE:HepG2 — AKNAD1 TSS HepG2 -5.54 -5.6 -+0.012 +2.14 +2.16 ++0.009 ≥99th 1.000 Minimal effect @@ -266,19 +266,19 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — SYPL2 TSS HepG2 -297 -300 -+0.011 +6.53 +6.58 ++0.009 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GSTM2 TSS +CAGE:HepG2 — GSTM1 TSS HepG2 -938 -932 --0.009 +210 +212 ++0.008 ≥99th 1.000 Minimal effect @@ -286,421 +286,421 @@

    TSS activity (CAGE/PRO-CAP) log2FC

    CAGE:HepG2 — ATXN7L2 TSS HepG2 -14.4 14.5 -+0.009 +14.6 ++0.008 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GSTM5 TSS +CAGE:HepG2 — AMPD2 TSS HepG2 -12.9 -12.9 -+0.009 +86.7 +87.2 ++0.008 ≥99th 1.000 Minimal effect -CAGE:HepG2 — ELAPOR1 TSS +CAGE:HepG2 — GPR61 TSS HepG2 -79.2 -79.6 -+0.008 +6.08 +6.11 ++0.006 ≥99th 1.000 Minimal effect -CAGE:HepG2 — AMPD2 TSS +CAGE:HepG2 — GSTM3 TSS HepG2 -92.7 -92.3 --0.007 +6.25 +6.22 +-0.006 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GSTM3 TSS +CAGE:HepG2 — PSMA5 TSS HepG2 -2.33e+03 -2.34e+03 -+0.007 +1.16e+04 +1.17e+04 ++0.005 ≥99th 1.000 Minimal effect -CAGE:HepG2 — SARS1 TSS +CAGE:HepG2 — ELAPOR1 TSS HepG2 -1.3e+04 -1.31e+04 -+0.006 +0.791 +0.797 ++0.005 ≥99th 1.000 Minimal effect -CAGE:HepG2 — EPS8L3 TSS +CAGE:HepG2 — TAF13 TSS HepG2 -39 -38.8 --0.006 +42.2 +42.4 ++0.005 ≥99th 1.000 Minimal effect -CAGE:HepG2 — EPS8L3 TSS +CAGE:HepG2 — SARS1 TSS HepG2 -3.87e+03 -3.85e+03 --0.006 +1.29e+04 +1.3e+04 ++0.005 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GNAT2 TSS +CAGE:HepG2 — AMIGO1 TSS HepG2 -1.67e+03 -1.66e+03 --0.005 +2.07 +2.08 ++0.005 ≥99th 1.000 Minimal effect -CAGE:HepG2 — AMPD2 TSS +CAGE:HepG2 — TAF13 TSS HepG2 -2.7e+03 -2.69e+03 +4.03e+03 +4.02e+03 -0.005 ≥99th 1.000 Minimal effect -CAGE:HepG2 — ATXN7L2 TSS +CAGE:HepG2 — WDR47 TSS HepG2 -1.45e+03 -1.45e+03 +1.62e+03 +1.63e+03 +0.005 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GSTM1 TSS +CAGE:HepG2 — GNAT2 TSS HepG2 -0.611 -0.616 -+0.005 +1.82e+03 +1.83e+03 ++0.004 ≥99th 1.000 Minimal effect -CAGE:HepG2 — CYB561D1 TSS +CAGE:HepG2 — AMPD2 TSS HepG2 -877 -874 --0.005 +2.92e+03 +2.93e+03 ++0.004 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GPR61 TSS +CAGE:HepG2 — GSTM2 TSS HepG2 -5.81 -5.83 +829 +831 +0.004 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GNAI3 TSS +CAGE:HepG2 — GNAT2 TSS HepG2 -381 -380 --0.004 +63.9 +64.1 ++0.004 ≥99th 1.000 Minimal effect -CAGE:HepG2 — CLCC1 TSS +CAGE:HepG2 — AKNAD1 TSS HepG2 -27.9 -27.8 --0.004 +2.67 +2.66 +-0.003 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GPSM2 TSS +CAGE:HepG2 — EPS8L3 TSS HepG2 -23.6 -23.7 -+0.003 +3.85e+03 +3.84e+03 +-0.003 ≥99th 1.000 Minimal effect -CAGE:HepG2 — WDR47 TSS +CAGE:HepG2 — GSTM3 TSS HepG2 -2.36 -2.37 -+0.003 +2.3e+03 +2.3e+03 +-0.003 ≥99th 1.000 Minimal effect -CAGE:HepG2 — TMEM167B TSS +CAGE:HepG2 — CLCC1 TSS HepG2 -423 -424 +4.15e+03 +4.16e+03 +0.003 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GPSM2 TSS +CAGE:HepG2 — GSTM4 TSS HepG2 -2.25e+03 -2.25e+03 --0.003 +3.98e+03 +3.99e+03 ++0.003 ≥99th 1.000 Minimal effect -CAGE:HepG2 — ELAPOR1 TSS +CAGE:HepG2 — CYB561D1 TSS HepG2 -0.804 -0.808 -+0.003 +841 +843 ++0.002 ≥99th 1.000 Minimal effect -CAGE:HepG2 — PSMA5 TSS +CAGE:HepG2 — TMEM167B TSS HepG2 -1.1e+04 -1.1e+04 -+0.003 +354 +354 +-0.002 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GSTM4 TSS +CAGE:HepG2 — GNAI3 TSS HepG2 -3.85e+03 -3.86e+03 -+0.003 +8.77e+03 +8.76e+03 +-0.002 ≥99th 1.000 Minimal effect -CAGE:HepG2 — AKNAD1 TSS +CAGE:HepG2 — GSTM2 TSS HepG2 -2.05 -2.04 --0.003 +1.22 +1.22 +-0.002 ≥99th 1.000 Minimal effect -CAGE:HepG2 — PSMA5 TSS +CAGE:HepG2 — GNAI3 TSS HepG2 -94.3 -94.4 +352 +353 +0.002 ≥99th 1.000 Minimal effect -CAGE:HepG2 — AKNAD1 TSS +CAGE:HepG2 — GPSM2 TSS HepG2 -2.89 -2.88 --0.002 +23.3 +23.3 ++0.002 ≥99th 1.000 Minimal effect -CAGE:HepG2 — CFAP276 TSS +CAGE:HepG2 — AMIGO1 TSS HepG2 -14.8 -14.7 +275 +274 -0.002 ≥99th 1.000 Minimal effect -CAGE:HepG2 — AMIGO1 TSS +CAGE:HepG2 — ATXN7L2 TSS HepG2 -2.07 -2.08 -+0.002 +1.37e+03 +1.38e+03 ++0.001 ≥99th 1.000 Minimal effect -CAGE:HepG2 — TMEM167B TSS +CAGE:HepG2 — GSTM1 TSS HepG2 -2.99e+03 -2.99e+03 -+0.002 +0.64 +0.639 +-0.001 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GSTM3 TSS +CAGE:HepG2 — GSTM4 TSS HepG2 -7.07 -7.06 --0.002 +59.8 +59.9 ++0.001 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GNAT2 TSS +CAGE:HepG2 — GSTM5 TSS HepG2 -63.9 -64 -+0.002 +12.4 +12.4 ++0.001 ≥99th 1.000 Minimal effect -CAGE:HepG2 — TAF13 TSS +CAGE:HepG2 — SYPL2 TSS HepG2 -42.3 -42.3 -+0.002 +362 +362 ++0.001 ≥99th 1.000 Minimal effect -CAGE:HepG2 — CYB561D1 TSS +CAGE:HepG2 — PSMA5 TSS HepG2 -9.32 -9.31 +100 +100 -0.001 ≥99th 1.000 Minimal effect -CAGE:HepG2 — GSTM4 TSS +CAGE:HepG2 — TMEM167B TSS HepG2 -61.7 -61.7 --0.001 +3.3e+03 +3.31e+03 ++0.001 ≥99th 1.000 Minimal effect -CAGE:HepG2 — TAF13 TSS +CAGE:HepG2 — GPSM2 TSS HepG2 -4.04e+03 -4.04e+03 +2.26e+03 +2.26e+03 -0.001 -≥99th +near-zero 1.000 Minimal effect -CAGE:HepG2 — GNAI3 TSS +CAGE:HepG2 — WDR47 TSS HepG2 -9.12e+03 -9.12e+03 +2.25 +2.25 +0.001 near-zero 1.000 Minimal effect -CAGE:HepG2 — WDR47 TSS +CAGE:HepG2 — GSTM5 TSS HepG2 -1.61e+03 -1.61e+03 -+0.001 +0.11 +0.109 +-0.001 near-zero -1.000 +0.804 Minimal effect -CAGE:HepG2 — GPR61 TSS +CAGE:HepG2 — EPS8L3 TSS HepG2 -0.0637 -0.0642 +34.9 +34.9 +0.001 near-zero -0.598 +1.000 Minimal effect CAGE:HepG2 — CLCC1 TSS HepG2 -4.34e+03 -4.33e+03 --0.001 +28.9 +28.9 ++0.001 near-zero 1.000 Minimal effect -CAGE:HepG2 — GSTM2 TSS +CAGE:HepG2 — CFAP276 TSS HepG2 -1.24 -1.24 +11.8 +11.8 +0.000 near-zero 1.000 Minimal effect -CAGE:HepG2 — AMIGO1 TSS +CAGE:HepG2 — CYB561D1 TSS HepG2 -259 -259 -+0.000 +9.48 +9.48 +-0.000 near-zero 1.000 Minimal effect -CAGE:HepG2 — GSTM5 TSS +CAGE:HepG2 — GPR61 TSS HepG2 -0.105 -0.105 --0.000 +0.0612 +0.0612 ++0.000 near-zero -0.788 +0.580 Minimal effect @@ -782,7 +782,7 @@

    Interactive Genome Browser

    try { const browser = await igv.createBrowser( document.getElementById("igv-div"), - {"genome":"hg38","locus":"chr1:108750680-109799256","showRuler":true,"showNavigation":true,"showCenterGuide":true,"roi":[{"name":"Modification","color":"rgba(255, 0, 0, 0.12)","features":[{"chr":"chr1","start":109274967,"end":109274969}]}],"tracks":[{"name":"Modification: G>T","type":"annotation","displayMode":"EXPANDED","height":25,"color":"red","features":[{"chr":"chr1","start":109274967,"end":109274969,"name":"chr1:109,274,968 G>T"}]},{"name":"DNASE:HepG2","type":"merged","height":80,"tracks":[{"type":"wig","name":"DNASE:HepG2 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); console.log("IGV browser created successfully"); } catch(e) { diff --git a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_chrombpnet_report.html b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_chrombpnet_report.html index 3c60ad9..81858a6 100644 --- a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_chrombpnet_report.html +++ b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_chrombpnet_report.html @@ -57,14 +57,14 @@

    Analysis Request

  • Oracle: chrombpnet
  • Normalizer: chorus per-track v1
  • Tracks requested: 1 tracks
    • -
  • Generated: 2026-04-21 13:10 UTC
    • +
  • Generated: 2026-05-09 22:16 UTC

    • Variant: chr1:109274968 G>T

    Oracle: chrombpnet

    Gene: SORT1

    -

    Other nearby genes: CELSR2

    -

    Summary: Chromatin accessibility (DNASE/ATAC): strong opening (+0.53, ATAC:HepG2).

    +

    Other nearby genes: PSRC1, CELSR2, MYBPHL, SARS1

    +

    Summary: Chromatin accessibility (DNASE/ATAC): very strong opening (+1.24, DNASE:HepG2).

    How to read this report. Every numeric effect below is produced by a deep-learning model. The scale depends on the regulatory layer — see the formulas below so you can interpret +0.3 correctly.

    Effect %ile
    How unusual is this variant's effect? Ranked against ~10,000 random SNPs scored genome-wide. 95% means the effect is larger than 95% of random variants. Range [0,1] for unsigned layers (chromatin, TF, histone, TSS, splicing); [−1,1] for signed layers (gene expression, MPRA).
    Activity %ile
    How active is this region genome-wide? Reference signal ranked against ~26,000 ENCODE SCREEN cCREs and random regions. 0.95 = predicted signal exceeds 95% of genome-wide positions — a highly active regulatory element.
    Per-layer effect
    Unit depends on the layer:
    • Chromatin accessibility (DNASE/ATAC) log2FC — log2((alt+1)/(ref+1)). +0.3 ≈ alt signal 1.23× ref; +1.0 ≈ 2× ref; negative values = loss of signal.

    Chromatin accessibility (DNASE/ATAC) log2FC

    @@ -73,14 +73,14 @@

    Chromatin accessibility (DNASE/ATAC) log2FCActivity %ile

    - + - - - + + + - - + +
    Interpretation
    ATAC:HepG2DNASE:HepG2 HepG2636917+0.529256606+1.241 ≥99th0.809Strong opening0.897Very strong opening

    Interactive Genome Browser

    @@ -161,7 +161,7 @@

    Interactive Genome Browser

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); console.log("IGV browser created successfully"); } catch(e) { diff --git a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_legnet_report.html b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_legnet_report.html index d780ed6..9804311 100644 --- a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_legnet_report.html +++ b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_legnet_report.html @@ -57,14 +57,14 @@

    Analysis Request

  • Oracle: legnet
  • Normalizer: chorus per-track v1
  • Tracks requested: 1 tracks
    • -
  • Generated: 2026-04-22 17:20 UTC
    • +
  • Generated: 2026-05-09 22:19 UTC

    • Variant: chr1:109274968 G>T

    Oracle: legnet

    Gene: SORT1

    -

    Other nearby genes: CELSR2

    -

    Summary: Promoter activity (MPRA): moderate activation (+0.30, LentiMPRA:HepG2).

    +

    Other nearby genes: PSRC1, CELSR2, MYBPHL, SARS1

    +

    Summary: No strong regulatory effects detected across any layer.

    How to read this report. Every numeric effect below is produced by a deep-learning model. The scale depends on the regulatory layer — see the formulas below so you can interpret +0.3 correctly.

    Per-layer effect
    Unit depends on the layer:
    • Promoter activity (MPRA) Δ (alt−ref) — alt − ref. Raw difference in predicted value (not a ratio). Useful when ref is near zero.

    Promoter activity (MPRA) Δ (alt−ref)

    @@ -73,10 +73,10 @@

    Promoter activity (MPRA) Δ (alt−ref)

    - - - - + + + +
    LentiMPRA:HepG2 HepG20.3720.669+0.297Moderate activation-0.739-0.739+0.000Minimal effect

    Interactive Genome Browser

    @@ -157,7 +157,7 @@

    Interactive Genome Browser

    try { const browser = await igv.createBrowser( document.getElementById("igv-div"), - {"genome":"hg38","locus":"chr1:109274868-109275068","showRuler":true,"showNavigation":true,"showCenterGuide":true,"roi":[{"name":"Modification","color":"rgba(255, 0, 0, 0.12)","features":[{"chr":"chr1","start":109274967,"end":109274969}]}],"tracks":[{"name":"Modification: G>T","type":"annotation","displayMode":"EXPANDED","height":25,"color":"red","features":[{"chr":"chr1","start":109274967,"end":109274969,"name":"chr1:109,274,968 G>T"}]},{"name":"LentiMPRA:HepG2","type":"merged","height":80,"tracks":[{"type":"wig","name":"LentiMPRA:HepG2 ref","color":"rgb(180,180,180)","autoscale":true,"autoscaleGroup":"LentiMPRA_HepG2","features":[{"chr":"chr1","start":109274868,"end":109274918,"value":0.3724}]},{"type":"wig","name":"LentiMPRA:HepG2 alt","color":"rgb(230,120,0)","autoscale":true,"autoscaleGroup":"LentiMPRA_HepG2","features":[{"chr":"chr1","start":109274868,"end":109274918,"value":0.6693}]}]}]} + 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t":109799118,"end":109799168,"value":-0.4533},{"chr":"chr1","start":109799168,"end":109799218,"value":-0.6537},{"chr":"chr1","start":109799218,"end":109799268,"value":-0.4473}]}]}]} ); console.log("IGV browser created successfully"); } catch(e) { diff --git a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_multioracle_report.html b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_multioracle_report.html index cbf9301..b574638 100644 --- a/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_multioracle_report.html +++ b/examples/walkthroughs/validation/SORT1_rs12740374_multioracle/rs12740374_SORT1_multioracle_report.html @@ -86,7 +86,7 @@

    Analysis Request

  • Oracle: chrombpnet, legnet, alphagenome
  • Normalizer: per-oracle chorus per-track v1
  • Tracks requested: assay_ids as listed in each per-oracle request
    • -
  • Generated: 2026-04-22 17:21 UTC
    • +
  • Generated: 2026-05-09 22:22 UTC

    • Variant: chr1:109,274,968 G>T

    @@ -102,38 +102,38 @@

    Cross-oracle consensus

    alphagenome Agreement Chromatin accessibility (DNASE/ATAC) log2FC -+0.529 · ≥99thATAC:HepG2 ++1.241 · ≥99thDNASE:HepG2 — -+1.398 · ≥99thDNASE:HepG2 ++1.336 · ≥99thDNASE:HepG2 ✅ all ↑ Promoter activity (MPRA) Δ (alt−ref) — -+0.297LentiMPRA:HepG2 ++0.000LentiMPRA:HepG2 — ↑ only (n=1) Transcription factor binding (ChIP-TF) log2FC — — -+2.759 · ≥99thCHIP:CEBPA:HepG2 ++2.777 · ≥99thCHIP:CEBPA:HepG2 ↑ only (n=1) Histone modifications (ChIP-Histone) log2FC — — -+1.332 · ≥99thCHIP:H3K27ac:HepG2 ++1.267 · ≥99thCHIP:H3K27ac:HepG2 ↑ only (n=1) TSS activity (CAGE/PRO-CAP) log2FC — — -+1.557 · ≥99thCAGE:HepG2 ++1.522 · ≥99thCAGE:HepG2 ↑ only (n=1)

    Cross-oracle genome browser

    -

    All oracles' ref (grey) / alt (coloured) signal tracks on a single IGV. Default locus is the widest oracle's prediction window — narrower-window oracles show blank outside their coverage (expected: LegNet is ~200 bp and ChromBPNet ~1 kb while AlphaGenome reaches ±500 kb). Signals are floor-rescaled to [0, 3.0] where 1.0 is the genome-wide p99 peak for that assay.

    +

    All oracles' ref (grey) / alt (coloured) signal tracks on a single IGV. Default locus is the widest oracle's prediction window — narrower-window oracles show blank outside their coverage (expected: LegNet is ~200 bp and ChromBPNet ~1 kb while AlphaGenome reaches ±500 kb).

    Signal rescaled using each track's genome-wide noise floor (p95) and peak threshold (p99): 0 = noise floor, 1.0 = top 1% of bins genome-wide. Peak shape preserved; tracks comparable across cell types.

    @@ -210,7 +210,7 @@

    Cross-oracle genome browser

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); } catch(e) { console.error("IGV error:", e); @@ -223,31 +223,31 @@

    Cross-oracle genome browser

    Per-oracle evidence

    Each block expands to the strongest track per layer for that oracle. For the full signal overlays and every track scored, open the standalone per-oracle report.

    -chrombpnet · 1 tracks · strongest: Chromatin accessibility (DNASE/ATAC) +0.529 +chrombpnet · 1 tracks · strongest: Chromatin accessibility (DNASE/ATAC) +1.241
    - +
    LayerTop assayCell typeRefAltEffect%ile
    Chromatin accessibility (DNASE/ATAC) log2FCATAC:HepG2HepG2636917+0.529≥99th
    Chromatin accessibility (DNASE/ATAC) log2FCDNASE:HepG2HepG2256606+1.241≥99th

    Open chrombpnet standalone report →

    -legnet · 1 tracks · strongest: Promoter activity (MPRA) +0.297 +legnet · 1 tracks · strongest: Promoter activity (MPRA) +0.000
    - +
    LayerTop assayCell typeRefAltEffect%ile
    Promoter activity (MPRA) Δ (alt−ref)LentiMPRA:HepG2HepG20.3720.669+0.297—
    Promoter activity (MPRA) Δ (alt−ref)LentiMPRA:HepG2HepG2-0.739-0.739+0.000—

    Open legnet standalone report →

    -alphagenome · 61 tracks · strongest: Transcription factor binding (ChIP-TF) +2.759 +alphagenome · 61 tracks · strongest: Transcription factor binding (ChIP-TF) +2.777
    - - - - + + + +
    LayerTop assayCell typeRefAltEffect%ile
    Transcription factor binding (ChIP-TF) log2FCCHIP:CEBPA:HepG2HepG22.54e+031.72e+04+2.759≥99th
    TSS activity (CAGE/PRO-CAP) log2FCCAGE:HepG2HepG222.969.3+1.557≥99th
    Chromatin accessibility (DNASE/ATAC) log2FCDNASE:HepG2HepG25961.57e+03+1.398≥99th
    Histone modifications (ChIP-Histone) log2FCCHIP:H3K27ac:HepG2HepG21.43e+043.6e+04+1.332≥99th
    Transcription factor binding (ChIP-TF) log2FCCHIP:CEBPA:HepG2HepG22.57e+031.76e+04+2.777≥99th
    TSS activity (CAGE/PRO-CAP) log2FCCAGE:HepG2HepG225.675.3+1.522≥99th
    Chromatin accessibility (DNASE/ATAC) log2FCDNASE:HepG2HepG26691.69e+03+1.336≥99th
    Histone modifications (ChIP-Histone) log2FCCHIP:H3K27ac:HepG2HepG21.59e+043.82e+04+1.267≥99th

    Open alphagenome standalone report →

    -
    Generated by Chorus MultiOracleReport on 2026-04-22 17:21 UTC
    +
    Generated by Chorus MultiOracleReport on 2026-05-09 22:22 UTC
    \ No newline at end of file diff --git a/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/example_output.json b/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/example_output.json index 4295211..0e38f8a 100644 --- a/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/example_output.json +++ b/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/example_output.json @@ -19,43 +19,43 @@ "scores_by_layer": { "chromatin_accessibility": [ { - "assay_id": "ATAC:HepG2", - "assay_type": "ATAC", + "assay_id": "DNASE:HepG2", + "assay_type": "DNASE", "cell_type": "HepG2", "layer": "chromatin_accessibility", - "ref_value": 635.6930961374892, - "alt_value": 917.4119157849345, - "raw_score": 0.528543239432768, - "description": "ATAC:HepG2", - "quantile_score": 1.0, - "ref_signal_percentile": 0.8088 + "ref_value": 48.525416523218155, + "alt_value": 60.72449456900358, + "raw_score": 0.3176740092562657, + "description": "DNASE:HepG2", + "quantile_score": 0.9616, + "ref_signal_percentile": 0.6046 } ] }, "all_scores": [ { - "assay_id": "ATAC:HepG2", - "assay_type": "ATAC", + "assay_id": "DNASE:HepG2", + "assay_type": "DNASE", "cell_type": "HepG2", "layer": "chromatin_accessibility", - "ref_value": 635.6930961374892, - "alt_value": 917.4119157849345, - "raw_score": 0.528543239432768, - "description": "ATAC:HepG2", - "quantile_score": 1.0, - "ref_signal_percentile": 0.8088 + "ref_value": 48.525416523218155, + "alt_value": 60.72449456900358, + "raw_score": 0.3176740092562657, + "description": "DNASE:HepG2", + "quantile_score": 0.9616, + "ref_signal_percentile": 0.6046 } ] } }, "analysis_request": { - "user_prompt": "Score chr1:109274968 G>T using ChromBPNet ATAC model in HepG2. Gene: SORT1.", + "user_prompt": "Score chr1:109274968 G>T using ChromBPNet DNASE model in HepG2. Gene: SORT1.", "tool_name": "analyze_variant_multilayer", "oracle_name": "chrombpnet", "normalizer_name": "per-track background CDFs", - "tracks_requested": "ATAC:HepG2", + "tracks_requested": "DNASE:HepG2", "cell_types": [], "notes": [], - "generated_at": "2026-04-21 13:08 UTC" + "generated_at": "2026-05-09 21:25 UTC" } } \ No newline at end of file diff --git a/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/example_output.md b/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/example_output.md index 4eafa4a..2dcbede 100644 --- a/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/example_output.md +++ b/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/example_output.md @@ -1,12 +1,12 @@ ## Analysis Request -> Score chr1:109274968 G>T using ChromBPNet ATAC model in HepG2. Gene: SORT1. +> Score chr1:109274968 G>T using ChromBPNet DNASE model in HepG2. Gene: SORT1. - **Tool**: `analyze_variant_multilayer` - **Oracle**: chrombpnet - **Normalizer**: per-track background CDFs -- **Tracks requested**: ATAC:HepG2 -- **Generated**: 2026-04-21 13:08 UTC +- **Tracks requested**: DNASE:HepG2 +- **Generated**: 2026-05-09 21:25 UTC ## Multi-Layer Variant Effect Report @@ -15,13 +15,13 @@ **Gene**: SORT1 **Other nearby genes**: CELSR2 -**Summary**: Chromatin accessibility (DNASE/ATAC): strong opening (+0.53, ATAC:HepG2). +**Summary**: Chromatin accessibility (DNASE/ATAC): strong opening (+0.32, DNASE:HepG2). #### Chromatin accessibility (DNASE/ATAC) | Track | Ref | Alt | Effect | Effect %ile | Activity %ile | Interpretation | |---|---|---|---|---|---|---| -| ATAC:HepG2 | 636 | 917 | +0.529 | ≥99th | 0.809 | Strong opening | +| DNASE:HepG2 | 48.5 | 60.7 | +0.318 | 0.96 | 0.605 | Strong opening | --- **Score guide:** diff --git a/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/rs12740374_SORT1_chrombpnet_report.html b/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/rs12740374_SORT1_chrombpnet_report.html index d37a17f..263a53d 100644 --- a/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/rs12740374_SORT1_chrombpnet_report.html +++ b/examples/walkthroughs/variant_analysis/SORT1_chrombpnet/rs12740374_SORT1_chrombpnet_report.html @@ -51,20 +51,20 @@

    Multi-Layer Variant Effect Report

    Analysis Request

    -
    Score chr1:109274968 G>T using ChromBPNet ATAC model in HepG2. Gene: SORT1.
    +
    Score chr1:109274968 G>T using ChromBPNet DNASE model in HepG2. Gene: SORT1.
    • Tool: analyze_variant_multilayer
    • Oracle: chrombpnet
    • Normalizer: per-track background CDFs
      • -
    • Tracks requested: ATAC:HepG2
      • -
    • Generated: 2026-04-21 13:08 UTC
      • +
    • Tracks requested: DNASE:HepG2
      • +
    • Generated: 2026-05-09 21:25 UTC

    Variant: chr1:109274968 G>T

    Oracle: chrombpnet

    Gene: SORT1

    Other nearby genes: CELSR2

    -

    Summary: Chromatin accessibility (DNASE/ATAC): strong opening (+0.53, ATAC:HepG2).

    +

    Summary: Chromatin accessibility (DNASE/ATAC): strong opening (+0.32, DNASE:HepG2).

    How to read this report. Every numeric effect below is produced by a deep-learning model. The scale depends on the regulatory layer — see the formulas below so you can interpret +0.3 correctly.

    Effect %ile
    How unusual is this variant's effect? Ranked against ~10,000 random SNPs scored genome-wide. 95% means the effect is larger than 95% of random variants. Range [0,1] for unsigned layers (chromatin, TF, histone, TSS, splicing); [−1,1] for signed layers (gene expression, MPRA).
    Activity %ile
    How active is this region genome-wide? Reference signal ranked against ~26,000 ENCODE SCREEN cCREs and random regions. 0.95 = predicted signal exceeds 95% of genome-wide positions — a highly active regulatory element.
    Per-layer effect
    Unit depends on the layer:
    • Chromatin accessibility (DNASE/ATAC) log2FC — log2((alt+1)/(ref+1)). +0.3 ≈ alt signal 1.23× ref; +1.0 ≈ 2× ref; negative values = loss of signal.

    Chromatin accessibility (DNASE/ATAC) log2FC

    @@ -73,13 +73,13 @@

    Chromatin accessibility (DNASE/ATAC) log2FCActivity %ile

    - + - - - - - + + + + +
    Interpretation
    ATAC:HepG2DNASE:HepG2 HepG2636917+0.529≥99th0.80948.560.7+0.3180.960.605 Strong opening
    @@ -161,7 +161,7 @@

    Interactive Genome Browser

    try { const browser = await igv.createBrowser( document.getElementById("igv-div"), - {"genome":"hg38","locus":"chr1:109274468-109275468","showRuler":true,"showNavigation":true,"showCenterGuide":true,"roi":[{"name":"Modification","color":"rgba(255, 0, 0, 0.12)","features":[{"chr":"chr1","start":109274967,"end":109274969}]}],"tracks":[{"name":"Modification: G>T","type":"annotation","displayMode":"EXPANDED","height":25,"color":"red","features":[{"chr":"chr1","start":109274967,"end":109274969,"name":"chr1:109,274,968 G>T"}]},{"name":"ATAC:HepG2","type":"merged","height":80,"tracks":[{"type":"wig","name":"ATAC:HepG2 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); console.log("IGV browser created successfully"); } catch(e) { diff --git a/scripts/build_backgrounds_chrombpnet.py b/scripts/build_backgrounds_chrombpnet.py index 340cd8b..05dc132 100644 --- a/scripts/build_backgrounds_chrombpnet.py +++ b/scripts/build_backgrounds_chrombpnet.py @@ -41,14 +41,7 @@ "JASPAR models (~3 min/model on Metal — much smaller arch). " "all = both, sequentially.", ) -parser.add_argument( - "--gpu", - type=int, - default=0, - help="Pin TensorFlow to this GPU index. No-op if CUDA_VISIBLE_DEVICES " - "is already set in the calling shell — the outer env var wins, so " - "`CUDA_VISIBLE_DEVICES=1 ... --gpu 0` puts the work on physical GPU 1.", -) +parser.add_argument("--gpu", type=int, default=0) parser.add_argument("--fold", type=int, default=0) parser.add_argument( "--model-type", @@ -64,6 +57,12 @@ "for the rebuild against `chrombpnet_nobias`.", ) parser.add_argument("--n-variants", type=int, default=10000) +parser.add_argument("--n-dhs-variants", type=int, default=10000, + help="DHS-based SNPs (summit ±150 bp) to add to the effect CDF. 0 to disable.") +parser.add_argument("--n-dhs-peaks", type=int, default=5000, + help="DHS peak summits to add to the baseline (activity) CDF. 0 to disable.") +parser.add_argument("--dhs-path", type=str, default=None, + help="Path to dhs_vocabulary_hg38.txt.gz. Defaults to annotations/ in repo root.") parser.add_argument("--reservoir-size", type=int, default=50000) parser.add_argument("--n-cdf-points", type=int, default=10000) parser.add_argument("--batch-size", type=int, default=64) @@ -74,15 +73,6 @@ "chrombpnet_pertrack.npz. Pair with --part merge-incremental to " "stitch new rows into the existing NPZ.", ) -parser.add_argument( - "--force", - action="store_true", - help="Overwrite an existing interim NPZ even if its track-id set " - "differs from the current run. Default: refuse to overwrite and " - "exit with a diff, to protect the documented two-pass flow " - "(--assay ATAC_DNASE then --assay CHIP) which would otherwise " - "silently lose the first pass's tracks.", -) parser.add_argument( "--shard", type=int, @@ -211,54 +201,9 @@ def _interim_suffix() -> str: return f".shard{args.shard}of{args.shard_of}" -def _check_interim_compatibility(interim_path: str, new_track_ids, force: bool, label: str) -> None: - """Refuse to overwrite an interim NPZ whose track-id set differs from - the current run, unless --force was passed. Closes #71/#73. - - The documented two-pass flow (``--assay ATAC_DNASE`` then ``--assay - CHIP``) would otherwise silently overwrite the first pass's interim - with the second pass's smaller track set, producing a 744-track - final NPZ where 786 was expected. - """ - if not os.path.exists(interim_path): - return - try: - existing = list(np.load(interim_path, allow_pickle=False)["track_ids"].astype(str)) - except Exception as exc: - if force: - return - raise SystemExit( - f"Existing {label} interim at {interim_path} is unreadable " - f"({exc}); pass --force to overwrite." - ) - new_set, old_set = set(new_track_ids), set(existing) - if new_set == old_set: - return # same tracks → plain overwrite is harmless - if force: - return - only_existing = sorted(old_set - new_set) - only_new = sorted(new_set - old_set) - raise SystemExit( - f"Refusing to overwrite {label} interim at {interim_path}.\n" - f" Existing tracks: {len(existing)} (e.g. {only_existing[:3]})\n" - f" New tracks: {len(new_track_ids)} (e.g. {only_new[:3]})\n" - f" Only in existing: {len(only_existing)}; only in new: {len(only_new)}.\n" - f"This usually means a previous staged run wrote tracks for a " - f"different --assay group (the documented two-pass flow). Run " - f"`--part merge` (or `--part merge-incremental`) to consume the " - f"existing interim first, then re-run, or pass --force to discard " - f"the existing interim and write only the current run's tracks." - ) - - def load_models_and_setup(): """Load reference, set up GPU, return (oracle, models_to_score, ref).""" - # Honour pre-set CUDA_VISIBLE_DEVICES from the calling shell so the - # documented parallel-launch pattern works as cluster-user mental model - # expects (`CUDA_VISIBLE_DEVICES=N ... --gpu 0` per terminal pins the - # outer physical GPU, not the inner --gpu arg). Closes #72/#74. - if "CUDA_VISIBLE_DEVICES" not in os.environ: - os.environ["CUDA_VISIBLE_DEVICES"] = str(args.gpu) + os.environ["CUDA_VISIBLE_DEVICES"] = str(args.gpu) try: import nvidia @@ -430,7 +375,38 @@ def build_all_models(do_variants: bool, do_baselines: bool): "alt": random.choice([b for b in "ACGT" if b != ref_base])}) random.shuffle(snps) snps = snps[:args.n_variants] - logger.info("Generated %d SNPs", len(snps)) + logger.info("Generated %d random SNPs", len(snps)) + + # ── DHS-based SNPs (for effect CDF) ── + dhs_snps = [] + if do_variants and args.n_dhs_variants > 0: + try: + from chorus.utils.annotations import sample_dhs_positions + dhs_path = args.dhs_path or os.path.join(REPO_ROOT, "annotations", + "dhs_vocabulary_hg38.txt.gz") + dhs_summit_positions = sample_dhs_positions( + args.n_dhs_variants, dhs_path=dhs_path, seed=43, + ) + random.seed(44) + for chrom, summit in dhs_summit_positions: + offset = random.randint(-150, 150) + pos = summit + offset + chrom_len = ref.get_reference_length(chrom) + if pos < 5_000_000 or pos > chrom_len - 5_000_000: + continue + ref_base = ref.fetch(chrom, pos - 1, pos).upper() + if ref_base not in "ACGT": + continue + dhs_snps.append({"chrom": chrom, "pos": pos, "ref": ref_base, + "alt": random.choice([b for b in "ACGT" if b != ref_base])}) + logger.info("Generated %d DHS SNPs", len(dhs_snps)) + except FileNotFoundError as exc: + logger.warning("DHS vocabulary not found — skipping DHS variants: %s", exc) + + all_snps = snps + dhs_snps + if do_variants: + logger.info("Total SNPs for effect CDF: %d (random=%d, DHS=%d)", + len(all_snps), len(snps), len(dhs_snps)) # ── Baseline positions ── baseline_positions = [] @@ -481,9 +457,25 @@ def build_all_models(do_variants: bool, do_baselines: bool): baseline_positions.append((chrom, pos)) for chrom, pos in tss_list: baseline_positions.append((chrom, int(pos))) + + # ── DHS peak positions (for activity CDF) ── + dhs_baseline = [] + if args.n_dhs_peaks > 0: + try: + from chorus.utils.annotations import sample_dhs_positions + dhs_path = args.dhs_path or os.path.join(REPO_ROOT, "annotations", + "dhs_vocabulary_hg38.txt.gz") + dhs_baseline = sample_dhs_positions( + args.n_dhs_peaks, dhs_path=dhs_path, seed=567, + ) + baseline_positions.extend(dhs_baseline) + except FileNotFoundError as exc: + logger.warning("DHS vocabulary not found — skipping DHS baselines: %s", exc) + random.shuffle(baseline_positions) - logger.info("Total baseline positions: %d (random=%d, cCRE=%d, TSS=%d)", - len(baseline_positions), len(rand_positions), len(ccre_positions), len(tss_list)) + logger.info("Total baseline positions: %d (random=%d, cCRE=%d, TSS=%d, DHS=%d)", + len(baseline_positions), len(rand_positions), len(ccre_positions), + len(tss_list), len(dhs_baseline)) # Iterate over models for model_idx, spec in enumerate(models_to_score): @@ -509,10 +501,10 @@ def build_all_models(do_variants: bool, do_baselines: bool): model = oracle.model # ── Variant scoring ── - if do_variants and snps: + if do_variants and all_snps: t0 = time.time() ref_seqs, alt_seqs = [], [] - for snp in snps: + for snp in all_snps: seq_ref = get_sequence(ref, snp["chrom"], snp["pos"]) if seq_ref is None: continue @@ -576,7 +568,6 @@ def build_all_models(do_variants: bool, do_baselines: bool): if do_variants: effect_matrix = effect_reservoir.to_cdf_matrix(n_points=args.n_cdf_points) interim_path = os.path.join(cache_dir, f"chrombpnet_effect_cdfs_interim{suffix}.npz") - _check_interim_compatibility(interim_path, track_ids, args.force, "effect-CDF") np.savez_compressed( interim_path, track_ids=np.array(track_ids, dtype='U'), @@ -590,7 +581,6 @@ def build_all_models(do_variants: bool, do_baselines: bool): summary_matrix = summary_reservoir.to_cdf_matrix(n_points=args.n_cdf_points) perbin_matrix = perbin_reservoir.to_cdf_matrix(n_points=args.n_cdf_points) interim_path = os.path.join(cache_dir, f"chrombpnet_baseline_cdfs_interim{suffix}.npz") - _check_interim_compatibility(interim_path, track_ids, args.force, "baseline-CDF") np.savez_compressed( interim_path, track_ids=np.array(track_ids, dtype='U'), diff --git a/scripts/regenerate_examples.py b/scripts/regenerate_examples.py index f99d3f0..c2c50a4 100644 --- a/scripts/regenerate_examples.py +++ b/scripts/regenerate_examples.py @@ -45,6 +45,7 @@ HEPG2_TRACKS = [ "DNASE/EFO:0001187 DNase-seq/.", # DNASE + "ATAC/EFO:0001187 ATAC-seq/.", # ATAC "CHIP_TF/EFO:0001187 TF ChIP-seq CEBPA genetically modified (insertion) using CRISPR targeting H. sapiens CEBPA/.", # CEBPA "CHIP_TF/EFO:0001187 TF ChIP-seq CEBPB/.", # CEBPB "CHIP_HISTONE/EFO:0001187 Histone ChIP-seq H3K27ac/.", # H3K27ac @@ -76,43 +77,43 @@ "html_name": "rs12740374_SORT1_alphagenome_report.html", "user_prompt": "Analyze rs12740374 (chr1:109274968 G>T) in HepG2 liver cells using DNASE, CEBPA/CEBPB ChIP, H3K27ac, and CAGE tracks. Gene is SORT1.", }, - { - "name": "BCL11A rs1427407 (K562 erythroid)", - "dir": f"{BASE}/variant_analysis/BCL11A_rs1427407", - "type": "variant", - "position": "chr2:60490908", - "ref": "G", "alt": "T", - "gene": "BCL11A", - "assay_ids": K562_TRACKS, - "cell_type": "K562", - "html_name": "rs1427407_BCL11A_alphagenome_report.html", - "user_prompt": "Analyze rs1427407 (chr2:60490908 G>T) in K562 erythroid cells using DNASE, GATA1/TAL1 ChIP, H3K27ac, and CAGE tracks. Gene is BCL11A.", - }, - { - "name": "FTO rs1421085 (HepG2 — nearest liver/metabolic)", - "dir": f"{BASE}/variant_analysis/FTO_rs1421085", - "type": "variant", - "position": "chr16:53767042", - "ref": "T", "alt": "C", - "gene": "FTO", - "assay_ids": HEPG2_TRACKS, - "cell_type": "HepG2", - "html_name": "rs1421085_FTO_alphagenome_report.html", - "user_prompt": "Analyze rs1421085 (chr16:53767042 T>C) in HepG2 cells. Gene is FTO. Using HepG2 as the nearest available metabolic cell type.", - }, - # validation — forced HepG2 CEBP tracks to match the paper - { - "name": "SORT1 with CEBP (validation)", - "dir": f"{BASE}/validation/SORT1_rs12740374_with_CEBP", - "type": "variant", - "position": "chr1:109274968", - "ref": "G", "alt": "T", - "gene": "SORT1", - "assay_ids": HEPG2_TRACKS, - "cell_type": "HepG2", - "html_name": "rs12740374_SORT1_CEBP_validation_report.html", - "user_prompt": "Validate AlphaGenome paper finding: rs12740374 (chr1:109274968 G>T) should show CEBPA/CEBPB binding gain in HepG2. Using forced HepG2 tracks.", - }, + # { + # "name": "BCL11A rs1427407 (K562 erythroid)", + # "dir": f"{BASE}/variant_analysis/BCL11A_rs1427407", + # "type": "variant", + # "position": "chr2:60490908", + # "ref": "G", "alt": "T", + # "gene": "BCL11A", + # "assay_ids": K562_TRACKS, + # "cell_type": "K562", + # "html_name": "rs1427407_BCL11A_alphagenome_report.html", + # "user_prompt": "Analyze rs1427407 (chr2:60490908 G>T) in K562 erythroid cells using DNASE, GATA1/TAL1 ChIP, H3K27ac, and CAGE tracks. Gene is BCL11A.", + # }, + # { + # "name": "FTO rs1421085 (HepG2 — nearest liver/metabolic)", + # "dir": f"{BASE}/variant_analysis/FTO_rs1421085", + # "type": "variant", + # "position": "chr16:53767042", + # "ref": "T", "alt": "C", + # "gene": "FTO", + # "assay_ids": HEPG2_TRACKS, + # "cell_type": "HepG2", + # "html_name": "rs1421085_FTO_alphagenome_report.html", + # "user_prompt": "Analyze rs1421085 (chr16:53767042 T>C) in HepG2 cells. Gene is FTO. Using HepG2 as the nearest available metabolic cell type.", + # }, + # # validation — forced HepG2 CEBP tracks to match the paper + # { + # "name": "SORT1 with CEBP (validation)", + # "dir": f"{BASE}/validation/SORT1_rs12740374_with_CEBP", + # "type": "variant", + # "position": "chr1:109274968", + # "ref": "G", "alt": "T", + # "gene": "SORT1", + # "assay_ids": HEPG2_TRACKS, + # "cell_type": "HepG2", + # "html_name": "rs12740374_SORT1_CEBP_validation_report.html", + # "user_prompt": "Validate AlphaGenome paper finding: rs12740374 (chr1:109274968 G>T) should show CEBPA/CEBPB binding gain in HepG2. Using forced HepG2 tracks.", + # }, ] ENFORMER_EXAMPLES = [ @@ -141,7 +142,7 @@ "position": "chr1:109274968", "ref": "G", "alt": "T", "gene": "SORT1", - "assay": "ATAC", "cell_type": "HepG2", + "assay": "DNASE", "cell_type": "HepG2", "html_name": "rs12740374_SORT1_chrombpnet_report.html", }, ] diff --git a/scripts/regenerate_multioracle.py b/scripts/regenerate_multioracle.py index e35a401..62c6557 100644 --- a/scripts/regenerate_multioracle.py +++ b/scripts/regenerate_multioracle.py @@ -69,6 +69,22 @@ "agree on direction, and which assay/cell type drove each call." ) +def get_max_output_size(): + """Returns the maximum output size across all possible models.""" + from chorus.oracles.chrombpnet import ChromBPNetOracle + from chorus.oracles.legnet import LegNetOracle + from chorus.oracles.alphagenome import AlphaGenomeOracle + + sizes = [] + sizes.append(ChromBPNetOracle().output_size) + sizes.append(LegNetOracle().sequence_length) # to match output size + sizes.append(AlphaGenomeOracle().output_size) + + if not sizes: + raise RuntimeError("Could not determine any oracle output_size") + + return max(sizes) + # --------------------------------------------------------------------------- # Per-oracle runners @@ -91,8 +107,16 @@ def _build_variant_report(oracle, oracle_name: str, assay_ids=None): # Provide a small genomic region centred on the variant. Most oracles # only look ±half-window-size around the variant position; passing a 2bp # region here keeps the API contract satisfied without wasting compute. + max_window = get_max_output_size() + half_window = max_window // 2 + + start = VARIANT["position"] - half_window + end = VARIANT["position"] + half_window + + region_str = f"{VARIANT['chrom']}:{start}-{end}" position_str = f"{VARIANT['chrom']}:{VARIANT['position']}" - region_str = f"{VARIANT['chrom']}:{VARIANT['position']}-{VARIANT['position'] + 1}" + # position_str = f"{VARIANT['chrom']}:{VARIANT['position']}" + # region_str = f"{VARIANT['chrom']}:{VARIANT['position']}-{VARIANT['position'] + 1}" # Oracles use different attribute names for their single-track id: # LegNetOracle exposes ``assay_id`` (e.g. "LentiMPRA:HepG2"); ChromBPNet # stores ``assay`` + ``cell_type`` separately. Build the per-oracle @@ -163,9 +187,50 @@ def _save_oracle_artefacts(report, oracle_name: str): def run_chrombpnet(): from chorus.oracles.chrombpnet import ChromBPNetOracle - oracle = ChromBPNetOracle() - oracle.load_pretrained_model(assay="ATAC", cell_type="HepG2", fold=0) + from chorus.core.interval import Interval, GenomeRef + # use_environment=False so predict_sliding can call self.model directly; + # we're already inside chorus-chrombpnet env via mamba run. + oracle = ChromBPNetOracle(use_environment=False, reference_fasta=GENOME_REF) + oracle.load_pretrained_model(assay="DNASE", cell_type="HepG2", fold=0) report = _build_variant_report(oracle, oracle_name="chrombpnet") + + # ChromBPNet's intrinsic prediction window is 2114 bp. At the + # multi-oracle locus (1 Mb wide because AlphaGenome's output_size is + # 1,048,576 bp), that's 0.2 % of the IGV view → invisible at zoom-out. + # Generate a sliding-window track over a wider region for IGV + # display only. Variant scoring (table values, percentiles) is + # unchanged — those were already computed inside _build_variant_report + # from the canonical narrow window. We only swap the IGV-display + # ``_predictions`` for ref/alt with the wide-locus sliding versions. + HALF = 524288 # ±~512 kb (covers the 1 Mb AlphaGenome window) + variant_pos = VARIANT["position"] + chrom = VARIANT["chrom"] + wide_start = max(0, variant_pos - HALF) + wide_end = variant_pos + HALF + + logger.info( + "Sliding chrombpnet across %s:%d-%d (%.0f kb) for IGV display ...", + chrom, wide_start, wide_end, (wide_end - wide_start) / 1000, + ) + ref_iv = Interval.make(GenomeRef( + chrom=chrom, start=wide_start, end=wide_end, fasta=GENOME_REF, + )) + real_pos = (variant_pos - 1) - wide_start # 0-based variant index + alt_iv = ref_iv.replace(seq=VARIANT["alt"], start=real_pos, end=real_pos + 1) + + ref_pred = oracle.predict_sliding(ref_iv) + alt_pred = oracle.predict_sliding(alt_iv) + + if report._predictions is None: + report._predictions = {} + report._predictions["reference"] = ref_pred + alt_key = next( + (k for k in (report._predictions.keys() if report._predictions else []) + if k != "reference"), + "alt_1", + ) + report._predictions[alt_key] = alt_pred + return _save_oracle_artefacts(report, "chrombpnet") @@ -226,6 +291,12 @@ def consolidate(): import pickle from chorus.analysis import MultiOracleReport from chorus.analysis.analysis_request import AnalysisRequest + # Fix numpy pickle compatibility (old -> new internal paths) + try: + import numpy.core.numeric as numeric + sys.modules["numpy._core.numeric"] = numeric + except Exception: + pass per_oracle = {} reports = [] diff --git a/setup.py b/setup.py index 4d9527a..e8bfae8 100644 --- a/setup.py +++ b/setup.py @@ -8,7 +8,7 @@ setup( name="chorus", - version="0.4.0", + version="0.5.0", author="Pinello Lab", author_email="lucapinello@gmail.com", description="A unified interface for genomic sequence oracles", diff --git a/tests/test_analysis.py b/tests/test_analysis.py index 1f0a9e6..b9b67b4 100644 --- a/tests/test_analysis.py +++ b/tests/test_analysis.py @@ -2153,7 +2153,17 @@ def test_missing_oracle_returns_none(self): assert norm.effect_percentile("no_oracle", track_ids[0], 0.5) is None def test_perbin_none_for_scalar_oracles(self): - """When perbin_cdfs is absent, perbin methods return None.""" + """When perbin_cdfs is absent. + + ``perbin_percentile_batch`` (used for the effect/activity tables) + still returns None — it specifically wants the per-bin CDF. + + ``perbin_floor_rescale_batch`` (used for IGV display) now falls + back to summary_cdfs → effect_cdfs via ``_find_matching_cdf``, + so scalar oracles like LegNet still get a usable rescale rather + than the panel autoscaling per-track. This is PR #79's + intentional behaviour change. + """ norm, track_ids, _ = self._make_normalizer(with_perbin=False) result = norm.perbin_percentile_batch( "test_oracle", track_ids[0], np.array([1.0]), @@ -2162,7 +2172,50 @@ def test_perbin_none_for_scalar_oracles(self): result2 = norm.perbin_floor_rescale_batch( "test_oracle", track_ids[0], np.array([1.0]), ) - assert result2 is None + # Falls back to summary_cdfs → returns a rescaled value + assert result2 is not None + assert result2.shape == (1,) + + def test_rescale_for_display_unified_helper(self): + """``rescale_for_display`` is the single source of truth for the + IGV / matplotlib / CoolBox / notebook rendering paths. Verify + each branch returns the right (values, cfg) pair. + """ + from chorus.analysis._igv_report import rescale_for_display, _DISPLAY_MAX + norm, track_ids, _ = self._make_normalizer() + vals = np.array([0.0, 1.0, 5.0, 10.0, 30.0]) + + # Unsigned track (track_ids[0] has signed_flags[0]=False) → + # rescaled to [0, DISPLAY_MAX], cfg.signed=False. + out, cfg = rescale_for_display( + vals, "chromatin_accessibility", normalizer=norm, + oracle_name="test_oracle", assay_id=track_ids[0], + ) + assert cfg["rescaled"] is True + assert cfg["signed"] is False + assert cfg["ymin"] == 0.0 + assert cfg["ymax"] == _DISPLAY_MAX + assert out.min() >= 0.0 and out.max() <= _DISPLAY_MAX + + # Signed track (track_ids[1] has signed_flags[1]=True) → + # rescaled to [-DISPLAY_MAX, +DISPLAY_MAX] symmetrically. + out2, cfg2 = rescale_for_display( + np.array([-1.0, 0.0, 1.0]), + "promoter_activity", normalizer=norm, + oracle_name="test_oracle", assay_id=track_ids[1], + ) + assert cfg2["rescaled"] is True + assert cfg2["signed"] is True + assert cfg2["ymin"] == -_DISPLAY_MAX + assert cfg2["ymax"] == _DISPLAY_MAX + + # No normalizer → passthrough (values unchanged, cfg.rescaled=False). + out3, cfg3 = rescale_for_display(vals, "chromatin_accessibility") + assert cfg3["rescaled"] is False + assert cfg3["signed"] is False + # ymin/ymax fall back to data min/max for autoscale + assert cfg3["ymin"] == float(vals.min()) + assert cfg3["ymax"] == float(vals.max()) def test_get_denominator_padding_vs_compaction(self): """Denominator uses count when < CDF width (padding case).""" @@ -2958,8 +3011,11 @@ def test_apply_floor_rescale_passthrough(self): """``apply_floor_rescale`` should passthrough cleanly when it can't rescale. A None normalizer or a wrong-type normalizer must return - ``(False, ref_unchanged, alt_unchanged)`` so the causal + variant - renderers can fall back to raw autoscale without extra guards. + ``(False, ref_unchanged, alt_unchanged, signed=False)`` so the + causal + variant renderers can fall back to raw autoscale without + extra guards. The fourth tuple element distinguishes signed + symmetric rescale (when True) from unsigned floor-rescale (when + False) — see the signed_floor_rescale_batch path. """ import numpy as np from chorus.analysis._igv_report import apply_floor_rescale @@ -2968,17 +3024,21 @@ def test_apply_floor_rescale_passthrough(self): alt = np.array([1.2, 2.1, 2.8]) # None normalizer — passthrough - ok, r, a = apply_floor_rescale(None, None, "x", "chromatin_accessibility", - ref, alt) + ok, r, a, signed = apply_floor_rescale( + None, None, "x", "chromatin_accessibility", ref, alt, + ) assert ok is False + assert signed is False assert r is ref and a is alt # unchanged references # Non-PerTrackNormalizer type — passthrough class _NotPT: pass - ok, r, a = apply_floor_rescale(_NotPT(), "oracle", "assay", - "tf_binding", ref, alt) + ok, r, a, signed = apply_floor_rescale( + _NotPT(), "oracle", "assay", "tf_binding", ref, alt, + ) assert ok is False + assert signed is False assert r is ref and a is alt def test_markdown_summary_contains_consensus_table(self): diff --git a/tests/test_normalization_chip_strand.py b/tests/test_normalization_chip_strand.py new file mode 100644 index 0000000..44ce22f --- /dev/null +++ b/tests/test_normalization_chip_strand.py @@ -0,0 +1,74 @@ +"""Tests that CHIP strand-suffixed track IDs (e.g. CHIP:K562:REST:+) resolve +to the correct CDF row even though the NPZ stores the strand-less key +CHIP:K562:REST. This covers the silent fallback bug where all CHIP +normalization lookups returned None and IGV reports fell back to raw values. +""" + +import numpy as np +import pytest + +from chorus.analysis.normalization import PerTrackNormalizer + + +def _make_normalizer(monkeypatch): + """Return a PerTrackNormalizer whose _ensure_loaded is monkeypatched to + return a minimal in-memory dict with one CHIP track (no strand suffix). + """ + norm = PerTrackNormalizer.__new__(PerTrackNormalizer) + norm.cache_dir = None + norm._loaded = {} + + cdf = np.linspace(0.0, 10.0, 100) # simple monotone CDF + entry = { + "track_ids": ["CHIP:K562:REST"], + "track_index": {"CHIP:K562:REST": 0}, + "effect_cdfs": cdf[np.newaxis, :], + "summary_cdfs": cdf[np.newaxis, :], + "perbin_cdfs": cdf[np.newaxis, :], + "effect_counts": np.array([100], dtype=np.int64), + "summary_counts": np.array([100], dtype=np.int64), + "perbin_counts": np.array([100], dtype=np.int64), + "signed_flags": np.array([False]), + } + + def _fake_ensure_loaded(oracle_name): + return entry + + monkeypatch.setattr(norm, "_ensure_loaded", _fake_ensure_loaded) + return norm + + +@pytest.mark.parametrize("strand", ["+", "-"]) +def test_effect_percentile_chip_strand(monkeypatch, strand): + norm = _make_normalizer(monkeypatch) + track_id = f"CHIP:K562:REST:{strand}" + result = norm.effect_percentile("chrombpnet", track_id, 5.0) + assert result is not None, f"effect_percentile returned None for {track_id}" + assert 0.0 <= result <= 1.0 + + +@pytest.mark.parametrize("strand", ["+", "-"]) +def test_activity_percentile_chip_strand(monkeypatch, strand): + norm = _make_normalizer(monkeypatch) + track_id = f"CHIP:K562:REST:{strand}" + result = norm.activity_percentile("chrombpnet", track_id, 5.0) + assert result is not None, f"activity_percentile returned None for {track_id}" + assert 0.0 <= result <= 1.0 + + +@pytest.mark.parametrize("strand", ["+", "-"]) +def test_perbin_floor_rescale_chip_strand(monkeypatch, strand): + norm = _make_normalizer(monkeypatch) + track_id = f"CHIP:K562:REST:{strand}" + result = norm.perbin_floor_rescale_batch( + "chrombpnet", track_id, np.array([3.0, 5.0, 8.0]) + ) + assert result is not None, f"perbin_floor_rescale_batch returned None for {track_id}" + assert result.shape == (3,) + + +def test_strandless_key_still_works(monkeypatch): + """Strand-less CHIP keys (e.g. from direct lookup) must still resolve.""" + norm = _make_normalizer(monkeypatch) + result = norm.effect_percentile("chrombpnet", "CHIP:K562:REST", 5.0) + assert result is not None