# K562 chr11 — ENCFF534PXC

Open **chr11.json**:
https://vitessce.io/?url=https%3A%2F%2Fusers.abdenlab.org%2Fvoy%2Fvitessce_cvh%2Fk562_sci%2Fchr11.json

Source: ENCODE-rE2G extended predictions for K562, ENCFF534PXC / ENCSR621BIJ, GRCh38. The downloaded bigInteract file was verified against ENCODE's MD5 checksum. Source metadata and the original file are preserved under `sources/`.

## Why chr11

Chr11 is recommended for a globin-focused K562 regulatory view. This exact file contains HBB (31 links), HBG2 (24), HBG1 (16), HBE1 (12), and HBD (9). The chromosome has 3,551 regulatory elements, 874 gene/TSS columns, and 9,645 links. This is a biological choice, not a claim that chr11 has the most links overall. `sources/chromosome_summary.json` records the comparison: chr1 includes TAL1, chrX includes GATA1, and chr16 includes HBA1. chr9 and chr22 include ABL1 and BCR respectively; this cis-link matrix does not represent the BCR::ABL1 fusion.

## Matrix and annotations

- `chr11.matrix.csv`: regulatory elements × target gene/TSS. Values are the original bigInteract `value` field (column 6), not the 0–1000 display `score`. Zero denotes an unreported link.
- Element coordinates come from sourceChrom/sourceStart/sourceEnd, not the interaction arc's outer bounds. Target anchors come from targetChrom/targetStart/targetEnd. All chr11 links are cis, target spans are one base, and duplicate element/target keys were checked absent.
- Gene labels use `SYMBOL|CHROM:TSS`; the requested bigInteract file does not provide Ensembl IDs. No IDs were inferred.
- `chr11.source_links.csv`: all 18 original bigInteract fields for the chr11 links.
- `chr11.ccre.matrix.csv`, `chr11.ccre_metadata.csv`: class overlaps with the local GRCh38 cCRE registry, aligned to the gene-matrix rows.
- `chr11.clinvar.matrix.csv`, `chr11.clinvar.metadata.csv`, `chr11.clinvar.obsSets.json`: counts, complete metadata, and selectable overlap groups.
- `chr11.clinvar.variants.csv`, `chr11.clinvar.links.csv`: 261,217 chr11 ClinVar records and 19,333 element–variant pairs. There are 19,308 distinct overlapping variants across 908 elements.

ClinVar uses `https://users.abdenlab.org/voy/clinvar_hg38_all.vcf.gz`, with 4,471,367 records across all chromosomes. All clinical-significance categories are included; no phenotype filter is applied. The older pathogenic/likely-pathogenic VCF copy is retained but is no longer used. REF-span overlaps use `[POS-1, POS-1+len(REF))`, including indel anchors. These reference annotations do not establish K562 genotypes or regulatory effects. cCRE overlap does not establish K562-specific cCRE activity.

Layout: cCRE class heatmap → ClinVar count strip → gene-score heatmap, with gene list and overlap groups at the right. Only the leftmost panel displays the regulatory-element axis title; the stock Vitessce axis margins remain. Tooltips show cCRE IDs/classes and count on the left, ClinVar count in the middle, and cCRE/ClinVar counts on the gene panel. Full variant descriptions remain in the CSVs.

## Rebuild and validation

Run `python build_chr11.py` in this folder; it requires pybigtools and bedtools. The cCRE reference path is in the script. `python validate_build.py` checks row order, config dependencies, tooltip settings, and ClinVar overlaps independently with bedtools. Every nonzero gene matrix value was also compared directly to the requested bigInteract source. Validation reports are `validation.json` and `clinvar.validation.json`. Browser rendering remains unverified.

`python serve.py` provides a local preview. Published files live under `/net/public_html/users/voy/vitessce_cvh/k562_sci/`. All active config URLs use `https://users.abdenlab.org/voy/vitessce_cvh/k562_sci/`. Existing HepG2 and older K562 folders are unchanged.

References:
- https://www.encodeproject.org/files/ENCFF534PXC/
- https://www.encodeproject.org/annotations/ENCSR621BIJ/
- https://genome.ucsc.edu/goldenPath/help/interact.html
- https://www.ncbi.nlm.nih.gov/gene/109580095

## All-variants refresh (2026-10-08)

Only the existing ClinVar artifact files were replaced; config JSON, gene scores, cCRE annotations, layout and URLs were preserved. Counts now summarize all significance categories and are not pathogenicity scores. The existing config description is left for manual editing as requested; full rebuilds will generate the new source description.

`python update_clinvar.py --chrom chr11` refreshes only ClinVar artifacts without changing the config. The default source is `/net/public_html/users/voy/clinvar_hg38_all.vcf.gz`; use `--source PATH` to override it. Full builders call this same routine. New reports record the source checksum, significance-category counts, and overlap checks.