sigmutselcovs covariate matrices: TCGA-READ
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Pre-built per-gene covariate matrices for TCGA-READ (Rectum adenocarcinoma. Biologically and genomically the same disease as COAD (TCGA's own marker paper pooled them as COADREAD), so every covariate source is COAD's, re-verified 2026-10-03: GTEx maps to the colon tissues (representative Colon_Transverse_Mucosa, the epithelial cell of origin; GTEx has no rectum). No TCGA ATAC-seq for READ (atac: null). Roadmap uses COAD's E075 (colonic mucosa), E106 (sigmoid colon, 6/7 marks -- H3K9ac 404s) and E101/E102 (rectal mucosa, the direct organ match, 7/7 each); all 27 live (EID, mark) pairs checked 2026-10-03; E103 (rectal smooth muscle) rejected as the wrong compartment. ENCODE's adult rectal-mucosa histone experiments (two donors, 50y/61y, Bernstein lab, Roadmap award, 2013) are E101/E102's own sources and are not added, to avoid duplicating them in another assembly; no rectum DNase exists. encode_chromatin is COAD's: adult colonic mucosa DNase and the six colorectal cancer lines HCT116, Caco-2, LoVo, SW480, HT-29 and RKO (native GRCh38, all 19 files re-checked released). Replication timing is COAD's HCT116 16-fraction MAT (GSE137764), a colorectal cancer line, the same disease. Assemblies: Roadmap hg19; RT (MAT), encode_chromatin GRCh38/hg38; expression TCGA-READ (166 tumor and 10 normal RNA-seq files, so the default Tumor+Normal pair).), built with sigmutselcovs: GTEx tissue-matched gene expression, TCGA per-sample gene expression, replication timing (mean replication time and CLR-transformed S-phase fractions), Roadmap Epigenomics histone marks, and TCGA ATAC-seq accessibility, indexed by Ensembl gene ID. Files: cov_matrix_full.parquet — the full matrix (all covariate columns) cov_matrix_pca.parquet — PCA-reduced to 956 components, the smallest number reaching 99% cumulative explained variance (see pca_manifest.json) cov_matrix_columns.csv — a data dictionary: one row per column of the full matrix, with source, description, assembly, and units build_manifest.json, pca_manifest.json — build provenance and PCA parameters Full source citations and methodology: SOURCES.md. Release of 2026-10-26. Every chromatin and ATAC column is one track, summarized as log1p of the mean signal over the gene's CDS span (first to last coding base); replication timing covers chrX. cov_matrix_pca.parquet now reduces the combined matrix: this cohort's own covariates plus the tissue-agnostic GENERIC pool (GENERIC record), with the pool's columns for chromatin tracks this cohort already has left out. That is the matrix the sigmutsel covariate model is fitted on; it predicts held-out mutation counts better than the cohort's own matrix alone in the cohorts tested, so the first components of this artifact are the ones a model should use. Versions before 2026-10-26 reduced the own matrix alone. cov_matrix_full.parquet is still the cohort's own matrix; GENERIC's is in its record. pca_manifest.json records which matrix was reduced (matrix) and the column counts. To rebuild: sigmutselcovs pca-artifact READ --data-dir DIR --generic-dir GENERIC_DIR.



