sigmutselcovs covariate matrices: TCGA-PCPG

Pre-built per-gene covariate matrices for TCGA-PCPG (Pheochromocytoma and paraganglioma: tumors of neural-crest-derived chromaffin cells, in the adrenal medulla (pheochromocytoma) or extra-adrenal paraganglia. GTEx maps to Adrenal_Gland and Nerve_Tibial; representative column gtex_adrenal_gland. TCGA ATAC-seq covered (Corces et al. 2018; the tarball's bigWigs are named PCPG_..., read from its first member). Expression: TCGA-PCPG tumor and normal (3 normal samples, so the default Tumor+Normal pair stays). Roadmap null: its only adrenal epigenome is E080 (fetal adrenal gland), rejected as non-adult, as for ACC; no adult chromaffin, sympathetic or paraganglion epigenome exists. encode_chromatin: adult adrenal gland tissue from one ENCODE donor (ENCDO575WHY, 41y; ACC's donor) -- H3K27ac, H3K27me3, H3K36me3, H3K4me1, H3K4me3, H3K9me3 and DNase. Caveat: whole adrenal gland is mostly cortex (the medulla is about a tenth of it), so this is an organ-level source that mainly carries adrenocortical chromatin, the wrong compartment for chromaffin tumors. No pheochromocytoma or paraganglioma line exists in ENCODE (pheochromocytoma, paraganglioma, hPheo1, PC12 and chromaffin all return zero experiments). As the closest available lineage -- sympathoadrenal neural crest, the common progenitor of chromaffin cells and sympathetic neuroblasts -- the row adds neuroblastoma lines: SK-N-SH (untreated, one lab, all 7 default marks plus DNase) and DNase from BE2C and SK-N-DZ (untreated). They are a different, pediatric embryonal disease, so this is a lineage proxy supplying the medullary chromatin the adrenal tissue lacks, not a disease match; retinoic-acid- and DMSO-treated experiments rejected. repliseq: SK-N-SH UW 6-fraction Repli-seq (hg19), the only sympathoadrenal-lineage source in the replication-timing catalog, registered on the same lineage argument and to be measured (rt_block_scoping.py) and dropped if it moves nothing; the hESC-derived neural crest Repli-chip profiles are rejected as embryonic. Assemblies: repliseq hg19; encode_chromatin and ATAC GRCh38.), 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 976 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 PCPG --data-dir DIR --generic-dir GENERIC_DIR.