AlphaGenome Cardiovascular Non-Coding Variant Analysis — Data Deposit

This deposit contains all intermediate and final data artifacts for the manuscript "Systematic Characterization of Cardiovascular Non-Coding Variants Using AlphaGenome". We used Google DeepMind's AlphaGenome model (Nature, 2026) to score 200,813 cardiovascular non-coding variants from ClinVar (n=15,623) and fine-mapped Open Targets GWAS (n=185,198) across 19 variant scorers at 1 Mb context, single-base resolution. Filtering to cardiac-relevant GTEx tissues and ENCODE biosamples retained 452.7 million cardiac score rows covering 104,473 unique variants with regulatory signal. Multimodal analysis identified a convergent LMNA promoter VUS cluster as a high-priority candidate set for functional validation under ACMG PP3. File organization. Files are grouped by numeric prefix corresponding to pipeline stage: 01 — Input variants (curated catalogues before AlphaGenome scoring): clinvar_cardio_extract.tsv — ClinVar cardiovascular non-coding variants after filtering (15,623 variants) gwas_cardio_credible_sets.tsv — Open Targets fine-mapped GWAS credible-set variants (185,198) merged_cardio_variants.tsv — Deduplicated merge of the two sources (200,813) scoring_intervals.tsv — 1 Mb intervals centred on each variant, used as AlphaGenome input 02 — AlphaGenome scores (variant scoring across all 19 recommended scorers): all_scores.parquet — Full unfiltered scoring output (3,572,509,053 rows) cardiac_scores.parquet — Cardiac-tissue-filtered subset (452,688,226 rows; GTEx heart/artery + ENCODE cardiac biosamples) 03 — Analysis outputs (post-processing feeding directly into manuscript Figures and Tables): variant_multimodal_summary.tsv — Per-variant summary across 6 modality groups (Fig 3) modality_enrichment.tsv — Per-modality strong-signal rates (Fig 3C) multimodal_hits.tsv — Variants with signal in ≥2 modalities (Fig 2A, Fig 3A) ranked_variant_table.tsv — Composite-score-ranked full catalogue (Fig 4, Tables 2 and 4) gwas_direction_of_effect.tsv — Direction-of-effect calls for all variant–gene pairs (Fig 5, Table 3) gwas_direction_of_effect_cardiac.tsv — Filtered to cardiac-trait pairs (Fig 5, Table 3) 04 — Manuscript supplementary tables (Tables S1–S4 as deposited with the manuscript): supp_S1_gene_panel.tsv — Curated cardiovascular gene panel (101 genes, 10 categories) supp_S2_trait_keywords.tsv — Cardiovascular-trait include/exclude keyword lists supp_S3_full_ranked_variants.{tsv,xlsx} — Full ranked variant table supp_S4_doe_cardiac_full.tsv — Cardiac-trait DoE pairs 05 — Vignettes (mechanistic ISM and REF/ALT figures for Figure 6): ism_logo_*.png — ISM sequence-logo plots ism_*.npy — Raw per-base ISM effect arrays (numpy format) ref_alt_*.png — REF vs ALT predicted RNA-seq track plots Vignettes cover the LMNA promoter VUS cluster (chr1:156115264, chr1:156115279, chr1:156115286), DUSP1 (chr5:172770036), and VIM (chr10:17229111). Schema for parquet files (all_scores.parquet, cardiac_scores.parquet): variant_id (string) — chr:pos:ref>alt output_type (string) — AlphaGenome scorer (RNA_SEQ, SPLICE_JUNCTIONS, CHIP_HISTONE, CAGE, DNASE, CHIP_TF, SPLICE_SITE_USAGE, CONTACT_MAPS, ATAC, PROCAP) gene_name (string) — target gene gtex_tissue (string, nullable) — GTEx tissue for RNA-seq/splicing rows biosample_name (string, nullable) — ENCODE biosample for accessibility/TF/histone/contact map rows raw_score, quantile_score (float) — AlphaGenome predictions variant_scorer, track_name, biosample_type — scoring metadata Reproducibility. SHA-256 checksums for every file are in CHECKSUMS.sha256. Verify with sha256sum -c CHECKSUMS.sha256. Companion code: https://github.com/patricio-astudillo/alphagenome-cardio (MIT license; 10.5281/zenodo.19591759). Upstream data sources: ClinVar variant_summary.txt.gz, NCBI release 2024-03-31, retrieved 2026-04-05 from https://ftp.ncbi.nlm.nih.gov/pub/clinvar/tab_delimited/ Open Targets Platform release 26.03, queried via GraphQL at https://api.platform.opentargets.org/api/v4/graphql AlphaGenome model and API: https://github.com/google-deepmind/alphagenome