v1.0.0 — Initial Release

varTFBridge v1.0.0

First public release of varTFBridge, an integrative framework combining TF footprinting data with genome-wide association analyses to identify causal noncoding variants and elucidate their regulatory mechanisms.

Pipelines

• Common variant pipeline (9 steps): liftover → credible set filtering → footprint overlap → VAR2TFBS → variant-to-gene linking → AlphaGenome scoring → linkage table → TF ChIP annotation
• Rare variant pipeline (4 steps): driver variant identification → variant-to-gene linking → AlphaGenome scoring → linkage table
• End-to-end runner scripts with --from, --only, and --skip-alphag options

Key Components

• VAR2TFBS: FIMO-based motif scanning to classify variant effects on TF binding (Create/Disrupt/Increase/Decrease/Unchange)
• ABC-FP-Max: Footprint-to-gene linkage via Activity-by-Contact scoring adapted for TF footprints
• AlphaGenome integration: Batch variant effect scoring with checkpoint/resume support
• Linkage tables: Integrated variant → TF → gene → trait maps

Results

Using 490,640 UK Biobank whole-genome sequences across 13 erythroid traits:

• K562 FOODIE footprints show ~70-fold heritability enrichment (comprising <0.5% of the genome)
• 209 common variants and 18 rare variants linked to TF binding sites and target genes
• 207 unique target genes identified
• Case study: rs112233623 → GATA1/TAL1 co-binding disruption → CCND3 regulation → RBC count variation

Data

• FOODIE footprints for K562 and GM12878
• JASPAR motif files
• ABC-FP model predictions
• Reference data and liftover chains