TFXcan reveals transcription factor programs driving GWAS loci.

TFXcan predicts transcription factor binding from genotype data at scale, and Enpact links predicted binding for 700 TF-tissue pairs to prostate cancer risk at GWAS risk loci.

• Why it matters: GWAS loci may affect traits by changing TF binding, but population-level TF-binding data are scarce, making it hard to identify which TFs and tissues are disrupted.
• What they did: TFXcan correlates genetically predicted TF binding with phenotypes; Enpact uses Enformer and IMPACT to infer personalized TF-binding events, then tests 700 TF-tissue pairs against prostate cancer risk.
• The result: Predicted binding profiles identify multiple implicated TFs at risk loci, and matrix decomposition reveals TF-tissue “programs” linked to disease risk, enabling systematic TF and regulatory program discovery.