Annotation-Informed Block-Sparse Bayesian Modeling for cis-Expression Prediction
arXiv:2606.00483v1 Announce Type: cross Abstract: Genotype-based cis-expression prediction depends on accurately modeling local regulatory architecture. We present block-sparse Bayesian sparse linear mixed model (bsBSLMM), an extension of Bayesian sparse linear mixed model (BSLMM) that incorporates linkage disequilibrium (LD)-block spike-and-slab sparsity and a transcription start site (TSS)-informed SNP inclusion prior. Across 23,098 genes from GEUVADIS European-ancestry lymphoblastoid cell lines, bsBSLMM retained more predictable genes than BSLMM, LASSO, BLUP, TIGAR elastic net, and TIGAR Dirichlet-process regression under matched evaluation criteria. Compared with BSLMM, bsBSLMM improved held-out prediction performance for most shared genes, with gains driven primarily by LD-block sparsity and further enhanced by the TSS-informed prior. Variants selected by bsBSLMM showed stronger enrichment in GM12878 DNase and H3K27ac regulatory regions than variants selected by BSLMM. In transcri