Federal Project Grant Award Summary

The University of Massachusetts Medical School received a $418,750 Project Grant from the National Human Genome Research Institute (NHGRI) under the Human Genome Research program (CFDA 93.172), effective April 1, 2026 through March 31, 2028. This award funds the development of a cis-regulatory element (cCRE)-centric infrastructure within the ANVIL (Analysis Visualization Lab) cloud-based platform to advance understanding of how genetic variation affects gene regulation. The project integrates the ENCODE Registry of cCREs with allele-specific analyses at the single-cell level to enable scalable and reproducible investigations of transcriptional regulation. Deliverables include establishment of a cCRE workspace and analysis framework in ANVIL, modular computational workflows for cCRE annotation, cell type-specific scoring and transcription factor footprinting, and development of the STELLA Suite—a collection of computational tools for regulatory genomics.

The award supports investigation of how allele-specific cCRE activity influences alternative isoform usage in individual cell types using genomic data from the Genomic Answers for Kids (GA4K) project. Key research products include construction of personalized diploid genomes, identification of allele-specific cCREs through single-cell ATAC-seq analysis, determination of allele-specific isoform usage through bulk long-read RNA-seq, and development of statistical models (Dirichlet-multinomial deconvolution and hierarchical regression) to predict relationships between allele-specific regulatory elements and transcript isoform expression. These outputs are designed to improve understanding of how noncoding variants contribute to transcriptional dysregulation and disease risk.