Program in Bioinformatics and Integrative Biology; Graduate School of Biomedical Sciences
Bioinformatics | Computational Biology | Genomics | Integrative Biology
Evaluating the impact of genetic variants on transcriptional regulation is a central goal in biological science that has been constrained by reliance on a single reference genome. To address this, we constructed phased, diploid genomes for four cadaveric donors (using long-read sequencing) and systematically charted noncoding regulatory elements and transcriptional activity across more than 25 tissues from these donors. Integrative analysis revealed over a million variants with allele-specific activity, coordinated, locus-scale allelic imbalances, and structural variants impacting proximal chromatin structure. We relate the personal genome analysis to the ENCODE encyclopedia, annotating allele- and tissue-specific elements that are strongly enriched for variants impacting expression and disease phenotypes. These experimental and statistical approaches, and the corresponding EN-TEx resource, provide a framework for personalized functional genomics.
Genomics, genetic variants, transcriptional regulation, personal epigenomes, personal genomics, integrative analysis
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DOI of Published Version
bioRxiv 2021.04.26.441442; doi: https://doi.org/10.1101/2021.04.26.441442. Link to preprint on bioRxiv.
Rozowsky J, Moore JE, Pratt HE, Weng Z, Gerstein M. (2021). Multi-tissue integrative analysis of personal epigenomes [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2021.04.26.441442. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2031
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