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Published April 27, 2021 | Version Submitted
Discussion Paper Open

Multi-tissue integrative analysis of personal epigenomes

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Abstract

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.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. This version posted April 26, 2021. The authors have declared no competing interest.

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Submitted - 2021.04.26.441442v1.full.pdf

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2021.04.26.441442v1.full.pdf

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Eprint ID
108899
Resolver ID
CaltechAUTHORS:20210430-100605150

Dates

Created
2021-04-30
Created from EPrint's datestamp field
Updated
2021-11-16
Created from EPrint's last_modified field

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Caltech groups
Division of Biology and Biological Engineering (BBE)