Multi-tissue integrative analysis of personal epigenomes

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.
Competing Interest Statement
The authors have declared no competing interest.
Subject Area
- Biochemistry (7346)
- Bioengineering (5323)
- Bioinformatics (20263)
- Biophysics (10016)
- Cancer Biology (7743)
- Cell Biology (11300)
- Clinical Trials (138)
- Developmental Biology (6437)
- Ecology (9951)
- Epidemiology (2065)
- Evolutionary Biology (13322)
- Genetics (9361)
- Genomics (12583)
- Immunology (7701)
- Microbiology (19021)
- Molecular Biology (7441)
- Neuroscience (41036)
- Paleontology (300)
- Pathology (1229)
- Pharmacology and Toxicology (2137)
- Physiology (3160)
- Plant Biology (6860)
- Synthetic Biology (1896)
- Systems Biology (5311)
- Zoology (1089)