Allele-Specic QTL fine-mapping with PLASMA

We introduce PLASMA (PopuLation Allele-Specic MApping), a statistical ne- mapping method that leverages allele-specic (AS) genomic data to improve detection of quantitative trait loci (QTLs) with causal effects on molecular traits. In simulations, PLASMA accurately prioritizes causal QTL variants over a wide range of genetic architectures. Applied to RNA-Seq data from 524 kidney tumor samples, PLASMA achieves a greater power at 50 samples than conventional QTL-based ne-mapping at 500 samples: with over 17% of loci ne-mapped to within 5 causal variants compared to 2% by QTL-based ne-mapping, and a 6.9-fold overall reduction in median credible set size. PLASMA offers high accuracy even at small sample sizes, yielding a 1.3-fold reduction in median credible set size compared to QTL-based ne-mapping when applied to H3K27AC ChIP-Seq from just 28 prostate tumor/normal samples. Our results demonstrate how integrating AS activity can substantially improve the detection of causal variants from existing molecular data.

Name thesis:degree_name

Master

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2020

Author dc:creator

• Wang, Austin T.

Advisor dc:contributor.advisor

• Manolis Kellis and Alexander Gusev.

• Electrical Engineering and Computer Science.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/129928

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/129928