Statistical methods to infer biological interactions

Biological systems are extremely complex, and our ability to experimentally measure interactions in these systems is limited by inherent noise. Technological advances have allowed us to collect unprecedented amounts of raw data, increasing the need for computational methods to disentangle true interactions from noise. In this thesis, we focus on statistical methods to infer two classes of important biological interactions: protein-protein interactions and the link between genotypes and phenotypes. In the first part of the thesis, we introduce methods to infer protein-protein interactions from affinity purification mass spectrometry (AP-MS) and from luminescence-based mammalian interactome mapping (LUMIER). Our work reveals novel context dependent interactions in the MAPK signaling pathway and insights into the protein homeostasis machinery. In the second part, we focus on methods to understand the link between genotypes and phenotypes. First, we characterize the effects of related individuals on standard association statistics for genome-wide association studies (GWAS) and introduce a new statistic that corrects for relatedness. Then, we introduce a statistically powerful association testing framework that corrects for confounding from population structure in large scale GWAS. Lastly, we investigate regularized regression for phenotype prediction from genetic data.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Mathematics.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2014

Author dc:creator

• Tucker, George Jay

Advisor dc:contributor.advisor

• Bonnie Berger.

• Mathematics.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

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

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/89874

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/89874