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Statistical methods to infer biological interactions

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Mathematics, 2014. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / 169 / Cataloged from student-submitted PDF version of thesis. / Includes bibliographical references (pages 153-170). / 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. / by George Jay Tucker. / Ph. D.

Identiferoai:union.ndltd.org:MIT/oai:dspace.mit.edu:1721.1/89874
Date January 2014
CreatorsTucker, George Jay
ContributorsBonnie Berger., Massachusetts Institute of Technology. Department of Mathematics., Massachusetts Institute of Technology. Department of Mathematics.
PublisherMassachusetts Institute of Technology
Source SetsM.I.T. Theses and Dissertation
LanguageEnglish
Detected LanguageEnglish
TypeThesis
Format170 pages, application/pdf
RightsM.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., http://dspace.mit.edu/handle/1721.1/7582

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