Statistical methods to infer biological interactions
Name
890211832-MIT.pdf
Description
Full printable version
Size
8.36 MB
Format
Adobe PDF
Checksum (MD5)
68249636543c4d1c489ffdd495428a30
Author(s)
Tucker, George Jay
Advisor(s)
Bonnie Berger.
Date Issued
2014
Publisher
Massachusetts Institute of Technology
Abstract
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.
Description
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).
Subjects
Mathematics.
MIT Department
Massachusetts Institute of Technology. Department of Mathematics
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