Computation identification of transcription factor binding using DNase-seq
Name
880413424-MIT.pdf
Description
Full printable version
Size
4.02 MB
Format
Adobe PDF
Checksum (MD5)
3ae407535e305164b748f7441d14f0d4
Author(s)
Hashimoto, Tatsunori B. (Tatsunori Benjamin)
Advisor(s)
David Gifford and Tommi Jaakkola.
Alternative Title
Computation identification of TF binding using DNase-seq
Date Issued
2014
Publisher
Massachusetts Institute of Technology
Abstract
Here we describe Protein Interaction Quantitation (PIQ), a computational method that models the magnitude and shape of genome-wide DNase profiles to facilitate the identification of transcription factor (TF) binding sites. Through the use of machine learning techniques, PIQ identified binding sites for >700 TFs from one DNase-seq experiment with accuracy comparable to ChIP-seq for motif-associated TFs (median AUC=0.93 across 303 TFs). We applied PIQ to analyze DNase-seq data from mouse embryonic stem cells differentiating into pre-pancreatic and intestinal endoderm. We identified (n=120) and experimentally validated eight 'pioneer' TF families that dynamically open chromatin, enabling other TFs to bind to adjacent DNA. Four pioneer TF families only open chromatin in one direction from their motifs. Furthermore, we identified a class of 'settler' TFs whose genomic binding is principally governed by proximity to open chromatin. Our results support a model of hierarchical TF binding in which directional and non-directional pioneer activity shapes the chromatin landscape for population by settler TFs. Substational parts of this thesis are taken from our publication on PIQ currently in press at Nature biotechnology.
Description
Thesis: S.M., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2014.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 41-43).
Subjects
Electrical Engineering and Computer Science.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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