Whole-organism integrative expressome for C. elegans enables in silico study of developmental regulation

The C. elegans nematode has been extensively studied as a model organism since the 1970s, and is the only organism for which the complete cell division tree and the genome are both available. These two datasets were integrated with a number of other datasets available at WormBase.org, such as the anatomy ontology, gene expression profiles extracted from 8ooo peer-reviewed papers, and metadata about each gene, to produce the first ever whole-organism, cell-resolution map of gene expression across the entire developmental timeline of the organism, with the goal to find genomic features that regulate cell division and tissue differentiation. Contingency testing was performed to find correlations between thousands of gene attributes (e.g. the presence or absence of a specific 8-mer in the 3' UTR, the CG-content of the sequence upstream of the transcriptional start site, etc.) and thousands of cell attributes (e.g. whether cells that express specific genes die through apoptosis, whether cells become neurons or not, whether cells move in the anterior or posterior direction after division). The resulting database of contingency test scores allow us to quickly ask a large number of biologically-interesting questions, like, "Does the length of introns of expressed genes increase across the developmental timeline?"; "Across what period of development and in which cell types is this specific gene most active?"; "Do regulatory motifs exist that switch on or off genes in whole subtrees of the cell pedigree?"; "Which genes are most strongly implicated in apoptosis?", etc. This whole-organism expressome enables direct and powerful in silico analysis of development.

Department dc:contributor.department

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

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2011

Author dc:creator

• Hutchison, Luke A. D. (Luke Alexander Daysh), 1976-

Advisor dc:contributor.advisor

• Isaac S. Kohane and Bonnie A. Berger.

• Electrical Engineering and Computer Science.

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/1721.1/66005

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/66005