Discovering Conserved Cis-regulatory Elements that Regulate Expression in Caenorhabditis Elegans
Author | : Nnamdi Ihuegbu |
Publisher | : |
Total Pages | : 154 |
Release | : 2011 |
ISBN-10 | : OCLC:795521103 |
ISBN-13 | : |
Rating | : 4/5 ( Downloads) |
Download or read book Discovering Conserved Cis-regulatory Elements that Regulate Expression in Caenorhabditis Elegans written by Nnamdi Ihuegbu and published by . This book was released on 2011 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aim of this dissertation is two-fold: (1) To catalog all cis-regulatory elements within the intergenic and intronic regions surrounding every gene in C.elegans (i.e. the regulome) and (2) to determine which cis-regulatory elements are associated with expression under specific conditions. We initially use PhyloNet to predict conserved motifs with instances in about half of the protein-coding genes. This initial first step was valuable as it recovered some known elements and cis-regulatory modules. Yet the results had a lot of redundant motifs and sites, and the approach was not efficiently scalable to the entire regulome of C. elegans or other higher-order eukaryotes. Magma (Multiple Aligner of Genomic Multiple Alignments) overcomes these shortcomings by using efficient clustering and memory management algorithms. Additionally, it implements a fast greedy set-cover solution to significantly reduce redundant motifs. These differences make Magma ~70 times faster than PhyloNet and Magma-based predictions occur near ~99% of all C. elegans protein-coding genes. Furthermore, we show tractable scaling for higher-order eukaryotes with larger regulomes. Finally, we demonstrate that a Magma-predicted motif, which represents the binding specificity for HLH-30, plays a critical role in the host-defense to pathogenic infections. This novel finding shows that hlh-30( - ) animals are more susceptible to S. aureus and P. aeruginosa than their wild type counterparts.