Title
Phylogenetically informed logic relationships improve detection of biological network organization.
Abstract
A "phylogenetic profile" refers to the presence or absence of a gene across a set of organisms, and it has been proven valuable for understanding gene functional relationships and network organization. Despite this success, few studies have attempted to search beyond just pairwise relationships among genes. Here we search for logic relationships involving three genes, and explore its potential application in gene network analyses.Taking advantage of a phylogenetic matrix constructed from the large orthologs database Roundup, we invented a method to create balanced profiles for individual triplets of genes that guarantee equal weight on the different phylogenetic scenarios of coevolution between genes. When we applied this idea to LAPP, the method to search for logic triplets of genes, the balanced profiles resulted in significant performance improvement and the discovery of hundreds of thousands more putative triplets than unadjusted profiles. We found that logic triplets detected biological network organization and identified key proteins and their functions, ranging from neighbouring proteins in local pathways, to well separated proteins in the whole pathway, and to the interactions among different pathways at the system level. Finally, our case study suggested that the directionality in a logic relationship and the profile of a triplet could disclose the connectivity between the triplet and surrounding networks.Balanced profiles are superior to the raw profiles employed by traditional methods of phylogenetic profiling in searching for high order gene sets. Gene triplets can provide valuable information in detection of biological network organization and identification of key genes at different levels of cellular interaction.
Year
DOI
Venue
2011
10.1186/1471-2105-12-476
BMC Bioinformatics
Keywords
DocType
Volume
microarrays,bioinformatics,algorithms
Journal
12
Issue
ISSN
Citations 
476
1471-2105
2
PageRank 
References 
Authors
0.43
9
4
Name
Order
Citations
PageRank
Jike Cui191.73
Todd F. DeLuca2414.08
Jae-Yoon Jung329731.94
Dennis P. Wall416922.14