Targeting differentially co-regulated genes by multiobjective and multimodal optimization

Oscar Harari, Cristina Rubio-Escudero, Igor Zwir

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

A critical challenge of the postgenomic era is to understand how genes are differentially regulated in and between genetic networks. The fact that such co-regulated genes may be differentially regulated suggests that subtle differences in the shared cis-acting regulatory elements are likely significant, however it is unknown which of these features increase or reduce expression of genes. In principle, this expression can be measured by microarray experiments, though they incorporate systematic errors, and moreover produce a limited classification (e.g. up/down regulated genes). In this work, we present an unsupervised machine learning method to tackle the complexities governing gene expression, which considers gene expression data as one feature among many. It analyzes features concurrently, recognizes dynamic relations and generates profiles, which are groups of promoters sharing common features. The method makes use of multiobjective techniques to evaluate the performance of profiles, and has a multimodal approach to produce alternative descriptions of same expression target. We apply this method to probe the regulatory networks governed by the PhoP/PhoQ two-component system in the enteric bacteria Es-cherichia coli and Salmonella enterica. Our analysis uncovered profiles that were experimentally validated, suggesting correlations between promoter regulatory features and gene expression kinetics measured by green fluorescent protein (GFP) assays.

Original languageEnglish
Title of host publicationEvolutionary Computation, Machine Learning and Data Mining in Bioinformatics - 5th European Conference, EvoBIO 2007, Proceedings
PublisherSpringer Verlag
Pages68-77
Number of pages10
ISBN (Print)9783540717829
DOIs
StatePublished - 2007
Event5th European Conference on Evolutionary Computation, Machine Learning and Data Mining in Bioinformatics, EvoBIO 2007 - Valencia, Spain
Duration: Apr 11 2007Apr 13 2007

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume4447 LNCS
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Conference

Conference5th European Conference on Evolutionary Computation, Machine Learning and Data Mining in Bioinformatics, EvoBIO 2007
Country/TerritorySpain
CityValencia
Period04/11/0704/13/07

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