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Bioinformatics Advance Access originally published online on December 14, 2004
Bioinformatics 2005 21(8):1550-1558; doi:10.1093/bioinformatics/bti215
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© The Author 2004. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

Balancing protein similarity and gene co-expression reveals new links between genetic conservation and developmental diversity in invertebrates

Céline Lefebvre 1,2, Jean-Christophe Aude 3, Eric Glémet 2 and Christian Néri 1,*

1INSERM, Avenir Group, Laboratory of Genomic Biology, Centre Paul Broca 75014 Paris, France
2Gene-IT S.A. 92500 Rueil-Malmaison, France
3CEA, Département de Biologie Joliot-Curie, Service de Biochimie et de Génétique Moléculaire, Saclay, 91191 Gif-sur-Yvette Cedex, France

*To whom correspondence should be addressed.

Motivation: To identify genetic conservation relative to precise aspects of developmental diversity, an essential question in computational biology, we developed a new comparative method that allows conserved modules for the best balance between protein sequence similarity and gene co-expression to be constructed, in invertebrates.

Results: Our method, referred to as the best-balance constraint procedure (BBCP), yielded 719 functionally conserved modules (FCMs) comprising 2–23 gene pairs. These modules were consistent with the developmental roles of orthologues as inferred from Gene Ontology, RNAi knockouts, InterPro and process-specific microarray data. New relationships were defined between genetic conservation and developmental diversity. Novel gene associations were indeed found in 94% of the FCMs, 150 modules being completely new. A significant proportion of the FCMs (18%, 132 modules) described cell type-specific mechanisms, comprising neuronal, muscle and germ cell signaling, new associations being found in 125 modules. Also found were gene associations for cell fate specification activities previously not highlighted by computational means, e.g. in FCMs containing homeogenes. These data indicate that highly discriminative description of genetic conservation can be deduced using BBCP, and reveal new correlations between cellular and developmental diversity and gene essentiality in invertebrates.

Contact: christian.neri{at}broca.inserm.fr

Supplementary information: For supplementary information, please refer to Bioinformatics online.


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