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Bioinformatics Advance Access published online on December 14, 2004
Bioinformatics, doi:10.1093/bioinformatics/bti215
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Bioinformatics © Oxford University Press 2004; all rights reserved.
Received September 29, 2004
Revised November 17, 2004
Accepted December 8, 2004

Article

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

Céline Lefebvre 1, Jean-Christophe Aude 2, Eric Glémet 3, and Christian Néri 4*

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

* To whom correspondence should be addressed.
Christian Néri, E-mail: christian.neri{at}broca.inserm.fr


  Abstract

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, here in invertebrates.

Results: Our method, referred here 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, for example 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.


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