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Determination of the role of certain bacterial peptidases by inference from heterogeneous and incomplete data

Abstract : The determination of the role of proteins is at the origin of most biological studies. It becomes currently more important since the advent of genome sequencing, which provides a great number of proteins of unknown roles. The sequencing of new genomes allows at the same time to obtain high-throughput post-genomic data as for example microarrays data. It allows also the construction of phylogenetic profiles. The approach we have used, couples statistics and biology and integrates this post-genomic data in order to predict and further validate the role of putative proteolytic enzymes of Lactococcus lactis. We worked in three different steps. First, we did a statistical inference of the predicted relationships between proteins of lactococci based on five different data sources: the graph of metabolic pathways, microarray data, phylogenetic profiles and the distance between genes in terms of base pairs on the chromosome and proteomic data from 2D gels. These relationships allowed us to pose biological hypotheses on the role of target proteins. Second, we carried out wet-lab experiments to validate the predictions comparing the wild type strain to knock-out mutants of PepF and YvjB. The third step consisted of a sensitivity analysis with the aim to outline the most important data in terms of contribution to the relationship prediction of our target proteins and to find a subset of data leading to the same predictions. Applied to two proteolytic enzymes of lactococci, PepF and YvjB, this approach allowed us to validate their participation in protein export predicted by the statistical analysis. We have shown that PepF participates in the export of proteins liberated in the supernatant by the hydrolysis of the signal peptide, which is cleaved by the signal peptidase I. PepF participates also in the synthesis of the cell wall and pyruvate metabolism, two functions also predicted by the statistical analysis. YvjB participates in the localization and maturation of lipoproteins, another group of exported proteins. It is necessary for the correct localization of certain lipoproteins and participates in their signal peptide cleavage. Our approach has shown to be very useful, as it allows to pose biological hypotheses that guide experimental validations. Moreover, this approach is applicable to all completely sequenced organisms for which enough post-genomic data is available.
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Submitted on : Friday, February 13, 2009 - 8:00:00 AM
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  • HAL Id : pastel-00004768, version 1



Liliana López Kleine. Determination of the role of certain bacterial peptidases by inference from heterogeneous and incomplete data. Life Sciences [q-bio]. AgroParisTech, 2008. English. ⟨NNT : 2008AGPT0056⟩. ⟨pastel-00004768⟩



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