Dataset Information

CASSIOPE: an expert system for conserved regions searches.

ABSTRACT: BACKGROUND: Understanding genome evolution provides insight into biological mechanisms. For many years comparative genomics and analysis of conserved chromosomal regions have helped to unravel the mechanisms involved in genome evolution and their implications for the study of biological systems. Detection of conserved regions (descending from a common ancestor) not only helps clarify genome evolution but also makes it possible to identify quantitative trait loci (QTLs) and investigate gene function.The identification and comparison of conserved regions on a genome scale is computationally intensive, making process automation essential. Three key requirements are necessary: consideration of phylogeny to identify orthologs between multiple species, frequent updating of the annotation and panel of compared genomes and computation of statistical tests to assess the significance of identified conserved gene clusters. RESULTS: We developed a modular system superimposed on a multi-agent framework, called CASSIOPE (Clever Agent System for Synteny Inheritance and Other Phenomena in Evolution). CASSIOPE automatically identifies statistically significant conserved regions between multiple genomes based on automated phylogenies and statistical testing. Conserved regions were searched for in 19 species and 1,561 hits were found. To our knowledge, CASSIOPE is the first system to date that integrates evolutionary biology-based concepts and fulfills all three key requirements stated above. All results are available at http://194.57.197.245/cassiopeWeb/displayCluster?clusterId=1 CONCLUSION: CASSIOPE makes it possible to study conserved regions from a chosen query genetic region and to infer conserved gene clusters based on phylogenies and statistical tests assessing the significance of these conserved regions.Source code is freely available, please contact: Pierre.pontarotti@univ-provence.fr.

SUBMITTER: Rascol VL

PROVIDER: S-EPMC2756280 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CASSIOPE: an expert system for conserved regions searches.

Rascol Virginie Lopez VL Levasseur Anthony A Chabrol Olivier O Grusea Simona S Gouret Philippe P Danchin Etienne G J EG Pontarotti Pierre P

BMC bioinformatics 20090910

<h4>Background</h4>Understanding genome evolution provides insight into biological mechanisms. For many years comparative genomics and analysis of conserved chromosomal regions have helped to unravel the mechanisms involved in genome evolution and their implications for the study of biological systems. Detection of conserved regions (descending from a common ancestor) not only helps clarify genome evolution but also makes it possible to identify quantitative trait loci (QTLs) and investigate gen ...[more]

PMID: 19740451

Similar Datasets

Project description:Conserved domains in proteins are one of the major sources of functional information for experimental design and genome-level annotation. Though search tools for conserved domain databases such as Hidden Markov Models (HMMs) are sensitive in detecting conserved domains in proteins when they share sufficient sequence similarity, they tend to miss more divergent family members, as they lack a reliable statistical framework for the detection of low sequence similarity. We have developed a greatly improved HMMerThread algorithm that can detect remotely conserved domains in highly divergent sequences. HMMerThread combines relaxed conserved domain searches with fold recognition to eliminate false positive, sequence-based identifications. With an accuracy of 90%, our software is able to automatically predict highly divergent members of conserved domain families with an associated 3-dimensional structure. We give additional confidence to our predictions by validation across species. We have run HMMerThread searches on eight proteomes including human and present a rich resource of remotely conserved domains, which adds significantly to the functional annotation of entire proteomes. We find ?4500 cross-species validated, remotely conserved domain predictions in the human proteome alone. As an example, we find a DNA-binding domain in the C-terminal part of the A-kinase anchor protein 10 (AKAP10), a PKA adaptor that has been implicated in cardiac arrhythmias and premature cardiac death, which upon stress likely translocates from mitochondria to the nucleus/nucleolus. Based on our prediction, we propose that with this HLH-domain, AKAP10 is involved in the transcriptional control of stress response. Further remotely conserved domains we discuss are examples from areas such as sporulation, chromosome segregation and signalling during immune response. The HMMerThread algorithm is able to automatically detect the presence of remotely conserved domains in proteins based on weak sequence similarity. Our predictions open up new avenues for biological and medical studies. Genome-wide HMMerThread domains are available at http://vm1-hmmerthread.age.mpg.de.

Dataset Information

CASSIOPE: an expert system for conserved regions searches.

Publications

CASSIOPE: an expert system for conserved regions searches.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets