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Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum
Published on: December 4, 2015
Assessing functional annotation transfers with inter-species conserved coexpression: application to Plasmodium
Laurent Bréhélin1, Isabelle Florent, Olivier Gascuel
1Méthodes et algorithmes pour la Bioinformatique, LIRMM, Univ, Montpellier 2, CNRS; 161 rue Ada, 34392 MONTPELLIER, France. brehelin@lirmm.fr
BMC Genomics
|January 19, 2010
Summary
This study introduces a novel method combining gene expression and sequence similarity for improved inter-species gene annotation. The approach enhances functional assignments for uncharacterized genes, particularly in Plasmodium falciparum, aiding malaria research.
Area of Science:
- Computational Biology
- Genomics
- Parasitology
Background:
- Plasmodium falciparum, the primary cause of malaria, has a large number of genes lacking functional annotation due to insufficient sequence similarity.
- Traditional methods struggle to assign functions to these uncharacterized genes, necessitating alternative approaches like non-homology methods.
- Gene expression data is increasingly utilized for functional annotation within species using the Guilt By Association (GBA) principle.
Purpose of the Study:
- To develop and validate a novel computational method for inter-species gene annotation transfer.
- To leverage conserved coexpression patterns between species to infer functions of uncharacterized genes.
- To improve the accuracy of functional annotation for Plasmodium falciparum genes, including hypothetical and putative ones.
Main Methods:
- The proposed method identifies likely orthologs between reference species (S. cerevisiae, D. melanogaster) and the query species (P. falciparum).
- It detects conserved clusters of coexpressed genes in the query species that show conserved coexpression in reference species.
- These conserved coexpression clusters facilitate annotation transfer for genes with low sequence similarity.
Main Results:
- The approach successfully transferred annotations between species using transcriptomic data from P. falciparum, S. cerevisiae, and D. melanogaster.
- It provided high-confidence functional annotations for numerous hypothetical and putative P. falciparum genes.
- Specific revisions were made to annotations of genes involved in ribosomal protein and ribosome biogenesis, identifying potential drug targets.
Conclusions:
- The developed strategy effectively integrates sequence similarity and gene expression data for inter-species gene annotation.
- This combined approach significantly improves annotation accuracy compared to using sequence similarity alone or the GBA method.
- The method demonstrates efficacy in inferring functions for a substantial number of hypothetical genes in P. falciparum.

