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Phylogenetic Identification and Functional Characterization of Orthologs and Paralogs across Human, Mouse, Fly, and Worm

Yi-Chieh Wu, Mukul S. Bansal, Matthew D. Rasmussen, Javier Herrero, Manolis Kellis
doi: https://doi.org/10.1101/005736
Yi-Chieh Wu
1Department of Electrical Engineering and Computer Science, Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA 02139
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  • For correspondence: yjw@mit.edu
Mukul S. Bansal
1Department of Electrical Engineering and Computer Science, Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA 02139
2Current address: Department of Computer Science and Engineering, University of Connecticut, Storrs, Connecticut, USA 06269
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Matthew D. Rasmussen
3Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York, USA 14850
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Javier Herrero
4European Bioinformatics Institute, European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton CB10 1SD, UK
5Current address: Bill Lyons Informatics Centre, UCL Cancer Institute, University College London London WC1E 6BT, UK
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Manolis Kellis
1Department of Electrical Engineering and Computer Science, Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA 02139
6Broad Institute, Cambridge, Massachusetts, USA 02142
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  • For correspondence: manoli@mit.edu
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Abstract

Model organisms can serve the biological and medical community by enabling the study of conserved gene families and pathways in experimentally-tractable systems. Their use, however, hinges on the ability to reliably identify evolutionary orthologs and paralogs with high accuracy, which can be a great challenge at both small and large evolutionary distances. Here, we present a phylogenomics-based approach for the identification of orthologous and paralogous genes in human, mouse, fly, and worm, which forms the foundation of the comparative analyses of the modENCODE and mouse ENCODE projects. We study a median of 16,101 genes across 2 mammalian genomes (human, mouse), 12 Drosophila genomes, 5 Caenorhabditis genomes, and an outgroup yeast genome, and demonstrate that accurate inference of evolutionary relationships and events across these species must account for frequent gene-tree topology errors due to both incomplete lineage sorting and insufficient phylogenetic signal. Furthermore, we show that integration of two separate phylogenomic pipelines yields increased accuracy, suggesting that their sources of error are independent, and finally, we leverage the resulting annotation of homologous genes to study the functional impact of gene duplication and loss in the context of rich gene expression and functional genomic datasets of the modENCODE, mouse ENCODE, and human ENCODE projects.

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Posted May 31, 2014.
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Phylogenetic Identification and Functional Characterization of Orthologs and Paralogs across Human, Mouse, Fly, and Worm
Yi-Chieh Wu, Mukul S. Bansal, Matthew D. Rasmussen, Javier Herrero, Manolis Kellis
bioRxiv 005736; doi: https://doi.org/10.1101/005736
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Phylogenetic Identification and Functional Characterization of Orthologs and Paralogs across Human, Mouse, Fly, and Worm
Yi-Chieh Wu, Mukul S. Bansal, Matthew D. Rasmussen, Javier Herrero, Manolis Kellis
bioRxiv 005736; doi: https://doi.org/10.1101/005736

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