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MSOAR 2.0: Incorporating tandem duplications into ortholog assignment based on genome rearrangement.

Shi G, Zhang L, Jiang T - BMC Bioinformatics (2010)

Bottom Line: Although the specificity of MSOAR 2.0 is slightly worse than that of InParanoid in the real data experiments, it is actually better than that of InParanoid in the simulation tests.Our preliminary experimental results demonstrate that MSOAR 2.0 is a highly accurate tool for one-to-one ortholog assignment between closely related genomes.The software is available to the public for free and included as online supplementary material.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science, University of California, Riverside, CA 92521, USA. gshi@cs.ucr.edu

ABSTRACT

Background: Ortholog assignment is a critical and fundamental problem in comparative genomics, since orthologs are considered to be functional counterparts in different species and can be used to infer molecular functions of one species from those of other species. MSOAR is a recently developed high-throughput system for assigning one-to-one orthologs between closely related species on a genome scale. It attempts to reconstruct the evolutionary history of input genomes in terms of genome rearrangement and gene duplication events. It assumes that a gene duplication event inserts a duplicated gene into the genome of interest at a random location (i.e., the random duplication model). However, in practice, biologists believe that genes are often duplicated by tandem duplications, where a duplicated gene is located next to the original copy (i.e., the tandem duplication model).

Results: In this paper, we develop MSOAR 2.0, an improved system for one-to-one ortholog assignment. For a pair of input genomes, the system first focuses on the tandemly duplicated genes of each genome and tries to identify among them those that were duplicated after the speciation (i.e., the so-called inparalogs), using a simple phylogenetic tree reconciliation method. For each such set of tandemly duplicated inparalogs, all but one gene will be deleted from the concerned genome (because they cannot possibly appear in any one-to-one ortholog pairs), and MSOAR is invoked. Using both simulated and real data experiments, we show that MSOAR 2.0 is able to achieve a better sensitivity and specificity than MSOAR. In comparison with the well-known genome-scale ortholog assignment tool InParanoid, Ensembl ortholog database, and the orthology information extracted from the well-known whole-genome multiple alignment program MultiZ, MSOAR 2.0 shows the highest sensitivity. Although the specificity of MSOAR 2.0 is slightly worse than that of InParanoid in the real data experiments, it is actually better than that of InParanoid in the simulation tests.

Conclusions: Our preliminary experimental results demonstrate that MSOAR 2.0 is a highly accurate tool for one-to-one ortholog assignment between closely related genomes. The software is available to the public for free and included as online supplementary material.

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An outline of MSOAR.
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Figure 1: An outline of MSOAR.

Mentions: For the convenience of the reader, an outline of the major algorithmic steps in MSOAR is sketched in Figure 1. In particular, MSOAR attempts to remove false one-to-one ortholog pairs that involve genes randomly duplicated after the speciation in the "noise" gene pair detection step. Such a (false) ortholog pair usually incurs a great cost in the rearrangement distance between the genomes, and thus we would be able to reduce the RD distance by "uncoupling" (i.e., removing) the pair. However, in reality, randomly duplicated genes only account for a part of all duplicated genes. Recent studies have shown that at least 30% of duplicated genes are found next to their original copies (i.e., in tandem positions) [23,24].


MSOAR 2.0: Incorporating tandem duplications into ortholog assignment based on genome rearrangement.

Shi G, Zhang L, Jiang T - BMC Bioinformatics (2010)

An outline of MSOAR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2821317&req=5

Figure 1: An outline of MSOAR.
Mentions: For the convenience of the reader, an outline of the major algorithmic steps in MSOAR is sketched in Figure 1. In particular, MSOAR attempts to remove false one-to-one ortholog pairs that involve genes randomly duplicated after the speciation in the "noise" gene pair detection step. Such a (false) ortholog pair usually incurs a great cost in the rearrangement distance between the genomes, and thus we would be able to reduce the RD distance by "uncoupling" (i.e., removing) the pair. However, in reality, randomly duplicated genes only account for a part of all duplicated genes. Recent studies have shown that at least 30% of duplicated genes are found next to their original copies (i.e., in tandem positions) [23,24].

Bottom Line: Although the specificity of MSOAR 2.0 is slightly worse than that of InParanoid in the real data experiments, it is actually better than that of InParanoid in the simulation tests.Our preliminary experimental results demonstrate that MSOAR 2.0 is a highly accurate tool for one-to-one ortholog assignment between closely related genomes.The software is available to the public for free and included as online supplementary material.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science, University of California, Riverside, CA 92521, USA. gshi@cs.ucr.edu

ABSTRACT

Background: Ortholog assignment is a critical and fundamental problem in comparative genomics, since orthologs are considered to be functional counterparts in different species and can be used to infer molecular functions of one species from those of other species. MSOAR is a recently developed high-throughput system for assigning one-to-one orthologs between closely related species on a genome scale. It attempts to reconstruct the evolutionary history of input genomes in terms of genome rearrangement and gene duplication events. It assumes that a gene duplication event inserts a duplicated gene into the genome of interest at a random location (i.e., the random duplication model). However, in practice, biologists believe that genes are often duplicated by tandem duplications, where a duplicated gene is located next to the original copy (i.e., the tandem duplication model).

Results: In this paper, we develop MSOAR 2.0, an improved system for one-to-one ortholog assignment. For a pair of input genomes, the system first focuses on the tandemly duplicated genes of each genome and tries to identify among them those that were duplicated after the speciation (i.e., the so-called inparalogs), using a simple phylogenetic tree reconciliation method. For each such set of tandemly duplicated inparalogs, all but one gene will be deleted from the concerned genome (because they cannot possibly appear in any one-to-one ortholog pairs), and MSOAR is invoked. Using both simulated and real data experiments, we show that MSOAR 2.0 is able to achieve a better sensitivity and specificity than MSOAR. In comparison with the well-known genome-scale ortholog assignment tool InParanoid, Ensembl ortholog database, and the orthology information extracted from the well-known whole-genome multiple alignment program MultiZ, MSOAR 2.0 shows the highest sensitivity. Although the specificity of MSOAR 2.0 is slightly worse than that of InParanoid in the real data experiments, it is actually better than that of InParanoid in the simulation tests.

Conclusions: Our preliminary experimental results demonstrate that MSOAR 2.0 is a highly accurate tool for one-to-one ortholog assignment between closely related genomes. The software is available to the public for free and included as online supplementary material.

Show MeSH