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MultiMSOAR 2.0: an accurate tool to identify ortholog groups among multiple genomes.

ABSTRACT: The identification of orthologous genes shared by multiple genomes plays an important role in evolutionary studies and gene functional analyses. Based on a recently developed accurate tool, called MSOAR 2.0, for ortholog assignment between a pair of closely related genomes based on genome rearrangement, we present a new system MultiMSOAR 2.0, to identify ortholog groups among multiple genomes in this paper. In the system, we construct gene families for all the genomes using sequence similarity search and clustering, run MSOAR 2.0 for all pairs of genomes to obtain the pairwise orthology relationship, and partition each gene family into a set of disjoint sets of orthologous genes (called super ortholog groups or SOGs) such that each SOG contains at most one gene from each genome. For each such SOG, we label the leaves of the species tree using 1 or 0 to indicate if the SOG contains a gene from the corresponding species or not. The resulting tree is called a tree of ortholog groups (or TOGs). We then label the internal nodes of each TOG based on the parsimony principle and some biological constraints. Ortholog groups are finally identified from each fully labeled TOG. In comparison with a popular tool MultiParanoid on simulated data, MultiMSOAR 2.0 shows significantly higher prediction accuracy. It also outperforms MultiParanoid, the Roundup multi-ortholog repository and the Ensembl ortholog database in real data experiments using gene symbols as a validation tool. In addition to ortholog group identification, MultiMSOAR 2.0 also provides information about gene births, duplications and losses in evolution, which may be of independent biological interest. Our experiments on simulated data demonstrate that MultiMSOAR 2.0 is able to infer these evolutionary events much more accurately than a well-known software tool Notung. The software MultiMSOAR 2.0 is available to the public for free.

SUBMITTER: Shi G

PROVIDER: S-EPMC3119667 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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MultiMSOAR 2.0: an accurate tool to identify ortholog groups among multiple genomes.

Shi Guanqun G Peng Meng-Chih MC Jiang Tao T

PloS one 20110621 6

The identification of orthologous genes shared by multiple genomes plays an important role in evolutionary studies and gene functional analyses. Based on a recently developed accurate tool, called MSOAR 2.0, for ortholog assignment between a pair of closely related genomes based on genome rearrangement, we present a new system MultiMSOAR 2.0, to identify ortholog groups among multiple genomes in this paper. In the system, we construct gene families for all the genomes using sequence similarity s ...[more]

PMID: 21712981

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Project description:BACKGROUND:Advances in sequencing technologies have led to the release of reference genomes and annotations for multiple individuals within more well-studied systems. While each of these new genome assemblies shares significant portions of synteny between each other, the annotated structure of gene models within these regions can differ. Of particular concern are split-gene misannotations, in which a single gene is incorrectly annotated as two distinct genes or two genes are incorrectly annotated as a single gene. These misannotations can have major impacts on functional prediction, estimates of expression, and many downstream analyses. RESULTS:We developed a high-throughput method based on pairwise comparisons of annotations that detect potential split-gene misannotations and quantifies support for whether the genes should be merged into a single gene model. We demonstrated the utility of our method using gene annotations of three reference genomes from maize (B73, PH207, and W22), a difficult system from an annotation perspective due to the size and complexity of the genome. On average, we found several hundred of these potential split-gene misannotations in each pairwise comparison, corresponding to 3-5% of gene models across annotations. To determine which state (i.e. one gene or multiple genes) is biologically supported, we utilized RNAseq data from 10 tissues throughout development along with a novel metric and simulation framework. The methods we have developed require minimal human interaction and can be applied to future assemblies to aid in annotation efforts. CONCLUSIONS:Split-gene misannotations occur at appreciable frequency in maize annotations. We have developed a method to easily identify and correct these misannotations. Importantly, this method is generic in that it can utilize any type of short-read expression data. Failure to account for split-gene misannotations has serious consequences for biological inference, particularly for expression-based analyses.

Project description:BackgroundOrtholog 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).ResultsIn 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.ConclusionsOur 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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MultiMSOAR 2.0: an accurate tool to identify ortholog groups among multiple genomes.

Publications

MultiMSOAR 2.0: an accurate tool to identify ortholog groups among multiple genomes.

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