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morFeus: a web-based program to detect remotely conserved orthologs using symmetrical best hits and orthology network scoring

Ines Wagner4, Michael Volkmer1, Malvika Sharan2, Jose M Villaveces1, Felix Oswald3, Vineeth Surendranath4 and Bianca H Habermann1*

Author Affiliations

1 Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried 82152, Germany

2 IMIB, Julius-Maximilians-University Würzburg, Josef-Schneider-Strasse 2 - Building D15, Würzburg 97080, Germany

3 Section Physics of Living Systems, Department of Physics and Astronomy & Laser Centre, VU University Amsterdam, De Boelelaan 1081, Office U0.30, Amsterdam 1081 HV, Netherlands

4 Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, Dresden 01307, Germany

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BMC Bioinformatics 2014, 15:263  doi:10.1186/1471-2105-15-263

Published: 6 August 2014

Abstract

Background

Searching the orthologs of a given protein or DNA sequence is one of the most important and most commonly used Bioinformatics methods in Biology. Programs like BLAST or the orthology search engine Inparanoid can be used to find orthologs when the similarity between two sequences is sufficiently high. They however fail when the level of conservation is low. The detection of remotely conserved proteins oftentimes involves sophisticated manual intervention that is difficult to automate.

Results

Here, we introduce morFeus, a search program to find remotely conserved orthologs. Based on relaxed sequence similarity searches, morFeus selects sequences based on the similarity of their alignments to the query, tests for orthology by iterative reciprocal BLAST searches and calculates a network score for the resulting network of orthologs that is a measure of orthology independent of the E-value. Detecting remotely conserved orthologs of a protein using morFeus thus requires no manual intervention. We demonstrate the performance of morFeus by comparing it to state-of-the-art orthology resources and methods. We provide an example of remotely conserved orthologs, which were experimentally shown to be functionally equivalent in the respective organisms and therefore meet the criteria of the orthology-function conjecture.

Conclusions

Based on our results, we conclude that morFeus is a powerful and specific search method for detecting remotely conserved orthologs. morFeus is freely available at http://bio.biochem.mpg.de/morfeus/ webcite. Its source code is available from Sourceforge.net (https://sourceforge.net/p/morfeus/ webcite).

Keywords:
Remote sequence conservation; Orthology; Alignment clustering; Reciprocal best hit; Orthology network; Eigenvector centrality; Meta-analysis based orthology finder using symmetrical best hits