title: morFeus: a web-based program to detect remotely conserved orthologs using symmetrical best hits and orthology network scoring.
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/. Its source code is available from Sourceforge.net (https://sourceforge.net/p/morfeus/).
authors.forename: Ines
authors.initials: I
authors.lastname: Wagner
authors.forename: Michael
authors.initials: M
authors.lastname: Volkmer
authors.forename: Malvika
authors.initials: M
authors.lastname: Sharan
authors.forename: Jose M
authors.initials: JM
authors.lastname: Villaveces
authors.forename: Felix
authors.initials: F
authors.lastname: Oswald
authors.forename: Vineeth
authors.initials: V
authors.lastname: Surendranath
authors.affiliation: Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried 82152, Germany. habermann@biochem.mpg.de.
authors.forename: Bianca H
authors.initials: BH
authors.lastname: Habermann
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D003627:Data Interpretation, Statistical; D006801:Humans; D020407:Internet; D017421:Sequence Analysis; D017385:Sequence Homology; D012984:Software
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