title: TopoICSim: a new semantic similarity measure based on gene ontology.
abstract: BACKGROUND
  The Gene Ontology (GO) is a dynamic, controlled vocabulary that describes the cellular function of genes and proteins according to tree major categories: biological process, molecular function and cellular component. It has become widely used in many bioinformatics applications for annotating genes and measuring their semantic similarity, rather than their sequence similarity. Generally speaking, semantic similarity measures involve the GO tree topology, information content of GO terms, or a combination of both.
  
  
  RESULTS
  Here we present a new semantic similarity measure called TopoICSim (Topological Information Content Similarity) which uses information on the specific paths between GO terms based on the topology of the GO tree, and the distribution of information content along these paths. The TopoICSim algorithm was evaluated on two human benchmark datasets based on KEGG pathways and Pfam domains grouped as clans, using GO terms from either the biological process or molecular function. The performance of the TopoICSim measure compared favorably to five existing methods. Furthermore, the TopoICSim similarity was also tested on gene/protein sets defined by correlated gene expression, using three human datasets, and showed improved performance compared to two previously published similarity measures. Finally we used an online benchmarking resource which evaluates any similarity measure against a set of 11 similarity measures in three tests, using gene/protein sets based on sequence similarity, Pfam domains, and enzyme classifications. The results for TopoICSim showed improved performance relative to most of the measures included in the benchmarking, and in particular a very robust performance throughout the different tests.
  
  
  CONCLUSIONS
  The TopoICSim similarity measure provides a competitive method with robust performance for quantification of semantic similarity between genes and proteins based on GO annotations. An R script for TopoICSim is available at http://bigr.medisin.ntnu.no/tools/TopoICSim.R .
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, P.O. Box 8905, NO-7491, Trondheim, Norway.|Department of Mathematics, University of Zabol, Zabol, Iran.
authors.forename: Rezvan
authors.initials: R
authors.lastname: Ehsani
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, P.O. Box 8905, NO-7491, Trondheim, Norway. finn.drablos@ntnu.no.
authors.forename: Finn
authors.identifier: http://orcid.org/0000-0001-5794-828X
authors.initials: F
authors.lastname: Drabløs
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D063990:Gene Ontology; D006801:Humans; D058977:Molecular Sequence Annotation; D012660:Semantics; D018875:Vocabulary, Controlled
keywords: Gene ontology; Semantic similarity measure; Tree topology