title: Functional analysis beyond enrichment: non-redundant reciprocal linkage of genes and biological terms.
abstract: Functional analysis of large sets of genes and proteins is becoming more and more necessary with the increase of experimental biomolecular data at omic-scale. Enrichment analysis is by far the most popular available methodology to derive functional implications of sets of cooperating genes. The problem with these techniques relies in the redundancy of resulting information, that in most cases generate lots of trivial results with high risk to mask the reality of key biological events. We present and describe a computational method, called GeneTerm Linker, that filters and links enriched output data identifying sets of associated genes and terms, producing metagroups of coherent biological significance. The method uses fuzzy reciprocal linkage between genes and terms to unravel their functional convergence and associations. The algorithm is tested with a small set of well known interacting proteins from yeast and with a large collection of reference sets from three heterogeneous resources: multiprotein complexes (CORUM), cellular pathways (SGD) and human diseases (OMIM). Statistical Precision, Recall and balanced F-score are calculated showing robust results, even when different levels of random noise are included in the test sets. Although we could not find an equivalent method, we present a comparative analysis with a widely used method that combines enrichment and functional annotation clustering. A web application to use the method here proposed is provided at http://gtlinker.cnb.csic.es.
authors.affiliation: Cancer Research Center (CiC-IBMCC, CSIC/USAL), Campus Miguel de Unamuno, Salamanca, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Fontanillo
authors.forename: Ruben
authors.initials: R
authors.lastname: Nogales-Cadenas
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual-Montano
authors.forename: Javier
authors.initials: J
authors.lastname: De las Rivas
mesh_terms: D000465:Algorithms; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D030541:Databases, Genetic; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D020407:Internet; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000145:classification / Q000235:genetics* / Q000502:physiology*; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000145:classification / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
chemical_list: D009687:Nuclear Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins