title: Combining evidence, biomedical literature and statistical dependence: new insights for functional annotation of gene sets.
abstract: BACKGROUND
  Large-scale genomic studies based on transcriptome technologies provide clusters of genes that need to be functionally annotated. The Gene Ontology (GO) implements a controlled vocabulary organised into three hierarchies: cellular components, molecular functions and biological processes. This terminology allows a coherent and consistent description of the knowledge about gene functions. The GO terms related to genes come primarily from semi-automatic annotations made by trained biologists (annotation based on evidence) or text-mining of the published scientific literature (literature profiling).
  
  
  RESULTS
  We report an original functional annotation method based on a combination of evidence and literature that overcomes the weaknesses and the limitations of each approach. It relies on the Gene Ontology Annotation database (GOA Human) and the PubGene biomedical literature index. We support these annotations with statistically associated GO terms and retrieve associative relations across the three GO hierarchies to emphasise the major pathways involved by a gene cluster. Both annotation methods and associative relations were quantitatively evaluated with a reference set of 7397 genes and a multi-cluster study of 14 clusters. We also validated the biological appropriateness of our hybrid method with the annotation of a single gene (cdc2) and that of a down-regulated cluster of 37 genes identified by a transcriptome study of an in vitro enterocyte differentiation model (CaCo-2 cells).
  
  
  CONCLUSIONS
  The combination of both approaches is more informative than either separate approach: literature mining can enrich an annotation based only on evidence. Text-mining of the literature can also find valuable associated MEDLINE references that confirm the relevance of the annotation. Eventually, GO terms networks can be built with associative relations in order to highlight cooperative and competitive pathways and their connected molecular functions.
authors: CNRS UMR 6061 Génétique et Développement, Université de Rennes 1, Groupe Oncogénomique, IFR140 GFAS, Faculté de Médecine, 2 avenue du Pr, Léon Bernard, CS 34317, 35043 Rennes Cedex, France. marc.aubry@univ-rennes1.fr
authors: Marc
authors: M
authors: Aubry
authors: Annabelle
authors: A
authors: Monnier
authors: Celine
authors: C
authors: Chicault
authors: Marie
authors: M
authors: de Tayrac
authors: Marie-Dominique
authors: MD
authors: Galibert
authors: Anita
authors: A
authors: Burgun
authors: Jean
authors: J
authors: Mosser