title: Determination and validation of principal gene products.
abstract: BACKGROUND
  Alternative splicing has the potential to generate a wide range of protein isoforms. For many computational applications and for experimental research, it is important to be able to concentrate on the isoform that retains the core biological function. For many genes this is far from clear.
  
  
  RESULTS
  We have combined five methods into a pipeline that allows us to detect the principal variant for a gene. Most of the methods were based on conservation between species, at the level of both gene and protein. The five methods used were the conservation of exonic structure, the detection of non-neutral evolution, the conservation of functional residues, the existence of a known protein structure and the abundance of vertebrate orthologues. The pipeline was able to determine a principal isoform for 83% of a set of well-annotated genes with multiple variants.
authors.affiliation: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid, Spain. mtress@cnio.es
authors.forename: Michael L
authors.initials: ML
authors.lastname: Tress
authors.forename: Jan-Jaap
authors.initials: JJ
authors.lastname: Wesselink
authors.forename: Adam
authors.initials: A
authors.lastname: Frankish
authors.forename: Gonzalo
authors.initials: G
authors.lastname: López
authors.forename: Nick
authors.initials: N
authors.lastname: Goldman
authors.forename: Ari
authors.initials: A
authors.lastname: Löytynoja
authors.forename: Tim
authors.initials: T
authors.lastname: Massingham
authors.forename: Fabio
authors.initials: F
authors.lastname: Pardi
authors.forename: Simon
authors.initials: S
authors.lastname: Whelan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Harrow
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
mesh_terms: D000465:Algorithms; D017398:Alternative Splicing / Q000235:genetics*; D019143:Evolution, Molecular; D020869:Gene Expression Profiling / Q000379:methods*; D020033:Protein Isoforms / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods*; D017421:Sequence Analysis / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020033:Protein Isoforms