title: Gene and alternative splicing annotation with AIR.
abstract: Designing effective and accurate tools for identifying the functional and structural elements in a genome remains at the frontier of genome annotation owing to incompleteness and inaccuracy of the data, limitations in the computational models, and shifting paradigms in genomics, such as alternative splicing. We present a methodology for the automated annotation of genes and their alternatively spliced mRNA transcripts based on existing cDNA and protein sequence evidence from the same species or projected from a related species using syntenic mapping information. At the core of the method is the splice graph, a compact representation of a gene, its exons, introns, and alternatively spliced isoforms. The putative transcripts are enumerated from the graph and assigned confidence scores based on the strength of sequence evidence, and a subset of the high-scoring candidates are selected and promoted into the annotation. The method is highly selective, eliminating the unlikely candidates while retaining 98% of the high-quality mRNA evidence in well-formed transcripts, and produces annotation that is measurably more accurate than some evidence-based gene sets. The process is fast, accurate, and fully automated, and combines the traditionally distinct gene annotation and alternative splicing detection processes in a comprehensive and systematic way, thus considerably aiding in the ensuing manual curation efforts.
authors.affiliation: Informatics Research, Applied Biosystems, Rockville, Maryland 20850, USA. florea@gwu.edu
authors.forename: Liliana
authors.initials: L
authors.lastname: Florea
authors.forename: Valentina
authors.initials: V
authors.lastname: Di Francesco
authors.forename: Jason
authors.initials: J
authors.lastname: Miller
authors.forename: Russell
authors.initials: R
authors.lastname: Turner
authors.forename: Alison
authors.initials: A
authors.lastname: Yao
authors.forename: Michael
authors.initials: M
authors.lastname: Harris
authors.forename: Brian
authors.initials: B
authors.lastname: Walenz
authors.forename: Clark
authors.initials: C
authors.lastname: Mobarry
authors.forename: Gennady V
authors.initials: GV
authors.lastname: Merkulov
authors.forename: Rosane
authors.initials: R
authors.lastname: Charlab
authors.forename: Ian
authors.initials: I
authors.lastname: Dew
authors.forename: Zuoming
authors.initials: Z
authors.lastname: Deng
authors.forename: Sorin
authors.initials: S
authors.lastname: Istrail
authors.forename: Peter
authors.initials: P
authors.lastname: Li
authors.forename: Granger
authors.initials: G
authors.lastname: Sutton
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D002415:Cats; D002417:Cattle; D002645:Chickens / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D004285:Dogs; D019143:Evolution, Molecular; D005796:Genes / Q000235:genetics*; D016678:Genome; D051379:Mice; D008957:Models, Genetic; D002679:Pan troglodytes / Q000235:genetics; D010215:Papio / Q000235:genetics; D011237:Predictive Value of Tests; D051381:Rats; D012984:Software / Q000592:standards; D013552:Swine / Q000235:genetics; D026801:Synteny / Q000235:genetics; D023741:Takifugu / Q000235:genetics; D015027:Zebrafish / Q000235:genetics