title: Chiropteran types I and II interferon genes inferred from genome sequencing traces by a statistical gene-family assembler.
abstract: BACKGROUND
  The rate of emergence of human pathogens is steadily increasing; most of these novel agents originate in wildlife. Bats, remarkably, are the natural reservoirs of many of the most pathogenic viruses in humans. There are two bat genome projects currently underway, a circumstance that promises to speed the discovery host factors important in the coevolution of bats with their viruses. These genomes, however, are not yet assembled and one of them will provide only low coverage, making the inference of most genes of immunological interest error-prone. Many more wildlife genome projects are underway and intend to provide only shallow coverage.
  
  
  RESULTS
  We have developed a statistical method for the assembly of gene families from partial genomes. The method takes full advantage of the quality scores generated by base-calling software, incorporating them into a complete probabilistic error model, to overcome the limitation inherent in the inference of gene family members from partial sequence information. We validated the method by inferring the human IFNA genes from the genome trace archives, and used it to infer 61 type-I interferon genes, and single type-II interferon genes in the bats Pteropus vampyrus and Myotis lucifugus. We confirmed our inferences by direct cloning and sequencing of IFNA, IFNB, IFND, and IFNK in P. vampyrus, and by demonstrating transcription of some of the inferred genes by known interferon-inducing stimuli.
  
  
  CONCLUSIONS
  The statistical trace assembler described here provides a reliable method for extracting information from the many available and forthcoming partial or shallow genome sequencing projects, thereby facilitating the study of a wider variety of organisms with ecological and biomedical significance to humans than would otherwise be possible.
authors.affiliation: Center for Computational Immunology, Duke University Medical Center, Durham, NC, USA. kepler@duke.edu
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.forename: Christopher
authors.initials: C
authors.lastname: Sample
authors.forename: Kathryn
authors.initials: K
authors.lastname: Hudak
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Roach
authors.forename: Albert
authors.initials: A
authors.lastname: Haines
authors.forename: Allyson
authors.initials: A
authors.lastname: Walsh
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ramsburg
mesh_terms: D000465:Algorithms; D000818:Animals; D002685:Chiroptera / Q000235:genetics*; D003001:Cloning, Molecular; D020869:Gene Expression Profiling; D016678:Genome / Q000235:genetics*; D023281:Genomics; D006801:Humans; D007370:Interferon Type I / Q000145:classification / Q000235:genetics*; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D008957:Models, Genetic; D010802:Phylogeny; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid
chemical_list: D007370:Interferon Type I; D007371:Interferon-gamma