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.
CONCLUSION: 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.
Type
Journal articleSubject
AlgorithmsAnimals
Chiroptera
Cloning, Molecular
Gene Expression Profiling
Genome
Genomics
Humans
Interferon Type I
Interferon-gamma
Male
Models, Genetic
Phylogeny
Reproducibility of Results
Sequence Analysis, DNA
Sequence Homology, Nucleic Acid
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https://hdl.handle.net/10161/4346Published Version (Please cite this version)
10.1186/1471-2164-11-444Publication Info
Kepler, Thomas B; Sample, Christopher; Hudak, Kathryn; Roach, Jeffrey; Haines, Albert;
Walsh, Allyson; & Ramsburg, Elizabeth A (2010). Chiropteran types I and II interferon genes inferred from genome sequencing traces
by a statistical gene-family assembler. BMC Genomics, 11. pp. 444. 10.1186/1471-2164-11-444. Retrieved from https://hdl.handle.net/10161/4346.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Thomas B. Kepler
Adjunct Professor in the Department of Immunology
Computational and Systems Immunology, Theoretical and Evolutionary Medicine
Elizabeth Anne Ramsburg
Adjunct Assistant Professor in the Department of Molecular Genetics and Microbiology
In principle, most viral infections can be prevented by effective and timely vaccination.
In the past several decades however, the rapid emergence and spread into new geographical
areas of viruses such as dengue, West Nile virus, HIV, and the highly pathogenic avian
influenzas has outpaced the development of preventative vaccines. The major focus
of research in the Ramsburg lab is to develop novel vaccines based on recombinant
viruses for the prevention of viral diseases, and to better char
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