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dc.contributor.author Cirulli, ET
dc.contributor.author Singh, A
dc.contributor.author Shianna, KV
dc.contributor.author Ge, D
dc.contributor.author Smith, JP
dc.contributor.author Maia, JM
dc.contributor.author Heinzen, EL
dc.contributor.author Goedert, JJ
dc.contributor.author Goldstein, DB
dc.contributor.author Center for HIV/AIDS Vaccine Immunology (CHAVI)
dc.coverage.spatial England
dc.date.accessioned 2011-06-21T17:30:30Z
dc.date.issued 2010
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20598109
dc.identifier gb-2010-11-5-r57
dc.identifier.citation Genome Biol, 2010, 11 (5), pp. R57 - ?
dc.identifier.uri http://hdl.handle.net/10161/4395
dc.description.abstract BACKGROUND: There is considerable interest in the development of methods to efficiently identify all coding variants present in large sample sets of humans. There are three approaches possible: whole-genome sequencing, whole-exome sequencing using exon capture methods, and RNA-Seq. While whole-genome sequencing is the most complete, it remains sufficiently expensive that cost effective alternatives are important. RESULTS: Here we provide a systematic exploration of how well RNA-Seq can identify human coding variants by comparing variants identified through high coverage whole-genome sequencing to those identified by high coverage RNA-Seq in the same individual. This comparison allowed us to directly evaluate the sensitivity and specificity of RNA-Seq in identifying coding variants, and to evaluate how key parameters such as the degree of coverage and the expression levels of genes interact to influence performance. We find that although only 40% of exonic variants identified by whole genome sequencing were captured using RNA-Seq; this number rose to 81% when concentrating on genes known to be well-expressed in the source tissue. We also find that a high false positive rate can be problematic when working with RNA-Seq data, especially at higher levels of coverage. CONCLUSIONS: We conclude that as long as a tissue relevant to the trait under study is available and suitable quality control screens are implemented, RNA-Seq is a fast and inexpensive alternative approach for finding coding variants in genes with sufficiently high expression levels.
dc.format.extent R57 - ?
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof Genome Biol
dc.relation.isversionof 10.1186/gb-2010-11-5-r57
dc.subject Base Sequence
dc.subject Databases, Genetic
dc.subject Exons
dc.subject Gene Expression Profiling
dc.subject Gene Expression Regulation
dc.subject Genome, Human
dc.subject Humans
dc.subject Leukocytes, Mononuclear
dc.subject Polymorphism, Single Nucleotide
dc.subject Sequence Alignment
dc.subject Sequence Analysis, DNA
dc.subject Sequence Homology, Nucleic Acid
dc.title Screening the human exome: a comparison of whole genome and whole transcriptome sequencing.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-00-00 en_US
duke.description.endpage R57 en_US
duke.description.issue 5 en_US
duke.description.startpage R57 en_US
duke.description.volume 11 en_US
dc.relation.journal Genome biology en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20598109
pubs.issue 5
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Duke Institute for Brain Sciences
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Center for Human Genome Variation
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Clinical Research Institute
pubs.publication-status Published
pubs.volume 11
dc.identifier.eissn 1474-760X

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