title: Simul-seq: combined DNA and RNA sequencing for whole-genome and transcriptome profiling.
abstract: Paired DNA and RNA profiling is increasingly employed in genomics research to uncover molecular mechanisms of disease and to explore personal genotype and phenotype correlations. Here, we introduce Simul-seq, a technique for the production of high-quality whole-genome and transcriptome sequencing libraries from small quantities of cells or tissues. We apply the method to laser-capture-microdissected esophageal adenocarcinoma tissue, revealing a highly aneuploid tumor genome with extensive blocks of increased homozygosity and corresponding increases in allele-specific expression. Among this widespread allele-specific expression, we identify germline polymorphisms that are associated with response to cancer therapies. We further leverage this integrative data to uncover expressed mutations in several known cancer genes as well as a recurrent mutation in the motor domain of KIF3B that significantly affects kinesin-microtubule interactions. Simul-seq provides a new streamlined approach for generating comprehensive genome and transcriptome profiles from limited quantities of clinically relevant samples.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Reuter
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Damek V
authors.initials: DV
authors.lastname: Spacek
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Reetesh K
authors.initials: RK
authors.lastname: Pai
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Snyder
mesh_terms: D004247:DNA / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D015723:Gene Library; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000235:genetics; D008297:Male; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D017423:Sequence Analysis, RNA / Q000379:methods*; D059467:Transcriptome; D019895:Transposases / Q000235:genetics
chemical_list: C095899:KIF3B protein, human; D012333:RNA, Messenger; C473503:Tn5 transposase; D004247:DNA; D019895:Transposases; D016547:Kinesins