title: The landscape of long noncoding RNAs in the human transcriptome.
abstract: Long noncoding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes including cancer. To delineate genome-wide lncRNA expression, we curated 7,256 RNA sequencing (RNA-seq) libraries from tumors, normal tissues and cell lines comprising over 43 Tb of sequence from 25 independent studies. We applied ab initio assembly methodology to this data set, yielding a consensus human transcriptome of 91,013 expressed genes. Over 68% (58,648) of genes were classified as lncRNAs, of which 79% were previously unannotated. About 1% (597) of the lncRNAs harbored ultraconserved elements, and 7% (3,900) overlapped disease-associated SNPs. To prioritize lineage-specific, disease-associated lncRNA expression, we employed non-parametric differential expression testing and nominated 7,942 lineage- or cancer-associated lncRNA genes. The lncRNA landscape characterized here may shed light on normal biology and cancer pathogenesis and may be valuable for future biomarker development.
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Computational Medicine and Bioinformatics, Ann Arbor, Michigan, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Iyer
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Yashar S
authors.initials: YS
authors.lastname: Niknafs
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Malik
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Udit
authors.initials: U
authors.lastname: Singhal
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Anirban
authors.initials: A
authors.lastname: Sahu
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Hosono
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Terrence R
authors.initials: TR
authors.lastname: Barrette
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Prensner
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Evans
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Anton
authors.initials: A
authors.lastname: Poliakov
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Cao
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Yi-Mi
authors.initials: YM
authors.lastname: Wu
authors.affiliation: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Dan R
authors.initials: DR
authors.lastname: Robinson
authors.affiliation: 1] Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA. [2] Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, USA. [3] Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: Department of Statistics, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Hariharan K
authors.initials: HK
authors.lastname: Iyer
authors.affiliation: 1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Computational Medicine and Bioinformatics, Ann Arbor, Michigan, USA. [3] Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA. [4] Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA. [5] Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA. [6] Department of Urology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D015870:Gene Expression; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods; D059467:Transcriptome
chemical_list: D062085:RNA, Long Noncoding