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PMID: 25599403 Published · ppublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The landscape of long noncoding RNAs in the human transcriptome.

Nature genetics ·Vol. 47 ·No. 3 ·2015-03-00 ·Pages 199-208

Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, Barrette TR, Prensner JR, Evans JR, Zhao S, Poliakov A, Cao X, Dhanasekaran SM, Wu YM, Robinson DR, Beer DG, Feng FY, Iyer HK, Chinnaiyan AM

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.

MeSH Terms
Cell Line Cell Line, Tumor Gene Expression Humans Neoplasms/genetics RNA, Long Noncoding/genetics Sequence Analysis, RNA/methods Transcriptome
Chemicals
RNA, Long Noncoding
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Iyer Matthew K
1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Computational Medicine and Bioinformatics, Ann Arbor, Michigan, USA.
Niknafs Yashar S
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.
Malik Rohit
1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Singhal Udit
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.
Sahu Anirban
1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Hosono Yasuyuki
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Barrette Terrence R
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Prensner John R
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Evans Joseph R
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.
Zhao Shuang
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.
Poliakov Anton
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Cao Xuhong
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.
Dhanasekaran Saravana M
1] Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Wu Yi-Mi
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Robinson Dan R
Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Beer David G
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.
Feng Felix Y
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.
Iyer Hariharan K
Department of Statistics, Colorado State University, Fort Collins, Colorado, USA.
Chinnaiyan Arul M
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.
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.3192
Published
2015-03-00
Epub
2015-00-19
Pages
199-208
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC4417758
Subset
IM
Grants
NCI NIH HHS · R01 CA132874 · United States
NIGMS NIH HHS · T32 GM007863 · United States
NCI NIH HHS · P50 CA69568 · United States
Howard Hughes Medical Institute · United States
NCI NIH HHS · P50 CA186786 · United States
NCI NIH HHS · P50 CA069568 · United States
NCI NIH HHS · U01 CA111275 · United States
NCI NIH HHS · F30 CA180376 · United States
NCI NIH HHS · R01 CA154365 · United States
NIGMS NIH HHS · T32 GM007315 · United States
External Links
PubMed source DOI: 10.1038/ng.3192 PMC Full Text View journal details
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