title: Comprehensive assembly of novel transcripts from unmapped human RNA-Seq data and their association with cancer.
abstract: Crucial parts of the genome including genes encoding microRNAs and noncoding RNAs went unnoticed for years, and even now, despite extensive annotation and assembly of the human genome, RNA-sequencing continues to yield millions of unmappable and thus uncharacterized reads. Here, we examined > 300 billion reads from 536 normal donors and 1,873 patients encompassing 21 cancer types, identified ~300 million such uncharacterized reads, and using a distinctive approach de novo assembled 2,550 novel human transcripts, which mainly represent long noncoding RNAs. Of these, 230 exhibited relatively specific expression or non-expression in certain cancer types, making them potential markers for those cancers, whereas 183 exhibited tissue specificity. Moreover, we used lentiviral-mediated expression of three selected transcripts that had higher expression in normal than in cancer patients and found that each inhibited the growth of HepG2 cells. Our analysis provides a comprehensive and unbiased resource of unmapped human transcripts and reveals their associations with specific cancers, providing potentially important new genes for therapeutic targeting.
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD, USA.
authors.forename: Majid
authors.initials: M
authors.lastname: Kazemian
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Ren
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Lin
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Liao
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD, USA.
authors.forename: Rosanne
authors.initials: R
authors.lastname: Spolski
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, MD, USA wjl@helix.nih.gov.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
mesh_terms: D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D016678:Genome / Q000235:genetics; D006071:Gorilla gorilla / Q000235:genetics; D057809:HEK293 Cells; D056945:Hep G2 Cells; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D058977:Molecular Sequence Annotation; D009369:Neoplasms / Q000235:genetics*; D002679:Pan troglodytes / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D017423:Sequence Analysis, RNA
chemical_list: D014408:Biomarkers, Tumor; D006657:Histones; D035683:MicroRNAs; D062085:RNA, Long Noncoding
keywords: cancer‐associated transcripts; long noncoding RNAs; unmapped sequencing reads