Comprehensive assembly of novel transcripts from unmapped human RNA-Seq data and their association with cancer

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.
Source: Molecular Systems Biology - Category: Molecular Biology Authors: Tags: Cancer, Chromatin, Epigenetics, Genomics & Functional Genomics Articles Source Type: research