Ab initio reconstruction of transcriptomes of pluripotent and lineage committed cells reveals gene structures of thousands of lincRNAs
By M. Guttman, Manuel Garber, J. Levin, Julie Donaghey, James T. Robinson, Xian Adiconis, Lin Fan, Magdalena J. Koziol, Andreas Gnirke, Chad Nusbaum and 3 more. Nature Biotechnology, 2010
1,265 citations recorded by the source corpus.
Massively parallel cDNA sequencing (RNA-Seq) provides an unbiased way to study a transcriptome, including both coding and noncoding genes. Until now, most RNA-Seq studies have depended crucially on existing annotations and thus focused on expression levels and variation in known transcripts. Here, we present Scripture, a method to reconstruct the transcriptome of a mammalian cell using only RNA-Seq reads and the genome sequence. We applied it to mouse embryonic stem cells, neuronal precursor cells and lung fibroblasts to accurately reconstruct the full-length gene structures for most known expressed genes. We identified substantial variation in protein coding genes, including thousands of novel 5′ start sites, 3′ ends and internal coding exons. We then determined the gene structures of more than a thousand large intergenic noncoding RNA (lincRNA) and antisense loci. Our results open the way to direct experimental manipulation of thousands of noncoding RNAs and demonstrate the power of ab initio reconstruction to render a comprehensive picture of mammalian transcriptomes.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/5272f35538c6b69806971b19d2f9b59640daedf9
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In Molecular Biology
- David P. Bartel
- Howard Y. Chang
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Citations in the corpus
- Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs (2013, background): “While current lncRNA catalogs, such as those we used, are still far from exhaustive and almost certainly contain false positives, they indicate that the abundance and complexity of lncRNAs in mammalian genomes may rival or exceed that of protein-coding genes [9,10,13,16].”