Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs
biocq 添加于 2012-3-25 14:09
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作 者
Guttman M, Garber M, Levin JZ, Donaghey J, Robinson J, Adiconis X, Fan L, Koziol MJ, Gnirke A, Nusbaum C, Rinn JL, Lander ES, Regev A 摘 要
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.-
详细资料
- 关键词: Animals; Cell Line; Computational Biology/*methods; DNA, Intergenic/*genetics; Embryonic Stem Cells; Gene Expression Profiling/*methods; Gene Library; Mice; Models, Genetic; RNA, Messenger/*genetics; Sequence Analysis, RNA/*methods; Transcription, Genetic
- 文献种类: Journal Article
- 期刊名称: Nature Biotechnology
- 期刊缩写: Nat Biotechnol
- 期卷页: 2010年 第28卷 第5期 503-510页
- 地址: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. mguttman@mit.edu
- ISBN: 1087-0156
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学科领域 生物医药 » 生物学
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