A novel computational framework for transcriptome analysis with RNA-seq data.

摘要

The advance of high-throughput sequencing technologies and their application on mRNA transcriptome sequencing (RNA-seq) have enabled comprehensive and unbiased profiling of the landscape of transcription in a cell. In order to address the current limitation of analyzing accuracy and scalability in transcriptome analysis, a novel computational framework has been developed on large-scale RNA-seq datasets with no dependence on transcript annotations. Directly from raw reads, a probabilistic approach is first applied to infer the best transcript fragment alignments from paired-end reads. Empowered by the identification of alternative splicing modules, this framework then performs precise and efficient differential analysis at automatically detected alternative splicing variants, which circumvents the need of full transcript reconstruction and quantification. Beyond the scope of classical group-wise analysis, a clustering scheme is further described for mining prominent consistency among samples in transcription, breaking the restriction of presumed grouping. The performance of the framework has been demonstrated by a series of simulation studies and real datasets, including the Cancer Genome Atlas (TCGA) breast cancer analysis. The successful applications have suggested the unprecedented opportunity in using differential transcription analysis to reveal variations in the mRNA transcriptome in response to cellular differentiation or effects of diseases.;KEYWORDS: RNA-seq, transcriptome, algorithm, statistical inference, data mining.