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Abstract RNA-Seq is a new experimental technique for trancriptome research based on highthroughput sequencing. It is increasingly used in the research of alternative splicing variation. There are two difficulties in the analysis of RNA-Seq data. One is readisoform multimapping, the other is nonuniform distribution of reads along the gene reference sequence. This paper proposed a new method, so called LDAseq, to calculate isoform expression level based on LDA (Latent Dirichlet Allocation) commonly used to model text corpora. LDAseq utilized the known geneisoform annotation to constrain the hyperparameters for dealing with readisoform multimapping. To modeling the non-uniform distribution of reads along reference sequence, LDAseq introduced “probes” with fixed length to break up the long reference sequence. We applied LDAseq to a mouse dataset and a human breast cancer dataset, and compared the performance of LDAseq with currently used alternatives, such as Cufflinks and RSEM. Results showed that the computation accuracy of LDAseq was increased 75.5% and 62.8% compared with that of Cufflinks and RSEM, respectively.
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