Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí y học Molecular Biology cung cấp cho các bạn kiến thức về ngành sinh học đề tài: Estimation of alternative splicing isoform frequencies from RNA-Seq data. | Nicolae et al. Algorithms for Molecular Biology 2011 6 9 http content 6 1 9 AMR ALGORITHMS FOR MOLECULAR BIOLOGY RESEARCH Open Access Estimation of alternative splicing isoform frequencies from RNA-Seq data Marius Nicolae1 Serghei Mangul2 Ion I Măndoiu1 and Alex Zelikovsky2 Abstract Background Massively parallel whole transcriptome sequencing commonly referred as RNA-Seq is quickly becoming the technology of choice for gene expression profiling. However due to the short read length delivered by current sequencing technologies estimation of expression levels for alternative splicing gene isoforms remains challenging. Results In this paper we present a novel expectation-maximization algorithm for inference of isoform- and genespecific expression levels from RNA-Seq data. Our algorithm referred to as IsoEM is based on disambiguating information provided by the distribution of insert sizes generated during sequencing library preparation and takes advantage of base quality scores strand and read pairing information when available. The open source Java implementation of IsoEM is freely available at http software IsoEM . Conclusions Empirical experiments on both synthetic and real RNA-Seq datasets show that IsoEM has scalable running time and outperforms existing methods of isoform and gene expression level estimation. Simulation experiments confirm previous findings that for a fixed sequencing cost using reads longer than 25-36 bases does not necessarily lead to better accuracy for estimating expression levels of annotated isoforms and genes. Background Ubiquitous regulatory mechanisms such as the use of alternative transcription start and polyadenylation sites alternative splicing and RNA editing result in multiple messenger RNA mRNA isoforms being generated from a single genomic locus. Most prevalently alternative splicing is estimated to take place for over 90 of the multi-exon human genes across diverse cell types 1 with as much as 68
