BitSeq Method Yields Most Accurate Measures of Gene Expression

RNA-sequencing allows measuring the gene expression of humans or other organisms. The method has recently become very popular in bioscience and medical research, and it is being adopted to clinical applications. Compared to previous methods, RNA-sequencing enables the study of alternative gene isoforms or transcripts, which are formed, for example, through the process of alternative splicing. The analysis of the large amount of data produced by RNA-sequencing requires many advanced computational methods. Analysis of transcript level data is especially demanding and the differences between alternative methods can be large. In the recent assessment (“A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium,” published online in Nature Biotechnology on August 24, 2014), the BitSeq method developed by the University of Helsinki and the University of Manchester researchers produced clearly the most reliable results in this task. In one subtask, BitSeq could produce equally accurate results using only half the data needed by a very popular alternative method. The BitSeq method ( is based on probabilistic modelling that allows comparing different possible origins for observed sequences that cannot be identified uniquely. This allows computing probability distributions over the expression levels of each transcript of every gene in a way that captures the uncertainty and possible sources of error in the measurements. Accounting for this uncertainty through probabilities is essential for the accuracy of the method.
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