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Summary Alternative splicing is an important mechanism involved in health and disease. Recent work highlights the importance of investigating genome-wide changes in splicing patterns and the subsequent functional consequences. Current computational methods only support such analysis on a gene-by-gene basis. Therefore, we extended IsoformSwitchAnalyzeR R library to enable analysis of genome-wide changes in specific types of alternative splicing and predicted functional consequences of the resulting isoform switches. As a case study, we analyzed RNA-seq data from The Cancer Genome Atlas and found systematic changes in alternative splicing and the consequences of the associated isoform switches. Availability and implementation Windows, Linux and Mac OS: http://bioconductor.org/packages/IsoformSwitchAnalyzeR. Supplementary information Supplementary data are available at Bioinformatics online.

Summary: GMD (generalized minimum distance of distributions) is an R package to assess the similarity between spatial distributions of read-based sequencing data such as ChIP-seq and RNA-seq. GMD calculates the optimal distance between pairs of normalized signal distributions, optionally sliding one distribution over the other to ‘align’ the distributions. GMD also provides graphical and downstream clustering tools. Availability: The R package GMD source code is available at http://cran.r-project.org/web/packages/GMD/ under GPL license Contact: xiaobei@binf.ku.dk; mailto:albin@binf.ku.dk Supplementary information: Supplementary data are available at Bioinformatics online.

Motivation: Describing and modeling biological features of eukaryotic promoters remains an important and challenging problem within computational biology. The promoters of higher eukaryotes in particular display a wide variation in regulatory features, which are difficult to model. Often several factors are involved in the regulation of a set of co-regulated genes. If so, promoters can be modeled with connected regulatory features, where the network of connections is characteristic for a particular mode of regulation. Results: With the goal of automatically deciphering such regulatory structures, we present a method that iteratively evolves an ensemble of regulatory grammars using a hidden Markov Model (HMM) architecture composed of interconnected blocks representing transcription factor binding sites (TFBSs) and background regions of promoter sequences. The ensemble approach reduces the risk of overfitting and generally improves performance. We apply this method to identify TFBSs and to classify promoters preferentially expressed in macrophages, where it outperforms other methods due to the increased predictive power given by the grammar. Availability: The software and the datasets are available from http://modem.ucsd.edu/won/eHMM.tar.gz Contact: krogh@binf.ku.dk Supplementary information: Supplementary data are available at Bioinformatics online.