Posted: September 22nd, 2016

Exon-centric analysis of differential alternative splicing

Project Title: Exon-centric analysis of differential alternative splicing Description: Alternative splicing is one of the major contributors to the diversity of proteins in higher eukaryotes. According to recent studies more than 90% of the human genes are alternatively spliced [1]. The analysis of differential alternative splicing typically focusses on the quantification of splice variants at transcript level. An alternative to the transcript-centric approach is an exon-centric approach which aims to quantify the frequency of individual splice events such as exon skipping, alternative use of exons, mutually exclusive exons, retained introns etc. One advantage of the latter approach is that quantitative knowledge of such splice events allows at least in principle to correlate splice events with the expression of known splice factors. The specific aims of the project are to test the three recently published approaches for exon centric analysis: MATS [2], MISO [3], and SUPPA [4], to compare their performance, and to explore their suitability for a full scale exon-centric analysis of differential alternative splicing of the toxicogenomic RNA-seq datasets described in [5]. [6] is a paper where my supervisor participated and he gave it to me for help. See MISO analytical tool section and analysis of its output. [1] Wang et al. (2008). Alternative isoform regulation in human tissue transcriptomes. Nature, 456, 470- 476. [2] Shen et al. (2012). MATs : a Bayesian framework for flexible detection of differential alternative splicing from RNA-Seq data. Nucleic Acid Res., 40, e61. [3] Katz et al. (2010). Analysis and design of RNA sequencing experiments for identifying isoform regulation. Nature Methods, 7, 1009-1015. [4] Alamancos et al. (2015). Leveraging transcript quantification for fast computation of alternative splicing profiles. RNA, 21, 1521-1531. [5] Wang et al. (2014) Nat Biotech., 32, 926-932. [6] Schmid, R. et al., 2013. The splicing landscape is globally reprogrammed during male meiosis. Nucleic Acids Resea