Identification and Quantification of Alternative Splicing Events

Alternative splicing is a major contributing factor to transcriptome complexity in higher eukaryotes. Different transcript isoforms that result from alternative splicing play essential roles in gene regulation and development, as evidenced by their dysregulation in disease states. Despite its importance, only a fraction of the landscape of alternative splicing is known, leaving many aspects to be elucidated. We developed SplAdder [1], a software that augments existing gene annotation with evidence from RNA-Sequencing to identify all alternative splicing events that are possible and supported by the data. These events are quantified and can be used for downstream analysis, such as data visualisation or differential expression analysis.

Developed initially on model organisms (such as the plant A. thaliana and worm C. elegans), the approach has been adapted to work on large cohorts of human samples. In the context of The Cancer Genome Atlas project, we have studied the diversity and possible implication of cancer-specific splicing diversity across a population of more than 30 cancer types, comprising a cohort of more than 8’700 patients [2]. 

The SplAdder software is available as open source. [Download] [Documentation

Involved group members: Andre Kahles, Gunnar Rätsch

[1] Kahles, Andre, Cheng Soon Ong, Yi Zhong, and Gunnar Rätsch. "SplAdder: identification, quantification and testing of alternative splicing events from RNA-Seq data." Bioinformatics 32, no. 12 (2016): 1840-1847.
[2] Kahles, André, Kjong-Van Lehmann, Nora C. Toussaint, Matthias Hüser, Stefan G. Stark, Timo Sachsenberg, Oliver Stegle et al. "Comprehensive analysis of alternative splicing across tumours from 8,705 patients." Cancer cell 34, no. 2 (2018): 211-224.