What is RNA splicing & and how do we use it for drug discovery?
What is Alternative Splicing in RNA?
A source of biological diversity
Splicing is the process of removal of non-coding introns and assembly of coding exons into mature mRNAs. About 95% of human genes are alternatively spliced, leading to the expression of multiple mRNA isoforms from the same gene. While some splicing isoforms encode fully functional proteins, others lead to partially or non-functional variants that can cause disease.
Splicing as a Drug Target
A large number of diseases are caused by splicing defects
Typical Splicing Analysis
The previous methodology for alternative splicing analysis
Limitations and Solutions for Splicing Analysis
Envisagenics delivers the best isoform-level analysis of RNA-seq data
Predictive Analytics for Splicing Analysis
Envisagenics' novel approach for prioritizing drug targets and biomarkers
Genes & Development 2016. 30: 34-51
Application of SpliceCore algorithms to investigate alternative splicing implications in MALAT1-dependent breast cancer.
Molecular Cell 2015 1: 105-117
Over a hundred experimental validations for SpliceCore algorithms reveal the regulatory network of the SRSF1 oncogene. The CASC4 gene is predicted and confirmed to be involved in cancer progression.
Bioinformatics 2011 21: 3010–3016
Here we introduce SpliceTrap, a method to quantify exon inclusion levels using paired-end RNA-seq data. Unlike other tools, which focus on full-length transcript isoforms, SpliceTrap approaches the expression-level estimation of each exon as an independent Bayesian inference problem. In addition, SpliceTrap can identify major classes of alternative splicing events under a single cellular condition, without requiring a background set of reads to estimate relative splicing changes. We tested SpliceTrap both by simulation and real data analysis, and compared it to state-of-the-art tools for transcript quantification. SpliceTrap demonstrated improved accuracy, robustness and reliability in quantifying exon-inclusion ratios.