Abstract
Alternative splicing (AS) is a key post-transcriptional modification that helps in increasing protein diversity. Almost 90% of the protein-coding genes in humans are known to undergo AS and code for different transcripts. Some transcripts are associated with diseases such as breast cancer, lung cancer and glioblastoma. Hence, these transcripts can serve as novel therapeutic and prognostic targets for drug discovery. Herein, we have developed a pipeline, Finding Alternative Splicing Events (FASE), as the R package that includes modules to determine the structure and concentration of transcripts using differential AS. To predict the correct structure of expressed transcripts in given conditions, FASE combines the AS events with the information of exons, introns and junctions using graph theory. The estimated concentration of predicted transcripts is reported as the relative expression in terms of log2CPM. Using FASE, we were able to identify several unique transcripts of EMILIN1 and SLK genes in the TCGA-BRCA data, which were validated using RT-PCR. The experimental study demonstrated consistent results, which signify the high accuracy and precision of the developed methods. In conclusion, the developed pipeline, FASE, can efficiently predict novel transcripts that are missed in general transcript-level differential expression analysis. It can be applied selectively from a single gene to simple or complex genome even in multiple experimental conditions for the identification of differential AS-based biomarkers, prognostic targets and novel therapeutics.
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