Supporting data for "TranscriptAchilles: a genome-wide platform to predict isoform biomarkers of gene essentiality in cancer"

Résumé

Aberrant alternative splicing (AS) plays a key role in cancer development. In recent years, AS is being used as a prognosis biomarker, a therapy response biomarker and even as a therapeutic target. Next generation RNA sequencing has an unprecedented potential to measure the transcriptome. However, due to the complexity of dealing with isoforms, the scientific community has not sufficiently exploited this valuable resource in precision medicine. We present TranscriptAchilles, the first large-scale tool to predict transcript biomarkers associated with gene essentiality in cancer. This application integrates 412 loss-of-function RNA interference screens of over 17,000 genes together with their corresponding whole-transcriptome expression profiling. Using this tool, we have studied which are the cancer subtypes for which alternative splicing plays a significant role to state gene essentiality. In addition, we include a case study of renal cell carcinoma that shows the biological soundness of the results. TranscriptAchilles provides a user-friendly web interface to identify transcript or gene biomarkers of gene essentiality, which could be used as a starting point for a drug development project. This approach opens a wide range of translational applications in cancer.