Characterization of drug-induced splicing complexity in prostate cancer cell line using long read technology.

We characterize the transcriptional splicing landscape of a prostate cancer cell line treated with a previously identified synergistic drug combination. We use a combination of third generation long-read RNA sequencing technology and short-read RNAseq to create a high-fidelity map of expressed isoforms and fusions to quantify splicing events triggered by treatment. We find strong evidence for drug-induced, coherent splicing changes which disrupt the function of oncogenic proteins, and detect novel transcripts arising from previously unreported fusion events.