SURFR: genome-free discovery of cancer-unique small RNAs from cohort sequencing data

Small RNAs play numerous roles in cancer biology and function as biomarkers and therapeutic targets. A recently discovered class of small RNAs - the orphan non-coding RNAs (oncRNAs) - are uniquely present in cancer and absent from healthy tissues. Here, we developed a reference-free computational approach that is independent from the human genome and applied it on cohort sequencing data from five cancer types to discover 1211 novel oncRNAs. Most of these new sequences do not map perfectly to the human genome, and hundreds correlate with patient outcomes. Our new oncRNAs include the first bona fide cancer-unique microRNA; oncRNAs predictive of patient survival and a small RNA that is expressed from an evolutionarily ancestral part of the genome that has been lost in most human individuals. In summary, we provide our reference-free computational approach and more than thousand new cancer-unique RNAs as resources to the community.