Ouellette, B. F. F. | bioRxiv Science

bioRxiv2017

Pan-cancer study of heterogeneous RNA aberrations

We present the most comprehensive catalogue of cancer-associated gene alterations through characterization of tumor transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes project. Using matched whole-genome sequencing data, we attributed RNA alterations to germline and somatic DNA alterations, revealing likely genetic mechanisms. We identified 444 associations of gene expression with somatic non-coding single-nucleotide variants. We found 1,872 splicing alterations associated with somatic mutation in intronic regions, including novel exonization events associated with Alu elements. Somatic copy number alterations were the major driver of total gene and allele-specific expression (ASE) variation. Additionally, 82% of gene fusions had structural variant support, including 75 of a novel class called \"bridged\" fusions, in which a third genomic location bridged two different genes. Globally, we observe transcriptomic alteration signatures that differ between cancer types and have associations with DNA mutational signatures. Given this unique dataset of RNA alterations, we also identified 1,012 genes significantly altered through both DNA and RNA mechanisms. Our study represents an extensive catalog of RNA alterations and reveals new insights into the heterogeneous molecular mechanisms of cancer gene alterations.

genomics↗

bioRxiv2017

A global perspective on bioinformatics training needs

In the last decade, life-science research has become increasingly data-intensive and computational. Nevertheless, basic bioinformatics and data stewardship are still only rarely taught in life-science degree programmes, creating a widening skills gap that spans educational levels and career roles. To better understand this situation, we ran surveys to determine how the skills dearth is affecting the need for bioinformatics training worldwide. Perhaps unsurprisingly, we found that respondents wanted more short courses to help boost their expertise and confidence in data analysis and interpretation. However, it was evident that most respondents appreciated their need for training only after designing their experiments and collecting their data. This is clearly rather late in the research workflow, and suboptimal from a training perspective, as skills acquired to address a specific need at a particular time are seldom retained, engendering a cycle of low confidence in trainees. To ensure that such skill gaps do not continue to create barriers to the progress of research, we argue that universities should strive to bring their life-science curricula into the digital-data era. Meanwhile, the demand for point-of-need training in bioinformatics and data stewardship will grow. While this situation persists, international groups like GOBLET are increasing their efforts to enlarge the community of trainers and quench the global thirst for bioinformatics training.

scientific communication and education↗