GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution.

CanDIG: Federated network across Canada for multi-omic and health data discovery and analysis.

We present the Canadian Distributed Infrastructure for Genomics (CanDIG) platform, which enables federated querying and analysis of human genomics and linked biomedical data. CanDIG leverages the standards and frameworks of the Global Alliance for Genomics and Health (GA4GH) and currently hosts data for five pan-Canadian projects. We describe CanDIG's key design decisions and features as a guide for other federated data systems.

Author Correction: Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.

Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20128-w.

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations.

Detecting DNA cytosine methylation using nanopore sequencing.

In nanopore sequencing devices, electrolytic current signals are sensitive to base modifications, such as 5-methylcytosine (5-mC). Here we quantified the strength of this effect for the Oxford Nanopore Technologies MinION sequencer. By using synthetically methylated DNA, we were able to train a hidden Markov model to distinguish 5-mC from unmethylated cytosine.