In Nature Genetics this week, researchers from Seven Bridges Genomics publish a study demonstrating improved genomic analysis through the use of a graph genome reference. The team developed a computational graph reference genome implementation that enables read alignment across 2,800 diploid genomes encompassing more than 12 million SNPs and about 4 million insertions and deletions. The researchers show that using a graph genome reference improves read mapping sensitivity and produces a 0.5 percent increase in variant calling recall with unaffected specificity, and that iterative augmentation of graph genomes yields incremental gains in variant calling accuracy. This work, they write, represents "an important advance toward fulfilling the promise of graph genomes to radically enhance the scalability and accuracy of genomic analyses."
Also in Nature Genetics, a multi-institute team of investigators publish genome-wide association analyses of risky behavior such as smoking and alcohol use, as well as risk tolerance, in more than 1 million people. The researchers identify hundreds of associated loci, including 99 loci associated with general risk tolerance, and demonstrate substantial shared genetic influences across risk tolerance and risky behavior. They also discover that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues, and find no evidence of enrichment for genes previously hypothesized to relate to risk tolerance. GenomeWeb has more on this study, here.
Finally in Nature Genetics, a Memorial Sloan Kettering Cancer Center-led team presents data suggesting that tumor mutational burden (TMB) may be used to predict clinical response to immune checkpoint inhibitors (ICIs) across multiple cancer types. The researchers analyzed the clinical and genomic data on 1,662 advanced cancer patients treated with ICIs, as well as 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing. They find that for all patients, higher somatic TMB was associated with better overall survival. For most cancer histologies, meanwhile, an association between higher TMB and improved survival was found.