Volume 51 Issue 2, February 2019

Contemporary genomics and informatics technologies were used to provide a meaningful and insightful overview of more than 20,000 wild and domesticated barley genotypes from one of the largest crop germplasm collections. The data provide a framework for the rational exploitation of genetic resources in crop improvement, which will be central to addressing global food security.

Analysis of advanced cancer patients treated with immune-checkpoint inhibitors shows that tumor mutational burden, as assessed by targeted next-generation sequencing, predicts survival after immunotherapy across multiple cancer types.

Activating HER2 mutations are shown to confer resistance to ER-directed therapies in patients with ER⁺ metastatic breast cancer. Drug resistance caused by HER2 mutations was overcome by combining ER-directed therapy with a HER2 kinase inhibitor.

GADD45A directly binds to R-loops and mediates local DNA demethylation by recruiting TET1. lncRNA-mediated formation of R-loops at the promoter of the tumor suppressor TCF21 triggers GADD45A binding, demethylation and expression.

The improved genome assemblies of allotetraploid cotton species Gossypium hirsutum and Gossypium barbadense provide insights into cotton evolution and inform the construction of introgression lines used to identify loci associated with fiber quality.

Genome-wide meta-analysis of UK Biobank and arcOGEN (77,052 cases and 378,169 controls) identifies 52 new osteoarthritis risk loci. Integrated eQTL colocalization, fine-mapping, and rare-disease data identify putative effector genes for osteoarthritis.

Association studies of up to 1.2 million individuals identify 566 genetic variants in 406 loci associated with tobacco use and addiction (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci showing pleiotropic association.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Genome-wide association analyses identify 301 new loci influencing bone mineral density and 13 loci influencing fracture risk. Integrative analyses of epigenomic data and mouse knockout phenotypes provide additional insights into osteoporosis pathophysiology.

Genome-wide-association analyses of datasets from Iceland and the UK identify risk variants for nasal polyps and chronic rhinosinusitis. Notably, a loss-of-function missense variant in ALOX15 confers protection against both phenotypes, thus identifying a potential target for therapeutic intervention.

SumHer is a software for estimating SNP heritability from summary statistics using heritability models. Applying SumHer to publicly available results for 24 GWAS provides an improved understanding of the genetic architecture of complex traits.

Relocalization of one X-inactivation center (Xic) to the nuclear lamina does not influence choice between the two Xics at the onset of X-chromosome inactivation. Tethering of both Xics to the nuclear lamina reduces Xic pairing but does not affect monoallelic Xist upregulation.

Analysis of 1,988 cases of B-cell acute lymphoblastic leukemia characterizes 23 subtypes defined by genomic features and shows that two of the subtypes have frequent PAX5 alterations.

Analysis of signatures of hypoxia in more than 8,000 tumors from 19 cancer types identifies hypoxia-driven mutation signatures and dysregulation of microRNAs.

Analysis of genotyping-by-sequencing data for more than 20,000 barley accessions from a German genebank provides a framework for genomics-assisted genebank management and analysis of large germplasm collections for important crops.

Analysis of a health insurance dataset comprising more than 44 million individuals allows for the estimation of genetic and environmental contributions in 560 phenotypes by using twins and sibling pairs.

FitCons2 is a new framework that simultaneously clusters genomic sites by epigenomic features and evaluates the strength of natural selection on these sites. FitCons2 scores are used to generate fitness–consequence maps for 115 human cell types.

GARFIELD is a new approach that classifies genomic features related to phenotypes on the basis of integrating GWAS signals with functional annotations. GARFIELD is used to characterize enrichment patterns for 29 traits integrated with ENCODE and Roadmap Epigenomics annotations.

Graph Genome Pipeline is a read-alignment and variant-calling pipeline based on graph genomes that offers improved read-mapping and variant-calling accuracy while achieving speed comparable to those of linear reference genome pipelines.