Research articles

The authors perform meta-analysis of GWAS studies for asthma from multiancestral cohorts. They identify five new loci and find that the asthma-associated loci are enriched near enhancer marks in immune cells.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

Ron Wevers and colleagues report that mutations in the methanethiol oxidase gene SELENBP1 cause chronic extraoral halitosis. They find that enzyme deficiency leads to increased levels of methanethiol and dimethylsulfide in the breath and that knockout mice have similar biochemical phenotypes.

Analysis of 329,000 individuals in the UK Biobank identifies 116 loci associated with neuroticism. Genes implicated are enriched in neuronal differentiation pathways, and genetic correlations between neuroticism and other mental health traits are elucidated.

Rare cells resembling the 2-cell-stage embryo (2 C) arise in embryonic stem cell cultures. By performing single-cell analyses and an siRNA screen, the authors identify the intermediate cellular states and epigenetic regulators that underpin the transition to a 2C-like state.

A reference-quality genome assembly of a Drosophila melanogaster strain allows for accurate mapping of structural variants through comparative analysis with the existing Drosophila genome. Previously hidden structural variation alters a larger fraction of the genome than SNPs and often affects candidate genes underlying complex traits.

An analysis of single-cell DNA methylome sequencing data from human preimplantation embryos finds evidence for de novo methylation. Methylation reprogramming at this stage is a balance between global demethylation, which is faster in the paternal genome, and focused remethylation.

Comparative genomic analysis of 3,837 bacterial genomes, including new sequences from 484 root-associated isolates, identifies plant-associated gene clusters and plant-mimicking domains.

RNA-directed DNA methylation (RdDM) in the Arabidopsis thaliana male sexual lineage is shown here to regulate gene expression in meiocytes. Loss of sexual-lineage-specific RdDM causes mis-splicing of the MPS1 gene, thereby disrupting meiosis

The authors conduct mass spectrometry experiments identifying H3K4me1-associated proteins, including members of the BAF chromatin-remodeling complex. They show that H3K4me1 augments association of the BAF complex with enhancers in vivo and that H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex in vitro.

LeafCutter is a new tool that identifies variable intron splicing events from RNA-seq data for analysis of complex alternative splicing. The method does not require transcript annotation and can be used to map splicing quantitative trait loci.

This study identifies regulatory variants in sensory neurons derived from induced pluripotent stem cells. Despite differentiation-induced variability, an allele-specific method allowed detection of loci influencing gene expression, chromatin accessibility and RNA splicing.

Transcriptome, DNA methylome and Hi-C profiling of peri- and post-implantation mouse cell lineages identified allele- and lineage-specific methylation patterns. Global demethylation and remethylation correlate with megabase chromatin compartments.

TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) exhibit bivalent promoter hypermethylation without a corresponding decrease in gene expression in the undifferentiated state. However, PAX6 promoter hypermethylation in TKO hESCs impairs neural differentiation.

This study uses human astrocytes and glioma tumorspheres to generate an atlas of mutant-IDH1-induced epigenomic reprogramming. The findings have implications for understanding mutant IDH function and for optimizing approaches to target IDH-mutant tumors.

This study presents a probabilistic framework for inferring negative and positive selection in human cancers that addresses the problem of mutation rate variation. Applying the model to sequencing data from 17 cancer types identifies new significantly mutated genes and detects significant signals of negative selection in many cancer types.

Analysis of a large cohort of EGFR-mutant lung cancer cell-free DNA samples along with longitudinal samples from a patient with EGFR-mutant lung cancer identifies pathways that inhibit EGFR-inhibitor response. Co-occurring genetic alterations influence clinical outcomes and underscore the need for combination therapies.

RNA Capture Long Seq (CLS) is a new method for transcript annotation that combines targeted RNA capture with long-read sequencing. CLS reannotates GENCODE lncRNAs and increases the number of validated splice junctions and transcript models for targeted loci.

This analysis of cancer sequencing data identifies a reduced somatic mutation rate in exons and shows that this phenomenon is due to higher mismatch-repair activity in exons as compared to introns. These findings have implications for the understanding of mutational and DNA repair processes and for studying the evolution of both tumors and species.

Nelson Freimer and colleagues analyze gene expression data from multiple tissue samples combined with genotype data from vervet monkeys to catalog expression quantitative trait loci (eQTLs). They generate a transcriptome resource analogous to the GTEx project and perform comparative and eQTL enrichment analyses for various traits.