Articles in 2016

Gad Getz and colleagues analyze mutational patterns in urothelial cancer and find a strong association between mutations in the nucleotide excision repair gene ERCC2 and a distinct mutational signature. They also find that the activity of this signature is associated with smoking, independently of ERCC2 mutational status.

Chris Tyler-Smith, Carlos Bustamante and colleagues report an analysis of 1,244 human Y chromosomes from the 1000 Genomes Project. They find that copy number variants have a higher predicted functional impact than other variant classes and infer bursts of male population expansion corresponding to historical periods of migration and technological innovations.

John Perry, Ken Ong and colleagues perform a genome-wide association study for reproductive ability, behavior and success to determine underlying genetic factors. They find 38 variants associated with age of first sexual intercourse and show that both physical and neurobehavioral traits influence the onset of reproductive activity.

Yu Chen and colleagues describe a new constitutively activating mutation in the G-protein-coupled receptor CYSLTR2 in patients with uveal melanoma lacking mutations in the G-protein-encoding genes GNAQ and GNA11. They find that expression of the mutant leads to increased expression of melanocyte-lineage signature genes and promotes tumorigenesis in vivo.

Zhenglin Yang and colleagues use whole-exome sequencing to identify a rare variant in the FGD6 gene that is associated with the polypoidal choroidal vasculopathy subtype of wet age-related macular degeneration. They show that FGD6 regulates proangiogenic effects together with VEGF and that the mutation results in abnormal retinal vessel development.

Wendy Bickmore, Madapura Pradeepa and colleagues identify a new class of active enhancers marked by histones with modifications on residues in the globular domain. They find that H3K64ac and H3K122ac are markers for active promoters and enhancers in embryonic stem cells and human cancer cell lines.

Daniel Benjamin, Meike Bartels, Philipp Koellinger and colleagues report a genome-wide association meta-analysis of subjective well-being, depressive symptoms and neuroticism. The study leverages a large sample size together with genetic correlations between the phenotypes to identify, with high confidence, loci associated with each phenotype.

Meredith Yeager, Stephen Chanock and colleagues analyze mosaic loss of the Y chromosome in three prospective cohorts and observe association with age and smoking but not with cancer survival. They also identify common variation at TCL1A associated with increased risk of mosaic loss of the Y chromosome.

Hidewaki Nakagawa and colleagues report a comprehensive genome-wide mutational landscape of 300 liver cancers from Japanese individuals. They identify candidate driver mutations, including ones in noncoding regions, and structural mutations affecting the expression of nearby genes.

Douglas Epstein and colleagues use de novo motif analysis to identify sequence motifs and cognate transcription factors for brain enhancers of Shh active in the zona limitans intrathalamica (zli). They find new zli enhancers in mice and a functional equivalent in hemichordates, indicating an ancient origin of these sequence elements.

Alexander Pym, Ashlee Earl and colleagues use the whole-genome sequences from 498 strains of Mycobacterium tuberculosis to identify new genotypes conferring resistance to antitubercular drugs. They find that loss-of-function mutations in ald (Rv2780), encoding L-alanine dehydrogenase, are associated with unexplained drug resistance and demonstrate that these mutations confer resistance to D-cycloserine.

Sean Whalen and colleagues present a computational method, TargetFinder, for reconstructing three-dimensional regulatory landscapes using one-dimensional genomic features. TargetFinder identifies the minimal set of features necessary to predict individual interacting enhancer–promoter pairs and accurately distinguishes them from non-interacting pairs.

Chiea Chuen Khor, Tin Aung and colleagues report the results of a large genome-wide association study of primary angle closure glaucoma. They identify five new susceptibility loci and provide insights into disease pathogenesis.

The FAIR data principles are simple guidelines for ensuring that machines can find and use data, supporting data reuse by individuals. More—and better—research can be generated by designing data and algorithms to be findable, accessible, interoperable and reusable, together with the tools and workflows that led to these data.

A new study compares DNA methylation profiles in developing zebrafish, Xenopus tropicalis and mice and suggests roles for Tet proteins in demethylating conserved gene enhancers during the phylotypic period of early development. These findings provide an epigenetic underpinning for the 'hourglass' model.