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Zinc finger nucleases (ZFNs) are versatile tools for making precise modifications to genomes, and their use is now established in a range of model systems. ZFNs are also showing potential in human gene therapy, and several clinical trials are underway.

A new study assesses the impact of recent US Supreme Court rulings on the changing landscape of US patents claiming nucleic acids.

The Microarray Quality Control consortium pitted 36 teams against each other to evaluate methods for creating genomic classifiers, computational tools for interpreting gene expression profiles. The performance of the classifiers on blinded validation data—and metadata on the analytic methods—reveal the challenges facing the field.

Epilepsies are common brain disorders and are classified based on clinical phenotyping, imaging and genetics. Here, the authors perform genome-wide association studies for 3 broad and 7 subtypes of epilepsy and identify 16 loci - 11 novel - that are further annotated by eQTL and partitioned heritability analyses.

Neuromodulation and brain–computer interfaces are rapidly evolving fields with distinct origins but with the shared goal of improving the lives of people with neurological and psychiatric disorders or injuries. Their increasing technological overlap provides new opportunities for collaborative work and rapid progress in neurotechnology.

Light-driven electron transfer (ET) in bacterial photosynthetic reaction centers proceeds in a transmembrane protein complex with two symmetric pathways of cofactors – the A pathway operational, while the B pathway is effectively inoperative – leaving efficient activation of the B pathway a challenge. Here, the authors redesign the non-functional B branch in the Cereibacter sphaeroides photosynthetic reaction center, enhancing long-range ET by incorporating tryptophan residues at strategic positions between cofactors, achieving variants with impressive transmembrane charge separation yields due to the increased competency of secondary ET (up to 95%).

BET inhibitors that target bromodomain chromatin readers such as BRD4 are being explored as potential therapeutics in cancer; here, in a MLL–AF9 mouse leukaemia model, resistance to BET inhibitors is shown to emerge from leukaemia stem cells, and be partly due to increased Wnt/β-catenin signalling.

This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation. These loci are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Gregory Kimmel et al. model the population dynamics of public goods games in which interactions occur within local neighborhoods but density dependence is global. They find that neighborhood size drives changes between different evolutionary dynamics and apply their model to dynamics observed in cell populations.

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.

GWAS have so far identified 129 loci associated with type 2 diabetes (T2D). Here, the authors meta-analyse three large T2D GWA studies which uncovers 42 additional loci, further prioritize 33 functional genes using eQTL and mQTL data and propose regulatory mechanisms for three putative T2D genes.

Designing and mining a eukaryotic genomics resource.

Bin Tean Teh and colleagues report the genomic characterization of 100 breast fibroepithelial tumors, including benign fibroadenomas and benign, borderline and malignant phyllodes tumors. They identify mutations specific to phyllodes tumors and find somatic mutation patterns that distinguish borderline and malignant phyllodes tumors from the other tumor types.

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.

Hockemeyer et al. demonstrate targeted genetic modification of three genes in human embryonic stem cells and induced pluripotent stem cells using zinc-finger nucleases delivered on plasmids. They use the approach to generate a reporter cell line that monitors the pluripotent state, a drug-inducible overexpression system, and a reporter cell line for a gene that is not expressed in pluripotent stem cells.

Targeted genetic correction of hematopoietic stem cells is applied to X-linked chronic granulomatous disease.

Antibodies elicited by vaccination with influenza vaccine produced in eggs bind more strongly to the egg-adapted vaccine strain than to wild-type circulating strains.

The tuberculosis pandemic requires new methods for diagnosing and containing infections prior to active disease. Here, the authors performed a multi-site observational study within sub-Saharan Africa and present serum and plasma metabolic signatures that can predict the onset of active TB with a high degree of sensitivity and specificity.

Solveig Gretarsdottir, Kari Stefansson and colleagues report a genome-wide association study for abdominal aortic aneurysm. They identified a variant located within the DAB2IP gene on 9q33 associated with risk of developing abdominal aortic aneurysm.

Gerard Schellenberg and colleagues report a genome-wide association study of late-onset Alzheimer's disease (LOAD), as part of the Alzheimer Disease Genetics Consortium. They identify common variants in MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 associated with LOAD.

Genome editing mediated by zinc finger nucleases can be used to generate fluorescently labelled proteins that are expressed at endogenous levels from their native genetic loci. Applying this technology to the clathrin light chain A and dynamin-2 loci reveals that clathrin-mediated endocytosis is more regular and efficient than previously thought.

High concentrations of some types of plasma lipoproteins, such as low-density lipoprotein, promote atherosclerosis and a wide range of vascular-related diseases. These pathogenic lipoproteins have in common the protein component apolipoprotein B. Through study of the effects of modulating lipoprotein levels in experiments involving zebrafish, mice and cultured human endothelial cells, Inbal Avraham-Davidi et al. uncover a potentially deleterious role of apolipoprotein B–containing lipoproteins as direct inhibitors of the angiogenic behavior of vascular endothelial cells.

The Tuberculosis Drug Accelerator, an experiment designed to facilitate collaboration in tuberculosis drug discovery by breaking down barriers among competing labs and institutions, has reached a 10-year landmark. We review the consortium’s achievements, advantages and limitations and advocate for the application of similar models to other diseases.

Coupling the specificity of CRISPR-Cas nucleases and bacteriophage delivery enables exquisitely precise bacterial killing.

The authors employ targeted next-generation sequencing to identify driving oncogenic alterations in patients with lung cancer with no known oncogenes. They discover two gene fusions involving NTRK1 that lead to constitutive activation of the kinase TRKA and can drive transformation. The fusions can be targeted with available kinase inhibitors and may represent therapeutic targets.

Daniel Gudbjartsson and colleagues report results of a genome-wide association study for loci influencing eosinophil counts. Follow-up studies showed that a subset of the variants identified in this screen were associated with risk of asthma or myocardial infarction.

Genetic engineering in plants remains laborious and time consuming, with no precise genetic engineering methods comparable to those available in animal models. A new approach that relies on the use of designed zinc-finger nucleases is showcased here in maize, inducing herbicide tolerance that is stably inherited.

Detailed clinical and virologic characteristics of the first 12 individuals with COVID-19 in the United States from the US Centers for Disease Control and Prevention.

The metagenome of uncultured, Pacific Ocean viruses linked to a ubiquitous cyanobacteria is characterized using viral-tagging, revealing discrete populations in viral sequence space that includes previously cultivated populations and new populations missed in isolate-based studies.

Competition from the New World, a changing climate and technological advances have threatened the Burgundian notion that the quality of wine depends on regional geography and culture. Only flexibility can keep the concept of terroir alive.

Whole-exome sequencing (WES) has emerged as a transformative technology for biological discovery, but technical difficulties have so far prevented its widespread clinical use. Here, Eliezer Van Allen and colleagues are able to perform production-scale WES on small amounts of clinically acquired formalin-fixed, paraffin-embedded tumor tissues. Using a newly created WES clinical interpretation algorithm, they apply the complete clinical WES framework prospectively to patients and demonstrate how it can be used to directly affect patient care.