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A retrievable, porous and anti-fibrotic macrodevice for the encapsulation of cells provides long-term protection to human cells expressing therapeutic proteins after device implantation in the intraperitoneal space of immunocompetent mice.

A method in which pooled barcoded human cancer cell lines are injected into a mouse xenograft model enables simultaneous mapping of the metastatic potential of multiple cell lines, and shows that breast cancer cells that metastasize to the brain have altered lipid metabolism.

The mechanisms associated with Caveolin-1 (Cav-1) mediated metabolic changes in prostate cancer are unclear. Here, the authors show that Cav-1 promotes rewiring of cancer cell lipid metabolism towards a program of exogenous lipid scavenging and vesicle biogenesis that intersects with mitochondrial dynamics in prostate tumors.

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Martin Tobin and colleagues report a meta-analysis of 23 genome-wide association studies for pulmonary function. They identify 16 loci newly associated with variation in two cross-sectional measures of lung function, used to define airway obstruction and to grade the severity of obstruction.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease. Here, Wray and colleagues identify association of the GPX3-TNIP1 locus with ALS using cross-ethnic meta-analyses.

Alternative expression analysis by sequencing (ALEXA-seq) aligns RNA-seq reads from different cell types to a database of alternative expression sequence features and quantifies isoforms that are differentially expressed between samples.

Two high-quality genomes of petunia wild parents reveal two rounds of hexaploidization in the evolution of Petunia lineage and provide insights into the diversity of floral patterns and pollination systems — enhancing the model value of this genus.

The enzyme argininosuccinate lyase (ASL) generates the amino acid arginine, the precursor to both urea and nitric oxide. However, arginine supplementation is not sufficient to correct all of the symptoms of individuals with a congenital deficiency of this enzyme. Ayelet Erez et al. explain this paradox by showing that ASL has a role in nitric oxide synthesis that is independent of its catalytic activity and provide evidence that therapy with agents boosting nitric oxide levels might be beneficial in ASL-deficient individuals.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

Maha Farhat, Megan Murray and colleagues report whole-genome sequencing of 116 Mycobacterium tuberculosis strains selected to be representative of both global diversity and drug resistance. The authors develop a new method to search for resistance markers in microbial genomes based on reconstructing a genome-wide phylogeny and identifying regions showing convergent evolution, and they use this method to identify 39 new candidate drug resistance regions in the M. tuberculosis genome.

Sequencing of over 600 genes in a large collection of lung adenocarcinoma samples provides an overview of somatic mutations and signalling pathways altered in cancer genes in this tumour type.

The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

Anterior Uveitis is a common inflammatory eye disease that can result in vision loss. Here, the authors perform GWAS and whole-exome analyses of Anterior Uveitis to identify the underlying genetics of HLA-B*27 positive and negative forms of the disease.

Simon Gayther and colleagues report 3 new risk variants for mucinous ovarian carcinoma (MOC) on the basis of an analysis of 1,644 MOC cases and 21,693 controls. They confirm an eQTL association between the HOXD9 promoter and risk SNPs at 2q31.1 using chromosome conformation capture analysis and show that HOXD9 overexpression associates with neoplastic transformation.

Montserrat Garcia-Closas and colleagues report a meta-analysis of three genome-wide association studies for estrogen receptor (ER)-negative breast cancer, including 4,193 ER-negative breast cancer cases and 35,194 controls, with replication using the iCOGS custom genotyping array in 40 studies, including 6,514 cases and 41,455 controls. They identify four loci associated with ER-negative but not ER-positive breast cancer.

An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits.

Stroke is a multifactorial disease influenced by genetic and environmental factors. Here, the authors apply exome-wide association analysis to find rare coding variants associated with stroke in a Pakistani cohort, finding a significant association of a variant in NOTCH3 that is highly enriched in South Asians.

Marine systems around the world are increasingly affected by climate change. This Perspective describes emerging US initiatives aimed at enhancing ocean resilience to climate change. Ocean management issues that would benefit from more systematic consideration of climate information are identified, along with opportunities for advancing partnerships between scientists, policy makers and society to address ocean and climate issues.

The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies.

Samples of different body regions from hundreds of human donors are used to study how genetic variation influences gene expression levels in 44 disease-relevant tissues.

LKB1 tumour suppressor gene is frequently mutated in lung adenocarcinoma. Here the authors show that in genetically engineered mouse models of lung cancer Lkb1 restoration induces growth arrest and drives neoplastic cells toward a more differentiated and less proliferative alveolar type II cell-like state via C/EBP-mediated reprogramming.

During autophagy, phagophores elongate to form double-membrane vesicles but the mechanism behind their closure is unknown. Here, the authors develop an autophagy assay and find a role for the endosomal sorting complexes required for transport component CHMP2A as a phagophore closure regulator.

Supervised machine-learning models trained using Drosophila epigenetic and STARR-seq data can be transferred to predict mouse and human enhancers.

The transcription factor TOX is a central regulator of the transcriptional and epigenetic development of exhausted T cells.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Targeted sequencing of perturbation effects offers a sensitive approach to capture genes of interest in CRISPR-mediated screens, enabling genome-scale screens at higher scale and lower cost than whole-transcriptome Perturb-seq.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

This work repurposes the Type I-C Cascade–Cas3 system from Pseudomonas aeruginosa to achieve large deletions in bacterial genomes.

Whole-exome sequencing is not sensitive or specific enough to replace the gold standard of tandem mass spectrometry screening of rare inborn errors of metabolism, but can help to reduce false positives and facilitate the timely resolution of ambiguous cases.

It has been unclear at which stage of mouse development embryonic stem cells can be derived. Nichols and colleagues use single-cell cultures to demonstrate that derivation of cells able to proliferate without ERK signalling (a characteristic of ESCs) is limited to the early pre-implantation epiblast and is favoured by culture on a laminin substrate.

The accumulation of senescent cells is thought to contribute to the age-associated decline in tissue function. Here, the authors identify HSP90 inhibitors as a new class of senolytic compounds in an in vitro screening and show that administration of a HSP90 inhibitor reduces age-related symptoms in progeroid mice.

Although numerous studies have demonstrated anti-atherosclerotic effects of high-density lipoprotein (HDL), drugs that elevate HDL cholesterol levels have failed in the clinic. Stanley Hazen and colleagues provide a potential explanation for this paradox by showing that within human atherosclerotic plaques and plasma of individuals with coronary artery disease, apoA1—the major apolipoprotein present in HDL—is modified by oxidation of a specific tryptophan residue, impairing the anti-atherosclerotic function of apoA1 and HDL.

Ten-eleven translocation 1 (TET1) is a critical oncoprotein in AML. Here, the authors identify 2 compounds that target the binding of STAT3/5 specifically to the TET1 promoter, inhibiting its expression and AML cell viability.

The long-noted association of red meat with an increased risk of cardiovascular disease may be due to ingestion of a specific compound found in red meat, l-carnitine. The ability of this compound to promote atherosclerosis in mice requires that it be further metabolized by the gut microbiota. In humans, omnivores but not vegans or vegetarians metabolize l-carnitine in this manner, a difference which may be explained by effects of diet on the presence of specific types of bacteria in the gut.

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.