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Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Upstream open reading frames (uORFs), located in 5’ untranslated regions, are regulators of downstream protein translation. Here, Whiffin et al. use the genomes of 15,708 individuals in the Genome Aggregation Database (gnomAD) to systematically assess the deleteriousness of variants creating or disrupting uORFs.

A novel variant annotation metric that quantifies the level of expression of genetic variants across tissues is validated in the Genome Aggregation Database (gnomAD) and is shown to improve rare variant interpretation.

A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.

New approaches to develop antimicrobial agents are urgently needed. In this study, the authors develop a peptide language-based deep generative model to design broad-spectrum antimicrobial peptides against drug-resistant bacteria and validate promising candidates in a wound mouse model.

An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

The authors describe an integrated atlas of the diverse cell types in the mouse primary motor cortex.

Han et al. report that the Hippo pathway kinases LATS1 and LATS2 phosphorylate the heavy metal response transcription factor MTF1, leading to attenuation of heavy metal response gene transcription and cellular detoxification.

VDAC channels permeate metabolites from the mitochondrial intermembrane space to the cytosol. Markov state modeling, an approach used in protein-folding simulations, is now applied to examine ATP-permeation rates and pathways through mouse VDAC1.

Diversity-generating retroelements (DGRs) are genetic elements that introduce sequence variation within target genes in bacteria and their viruses. Here, Paul et al. report the discovery of DGRs in an archaeal virus and in two archaea from marine and terrestrial subsurface environments, respectively.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Scaling neural machine translation to 200 languages is achieved by No Language Left Behind, a single massively multilingual model that leverages transfer learning across languages.

A study demonstrates that metabolic signalling and inflammatory cues associated with obesity selectively induce expression of PD-1 on tumour-associated macrophages to suppress anti-tumour immunity.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

The generation of ultrashort X-ray pulses with a peak power exceeding 100 GW offers new opportunities for studying electron dynamics with nonlinear spectroscopy and single-particle imaging.

The authors report near-atomic resolution structures of the R-type bacteriocin from Pseudomonas aeruginosa in the pre-contraction and post-contraction states, and these structures provide insight into the mechanism of action of molecular syringes.

Although Huntington’s disease (HD) is a well-studied genetic disorder, less is known about the epigenetic changes underlying it. Here, the authors characterize DNA methylation levels in tissues from patients, a mouse huntingtin (Htt) gene knock-in model, and a transgenic HTT sheep model, and provide evidence that HD is accompanied by DNA methylation changes in these three species.

Genome editing in non-human primates with a PCSK9-targeted meganuclease lowers cholesterol levels.

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.

Croker and colleagues show that the phosphatase Ptpn6 functions to suppress neutrophil cell death pathways and IL-1 release, thereby limiting autoinflammatory responses.

The autistic spectrum disorders (ASDs) are highly heritable, yet the underlying genetic determinants remain largely unknown. Here, a genome-wide analysis of rare copy number variants (CNVs) has been carried out, revealing that ASD sufferers carry a higher load of rare, genic CNVs than do controls. Many of these CNVs are de novo and inherited. The results implicate several novel genes in ASDs, and point to the importance of cellular proliferation, projection and motility, as well as specific signalling pathways, in these disorders.

Pineoblastoma is a rare pediatric cancer. Here, the authors present inactivation of Rb plus p53 via a WAP-Cre transgene induces metastatic pineoblastoma resembling human disease, and using this model, predict tricyclic antidepressants as a potential therapy for pineoblastoma, supported by their pre-clinical model.

The Longmen Shan Mountains rise up 6,000 m over a distance of just 100 km, but the mechanisms driving formation of this striking topography are debated. Analyses of crustal movements during the 2008 Wenchuan earthquake suggest that fault-induced uplift plays a role in building the high topography.

While the impetus to develop lithium metal solid-state batteries is clear, identifying a practical manufacturing process is challenging. Herewith, authors study the underlying mechanisms controlling in-situ anode formation that could enable viable lithium-free manufacturing.

DNA methylation contributes to transcriptional silencing. Here, Groth et al.show that mutant plants defective in MTHFD1, an enzyme involved in folate metabolism, have a DNA hypomethylation phenotype highlighting the link between one-carbon metabolism and DNA methylation, which is mediated by SAM as a common methyl donor.

A study of more than one million 23andMe research participants identifies genetic and nongenetic associations with COVID-19 susceptibility and severity.

Our results show that unilateral partial adrenalectomy is not a good surgical option for the majority of lateralized PA patients. In clinically lateralized PA patients, no matter which group they are in the HISTALDO classification, they would benefit from unilateral total adrenalectomy.

Cardiovascular diseases (CVD) are associated with plasma lipid levels. Here, Tabassum et al. perform genome-wide association studies for lipidomic profiles with 141 (non-standard) lipid species which highlights shared genetic loci with CVD and that traditional lipids have low genetic correlation with other lipids.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

An anticancer agent, olsalazine, conjugated to a cell-penetrating peptide has been synthesized and shows the ability to self-assemble intracellularly by the tumour-associated enzyme furin, with the potential for tumour therapy and chemical exchange saturation transfer magnetic resonance imaging in vivo.

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.

Growth of malignant glioma involves a rare population of stem-like cells in the brain called brain tumor-initiating cells (BTICs). This study shows that immune cells in the brain can attenuate tumorigenic capacity of cancer patient-derived BTICs. The authors also identify a drug amphotericin B as an activator of microglia and macrophages that can enhance the microglial activation and mitigate BTIC proliferation in culture. This drug also improved the lifespan of a mouse model of malignant glioma in vivo.

Machine learning tools are used to greatly accelerate chip layout design, by posing chip floorplanning as a reinforcement learning problem and using neural networks to generate high-performance chip layouts.

But the two-day meeting was long on mutual understanding while being notably short on targets.

How genetic variation contributes to brain morphology is still poorly understood. Here Chenet al. combine brain imaging with single-nucleotide polymorphism data to discover that a substantial degree of cortical variation is derived from underlying genetic differences.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

microRNAs are known to be deregulated in cancer. Using a screen for microRNAs that alter cell migration, Zhanget al. show that mir-23b blocks cell migration in vitro and in vivoand is reduced in expression in human colon cancer, suggesting a therapeutic potential for this microRNA.

MiR-122 levels correlate with metastasis in human liver cancer but not in mouse models. Here the authors show that miR-122 targets TGFßR1 in mice but TGFß1 in humans, that swapping this specificity affects metastasis, and that many other receptor-ligand pairs are differentially targeted by miRNAs across species.

A high-resolution gene expression atlas of prenatal and postnatal brain development of rhesus monkey charts global transcriptional dynamics in relation to brain maturation, while comparative analysis reveals human-specific gene trajectories; candidate risk genes associated with human neurodevelopmental disorders tend to be co-expressed in disease-specific patterns in the developing monkey neocortex.