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Discovery of full-length antibodies can be slow and labor intensive. Here, the authors describe a robust genetic assay for facile isolation of IgG antibodies from combinatorial libraries expressed in the cytoplasm of redox-engineered bacteria.

Delaying a second COVID-19 vaccine dose is a common strategy to maximize vaccine coverage, but the immunological effects are unclear. Hall et al. demonstrate that a delayed second dose significantly enhances neutralizing humoral immunity.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

A century after being predicted by theory, the authors detect and quantify the genomic signature of assortative mating in ~400,000 contemporary human genomes, and report new genetic evidence for assortative mating on height and educational attainment.

Moisture-driven environmental changes in the terminal Pleistocene contributed to megafaunal extinction across four continents, as indicated by stable isotope analysis. Stable grasslands in Africa help to explain maintenance of African megafaunal populations.

P-selectin recruits leucocytes to regions of blood vessel damage. Using single molecule imaging, we find newly secreted P-selectin spreads rapidly across the plasma membrane and then becomes immobilized and better-suited to leucocyte capture.

The genes underlying stripe rust host specificity between wheat and barley remain unknown. Here, the authors report that Rps6, Rps7 and Rps8 determine host species specificity in barley at different stages of the pathogen lifecycle and the barley powdery mildew immune receptor Mla8 and Rps7 are the same gene.

The fields of medicine and marketing use large data volumes and computational power to target individuals. This Perspective argues that applied ecologists should draw on such approaches to provide decision-makers with specific, site-level intervention strategies.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

The number and diversity of organisms known to produce the environmentally important sulfur compound dimethylsulfoniopropionate (DMSP) is expanded with the discovery of a family of DMSP synthesis enzymes.

Few genome-wide association studies have explored the genetic architecture of age-of-onset for traits and diseases. Here, the authors develop a Bayesian approach to improve prediction in timing-related phenotypes and perform age-of-onset analyses across complex traits in the UK Biobank.

Focusing on the serial differentiation of the presacral column across 1,136 extant mammal species, the authors find evidence of high within-group variation and an evolutionary trend towards increasing complexity.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

A detailed parcellation (map) of the human cerebral cortex has been obtained by integrating multi-modal imaging data, including functional magnetic resonance imaging (fMRI), and the resulting freely available resources will enable detailed comparative studies of the human brain in health, ageing and disease.

Gasdermin D (GSDMD) is a pore forming protein activated by inflammasome derived caspases. Here the authors characterize the function of GSDMD in mouse influenza virus infection and show that immunopathology is reduced in the absence of GSDMD and involves changes in neutrophil function.

Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.

Motion detection by the retina is thought to rely largely on the biophysics of starburst amacrine cell dendrites; here machine learning is used with gamified crowdsourcing to draw the wiring diagram involving amacrine and bipolar cells to identify a plausible circuit mechanism for direction selectivity; the model suggests similarities between mammalian and insect vision.

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.

Mutations in the Wnt co-receptor, LRP5, lead to skeletal diseases in humans. Matthew Warman and his colleagues have now developed mutant mice with tissue-specific alterations of Lrp5 expression and found that these mice phenocopy the human skeletal diseases. They also found that Lrp5 acts locally to affect bone homeostasis. Their data suggest that increasing LRP5 signaling in mature bone cells may be a strategy to treat osteoporosis.

Polymyxins are last-resort antibiotics targeting lipid A in the gram-negative outer membrane. Here, the authors use surface plasmon resonance-based kinetics to reveal a three-state mechanism governing superstoichiometric accumulation of polymyxins.

Current methods for production of monoclonal antibodies often require refolding steps or secretion across biological membranes. Here, Robinson et al. describe engineered E. colistrains for efficient production of functional immunoglobulin G antibodies in the bacterial cytoplasm.

Global ocean microbiome survey reveals the bacterial family ‘Candidatus Eudoremicrobiaceae’, which includes some of the most biosynthetically diverse microorganisms in the ocean environment.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Sustained drug delivery is critical for patient adherence to chronic disease treatments. Here the authors apply machine learning to engineer multifunctional peptides with high melanin binding, high cell-penetration, and low cytotoxicity, enhancing the duration and efficacy of peptide-drug conjugates for sustained ocular delivery.

Neoantigen prediction from clinical samples is improved using a neural network model trained on a large HLA peptide and genomic tumor dataset.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Health effects of dietary restriction are uncoupled from longevity.

Patient-derived xenograft models (PDX) have been extensively used to study the molecular and clinical features of cancers. Here the authors present a cohort of 536 PDX models from 25 cancers, as well as their genomic and evolutionary profiles and their suitability for clinical trials.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Abrupt changes are developing across Antarctica’s ice, ocean and biological systems; some of these changes are intensifying faster than equivalent Arctic changes, potentially irreversibly, and their interactions are expected to worsen other impacts across the Antarctic environment and global climate system.

GROWdb defines US river microbiomes at the genome level.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

The efficacy of carbapenem antibiotics can be compromised by metallo-β-lactamases, but a high-throughput screen followed by optimization has now enabled the discovery of indole-2-carboxylates (InCs) as potent broad-spectrum metallo-β-lactamase inhibitors. The results highlight the potential of InC–carbapenem combinations for clinical use as well as mechanism-guided approaches to combatting globally disseminated antibiotic resistant mechanisms.

Imaging changes in molecular geometries with sufficient temporal and spatial resolution to image nuclei is a critical challenge in the chemical sciences. Here the authors report gasphase Megaelectronvolt electron diffraction with 100 fs temporal resolution and subAngstrom spatial resolution.

A spectroscopic thermal phase curve of GJ 1214b obtained with the JWST in the mid-infrared is reported and a planet with a high metallicity atmosphere blanketed by thick and reflective clouds or haze is found.

One way of discovering genes with key roles in cancer development is to identify genomic regions that are frequently altered in human cancers. Here, high-resolution analyses of somatic copy-number alterations (SCNAs) in numerous cancer specimens provide an overview of regions of focal SCNA that are altered at significant frequency across several cancer types. An oncogenic function is also found for the anti-apoptosis genes MCL1 and BCL2L1, which reside in amplified genome regions in many cancers.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

Clonal hematopoiesis, which increases with age and is implicated in a variety of age-related diseases, is shown here to be associated with a greater risk of acute kidney injury and worse outcome following injury, as demonstrated using multiple patient cohorts, Mendelian randomization analysis and mechanistic studies in mouse disease models.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Lim and colleagues present the UK PROSECO study where they assess humoral and cellular immune responses to one, two and three doses of vaccination against SARS-CoV-2 in patients with B-cell malignancies in a prospective observational study.

Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as FOXO1, and shows that these variants frequently exhibit convergent evolution.