Search

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.

Whole-genome sequencing of medulloblastoma samples reveals several recurrent mutations in genes not previously implicated in the disease, many of which affect components of the epigenetic machinery in different disease subgroups.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.

Nitrite tends to peak at the base of the sunlit zone in the ocean, but the ecological drivers of the local and global distributions of nitrite are not known. Here, Zakem et al. use a marine ecosystem model to show how the interactions of nitrifying microbes mediate nitrite accumulation.

Using whole-genome data for single-nucleotide polymorphism and results from genome-wide association studies, the authors show that people’s preference for pairing with those with similar phenotypic traits has genetic causes and consequences.

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.

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.

The widespread occurrence of young grabens associated with larger compressional structures on Mercury’s surface suggests contractional tectonism has continued on the planet into geologically recent times.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

The differential effects of targeting individual domains of multidomain enzymatic proteins are generally poorly understood. Here, the authors demonstrate lineage-specific sensitivities to domain-specific inhibition of EP300/CBP proteins across cancer and link these effects in group 3 medulloblastoma to control of a transcriptional dependency network.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

Human complex traits and disorders often show differentiation among populations. Here, the authors analyze SNPs associated with 10 complex traits using data of large sample size from African, East Asian and European populations, and find significant genetic differentiation among global populations shaped by natural selection.

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.

The components of the tumour microenvironment contribute to prostate cancer initiation and progression. Here the authors perform single-cell RNA sequencing and spatial transcriptomics analysis of prostate cancer stroma from mouse models at different stages of the disease and develop a gene signature to predict distant metastasis in patients.

Gene discovery and polygenic predictions from a genome-wide association study of educational attainment in 1.1 million individuals.

To facilitate the conversion of maize into biofuels, Shen et al. equip the plant with a thermoregulated intein-modified xylanase that does not compromise yield and allows cell-wall degradation at high temperatures.

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.

Predicted sea-level rise is widely anticipated to lead to increased coastal erosion, however, assessing how rocky coasts will respond to changes in marine conditions is difficult to constrain. Here, the authors find that a North Yorkshire rocky cliff has been eroding at a similar rate over the last 7 kyr, and they do not observe an increase in erosion rates in response to modern sea level rise.

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

A deep generative model using radar observations is used to create skilful precipitation predictions that are accurate and support real-world utility.

Yellow rain, purported to be an agent of toxin warfare in South-East Asia, contains a high percentage of pollen. Analysis of this pollen in yellow rain samples suggests that they are the faeces of honey bees.

Matthew Robinson, Peter Visscher and colleagues use phenotypic data on 172,000 sibling pairs and phenotypic and SNP data on 150,832 unrelated individuals to estimate the heritability of body mass index across a range of experimental designs. They conclude that substantially larger sample sizes across ages and lifestyle factors will be required to understand the full genetic architecture of this trait.

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.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Somatic mutations obtained from laser microdissected biopsies of human tissues are used to reconstruct the developmental phylogenies of these tissues back to the zygote.

Incorporating functional information has shown promise for improving polygenic risk prediction of complex traits. Here, the authors describe polygenic prediction method LDpred-funct, and demonstrate its utility across 21 heritable traits in the UK Biobank.

A longitudinal analysis of viral expansion and clearance rates in 60 individuals sampled daily during acute infection reveals high inter-individual variation in infectious virus shedding, which may contribute to superspreading.

Several animals and plants get their often spectacular colouration and iridescence from structural colouration. Here, Hsiung et al. show the 3-dimensional nanostructures that produce the rainbow colours on the abdomen of miniature peacock spiders.

Haplotype information inferred by phasing is useful in genetic and genomic analysis. Here, the authors develop SHAPEIT4, a phasing method that exhibits sub-linear running time, provides accurate haplotypes and enables integration of external phasing information.

Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.

Low read depth sequencing of whole genomes and high read depth exomes of nearly 10,000 extensively phenotyped individuals are combined to help characterize novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with lipid-related traits; in addition to describing population structure and providing functional annotation of rare and low-frequency variants the authors use the data to estimate the benefits of sequencing for association studies.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

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.

Senescent cells accumulate with age and contribute to the functional decline of many tissues; however, their role in skeletal muscle is not well understood. Here the authors comprehensively assess cellular senescence in skeletal muscle of young and old mice and detail senescence features in subpopulations of p16⁺ fibroadipogenic progenitors and p21⁺ myofibers.

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

High-quality genome assemblies of four Solanum Americanum accessions lead to the identification of three NLR-encoding genes, Rpi-amr4, R02860 and R04373, that recognize potato late blight pathogen Phytophthora infestans effectors.

Colorectal cancer cells can acquire resistance to MEK inhibition due to BRAF or KRAS amplification. Here, the authors show that while MEK inhibitor withdrawal in BRAF mutant cells restores sensitivity to the inhibitor through the loss of BRAF amplification mediated by a p57-dependent mechanism, drug withdrawal from KRAS mutant cells does not restore sensitivity but results in EMT and chemoresistance.

Matthew Horton introduces pymatgen, a free and open source code that can be used for materials screenings.

Matthew Brown and colleagues identify multiple susceptibility variants for ankylosing spondylitis through an association study based on high-density genotyping of immune-related loci. Their findings implicate numerous biological pathways in the pathogenesis of this disease and highlight shared risk factors with other autoimmune diseases.

Genetic methods are useful to test whether risk factors are causal for or consequence of disease. Here, Zhu et al. develop a generalized summary-based Mendelian Randomization (GSMR) method which uses summary-level data from GWAS to test for causal associations of health risk factors with common diseases.

Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.

Surveying next generation sequencing capabilities in 13 Asian countries identifies challenges to be met for improved implementation, pathogen surveillance and integration into public health decision-making.

Diamond quantum magnetometry is utilized to directly read the vorticity of antiferromagnetic spin textures through coupled multi-polar emergent magnetic charge distributions.