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Here the authors unveil the essential role of MCL-1 for adult hair follicle regeneration and inhibition of proliferation stress-induced apoptosis in mice. They also identify a P53/MCL-1/BAK axis balancing proliferation and death of activated hair follicle stem cells to ensure proper hair growth.

Single-cell RNA-Seq allows us to observe snapshots of how biological systems change over time at cellular resolution. Here, the authors develop a generative framework that uses time-resolved single-cell data to model how cells change in physical time, including in response to perturbations.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Sequencing and de novo assembly of seven wild relatives of soybean yields insights relevant to crop domestication and improvement.

Rhizosphere microbiota can influence plant pathogen interactions. Here the authors use field- and lab-based approaches to show that rhizosphere bacteria and fungi of healthy tomatoes can enhance tomato resistance against Fusarium wilt disease and formulate synthetic microbial communities that could help to control soil-borne disease.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Douglas Easton, Per Hall and colleagues report meta-analyses of genome-wide association studies for breast cancer, including 10,052 cases and 12,575 controls, followed by genotyping using the iCOGS array in an additional 52,675 cases and 49,436 controls from studies within the Breast Cancer Association Consortium (BCAC). They identify 41 loci newly associated with susceptibility to breast cancer.

The Krüppel-like factors Klf4 and Klf5 have wide roles in cell biology including the regulation of pluripotency. In this study, Aksoy et al. demonstrate that Klf4 preferentially blocks the expression of endodermal markers in embryonic stem cells, whereas Klf5 negatively regulates mesodermal factors.

Mathematical modelling of 15 years of data from South Africa reveals the spread and vaccine-driven changes in fitness and antimicrobial resistance of Streptococcus pneumoniae.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

Cytosine base editing is crucial for modeling human diseases in zebrafish. Here, the authors present zevoCDA1 and zevoCDA1-198, optimized editors that improve editing efficiency and precision, allowing zebrafish modeling for disease-related mutations which were previously limited by DNA sequence contexts.

A global multi-taxon extinction risk assessment of freshwater fauna for The IUCN Red List of Threatened Species finds one-quarter of species to be at high risk of extinction.

Trans-ancestry meta-analysis of estimated glomerular filtration rate (eGFR) from 1,046,070 individuals identifies 264 associated loci, providing a resource of molecular targets for translational research of chronic kidney disease.

Anderson and colleagues report that the kinesin-4 family member Kif7 binds to microtubule plus ends at cilium tips to regulate their length and structure, and to ensure the fidelity of Hedgehog signalling.

An explainable deep-learning system prospectively predicts clinical scores for breast cancer risk from multimodal breast-ultrasound images as accurately as experienced radiologists.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Grasslands tend to be limited by both nutrient and water availability. Here the authors use standardized field experiments to show that the effects of nutrient addition on grassland biomass may cancel out the negative impact of drought, but the outcome depends on aridity and other local conditions.

Mental stress is well known to cause cardiovascular disease. Here, the authors show that an imbalance in RBM24-S181 phosphorylation impairs cardiac translation of APOE, leading to cardiac contractile dysfunction, atrial fibrillation, fibrosis, and sudden death under psychological stress.

Iminium-catalysed cycloaddition is a prominent example of organocatalytic reactivity, yet a biological counterpart has not been identified. Now, the authors report biochemical, structural and computational evidence for iminium catalysis by the natural Diels–Alderase SdnG.

Chiea Chuen Khor, Tin Aung, Francesca Pasutto, Janey Wiggs and colleagues report a global genome-wide association study of exfoliation syndrome and a fine-mapping analysis of a previously identified disease-associated locus, LOXL1. They identify a rare protective variant in LOXL1 exclusive to the Japanese population and five new common variant susceptibility loci.

Analysis of ground-sourced and satellite-derived models reveals a global forest carbon potential of 226 Gt outside agricultural and urban lands, with a difference of only 12% across these modelling approaches.

The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

The spatial single-cell multiomic atlas of the first trimester human placenta at molecular resolution provides a blueprint for future studies on early placental development and pregnancy.

The anti-leprosy drug clofazimine inhibits coronavirus replication in several cell models and shows potent antiviral activity against SARS-CoV-2 infection in a hamster model, particularly when used in combination with remdesivir.

The second order nonlinear Hall effect leads to a direct voltage generated from the rectification effect. While this rectification property is appeal for use in devices, most materials exhibiting a second order nonlinear hall effect are constrained to low temperatures. Here, Lu et al demonstrate a second order nonlinear transport behaviour that persists above room temperature in BiTeBr, and construct a prototype rectifier based on this effect.

Federated learning, a method for training artificial intelligence algorithms that protects data privacy, was used to predict future oxygen requirements of symptomatic patients with COVID-19 using data from 20 different institutes across the globe.

Tissue nanotransfection (TNT) achieves non-viral vasculogenic reprogramming of the skin. Here the authors show that upregulation of TET1/2/3, limited under diabetic conditions, is effective in markedly improving TNT-induced vasculogenic outcomes thus rescuing ischemic diabetic tissue at risk.

A correlative AFM–fluorescence approach elucidates how epigenetic control of chromatin organization contributes to nuclear stiffness and its dysregulation in Rett syndrome.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Tailored to provide diabetes management recommendations from large training and validation datasets, an artificial intelligence system integrating language and computer vision capabilities is shown to improve self-management of patients in a prospective implementation study.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.