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A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

The authors present MorphoGenie, an unsupervised model that profiles cell shapes to predict cellular heterogeneity without manual labels. It provides a scalable, interpretable, and generalizable approach for data-driven exploration of cellular heterogeneity across diverse imaging modalities.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

HIV infection and substance use disorders converge in human midbrain. Here, authors show transcriptional impacts using single-nucleus RNA sequencing, linking dopaminergic vulnerability and microglial dysregulation, and in viremia, GABAergic deficits.

Transcription factor osr2 is identified as a specific marker and regulator of mural lymphatic endothelial cell (muLEC) differentiation and maintenance, and muLECs and border-associated macrophages share functional analogies but are not homologous, providing an example of convergent evolution.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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.

This analysis of individuals of admixed genetic ancestries suggests that complex trait causal variant effect sizes are, by and large, similar across ancestries, and discusses the implications for the study of these and other diverse populations.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

By combining modelling and simulated data with empirical data from 76 grassland sites across 6 continents, the authors show that the relative abundance of dominant species predicts species richness, while their absolute abundance predicts community biomass.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

A plate-based assay called CRAFTseq has been developed that uses ‘multi-omic’ single-cell RNA sequencing and direct genotyping of CRISPR edits to test the functional effects of genetic variants on cell state and function.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Histopathology can be limited by the time-consuming and labour-intensive preparation of slides from resected tissue. Here, the authors report DeepDOF-SE, a deep-learning-enabled microscope to rapidly scan intact tissue at cellular resolution without the need for physical sectioning.

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.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The antisense oligonucleotide rugonersen has acceptable safety and tolerability in children with Angelman syndrome and shows partial normalization of electroencephalogram abnormalities and clinical improvements relative to natural history.

The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Cytoskeletal remodeling is known to facilitate mitophagy, but the mechanism is not fully understood. Here, the authors show that damaged mitochondria recruit a RhoA GTPase activating protein that promotes their capture and encasement by autophagosomes.

Stress granules are non-membranous organelles connected to stress responses and age-related disease. Here, the authors identify a conserved yeast protein, Lsm7, that facilitates stress granule formation through dynamic liquid-liquid phase separation condensates upon 2-deoxy-D-glucose-induced stress.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Sea otters recolonizing an estuary in California indirectly reduce erosion by reducing burrowing crab abundance, suggesting that restoring predators could be a key mechanism to improve the stability of coastal wetlands and other ecosystems.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

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.

Multivariate genome-wide association analyses of the latent genetic architecture of frailty identify one general factor of genetic overlap across all frailty deficits and six factors indexing a shared genetic signal across specific groups of deficits.

Current methods for detection of tuberculosis rely mostly on bacterial culture from sputum. Here, the authors provide preclinical evidence that a positron-emitting mimic of the disaccharide trehalose ([¹⁸F]FDT) can be used as a radiotracer for the imaging of tuberculosis-associated lesions and monitoring the effects of treatment.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

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.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

In cancer, the impact on cellular fitness of copy-number gains affecting collaterally-amplified genes remains poorly understood compared to oncogenes. Here, the authors integrate genomic data from tumours and cell lines and identify a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes, with potential therapeutic applications.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Harnessing biomolecular systems to endow synthetic materials with life-like properties is a significant challenge. Here, the authors use the biomolecular KaiABC circadian clock proteins to control autonomous self-assembly and oscillation of colloids.

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.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

A nonlinear time-series analysis was used to identify antibiotic use thresholds that are associated with the emergence of antibiotic resistance.

End-stage kidney disease confers a high risk for severe COVID-19 infection. Using an at-risk group (end-stage kidney disease patients with COVID-19), authors using RNA-sequencing of immune cells and plasma proteomic profiling to investigate the host response to viral infection.

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