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

The timing of respiratory syncytial virus seasonal epidemic peaks in Japan shifted in 2016-17. Here, the authors use mathematical modelling to evaluate the hypothesis that this change in timing may be due to an increase in use of childcare facilities following a policy change

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).

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.

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 study found that the serial interval and incubation period of monkeypox virus Clade Ib are shorter for putative sexual versus non-sexual transmission, indicating that epidemiological context is crucial for developing effective public health policies.

Kim et al. show that nuclear pore complex (NPC) formation is strongly upregulated during a specific neurodevelopmental window. In neurons, torsinA is required for the maturation and normal localization of nascent NPCs, but not their density.

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.

Experiments show that olivine is transparent at high pressure and temperature, with radiative heat transport representing 40% of olivine’s thermal conductivity. Heat radiation enhances slab’s heating rate and affects subduction dynamics.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

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.

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.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

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.

Secretory autophagy (SA) plays a crucial role in neuroinflammation-driven neurodegeneration, through SKA2 and FKBP5. SKA2 regulation of SA can inhibit IL-1β release. Its dysfunction leads to neurodegeneration, and is linked to Alzheimer’s disease.

Single molecule nanopore analysis is used to reveal adenylate kinase global dynamics in real time. It was found that allosteric interactions guide domain motions and substrate affinity, with 10% of enzymes displaying alternative active forms, suggesting evolutionary paths for enzyme regulation.

Brain folds emerge in the womb and deepen throughout the first year of infant life. Early folds are deeper at birth but deepen slowly post-birth. Deepening is complex: folds widen, thicken, become more concave, and get denser with tissue after birth.

The detailed 3D organization of human centromere components is unknown. Here, the authors use super-resolution microscopy to present a working model for a common core centromere structure.

Selective autophagy helps to degrade aggregated proteins accumulating in neurodegenerative diseases. Here, the authors show that NEMO, a ubiquitin binding protein previously linked to innate immune signaling, is recruited to misfolded proteins and promotes their autophagic clearance by forming condensates with the autophagy receptor p62.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

During red blood cell infection, malaria parasites export hundreds of proteins that remodel the host cell surface. Cowman and colleagues identify a putative protein translocator complex spatially associated with exported proteins, revealing the cellular domains involved in protein export.

Rathmell and colleagues show that metabolic reprograming of regulatory T cells is associated with severity of critical illness in patients with and without sepsis.

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.

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.

Kubota et al. find that white matter connections of ventral temporal cortex are innately organized by cytoarchitecture, category and eccentricity from birth, and also develop in parallel within each cytoarchitectonic area from infancy to adulthood.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

High numbers of COVID-19-related deaths have been reported in the United States, but estimation of the true numbers of infections is challenging. Here, the authors estimate that on 1 June 2020, 3.7% of the US population was infected with SARS-CoV-2, and 0.01% was infectious, with wide variation by state.

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.

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

Multiscale and multiway brain network interactions during the first six months of life reveal rapid developmental changes. High-order triadic interactions provide insights beyond pairwise functional network connectivity by capturing nonlinear dynamics and yielding more reliable biomarkers of developmental trajectories.

Insecticide resistance can limit the effectiveness of insecticide-treated nets for malaria prevention, but other factors such as access and durability also contribute. Here, the authors quantify impacts of this ‘cascade’ of factors using a mathematical model.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

Analyses of the relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change.

Genes2Genes is a dynamic programming framework that enables precise alignment for single-cell trajectories at the per-gene level.

Many bacteria release DNA and membrane vesicles through unclear mechanisms. Here, the authors show that a prophage endolysin is involved in the explosive lysis of a sub-population of cells in Pseudomonas aeruginosa, releasing cytoplasmic content and membrane fragments that rapidly form membrane vesicles.

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.

β-PdBi2 superconducting properties have been known about since the 1950s, with various works since then indicating the possibility of multiple superconducting gaps and unconventional superconductivity. However, so far only a single gap s-wave superconductivity was detected. Here, using tunnelling spectroscopy under an applied magnetic field, Powell et al observe a transition from s-wave to nodal pairing.

Aberrant chromatin structure is often found in cancer. Here, the authors optimise super-resolution microscopy for pathological tissue and discovered a significant decompaction of chromatin folding in early carcinogenesis prior to tumour formation.

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.

Patients with neurodevelopmental conditions without a monogenic diagnosis have a higher polygenic burden than those with a monogenic diagnosis. Non-transmitted common alleles in the parents are associated with the child’s phenotype, and the common and rare variants conferring risk are correlated.

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.

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

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.

Seasonal influenza levels were unusually low when non-pharmaceutical interventions for COVID-19 were in place. Here, the authors analyse serological and epidemiological evidence for the hypothesis that such lulls in influenza transmission lead to reduced immunity and therefore larger epidemics in subsequent seasons.

Regional surface climate response to a future decline in solar activity remains uncertain. Here, via numerical simulations, the authors show that a return to Maunder Minimum-like lows by 2050 could lead to some areas of significantly reduced surface warming via modulation of the North Atlantic Oscillation.

Combining time-resolved IR spectroscopy, activation energy analyses, and computations, authors provide mechanistic insight into genetically altered reaction kinetics of light-driven oxygen evolution in photosystem II.

RNF4 is a prototypical single-subunit E3 enzyme that can bind both substrate and ubiquitin-loaded E2. Here, the authors show that the RNF4 N-terminal region, although lacking a defined secondary structure, maintains a compact global conformation to facilitate ubiquitin transfer to the substrate.

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.