Search

Calculations of relative binding free energy are crucial for lead optimization in structure-based drug design, but classical methods are computationally expensive. Here, the authors describe a more efficient method for calculating the free energy that is as accurate as thermodynamic integration.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Hypoglycemia is a serious and potentially life-threatening condition for people with insulin dependent diabetes, but preventative hypoglycemia therapies are elusive. Here, the authors report the use of catechol and boronic acid chemistry to design a self-crosslinkable hydrogel-based microneedle patch that delivers Zinc-Glucagon at low glucose levels and prevents insulin-induced hypoglycemia.

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.

Beyond the long-established chemolithoautotrophs, a new study by Shao et al. uncovers heterotrophic denitrifiers as previously concealed contributors to sulfur cycling, with profound implications for greenhouse gas mitigation.

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.

Nineteenth-century physicists couldn't agree about the speed of light.

Burr et al. analyze multiple primary EGFR-mutant lung tumors from ten patients and define developmental mosaicism as a mechanism underlying multiple tumor presentation in this setting.

A challenge with the use of metal anodes in batteries is their inability to sustain structural stability, especially at high currents. Here the authors examine electrochemomechanical properties of metal anodes and demonstrate an effective semi-solid electrode approach at practically relevant conditions.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic infection.

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.

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.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

PPARγ nuclear receptor ligand activities can span agonism to inverse agonism. Here, the authors use NMR to show how chemical changes within a ligand series shift the receptor’s dynamic conformational ensemble between active and repressive states.

Direct observation of ionic motion in buried metal/oxide interfaces and its correlation with physical properties is a challenging task. Here, the authors observe oxygen migration in a model system with controllable positive exchange bias, due to the redox-driven formation of a ferromagnetic interfacial layer.

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.

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.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

In situ corrosion monitoring is essential to unveil corrosion mechanisms and safeguard materials’ health. Here, the authors develop a radionuclide tracing based in situ corrosion monitoring technique that can monitor corrosion attack depth and corrosion product transport in flowing molten salts.

Erratic funding for basic research, coupled with concerns that science has fallen down the priority list for politicians, has contributed to a shift in researchers’ attitudes to lobbying.

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

The structure of the yeast nuclear pore complex, determined at sub-nanometre precision using an integrative approach that combines a wide range of data, reveals details of its architecture, transport mechanism and evolutionary origins.

ctDNA is a useful tool for the diagnosis of cancer, however, it is usually focused on targeted deep sequencing. Here, the authors develop a methodology to assess TET-assisted pyridine borane whole-genome sequencing data for cancer detection without a matched biopsy.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

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.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Leading political parties pay scant attention to research in run-up to general election.

The design of efficient and stable oxygen evolution catalysts has implications for water splitting and metal-air battery technology. Here, the authors fabricate double perovskite nanofibers and demonstrate the favourable effects of co-doping and nanostructuring on oxygen evolution performance.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Mastomys natalensis is a rodent species native to West Africa that is the primary reservoir host for Lassa virus. Here, the authors investigate whether the invasive rodent Rattus rattus decreases M. natalensis density and could therefore indirectly decrease zoonotic transmission of Lassa virus to humans.

A metanalysis, analytical and robophysical model reveal that nonlinear coupling in energy transduction govern a performance-efficiency tradeoff in muscle and cytoskeletal systems.

Progressive parties’ showing bodes well for action on climate policies and science funding, researchers say.

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.

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.

Understanding protein sequence-function relationships is complicated by high order epistatic interactions among residues, although the extent of these interactions remains uncertain. Here, the authors present a reference-free method which suggests that sequence-function relationships are relatively simple, with little influence from high order epistatic interactions.

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.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

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.

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.