Search

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

Nucleic acid aptamers have emerged as promising alternatives to antibodies. Here, we show that incorporating unnatural bases enhances binding affinity by stabilizing the aptamer conformation and enabling specific engagement with hydrophobic pockets— acting like both armor and sword.

Theoretical and experimental analysis of the effect of grain shape in bed load sediment transport is performed and a shape-corrected sediment transport law that provides greater accuracy in predictions is proposed.

As pressure mounts globally on drug pricing and development cost continues to rise, clinicians and translational scientists in biotech, academia and biopharma companies are re-evaluating when, where and how to launch early clinical programs. These initial patient data become critical to de-risk development programs and allow developers to deploy their limited time and resources on the most promising drugs. We evaluate four fundamental shifts in drug development that appear to be unfolding and may well become critical to future global biopharma success: use of large-scale high quality cohort studies, sponsor-driven investigator-initiated trials, the integration of affordable artificial intelligence with extensive high quality data registries, and China’s focus on precision medicine. —

 A bifunctional iminophosphorane-catalysed, stereo-controlled deconjugation for the synthesis of highly enantioenriched alkylidenecyclopropanes is described, alongside computational studies elucidating the mechanistic pathway and origins of diastereoselectivity and enantioselectivity.

Observations of a luminous quasar from the high-resolution spectrometer Resolve aboard XRISM revealed highly inhomogeneous wind structure outflowing from a supermassive black hole, which probably consists of up to a million clumps.

Nanostructure engineering enables transforming simple magnetic alloys into spincaloritronic materials with large transverse thermoelectric conversion. This has led to a high anomalous Nernst coefficient in flexible Fe-based amorphous alloys.

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.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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.

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.

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.

This study uses spatial proteomic and spatial compartment-based whole-transcriptome profiling to develop predictive models for immunotherapy outcomes in non-small cell lung cancer.

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.

Whilst neutron scattering is a powerful tool for studying spin fluctuations in materials, its availability is limited to large-scale user facilities. Here, the authors demonstrate how the pumping of pure spin currents can be used as a desktop probe to detect an antiferromagnetic transition.

A combination of AFM-based AM-FM and nDMA methods evidences the effect of the curing temperature on the structural heterogeneities in epoxy networks: a lower pre-curing temperature provides a less heterogeneous network, which in turn can control the thermal and mechanical properties of resultant epoxy resins.

Crohn’s disease (CD) is a complex disease associated with immune dysregulation. Here the authors use multimodal data to identify and characterize an epithelial cell population, termed ‘LND’ cells, in both terminal ileum and ascending colon, with LND interacting locally with immune cells and potentially contributing to CD pathology.

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.

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.

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.

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.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

There are no vaccines or antivirals available against enterovirus D68. Here, the authors report Jun6504 as a 2C inhibitor and show that it provides broad-spectrum antiviral activity against EV-D68, EV-A71, and CVB3 and potent antiviral efficacy in a neonatal neurological mouse model of EV-D68 infection.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

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.

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.

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.

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.

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

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 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.

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.

Transverse thermeoelectrics can simplify devices as the electric field and heat gradient are perpendicular, but the power output is much less than in standard devices. Here, by forming a closed circuit of thermoelectric and magnetic materials, a much larger transverse thermopower is generated.

The magnetic fields of an individual lattice plane inside materials with a non-uniform structure were observed under magnetic-field-free conditions by electron holography.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

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.

Energy metabolism and ATP levels are controlled by an interlocking network of pathways. Here, the authors apply a genome-wide CRISPR screen to define genes that increase or decrease ATP levels to define the “ATPome”, a map of pathways that contribute to cellular ATP regulation.

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.

New fern transcriptomes reveal repeated whole-genome duplications, unique gene families and distinct lignocellulosic evolution, providing a comprehensive database that underscores the ancient divergence and genetic uniqueness of ferns.

Proton migration in the acetylene cation is commonly used as a model to study isomerisation dynamics. Here, the authors use X-ray pump-probe experiments to study this process, and show that isomerization occurs significantly faster than expected—within the first 12 femtoseconds following core ionization.

The cofactor iron is essential for cellular energy metabolism. Proteomics reveals how the interplay of iron limitation with glucose signaling underlies how a green alga turns off photosynthesis during lipid accumulation.

Single-cell and spatial transcriptomic analysis of pulmonary pleomorphic carcinoma reveal epithelial–mesenchymal transitions and extracellular matrix remodeling that shape the distinct architecture of this rare lung cancer.