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

As the complexity of synthetic genetic circuits increases for biocomputing applications, there is a need to reduce the footprint of circuits to reduce burden on cells. Here, the authors develop wetware and software to design 3-input Boolean logic circuits that utilize fewer genetic parts.

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.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Genetic mapping in mice identified Homer1a as a key modifier of attention. Developmental downregulation in the prefrontal cortex enhances inhibitory tone, neural signal to noise and adult attentional performance, revealing a new control mechanism and target.

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

When interfaced with a current-carrying heavy metal, spin orbit effects can generate a torque on the magnetization of a ferromagnet, understood as a bulk effect. Here, the authors show evidence of an interfacial contribution to such spin orbit torque in O-doped W/CoFeB thin film systems.

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.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

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.

Up to 80% of the global seafloor may have been oxygenated some 1.4 billion years ago, according to molybdenum isotope of manganese- and iron-rich sedimentary rocks that reveal an expanded and prolonged global oxygenation event.

Although the trivalent actinides are similar to the lanthanide series in terms of chemistry and bonding, their structures and properties can diverge significantly. Here, the authors report a series of complexes of the trivalent actinides Np(III) through Cf(III) along with their lanthanide counterparts using a polarizable non-innocent, sulfur-donor ligand.

The growth of a biofilm—a bacterial colony attached to a surface—is governed by a trade-off between horizontal and vertical expansion. Now, it is shown that this process significantly depends on the contact angle at the biofilm’s edge.

The accretion geometry of X-ray binary Cygnus X-3 is determined here from IXPE observations. X-ray polarization reveals a narrow funnel with reflecting walls, which focuses emission, making Cyg X-3 appear as an ultraluminous X-ray source.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

High-throughput screening identifies opioid compounds and prodynorphin-derived peptide agonists of the G-protein-coupled receptor MRGPRX2 and informs a homology model that is used for in silico screening to find a small-molecule probe that provokes degranulation in mast cells, which express this receptor.

IXPE has revealed how the spin of the accreting neutron star Hercules X-1 changes in three dimensions. The spin axis of the star moves both through the star and across the sky, hinting that the crust of the star is asymmetric by almost one part in a million.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Molecular systems featuring a spin-optical interface offer a promising platform for quantum sensing, thanks to their low-cost synthesis and tunability. Here the authors use pentacene-doped molecular crystals for pressure and temperature sensing with improved temperature and record pressure sensitivities.

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.

A detailed molecular analysis of related yeast species shows that progressively opposed genetic logics can evolve while resulting in a conserved phenotypic output:mating-type determination. This is the first clear demonstration of the 'genetic drift' principle at a molecular level.

A UCP1-independent mechanism of thermogenesis involving ATP-consuming metabolism of monomethyl branched-chain fatty acids in peroxisomes is described and a previously unrecognized role for peroxisomes in adipose tissue thermogenesis is identified.

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.

CAR-T cell therapy has been shown to be effective in immunotherapy for treatment of several different tumours. Here the authors show pre-specified interim outcomes from a P-BCMA-ALLO1 trial with BCMA targeted CAR-T therapy in multiple myeloma.

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.

We develop a method for providing high-quality, holographic, three-dimensional augmented-reality images in a small form factor suitable for incorporation in eyeglass-scale wearables, using high-refraction-index glass waveguides with nanoscale metasurfaces, and incorporating artificial intelligence.

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.

Theoretically predicted in 1979, hyper-Raman optical activity is now experimentally observed through chirality conferral from the electromagnetic field of chiral plasmonic gold nanohelices to crystal violet molecules that are achiral, sparking new science at the organic–inorganic interface.

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.

The diversity of ponerine ants varies widely across the globe. This study finds that the origin and early colonization in Gondwana’s tropical regions mainly shaped this distribution, while differences in diversification and dispersal have balanced regional diversity over time.

Colobomatous microphthalmia often lacks a genetic diagnosis despite its developmental complexity. Here, the authors show that rare variants in NR6A1 cause a syndromic form with eye, kidney, and vertebral defects, supported by zebrafish functional validation.

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.

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.

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.

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.

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.

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.

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.