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In this work, authors present an automated, high-throughput platform that utilizes robotics and computer vision to enable creation of a therapeutic phage cocktail, LBP-EC01, effective against over 96% of tested Escherichia coli isolates from urinary tract infections.

Soil microbial populations bloom and then die-off in ecosystems with seasonal snowpack. This study showed that distinct taxa utilize different N sources for growth or energy during the microbial bloom and alter the fate of N after snowmelt.

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

Engineering polymerases to synthesize alternative genetic polymers remains a challenging problem in synthetic biology. Using DNA shuffling and droplet microfluidics, the current study provides a short evolutionary path from a DNA polymerase to one with robust RNA-synthesizing activity.

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.

Inspired by dynamic textural modulation in cephalopod skin, polymer films whose colour and surface texture can be dynamically and independently controlled are developed and demonstrated using standard electron-beam patterning tools.

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.

This Perspective article discusses the stratification of patients with knee osteoarthritis (OA) in the context of current guidelines, biomarkers and emerging and future developments of targeted treatment. The authors aim to highlight how these novel developments can enhance the stratification of patients with knee OA to improve patient outcomes.

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.

Despite extensive structural studies elucidating how antigens are anchored to antigen-presenting molecules and presented to T cells, little is known about the display mechanism of the lipid-antigen-presenting molecule CD1c. Here, by combining structural immunology, lipidomics, and biophysical analysis, the authors reveal that the CD1c binding cleft accommodates two different lipids, one of them with a bulky headgroup positioned sideways for display to T cells, rather than upwards, different from the conventional upright antigen-presentation mode

Water-vapor interfaces have been studied with many techniques, yet open questions persist about their electronic and molecular structure. Here, the authors demonstrate the application of soft x-ray second harmonic generation to study the water surface by leveraging attosecond pulses at the LCLS and a flat liquid sheet microjet, providing insights on the H-bond structure.

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.

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.

This study demonstrates that the extracellular matrix (ECM) of the developing brain stabilizes recently born synapses. The authors identify a microglial metalloprotease that digests the ECM to increase the plasticity of these newborn synapses.

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.

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.

Results from the phase ELAD 2 trial reveal that liraglutide is safe and well tolerated in people with mild to moderate Alzheimer’s disease but does not significantly slow brain metabolism decline.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Tree cover gains in the moist tropics (1982–2015) were 56% naturally regenerated forests and 27% managed tree systems, with forest type influencing carbon recovery. Effective forest restoration requires robust tracking of forest types established by restoration efforts.

In this work, Wilson et al., examined sharing of Salmonella between humans, animals and the environment using household samples from Malawi. They revealed an interconnected web of Salmonella circulation, underscoring the importance of the One Health concept.

α/β-hydrolase domain-containing protein 11 (ABHD11) is a mitochondrial hydrolase, and its expression in CD4 + T-cells has been linked to remission status in rheumatoid arthritis. Here the authors report that pharmacological inhibition of ABHD11 modulates T-cell effector function via increased 24,25-epoxycholesterol biosynthesis and subsequent liver X receptor activation.

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

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A redox reaction network, comprising concurrent oxidation and reduction pathways, is described that can drive autonomous unidirectional motion about a C–C bond in a structurally simple synthetic molecular motor based on an achiral biphenyl.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Diffusion models are reframed by developing a generative blood cell classifier that performs reliably in low-data regimes, adapts to domain shifts, detects anomalies with robustness and provides uncertainty estimates that surpass clinical expert benchmarks.

Strings of local excitations are interesting features of a strongly correlated topological quantum matter. Here, the authors show that Boltzmann-distributed strings of local excitations also describe the topological physics of the Santa Fe geometry of artificial spin ice, which is a classical thermal system.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

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.

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.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

DNA polymerases are the key enzymes responsible for DNA replication and repair. Here the authors reveal through time-lapsed images of X-ray crystal structures that translocation precedes phosphodiester bond formation in the mechanism of DNA synthesis.

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.

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.

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.

The spin–orbit interaction and the two-dimensional honeycomb structure of iridium-based oxides are promising for exotic electronic states. Here, the authors find an iridium oxide with a three-dimensional structure that preserves the features of the honeycomb systems, creating new material possibilities.

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.

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.

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.