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A computational approach is used to design modular proteins that bind to synthetic peptides and disordered regions of human proteins with high affinity and specificity.

Neutralisation assays are key to understanding immune responses to SARS-CoV-2 infection or vaccination. Here, the authors report a surrogate virus neutralization assay called Neu-SATiN, which measures neutralization directly from sera, and allows easy adaptation to variant-specific testing.

Alkaline-earth phenoxides show promise as optical cycling centres; however, their properties when connected to larger structures is unclear. Now it has been shown that their optical cycling remains efficient despite increasing molecular complexity, enabling the scaling of laser-coolable molecules toward larger structures and surface-bound quantum systems.

Researchers use a chimeric approach to reveal the first near-atomic resolution structures the yellow fever virion, showing key differences between vaccine and virulent strains that affect how antibodies recognise and neutralise the virus.

A dynamic interconversion of three nickel states in lithium nickel oxide is demonstrated using evidence from x-ray spectroscopic data and first-principles calculations, which explains many physical properties of this and similar materials.

An amphiphilic mimotope vaccine can be used in tandem with Food and Drug Administration (FDA)-approved CD19 CAR-T cell products.

Using cryo-electron microscopy and biochemistry, Zhang et al. reveal that the DNA helicase RECQL5 and the transcription-coupled DNA repair complex coordinate to regulate transcription elongation rates and maintain genome stability.

Development of VHL-recruiting PROTACs that degrade fall armyworm sfBRD3 and sfWDS proteins with high potencies in Sf9 cells and in full larvae, establishing the PROTAC modality as promising for agricultural applications.

The development of robust and active anode materials for oxygen evolution reaction is challenging. Perovskite nanocatalysts with high mass activity towards water splitting and electronic structures changing drastically during operando conditions are reported.

The spatial single-cell multiomic atlas of the first trimester human placenta at molecular resolution provides a blueprint for future studies on early placental development and pregnancy.

Protein phosphorylation helps to control many important cellular activities. Here the authors describe a genetic selection strategy to isolate designed ankyrin repeat proteins that bind specifically to phosphomodified targets.

Target 2035 aims to develop a potent and selective pharmacological modulator for every human protein by 2035 with the results made publicly available. This Roadmap article sets out how that will be achieved.

Small proteins are challenging targets for structure determination by cryo-electron microscopy. A new mass-enhancement strategy relies on rigid dimerization of a nanobody into a ‘di-gembody’ that increases protein mass by expanding the symmetry of small protein targets.

Interstitial oxygen conductors have the potential to enable efficient oxygen-ion transport at lower temperatures. An approach combining physically motivated structure and property descriptors, ab initio simulations and experiments is now proposed for the discovery of fast interstitial oxygen conductors.

Compared to monovalent lithium or sodium ions, the reversible insertion of multivalent ions into battery electrodes has proved challenging. An aliovalent doping strategy involving reversible Mg²⁺ and Al³⁺ insertion in anatase TiO₂ is now reported.

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.

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.

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.

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.

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.

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.

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.

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.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

MicroRNAs regulate many biological processes, including the development of cells of the immune response. Liu et al. demonstrate that a decrease in particular microRNAs prevents macrophage hyperactivation but primes their responsiveness to proinflammatory stimuli.

Small molecule probes used to trigger hypoxic response by activating hypoxia inducible factors (HIFs) often lack specificity. Here the authors report a potent small molecule inhibitor that induces hypoxic response by blocking VHL:HIF interactions, providing a selective route to probe hypoxic signalling.

Electric vehicles are increasingly adopted in the USA, with concurrent expansion of charging infrastructure and electricity demand. This Review details these trends and discusses their drivers and broader implications.

Arctic lakes are strong and increasing sources of atmospheric methane, but extreme conditions and limited observations hinder robust understanding. Here the authors show that microbes in the middle of Arctic lakes have elevated methane producing potential, and are poised to release even more in the future.

HLA-independent T cell receptors, in which the heavy and light chains of a chimeric antigen receptor are incorporated into the endogenous T cell receptor locus, are more effective than CD28-based chimeric antigen receptors at targeting tumors with low antigen expression.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Six WWE domain-containing proteins also contain domains with E3 ubiquitin ligase activity. We report structures, biophysical and biochemical assays for the discovery of novel WWE domain binders and their respective application.