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Stone tools illustrate behavioural complexities in Middle Pleistocene hominin populations. Here, the authors present small dimensional flakes and hafted tools from Xigou, central China, dated to ~160–72 thousand years ago that demonstrate early, complex technological advancements.

Non-traditional luminescent polymers are materials without extended π-conjugation. Here the authors develop highly luminescent supramolecular polymers using dynamic quadruple hydrogenbonded motifs with potential for sensing and fluorescent adhesives.

Tetrandrine is one of the most potent inhibitors of Ebola Virus infection. Here the authors identify LIMP-2 as a direct cellular target of Tetrandrine and establish a functional connection between lysosomal sphingosine homeostasis and calcium regulation.

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.

Topological effects known from condensed matter physics have recently also been explored in photonic systems. Here, the authors directly observe topological surface-state arcs in momentum space by near-field scanning the surface of a chiral hyperbolic metamaterial.

This Review covers the recent advances in the field of hydrogen atom transfer catalysis mediated by photoexcited transition metals without the use of external photosensitizers.

Typically, quantitative trait loci studies find genetic variants associated with the total quantity of a quantitative trait, but other measures, such as variance, can detect different biology. Here, the authors map variance quantitative trait loci for blood cell traits, finding associations with gene-by-environment interactions and genetically-predicted alcohol use.

Loss of function alleles of two genetically interacting loci mediate both segregation distortion and interspecific hybrid incompatible via epigenetic regulation in rice.

β-Lactone-containing natural products are rare. Now, a polyketide with a unique cyclopentane–β-lactone skeleton is reported. The key enzymes identified for the formation of the bicyclic core are a non-ribosomal peptide synthetase-like module with a β-lactone ring forming esterase and peptidyl carrier protein, thioester reductase and condensation domains.

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.

As Nature Chemical Biology approaches its third decade we asked a collection of chemical biologists, “What do you think are the most exciting frontiers or the most needed developments in your main field of research?” — here is what they said.

A microchip-based DNA synthesis method enables scalable production of complex DNA constructs.

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.

Antibody responses against Mycobacteria infection have been reported, but whether and how they impact anti-bacteria immunity in the host is unclear. Here the authors characterize human anti-Mycobacteria antibodies to find them targeting a Mycobacteria transporter protein, PstS1, show distinct interaction modes in crystal structure, and mediate protection in vitro.

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.

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.

This randomized trial assessed the effectiveness and safety of single blastocyst transfer vs single cleavage-stage embryo transfer among women with good prognosis. Here, the authors show improved cumulative live birth rates and relatively unfavorable perinatal outcomes after blastocyst transfer.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

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.

Organic solar cells processed from green solvents are easier to implement in manufacturing yet their efficiency is low. Chen et al. devise a guest molecule to improve the molecular packing, enabling devices with over 17% efficiency.

Although many room temperature phosphorescence host–guest systems with versatile performances have been developed, their photophysical mechanisms remain often unclear. Here the authors reveal that a dynamic coupling process in the excited state is crucial for inducing phosphorescence, where host and guest molecules firstly couple to enhance the intersystem crossing efficiency, and then decouple to transfer excitons to the triplet state of guest.

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.

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.

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.

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.

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.

Here the authors show that DNMT3A and DNMT3B are differentially regulated during endoderm and mesoderm differentiation in mouse development and characterize the dynamic DNMT3A and DNMT3B sequence specificity during gastrulation.

Multimodal AI combines different types of data to improve decision-making in fields such as healthcare and engineering, but work so far has focused on vision and language models. To make these systems more usable in the real world, Liu et al. discuss the need to develop approaches with deployment in mind from the start, working closely with experts across relevant disciplines.

Large-scale experimental analysis of Human Domainome 1, a library containing more than 500,000 missense mutation variants across more than 500 human protein domains, reveals that 60% of pathogenic missense variants reduce stability of protein domains.

Precise regulation of the phytohormone gibberellin to optimal levels may not only confer alkali–thermal tolerance to Green Revolution rice varieties but may also further enhance their yield, and ATT2, by enabling the fine-tuning of gibberellins, is expected to be a potential new post-Green Revolution gene.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

Simultaneous magnetic resonance optoacoustic readings reveal a high correspondence between BOLD and hemoglobin signals in mouse functional connectivity. Total and oxygenated hemoglobin exhibit stronger correlations with BOLD than deoxygenated hemoglobin.

Despite being a hallmark of cancer, the identification of targetable vulnerabilities of aneuploid cancer cells remains limited. Here, the authors develop RPE1-hTERT cell lines with varying degrees of aneuploidy to investigate the consequences of chromosomal imbalance, identifying CRAF as an aneuploid-selective therapeutically targetable vulnerability.

Analysis of SARS-CoV-2 genomes from around the world show that following initial importation largely from India, Delta spread in England was driven first by inter-regional travel and then by local population mixing.

Papillary thyroid cancers (PTC) generally have good prognosis, but their recurrence rate remains high. Here, the authors use proteogenomics and metabolomics to identify molecular features in PTC tumours and determine PTC subtypes that are associated with prognosis and potential targeted therapies.

Optical pooled CRISPR screening is improved by combinatorial oligo hybridization for barcode detection.

The use of Mn-rich layered cathodes in Na-based batteries is hindered by inadequate cycling reversibility and sluggish anionic redox kinetics. Here, the authors report a strategy to stabilize the structure and promote anionic redox via configurational entropy and ion-diffusion structural tuning.