Search

In this Expert Recommendation, Bowtell and colleagues outline progress made over the last decade in the research and treatment of high-grade serous carcinoma as well as current challenges and research priorities for the coming years to reduce incidence and improve patient outcomes.

New methods for targeted covalent protein modification at low reactivity aspartates and glutamates are of high interest. Here, the authors report a technique inspired by the HaloTag technology, which employs a covalent conjugation reaction between ligands with a reactive chloroalkane linker and a specific aspartic acid, and use it to covalently modify lipoprotein chaperone PDEδ at a binding site glutamic acid.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

Artificial intelligence is transforming materials research, yet its potential for sustainability remains underexploited. Artificial intelligence can enable circular materials systems by integrating materials performance, life-cycle assessment and sustainability metrics across design, use and recycling, accelerating the transition from linear innovation to closed-loop materials economies.

A new method is described that uses a periscope to generate high-speed, high-resolution projections of light fields, enabling sub-second volumetric 3D printing of millimetre-scale objects without rotating the sample.

Multi-omics profiling of Moso bamboo reveals that endophytic microbes—particularly Paenibacillus—modulate hormone signaling (auxin, cytokinin, and ABA) to fine-tune shoot development and accelerate rapid elongation.

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.

Synthesis of fluorinated organic molecules is of high interest for agrochemistry and pharmaceutics, but efficient and general reagents for introducing -CF₂- groups are lacking. Here, the authors report the synthesis of 3,3-difluoropropen-1-yl ammonium salts as stable and scalable gem-difluoromethylation reagents, which react with a range of nucleophiles under mild conditions and high regioselectivity.

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.

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.

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.

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.

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.

Humans have altered plant biogeography by introducing species from one region to another, but an analysis of how naturalized plant species affect the uniqueness of regional floras around the world was missing. This study presents an analysis using data from native and naturalized alien floras in 658 regions, finding strong taxonomic and phylogenetic floristic homogenization overall.

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.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

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.

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.

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.

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.

NiFe-based hydroxides are well-known for alkaline water oxidation but face efficiency issues due to unclear Fe dynamics. Here, the authors report that surface Fe dynamics are affected by Fe diffusion on the counter electrode and have developed a zinc-templated precursor to stabilize active Fe sites.

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.

Sympathetic innervation of brown and white adipose tissue is shown to be promoted by zinc released from thermogenic adipocytes, revealing a positive feedback mechanism for regulation of thermogenesis and thereby energy expenditure.

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 genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Exercise increases energy expenditure and suppresses obesity, but the effector mechanisms are not still unclear. Here the authors profile serum proteomics in exercised mice to find reduced parvalbumin levels that correlate with increased M2 macrophage and suppressed diet-induced obesity to hint parvalbumin as a potential therapy target against obesity.

Optical control is an alternative pathway to boost nonlinear transport in noncentrosymmetric systems. Here, the authors observe a light-induced giant enhancement of nonreciprocal transport coefficient as high as 10⁵A⁻¹ T⁻¹ at KTaO₃-based Rashba interfaces.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

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.

Electrochemical conversion of nitrate into ammonia offers a method for mitigating nitrate pollution in water. Here the authors report the electrochemical nitrate-to-ammonia conversion using high-entropy oxide Mg_0.2Co_0.2Ni_0.2Cu_0.2Zn_0.2O and find that the Co spin states are crucial for synergistic ammonia generation.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

By combining modelling and simulated data with empirical data from 76 grassland sites across 6 continents, the authors show that the relative abundance of dominant species predicts species richness, while their absolute abundance predicts community biomass.

As a result of unsupportive sanitation environments, women may cope by suppressing urges to urinate and defecate or by not eating food and/or drinking water. Among urban women in Uganda and India, nearly all women surveyed reported suppressing urination and defecation urges. Withholding food and water was less common. Perceived privacy, safety and health influenced these coping behaviours.

In two independent studies, Song et al. and Jiang, Dalgarno et al. present computational frameworks, perturbation-response score and Mixscale, respectively, to determine individual cellular variation in response to perturbation.