Search

Hong-Xuan Lin, Ji-Ping Gao, Jun-Xiang Shan and colleagues show that natural variation in a proteasome α2 subunit gene contributes to thermotolerance in African rice. Their follow-up studies suggest that the variant allele protects cells from heat stress by enhancing the elimination of cytotoxic denatured proteins and maintaining heat-response processes.

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.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Targeted deletion of integrin-associated protein CD47 enhances long-term engraftment of human CD34⁺ cells in immunodeficient pigs lacking IL2RG and RAG2, enabling large-scale production of functional human immune cells.

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.

Multiple genetic loci are associated with lung cancer risk, but the underlying genetic mechanisms remain poorly understood. Here, the authors perform single-cell RNA-seq and ATAC-seq analyses of lung cells from ever- and never-smokers; they report candidate cis-regulatory elements that colocalise with candidate causal variants in lung cancer risk loci and potential susceptibility genes.

Achieving generality in asymmetric catalysis with highly reactive radicals is a challenge. Now it is shown that a sequential copper-catalysed approach enables the efficient, enantioselective cross-coupling of over 50 diverse radicals, providing unified access to C-, P- and S-chiral products and advancing the asymmetric synthesis of challenging molecular architectures.

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.

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.

Semiconductor quantum dots that simultaneously support blue and yellow emission offer a route to realizing efficient white light-emitting diodes.

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.

In this Perspective, members of the Aging Biomarker Consortium outline the X-Age Project, an Aging Biomarker Consortium plan for building standardized aging clocks in China. The authors discuss the project roadmap and its aims of decoding aging heterogeneity, detecting accelerated aging early and evaluating geroprotective interventions.

Here, the authors provide evidence that SARS-CoV-2 N protein leads to autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inducing DNA damage and proteotoxic stress, eventually causing pneumonia. The small-molecule drug PJ34 or anastrozole alleviates N protein-induced pneumonia.

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.

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.

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.

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.

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.

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

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.

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.

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.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

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.

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 jujube is a major dry fruit crop in China and is commonly used for medicinal purposes. Here the authors sequence the genome and transcriptome of the most widely cultivated jujube cultivar, Dongzao, and highlight the genetic and molecular basis of agronomically important jujube traits, such as vitamin C content.

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.

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.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

The use of biomarkers of ageing is crucial for investigating age-related processes. This Review discusses biomarkers of ageing and of ageing-associated physiological changes, at the cellular, tissue and organism levels in humans and non-human primates.

A smartphone-based system, designed to induce a steady gaze in children using cartoon-like video stimuli, can identify visually impaired children across a wide range of ophthalmic disorders, based on analysis of gazing behaviors and facial features.

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.

Space–time-coding digital metasurfaces can be used to implement secure and low-cost space- and frequency-division multiplexing in a dual-channel wireless communication system.

The “storage” of sunlight as a chemical fuel can provide renewable on-demand energy, although current earth-abundant materials usually show low activities. Here, authors construct a carbon nitride material whose half-metallicity and micro grid resonance structure boost light-driven H₂ evolution.

Mutations in SPOP, the gene encoding a component of the E3 ubiquitin ligase complex, impair ubiquitination-dependent degradation of BRD2, BRD3 and BRD4 proteins and result in activation of ATK–mTORC1 signaling and resistance to BET inhibitors. Pharmacological blockade of AKT represents a viable strategy to restore the sensitivity of SPOP-mutant prostate tumors to BET inhibitors. These results, together with findings by Dai et al. and Janouskova et al., uncover a new nongenetic mechanism of resistance to BET inhibition involving cancer-type-specific mutations in SPOP, and support the evaluation of SPOP mutation status to inform the administration of BET inhibitors in the clinic.

Understanding origin and adaptation of weeds is important for their management. Here, via genome assembly, population genomics, and QTL mapping, the authors establish Cardamine occulta as a model to study weed ruderality and show FLC and CRY2 as genetic drivers for the establishment of short life cycle.

A dynamical study shows that vortices of electrical polarization have higher frequencies and smaller size than their magnetic counterparts, properties that are promising for electric-field-driven data processing.

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.

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

The F + para-H₂ → HF + H reaction is an important source of HF in interstellar clouds; however, its unusually high rate and its dynamics at low temperature are not fully understood. Now, quantum-state resolved crossed-beam scattering measurements and anion photoelectron spectroscopy have revealed that this reactivity is caused by a resonance-enhanced tunnelling effect involving a post-barrier resonance state.

Dai Zhang and colleagues report a genome-wide association study for schizophrenia in the Han Chinese population. They identify a new susceptibility locus at 11p11.2 and also identify a locus at 6p21-22.1 in the extended MHC region, which has previously been reported to be associated with schizophrenia in individuals of European descent.

Admixture with other hominin species helped humans to adapt to high-altitude environments; the EPAS1 gene in Tibetan individuals has an unusual haplotype structure that probably resulted from introgression of DNA from Denisovan or Denisovan-related individuals into humans, and this haplotype is only found in Denisovans and Tibetans, and at low frequency among Han Chinese.