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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.

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.

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.

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.

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.

Kitaev interactions on a honeycomb lattice can potentially lead to a quantum spin liquid state. Unfortunately, materials hosting Kitaev interactions also host Heisenberg interactions favouring long range order. Here, Sakrikar, Shen, Poldi and coauthors find that the relative strength of the Heisenberg and Kitaev interactions can be tuned by pressure in Ag₃LiRh₂O₆.

The authors report resonant soft x-ray scattering and polarimetry measurements on epitaxial thin films of La3Ni2O7. They find a diagonal bicollinear double spin stripe order, with no evidence of charge modulation.

Cellular spatial organisation is crucial for shaping tissue functions and phenotypes. Here, authors present TrimNN, a graph-based deep learning framework to identify conserved cellular community motifs, revealing links between spatially distributed cell-type patterns and diverse phenotypes.

A framework combining combinatorial CRISPR knockout in breast, lung and oropharyngeal cancer in vitro models with public data identifies synthetic lethal interactions, such as perturbed KDM5C sensitizing cells to PARP7 inhibition.

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.

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 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.

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.

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.

Here, the authors identify distinct gut microbiome and metabolome signatures in microscopic colitis, a condition causing chronic diarrhea, highlighting pro-inflammatory species and metabolites as potential non-invasive biomarkers and therapeutic targets.

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.

A subcortical circuit that regulates food consumption in mice is described, involving neurons in the ventromedial hypothalamus that are directly linked to motor centres that regulate feeding and jaw movements.

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.

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.

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.

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.

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.

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.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Dietary fructose enhances tumour growth in animal models of melanoma, breast cancer and cervical cancer indirectly via metabolite transfer.

Ionic substitution is a useful way to manipulate structural, electronic, magnetic phase transitions in strongly correlated materials. Here, the authors report electric-field controlled protonation in SrRuO₃, resulting in a large structural expansion and a ferromagnetic-to-paramagnetic phase transition.

Despite widespread use of azides across material science and various areas across chemistry, the underlying biosynthetic pathways for its formation have so far been unknown. Now, a promiscuous ATP-utilizing enzyme, Tri17, capable of synthesizing various azide molecules has been identified. Biochemical, structural and computational analyses support a potential molecular mechanism for azide formation by Tri17.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Cutaneous squamous cell of the skin is a common neoplasm that frequently arises from precancerous actinic keratoses. Here, the authors carry out genomic analysis on matched sets of human lesions and compare with those in ultraviolet treated mice and identify conserved drivers of tumour development.

The electronic interactions at the interface of oxide materials promise properties that can be very different from those of the parent compounds. The finding that many-body interactions in oxide superlattices can be used to engineer electronic properties offers a new strategy for designing oxide heterostructures.

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

During a photoinduced phase transition, electronic rearrangements are usually faster than lattice ones. Time-resolved measurements now show that the insulator-to-metal transition in a thin-film Mott insulator is preceded by lattice reconfiguration.

Food pantries are part of the emergency food network in the United States, but they are an understudied component of food access. The Pantry Accessibility Index and Individual Accessibility Index developed here allow measurement of the spatiotemporal availability of these services to the food insecure of south-central Indiana.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Gut microbiome has been linked to cavernous angioma (CA), a common vascular disease, but the role in humans remains unclear. Here, the authors combine 16S rRNA sequencing and shotgun metagenomics to profile the microbiome in a large cohort of human subjects with and without CA, and among subjects with different CA clinical features.

The Genomic Data Commons repository contains genomic, epigenomic, proteomic and clinical data from the TCGA and TARGET datasets. Here, the authors describe the analysis methods for how these divergent datasets were integrated together.

Histone H2AX is a central regulator in DNA repair. Here, the authors show that the H2AX C-terminal linker mediates recruitment of 53BP1, a mechanism which evolved to function independently of the canonical phospho-ubiquitin axis important for DNA repair regulation.

A cross-ancestry genome-wide association meta-analysis of lung cancer including 61,047 cases and 947,237 controls identifies five new cross-ancestry susceptibility loci and highlights ancestry-specific effects of common and rare variants on lung cancer risk.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.