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Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

Vault particles are giant ribonucleoprotein complexes with elusive cellular roles. Here, authors use cryo-electron tomography and proximity labeling to show that vaults associate with ER and nuclear envelope membranes and encapsulate 80S ribosomes in situ.

This study leveraged disease progression modeling to showcase task-based brain activity dysfunction as an important contributor to cognitive dysfunction along the Alzheimer’s disease cascade.

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.

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.

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.

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.

Grill et al. develop a personalized computer model of the human lungs based on CT scans to simulate airflow and aerosol deposition during inhalation therapy. They show that the model accurately predicts where inhaled drugs are delivered, providing a non-invasive tool for testing and improving respiratory treatments.

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.

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 authors propose a framework for clinical AI evaluation within simulated digital hospital environments that capture the evolving constraints, and cascading effects, of clinical decisions.

As protein synthesis takes place, newly synthesized polypeptide chain passes through the ribosomal exit tunnel, which can accommodate up to 70 residues in the case of a helical peptide. Here the authors show that oxidation of cysteine residues in the nascent chain can occur within the ribosome exit tunnel, where sufficient space exists for the formation of disulfide bonds.

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.

The CO dehydrogenase–acetyl-coenzyme A synthase complex produces acetyl-coenzyme A from CO₂, but its structural dynamics during catalysis remain unresolved. Now cryo-EM maps of six intermediate states reveal how ligand binding to a Ni–Fe cluster orchestrates the conformational changes of the complex during catalysis.

By integrating microglial transcriptomics with CSF proteomics, this study reveals protein markers that distinguish early and late Alzheimer’s disease and that have the potential to improve disease tracking and prediction.

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 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.

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.

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.

How carvedilol, a β1-blocker, activates β2-adrenoceptors, is unclear. Here, the authors resolve this enigma and show that carvedilol drives all of its detectable cellular β2-adrenoceptor signals by slow and low efficacy G protein activation.

BAC stepwise insertion synthesis (BASIS) can be used to build synthetic genomes for diverse organisms, and continuous genome synthesis (CGS) enables the rapid synthesis of entire Escherichia coli genomes from functional designs.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

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.

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.

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.

Using samples from the Danish Neonatal Screening Biobank, children with ASD and children with ADHD were found to have similar, significantly increased rates of rare protein-truncating variants in evolutionarily constrained genes.

De novo assembly of 23 Aspergillus section Nigri and 6 Aspergillus niger genome sequences allows for inter- and intraspecies comparisons and prediction of secondary metabolite gene clusters.

In a phase I/II dose-escalation clinical trial, the mRNA COVID-19 vaccine BNT162b1 elicits specific T cell and antibody responses that suggest it has protective potential.

Astrocytes play important roles in neuroinflammatory diseases. Here the authors characterize human glioblastoma-associated astrocytes by gene expression and demonstrate their immunosuppressive role promoted by interactions with tumor and microglia cells in an organotypic model.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

M. pneumoniae, a model organism for a minimal cell, has a dedicated protein, namely P116, to specifically extract essential lipids. The structure of P116 has a previously unseen fold, resembling a left-handed baseball glove forming a huge hydrophobic cavity.

Photosystems need auxiliary proteins to assist their assembly. Cryo-electron microscopy of a cyanobacterial photosystem II assembly intermediate at 2.94 Å reveals mechanisms protecting against photodamage during vulnerable stages of biogenesis.

A novel study led by scientists in Lübeck, Germany, shows that SARS-CoV-2-infected brain endothelial cells undergo cell death due to the cleavage of NEMO by the viral protease M^pro, potentially causing cerebral COVID-19 and ‘long COVID’ symptoms.