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The specific glycosylation patterns of biological drugs often impact the efficacy and safety of the therapeutic product. Here the authors describe a native mass spectrometry approach that allows the resolution of highly complex glycosylation patterns on large proteins, which they apply to the therapeutic Fc-fusion protein Etanercept.

Here the authors provide a deep tissue analysis of patients with autoimmune kidney diseases, identifying a conserved spatiotemporal immune program for the development of glomerular crescents and sclerosis.

Western Africa is one of the world’s largest cocoa-producing regions, with just two countries supplying up to 60% of global production, but at a high carbon cost. Incorporating shade trees into cocoa farms offsets the industry’s carbon cost, but existing coverage is low. Expanding coverage could substantially boost carbon stocks without reducing yield.

The Neolithic Revolution marked an important shift from foraging to farming in human society. Here, the authors show that in Europe the spread of farming involved mostly within-group mating and limited cultural transmission.

Volatile exsolution and crustal viscosity dictate that the optimum pressure for the growth of an eruptible magma reservoir is 2 kbar in all tectonic settings and crustal compositions, according to thermomechanical modelling.

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.

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.

Natural products have historically made a major contribution to pharmacotherapy, but also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization. This Review discusses recent technological developments — including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances — that are enabling a revitalization of natural product-based drug discovery.

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.

Apollo is a GPU-accelerated simulator of within-host viral evolution, spanning host populations, tissues, and cells. It scales to millions of viral genomes and supports complex demographic and population genetic models.

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

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.

Experiments to explore electron transport in single molecules generally involve the use of chemical linker groups at both ends of the molecule to firmly anchor it to the source and drain contacts. Here it is shown that oligo-phenylene ethynylene molecules with a single anchor group can form molecular junctions as well. The process is attributed to aromatic stacking between neighbouring molecules in nearby electrodes.

Dominance is difficult to measure in natural populations as it is confounded with fitness. Here, Huber et al. developed a new approach to co-estimate dominance and selection coefficients, and found that the observed relationship is best fit by a new model of dominance based on gene expression level.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

Glomerulonephritis is a frequent complication of autoimmune diseases, and involves aberrant activation of immune cells, but the underlying insights remain unclear. Here the authors use both patient data and a mouse glomerulonephritis model to show that increased type I interferon may expand a subset of pro-inflammatory T cells for subsequent kidney pathology.

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

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.

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.

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.

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.

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.

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.

In transition metal dichalcogenide monolayers, the spin and valley degrees of freedom are strongly coupled. Here, the authors engineer a WSe₂/MoSe₂ heterostructure in which inter-valley transitions of interlayer excitons exhibit a giant splitting and near-unity polarization in a magnetic field.

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.

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 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.

The Na⁺-pumping KR2 rhodopsin from Krokinobacter eikastus is a light-driven non-proton cation pump whose mechanism of pumping remains to be understood. Here authors solved crystal structures of the O-intermediate state of the pentameric form of KR2 and its D116N and H30A mutants, which sheds light on the mechanism of non-proton cation light-driven pumping.

gLike infers population demographic histories with a variety of complex admixture events by analysis of graphs of states, which conceptualize the relationships of all lineages found in trees encoded in the ancestral recombination graph.

Cancer is often associated with mutant transcription factors (TFs) but their functional characterization is challenging. Here, the authors describe a recurrent mutation within TF IRF4 in human lymphomas and they show how it causes a complex switch in TF specificity and functionality.

Metastatic dissemination in breast cancer patients occurs early in malignant transformation, raising questions about how disseminated cancer cells (DCC) progress at distant sites. Here, the authors show that DCCs in bone marrow are activated via IL6-trans-signaling and thereby acquire stemness traits relevant for metastasis formation.

Population-based studies of SARS-CoV-2 seroprevalence are needed to understand levels of immunity and antibody dynamics. Here, the authors show that the seroprevalence in Bonn, Germany was low (<1%) following the first epidemic wave, and that neutralising antibodies waned within a few months.

A European ancestry genome-wide meta-analysis of pregnancy-associated bleeding traits identifies five novel loci associated with postpartum hemorrhage, but none with early bleeding. Functional analysis highlights a role for progesterone receptor-mediated signaling.

The activity of immune cells can be regulated by the microbiome. Here, the authors show that the fatty acids pentanoate and butyrate—normally released by the microbiome—increase the anti-tumour activity of cytotoxic T lymphocytes and chimeric antigen receptor T cells through metabolic and epigenetic reprogramming.

Aberrant splicing is a major contributor to rare disease, but detection accuracy using current methods is limited. Here, the authors develop an algorithm that detects aberrant splicing and intron retention events from RNA-seq data and apply it to diagnosis in mitochondrial disease.