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Martini 3.0 is an updated and reparametrized force field for coarse-grained molecular dynamics simulations with new bead types and an expanded ability to model molecular packing and interactions.

Regrowth of lost enamel in tooth decay and sensitivity is a major obstacle to overcome. Here, the authors report on a protein-based material that mimics features of natural enamel formation, allowing for epitaxial growth of apatite nanocrystals to restore enamel structure and function.

The organization of membrane proteins is critical to cellular function. Here the authors explore how computational protein design, MD simulation, and cell-free systems can be combined to elucidate how membrane-protein hydrophobic mismatch affects protein folding and organization in synthetic lipid membranes.

The final step in an ECF transporters transport cycle involves the expulsion of the membrane embedded substrate binding protein (the S-component) from the motor (the ECF module). Here the authors show how the motor uses ATP binding to load a molecular spring, and adjusts the shape of the membrane, to achieve this step.

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 inherent toxicity of the aromatic compounds to the chassis strain hampers further improvement of bioproduction. Here, the authors show that membrane rigidifying effect of resveratrol can be attenuated by exogenous supplementation of palmitelaidic acid or linoleic acid in fermentation of Corynebacterium glutamicum.

Cholesterol can function as both a substrate and an inhibitor of the Hedgehog receptor Patched. Structural analysis and molecular dynamics simulations reveal that cholesterol inhibits Patched by inserting into its extracellular domain

Integrative molecular modelling of a mitochondrial crista demonstrates a pipeline for constructing biologically representative systems and addressing interactions in complex environments.

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.

Fibres formed by protein TasA are important components of the extracellular matrix in biofilms developed by the bacterium Bacillus subtilis. Here, Böhning et al. use electron cryomicroscopy and other techniques to show how TasA globular monomers assemble through donor-strand exchange into β-sheet-rich fibres, which in turn assemble into bundles.

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.

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.

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.

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.

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.

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.

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

Inhibition of specific metabolic pathways often drives metabolic adaptation. Here, the authors show that FLT3-ITD + acute myeloid leukemia cells are OXPHOS-driven, and inhibition of complex II activity results in increased lactate influx to drive respiration, which creates a targetable vulnerability.

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.

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.

Acute myeloid leukemia (AML) is genetically a very heterogeneous disease. Here, Erdem et al. uncover heterogeneity in the metabolic landscape of AML and identify Pyruvate dehydrogenase kinase 1 (PDK1) as a targetable determinant of different metabolic states in distinct subtypes of AML.

The cryo-EM structure of a megacomplex between chimeric GPCR, G protein and β-arrestin in their canonical active conformations provides insight into the basis of sustained G protein signaling upon megacomplex internalization.

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.

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.

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.

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Guido Sauter, Roland Eils, Christoph Plass, Raffaella Santoro and colleagues report that the gene encoding the epigenetic regulator BAZ2A is overexpressed in prostate cancer, where it interacts with EZH2 to induce aberrant gene silencing and cell proliferation. The authors find that BAZ2A levels are predictive of disease recurrence in patients with prostate cancer.

Wang et al. showed that genetic disruption of TFEB and v-ATPase-mediated lysosomal signaling leads to increased tau pathology but defective microglia activation, demonstrating an essential role of the lysosome in regulating microglia activity.

The transcriptional co-activator YAP is known to operate downstream of mechanical signals arising from the cell niche. Here the authors demonstrate that YAP controls cell mechanics, force development and adhesion strength by promoting the transcription of genes related to focal adhesions.

There are currently no drugs available to treat SARS-CoV-2 infection. A promising alternative treatment for COVID-19 patients is convalescent plasma. Here, Gharbharan et al. collect covalescent plasma and report no overall clinical benefit for 86 patients hospitalized for COVID-19 and treated with 300 mL convalescent plasma.

In patients with Crohn’s disease, CD4⁺ T cells with cytotoxic T_H1 cell-like effector functions reactive against dietary and commensal yeasts are increased in blood and inflamed tissue compared with patients with ulcerative colitis and healthy controls.

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

Expanding on their previous work, Bondar et al present open source software tools to reliably quantify linear dichroism and determine molecular orientations. They demonstrate the utility of the tools by imaging synthetic lipid vesicles and as well as fluorescently labelled proteins in living cells

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.

The realization that the cell is abundantly compartmentalized into biomolecular condensates has opened new opportunities for understanding the physics and chemistry underlying many cellular processes¹, fundamentally changing the study of biology². The term biomolecular condensate refers to non-stoichiometric assemblies that are composed of multiple types of macromolecules in cells, occur through phase transitions, and can be investigated by using concepts from soft matter physics³. As such, they are intimately related to aqueous two-phase systems⁴ and water-in-water emulsions⁵. Condensates possess tunable emergent properties such as interfaces, interfacial tension, viscoelasticity, network structure, dielectric permittivity, and sometimes interphase pH gradients and electric potentials^6–14. They can form spontaneously in response to specific cellular conditions or to active processes, and cells appear to have mechanisms to control their size and location^15–17. Importantly, in contrast to membrane-enclosed organelles such as mitochondria or peroxisomes, condensates do not require the presence of a surrounding membrane.

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.