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Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Stabilization of DNA quadruplex structures (G4) is lethal for cells with a compromised DNA repair pathway. Here, the authors show that CX-5461, a small molecule in clinical trials as RNA polymerase inhibitor, has G4-stablization properties and can be repurposed to target DNA repair-defective cancers cells.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

Mutations in the Wnt co-receptor, LRP5, lead to skeletal diseases in humans. Matthew Warman and his colleagues have now developed mutant mice with tissue-specific alterations of Lrp5 expression and found that these mice phenocopy the human skeletal diseases. They also found that Lrp5 acts locally to affect bone homeostasis. Their data suggest that increasing LRP5 signaling in mature bone cells may be a strategy to treat osteoporosis.

Plankton models have crucial applications in ecosystem management and climate change projections. This Perspective suggests that stronger alignment of plankton models with empirical knowledge is needed and recommends steps to close the gap between empirical research and modelling.

The most advanced P. falciparum circumsporozoite protein (PfCSP)-based malaria vaccine confers partial protection. Here, Pholcharee et al. present crystal structures, binding affinities/kinetics, and in vivo protection of 8 anti-NANP antibodies to understand in vivo protection of PfCSP-targeting antibodies.

Transposon based screens carried out in mice can identify genes critical for tumourigensis. Here, the authors describe transposon screens in mouse models of breast cancer and highlight a large group of tumour suppressors that could underlie selection for common chromosome arm losses in cancer.

Cryo-electron microscopy structures of connexin channels composed of connexin 46 and connexin 50 in an open-state reveal features that govern permselectivity and the location of mutated residues linked to herediatry cataracts.

Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.

C. elegans sleep can be used to model neural state transitions. Here the authors show that adult C. elegans show quiescent sleep-like behavior when in a microfluidic chamber, and that this is regulated by temperature, mechanosensation and satiety.

Synthetic lethality (SL) offers a new precision oncology approach, which is based on targeting cancer-specific vulnerabilities across the whole genome, going beyond cancer drivers. The authors develop an approach termed ISLE to identify clinically relevant SL interactions and use them for patient stratification and novel target identification.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

High-status journals or institutions no guarantees of carefully-reported trials.

The authors report the mutational landscape of 29 cell types from microdissected biopsies from 19 organs and explore the mechanisms underlying mutation rates in normal tissues.

A synaptic neuron and astrocyte program (SNAP) varies among healthy humans, may shape interindividual differences in synapses and plasticity, and is undermined in schizophrenia and with advancing age.

Elise Robinson and colleagues present the polygenic transmission disequilibrium test (pTDT) for evaluating transmission of polygenic risk in family-based study designs. The authors apply pTDT to a cohort of autism spectrum disorder (ASD) families and find that common polygenic variation acts additively with de novo variants to contribute to ASD risk.

Duan et al. find that the membrane skeleton protein spectrin is required for myoblast fusion in Drosophila, accumulating in a mechanosensitive manner in the receiving partner during cell–cell fusion to modulate adhesion and protrusion events.

Transcriptome deconvolution aims to estimate cellular composition based on gene expression data. Here the authors evaluate deconvolution methods for human brain transcriptome and conclude that partial deconvolution algorithms work best, but that appropriate cell-type signatures are also important.

Ant foragers actively abandon toxic baits, hampering control efforts. This abandonment process is driven at least in part by learning and memory, while aversive pheromones and passive mechanisms do not seem to play a role.

In this study, the authors show that MeCP2 interacts with the NCoR/SMRT co-repressor complex and that a discrete cluster of Rett syndrome–causing mutations in the C-terminal domain of MeCP2 disrupts this interaction, impairing transcriptional repression. Knock-in mice expressing one of these MeCP2 missense mutations exhibit severe motor phenotypes.

The role of subpatent infections for malaria transmission and elimination is unclear. Here, Slater et al. analyse several malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections.

The Sc2.0 consortia is reengineering the yeast genome. To expand the Sc2.0 genetic repertoire, the authors build a neo-chromosome comprising variable loci from diverse yeast isolates, providing phenotypic plasticity for use in synthetic backgrounds.

The Consortium for Top-Down Proteomics presents a decision-tree-based guide to sample preparation and analysis protocols for researchers performing top-down mass-spectrometry-based analysis of intact proteins.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

Characterization of ten temperate mycobacteriophages reveals at least five distinct prophage-expressed viral defence systems that interfere with infection by either closely related or unrelated lytic and temperate phages.

Human activities affect marine predators in complex ways, yet we lack spatial understanding of cumulative impacts across key habitats. Here the authors analyse distribution and movements of eight marine predators, and find that species and human impacts vary across space and overlap within marine sanctuaries.

With a comprehensive analysis of sequencing data, DNA copy number, gene expression and DNA methylation in a large number of human glioblastomas, The Cancer Genome Atlas project initiative provides a broad overview of the genes and pathways that are altered in this cancer type.

Suspended electrodes integrated into a scalable microfluidic device can be used for electrical measurements in large numbers of small organisms.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Extensive genetic analysis of over 2,000 individuals from different locations in Britain reveals striking fine-scale patterns of population structure; comparisons with similar genetic data from the European continent reveal the legacy of earlier population migrations and information about the ancestry of current populations in specific geographic regions.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

FLRT proteins are known to interact with Lphns and Unc5s, mediating cell adhesion and repulsion respectively. Here the authors use crystallography, native mass spectrometry, molecular dynamics simulations and cell-based assays to show that these three proteins form large super-complexes with functions distinct from their smaller subcomplexes.

Gram-negative bacteria assemble biofilms from amyloid fibres, which translocate across the outer membrane as unfolded amyloid precursors through a secretion system. Here, the authors characterise the structural details of the amyloid transporter FapF in Pseudomonas.

Massively parallel DNA sequencing allows entire genomes to be screened for genetic changes associated with tumour progression. Here, the genomes of four DNA samples from a 44-year-old African-American patient with basal-like breast cancer were analysed. The samples came from peripheral blood, the primary tumour, a brain metastasis and a xenograft derived from the primary tumour. The findings indicate that cells with a distinct subset of the primary tumour mutation might be selected during metastasis and xenografting.

Analysis of a global data set of local biodiversity comparisons reveals an average 13.6% reduction in species richness and 10.7% reduction in abundance as a result of past human land use, and projections based on these data under a business-as-usual land-use scenario predict further substantial loss this century, unless strong mitigation efforts are undertaken to reverse the effects.

Genomic analysis of 491 medulloblastoma samples, including methylation profiling of 1,256 cases, effectively assigns candidate drivers to most tumours across all molecular subgroups.

XFEL radiation is providing new opportunities for probing biological systems. Here the authors perform nanoscale x-ray imaging of microtubules with helical symmetry, by using imaging sorting and reconstruction techniques.

Cancer genetics has benefited from the advent of next generation sequencing, yet a comparison of sequencing and analysis techniques is lacking. Here, the authors sequence a normal-tumour pair and perform data analysis at multiple institutes and highlight some of the pitfalls associated with the different methods.

Zorowitz et al. show how careless and inattentive online participants can lead to false-positive correlations in computational psychiatry studies.

A study aimed at revealing the role of small-scale fisheries in sustainable development shows they provide at least 40% of the global fishing catch and affect the livelihoods of 1 in 12 people in the world, among other important contributions.

GenomeSpace is an open-source, cloud-based interoperability platform that facilitates integrative genomic analyses, allowing users to transition seamlessly between a diverse and growing set of bioinformatics tools and data resources.