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CaBLAM is a bioluminescent genetically encoded calcium indicator that delivers high-contrast signals as shown in cell culture, in the in vivo mouse brain and in zebrafish larvae.

The authors consider studies reporting species range shifts and demonstrate a geometric bias in sampling along latitudinal, rather than longitudinal, gradients. This bias may favour the corroboration of shift expectations with warming and mask other patterns and drivers of species movements.

An ‘intracrine’ signaling mechanism is proposed whereby a G-protein-coupled receptor (free fatty acid receptor 4) senses locally released fatty acids on intracellular membranes associated with lipid droplets to efficiently regulate lipolysis in adipocytes.

Plant taxonomic richness and average range-size commonly exhibit a negative relationship, though the mechanisms are still debated. Liu et al. reveal that in northeast Siberia and Alaska, this relationship shifted from positive to negative at the glacial to Holocene transition, associated with changing plant interactions.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

Melting temperature is the parameter generally used as a measure for stability of enzymes. Here, the authors show that that the melting temperature does not necessarily correlate to the activity observed in the presence of the solvent, and introduce an alternative parameter, the concentration of the co-solvent at the point of 50% protein unfolding at a specific temperature T.

Adipogenesis associated Mth938 Domain Containing gene (AAMDC) is frequently amplified in the IntClus2 subgroup of ER + breast cancer. Here, the authors show that AAMDC drives tumourigenesis through activating PI3K-AKT-mTOR pathway for metabolic reprogramming.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

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 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.

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.

Co-operativity is an effect where initial reaction events influence later events. Here, White et al.find evidence for co-operativity in the cation exchange process of nanocrystals, as cadmium selenide transforms into the copper selenide phase.

Accurate seasonal forecasts of sea ice are highly valuable, particularly in the context of sea ice loss due to global warming. A new machine learning tool for sea ice forecasting offers a substantial increase in accuracy over current physics-based dynamical model predictions.

Despite the clear need for better therapies for psychiatric disorders such as depression and schizophrenia, novel drugs — particularly those that could revolutionize treatment — have been rare in recent years. Following a symposium in which the underlying reasons for this problem were discussed, a group of experts from across the field of neuroscience highlight key advances in our understanding of psychiatric disorders, and propose steps that can be taken to improve the effectiveness of drug discovery in this field.

High-precision polarization observations of the binary star system Spica reveal that the amount of light from the primary component that is reflected off the secondary component (and vice versa) is a few per cent of the incident light. Such observations will be useful in identifying close binary systems.

This work describes the identification and characterization of novel small molecule activators of SIRT1, an NAD⁺-dependent deacetylase that mediates the beneficial effects of caloric restriction. These small molecules are structurally unrelated to, and much more potent than, resveratrol, and improve metabolic function in animal models of diabetes and obesity.

Mutations in the GABA A receptor have been implicated in alcohol dependence in humans. In this study, the authors show that mice with mutations in the beta 1 subunit of the GABA A receptor exhibit spontaneous GABA A channel opening and preferentially consume alcohol, working harder to access it.

Longitudinal tracing of antibody responses to the ChAdOx1 and the BNT162b2 COVID-19 vaccines in 45,965 adults from the United Kingdom give indications for vaccine prioritization.

This protocol explains how to use and apply COMETS (computation of microbial ecosystems in time and space), which extends dynamic flux balance analysis to generate simulations of multiple microbial species in molecularly complex and spatially structured environments.

Abnormal functions of RNA-binding proteins TAF15, FUS and TDP43 are associated with amyotrophic lateral sclerosis. Here, Kapeli et al. characterize the RNA targets of TAF15 and identify points of convergence and divergence between the targets of TAF15, FUS and TDP43 in several neuronal systems.

Clinical diagnosis of paraneoplastic syndromes not only leads to detection of the underlying malignancy but can also influence treatment. Here, Hong et al. outline the various syndromes associated with prostate cancer, focusing particularly on the identification of putative markers in prostate cancer tissue that might provide a link to the associated syndrome.

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.

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.

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

Genome-wide meta-analysis, fine-mapping and integrative prioritization using expression quantitative trait loci, protein interaction networks and tissue-specific expression implicate new candidate susceptibility genes for Alzheimer’s disease.