Search

There is still a need for effective HIV vaccines. In this phase I clinical trial, the authors show that an HIV-1 vaccine candidate, ConM SOSIP.v7, is well-tolerated in HIV-negative adults and that it elicits a strain-specific neutralising antibody response that differed between female and male participants.

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.

Knee osteoarthritis has a sex-specific phenotype with post-menopausal persons experiencing the highest incidence. Here the authors investigate the underlying mechanisms in a mouse model of menopause and find that the loss of 17β-estradiol and progesterone enhanced susceptibility to senescence, extracellular matrix disassembly and cartilage degradation.

Using transcriptomic data from human brain cells, the authors show that the expression patterns of the genes implicated in human cognition and brain evolution overlap in specific neuron types, and relate to cellular function and structure.

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.

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.

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.

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.

How astrocytes influence neuronal plasticity remains unclear, as they are typically considered as modulators of core mechanisms driven by neuronal components. Here, authors show that Long-term depression (LTD) induction in the hippocampus triggers calcium signaling in the astrocyte and enhances SNARE-dependent astrocytic glutamate release, which is then responsible for the activation of postsynaptic NMDA receptors and synaptic depression.

Rapid genetic adaptation to environmental change, or evolutionary rescue, can be constrained by a less adaptable mutualistic partner. Here, the authors explore evolutionary rescue in an obligate mutualism between crossfeeding E. coli strains, finding that stress can lead to mutualism breakdown through the reversion to autonomy of one partner.

Survival of competing microbial species pairs predicts competition outcome between a greater number of species: species that coexist with each other in pairs will survive, species that are excluded by any of the surviving species will go extinct.

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.

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.

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.

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.

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.

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.

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.

Streptococcus pyogenes is a deadly bacteria without a vaccine. Here, researchers measured antibodies in serum and saliva from a strep throat human challenge trial. Baseline antibodies led to variable responses and affected susceptibility to strep throat.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

della Volpe et al. augment the ex vivo expansion potential of human haematopoietic stem cells (HSCs) by inhibiting ferroptosis with liproxstatin-1 or ferrostatin-1. Treated HSCs have enhanced in vivo repopulation capacity.

CAR-T cells have been found to be less effective as treatment for solid tumours. Here the authors, utilising B7H3 as an antigen, consider how changes in B7H3 binders lead to functional changes of CAR-T cells and differences in tumour outcomes in humanised mouse tumour models.

Tailored to provide diabetes management recommendations from large training and validation datasets, an artificial intelligence system integrating language and computer vision capabilities is shown to improve self-management of patients in a prospective implementation study.

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that has caused outbreaks in various regions of the world. Here the authors present safety and immunogenicity data from a phase 1 trial with the simian adenovirus vectored vaccine ChAdOx1 Chik, showing induction of neutralizing antibodies to four CHIKV lineages.

Monitoring internal loads in the human musculoskeletal system has been challenging, especially during dynamic movement. Here, the authors present a wearable joint torque estimation strategy using A-mode ultrasound and demonstrate its effectiveness during various real-world activities.

Here, the authors show that pharmacological and genetic mineralocorticoid receptor antagonism reduces intestinal fibrosis in mice and that NGAL is involved in mineralocorticoid receptor-mediated intestinal fibrogenesis.

Convalescent plasma (CP) has been trialed as a therapy for SARS-CoV-2 symptoms, but its heterogenous nature precludes uniform outcomes. Here the authors perform deep profiling of CP, as well as plasma of CP recipients before and after transfer, to find CP-mediated, spike/nucleocapsid-focused modulations of humoral responses in the recipient.

Single cell profiling of tissue from patients undergoing therapy has the potential to identify drug-induced immune changes. Here the authors show a skin scRNA-seq study of psoriasis patients treated with an IL-23 inhibitor and characterize changes in cell states during early treatment.

High numbers of COVID-19-related deaths have been reported in the United States, but estimation of the true numbers of infections is challenging. Here, the authors estimate that on 1 June 2020, 3.7% of the US population was infected with SARS-CoV-2, and 0.01% was infectious, with wide variation by state.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

New olfactory sensory neurons (OSNs) wire into highly organized olfactory bulb circuits throughout life. Here, the authors show that immature OSNs provide behaviourally relevant sensory input to olfactory bulb neurons that is functionally distinct from that provided by mature OSNs.

Jonathan Hodgkin enjoys a life story of Sydney Brenner, one of the fathers of molecular biology.

Whilst the ChAdOx1 nCoV-19 (AZD1222) vaccine has demonstrated efficacy against symptomatic disease, variants of concern (VOCs) with spike protein substitutions have led researchers to explore updating vaccines from ancestral spike protein. Authors use a Syrian hamster model to evaluate a vaccine encoding the spike protein of Beta VOC and assess efficacy against VOCs.

Natural disturbances imperil healthy and productive forests, but quantifying their effects at large scales is challenging. Here the authors apply machine learning to disturbance records and satellite data to quantify and map European forest vulnerability to fires, windthrows, and insect outbreaks through 1979-2018.

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