Search

This Review outlines the fundamental role of chimeric antigen receptor (CAR) T cell therapy for children, adolescents and young adults (CAYAs) with relapsed and/or refractory B cell acute lymphoblastic leukaemia, emphasizing the crucial need to further exploit CAR T cells and other immunotherapies to improve survival with broadened access across disease states. Opportunities and challenges for expanding CAR T cell therapy to other haematological and non-haematological malignancies in CAYAs are also discussed.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

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.

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.

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.

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.

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.

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.

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.

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.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

This study supports neurofilament light chain protein (NfL) in both cerebrospinal fluid (CSF) and blood as an early marker of neurodegeneration in Alzheimer’s disease but suggests that NfL in CSF may be better suited than blood for monitoring clinical trial outcomes in symptomatic patients.

In this work, authors develop a live vaccine candidate against Pseudomonas aeruginosa using an unnatural amino acid-based auxotrophic strategy. They provide insight on the vaccine’s in vivo safety profile and protection of mice against lethal P. aeruginosa challenge.

The early Eocene was characterized by exceptionally high global temperatures and no polar ice. Here, clumped isotope paleothermometry of glendonite calcite from the Danish Basin shows that these were formed in waters below 5 °C, indicating that regionalised cool episodes punctuated the background warmth of the early Eocene.

The presence of guest atoms—known as rattlers—in the cages of some clathrate structures is considered to be responsible for the low thermal conductivity of the materials. Neutron spectroscopy provides important evidence regarding the actual phonon dispersion in the material, and the precise way in which this is influenced by rattlers.

This study employs a citizen science approach to identify and classify over 230,000 light sources in German city centers, suburbs and villages. The results underscore the pivotal role of citizen science in expanding knowledge of artificial light emissions and bolstering policymaking efforts to mitigate urban light pollution.

Evidence synthesized from 252 large-herbivore exclusion studies suggests that herbivore-induced change in dominance, independent of site productivity or precipitation, best predicts herbivore effects on biodiversity in grassland and savannah sites.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Type-1 innate lymphoid cells have been shown to drive intestinal epithelial proliferation and extracellular matrix remodelling through TGF-β1 secretion, which could exacerbate inflammatory bowel disease comorbidities such as cancer and fibrosis.

Flickering gamma-ray flashes associated with terrestrial thunderstorms have been observed, which may be the missing link between gamma-ray glows and TGFs.

Tropical thunderclouds over ocean and coastal regions are shown to emit gamma rays for several hours over areas of up to a few thousand square kilometres, contradicting the quasi-stationary picture of glows.

In order to make optimal choices, it is adaptive for the brain to build a model of the world to enable predictions about likely later events. Here, the authors show that activity across learning in the orbitofrontal cortex comes to represent expected states, up to 30 s in the future.

Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions.

A newly developed RIPK3 inhibitor blocks necroptosis of lung cells, reduces lung inflammation and prevents mortality in a mouse model of influenza A virus infection.

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.

The potential use of circulating tumour DNA in classic Hodgkin lymphoma detection, classification and monitoring is defined.

Analysing occurrence records from >200,000 plant species across 1,103 regions, the authors show that mycorrhizal associations are less common among native island plants than native mainland plants and decline with increasing island isolation.