Search

In a large single-arm phase 2 trial, the anti-PD-1 inhibitor tislelizumab combined with the next-generation BTK inhibitor zanubrutinib had an overall response rate of 58.3% and was well tolerated in patients with Richter’s transformation.

Richter syndrome (RS) is the transformation of chronic lymphocytic leukaemia (CLL) into aggressive lymphoma, in most cases diffuse large B-cell lymphoma (DLBCL). Here, the authors characterize the DNA methylation and transcriptomic profiles of RS samples, find a clonally-related CLL epigenetic imprint, and develop classifiers for “RS-type” de novo DLBCLs.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

By assessing different clinical, behavioral and welfare parameters, the authors demonstrate that the oral administration of tramadol is more suitable than metamizole as on-demand analgesia in mouse models of acute lymphoblastic leukemia.

By integrating single-cell RNA and physically interacting cell sequencing analysis, here Cohen and colleagues report that neutrophils are enriched in physical crosstalk with breast tumor cells, promoting cancer aggressiveness.

This work compares the preclinical lung biodistribution and efficacy profile of inhaled anti-CCN2 (cellular communication network factor 2) Anticalin® protein PRS-220 for the treatment for idiopathic pulmonary fibrosis (IPF) compared to systemic delivery of a CCN2 inhibitor.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

SNURPORTIN-1, encoded by the SNUPN gene, plays a key role in the nuclear import of spliceosomal small nuclear ribonucleoproteins, however its physiological function remains unclear. Here the authors report that recessive SNUPN mutations cause a distinct subtype of childhood muscular dystrophy and reveal SNURPORTIN-1’s role in muscle homeostasis, offering insights for new therapeutic strategies.

Intravenous delivery of an adenine base editor and a single-guide RNA for the Fah gene can correct an A>G splice-site mutation in an adult mouse model of tyrosinaemia.

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.

CD3 bispecific antibodies (bsAbs) have demonstrated promising clinical responses in hematological malignancies but clinical benefit in solid tumors has been limited. Here the authors report that pre-treatment vaccination promotes the infiltration of tumor-(un)related effector CD8 T cells, improving the efficacy of CD3 bsAbs in solid tumors.

Whole-genome sequencing of chronic lymphocytic leukemia from 485 patients identifies putative coding and noncoding drivers of disease. Genomically defined subgroups show distinct clinical and biological characteristics.

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.

Ancient genome-wide data of 722 individuals and interdisciplinary analysis of large seventh- to eighth-century ce neighbouring cemeteries near Vienna are used to address the impact of the encounter between Eastern Asian Avars and Europeans.

Using brain organoids models, Prigione and colleagues uncovered the impact of Huntington’s disease on human brain developmental and identified early dysregulation of CHCHD2, which disrupted mitochondria and might serve as a therapeutic target.

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.

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.

Dilanthanide complexes that possess radical bridges exhibit enhanced magnetic exchange coupling, affording molecular magnets with high blocking temperatures. Here, the authors explore a series of dilanthanide-encapsulated fullerenes where the radical bridge is taken to its limit and the role is played by a single unpaired electron.

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.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Oligodendrocyte differentiation is known to depend on transcription factors Sox10, Nkx2.2, and Olig2. Here, the authors show that Nfat/calcineurin signaling contributes to oligodendrocyte differentiation by relieving mutual repression of Nkx2.2 and Olig2.

A single cell type in the Drosophila visual system implements motion-opponent inhibition at multiple consecutive circuit levels. This neural architecture enables high stimulus selectivity without compromising sensitivity under noisy conditions.

The authors investigate the broad-scale climatological and soil properties that co-vary with major axes of plant functional traits. They find that variation in plant size is attributed to latitudinal gradients in water or energy limitation, while variation in leaf economics traits is attributed to both climate and soil fertility including their interaction.

The clinical application of T cell bispecific antibodies (TCBs) is often limited by the lack of tumour-specific antigens. In this study, the authors present a strategy to increase TCB tumour-selectivity by adding an anti-CD3 moiety that can be specifically activated by tumor specific proteases in the tumor microenvironment.

The closest homologue of GNOM in Arabidopsis thaliana, GNOM-LIKE1 (GNL1) performs the regulation of endoplasmic reticulum–Golgi transport in plants.

GNL1 localizes to and acts primarily at Golgi stacks, regulating COPI-coated vesicle formation. GNOM can functionally substitute for GNL1, but not vice versa. Hence the ARF–GEFs of the GBF1 class perform a conserved role in the endoplasmic reticulum–Golgi trafficking which is done by GNOM and GNL1 in plants

Authors present both preclinical data in mice and clinical data from humans in support of the hypothesis that stress negatively affects bone growth and repair. These effects are mediated by neutrophil-derived catecholamines inhibiting cartilage-to-bone transition via β2-adrenoceptor signaling in chondrocytes.

Here, the authors show that IFNγ binding to heparan sulfate is a mechanism to restrain IFNγ at the site of production, thereby preventing high systemic levels of this cytokine and associated immunopathology.

Using a composite bioinformatics approach, the DNA:DNA:RNA triplex-forming lncRNAs HIF1α-AS1 was identified in human endothelial cells which recruits an epigenetic silencing complex to limit expression of triplex target genes.