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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.

Treatment strategy of solid tumors requires continuous development. Here the authors develop a Macrophage Drug Conjugate (MDC) platform by loading ferritin-drug complexes to macrophages. MDC transfers the ferritin to cancer cells via ‘TRAnsfer of Iron binding protein’ (TRAIN) process and reduces tumor volume in various mouse tumor models.

Ceremonial feasting in Early Neolithic Asiab, western Iran, involved transport of animals over substantial distances to celebrate far-flung social networks, according to analysis of microscopic tooth growth patterns and geochemistry.

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.

Atomically thin transition metal dichalcogenides host excitons and trions, however higher-order states, although possible, are difficult to identify experimentally. Here, the authors perform polarization-resolved coherent spectroscopy to unveil the signature of neutral and charged inter-valley biexcitons in monolayer MoSe₂.

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.

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.

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.

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.

Linking structural variants to gene expression information identifies aberrant signaling pathways.

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.

Understanding how biosilica forms is crucial to our knowledge of this important biomaterial. Now, the role of collagen as structuring agent for the metre-long spicules of a primitive glass sponge has been revealed and found to have an unusual peptide motif.

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.

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.

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.

An intercomparison exercise reassesses mass loss from glaciers worldwide based on the main in situ and satellite methods from 2000 to 2023; the results are consistent with previous assessments and provide a refined and comprehensive observational baseline for future impact and modelling studies.

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.

Here the authors present a SARS-CoV2 seroepidemiological observational study from a random, household-based study population in a small town in Germany, showing the effect of a super-spreading event on infection rate, severity, and potentially infection fatality rate.

Lim and colleagues present the UK PROSECO study where they assess humoral and cellular immune responses to one, two and three doses of vaccination against SARS-CoV-2 in patients with B-cell malignancies in a prospective observational study.

Nanobodies are normally made from immunized camelids, Ig transgenic mice or synthetic libraries. In this study, the authors introduce the llama Ig heavy chain locus into mice lacking this locus, thereby generating a line in which nanobodies can be made by direct immunization in the absence of an endogenous antibody repertoire.

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.

Complex structural variations in single cells are detected by integrating read depth, template strand and haplotype phase information.

Genetic association signals for fractures have been reported at the RSPO3 locus, but the causal gene and the underlying mechanism are unknown. Here, the authors show that RSPO3 exerts an important role for vertebral trabecular bone mass and bone strength in mice and fracture risk in humans.

This study unveils that stop codon readthrough is prevalent in E. coli, particularly under stress conditions. It highlights the influence of stop codon type and genetic context, with both transcriptional and translational origins.

Silencing of endogenous retroviruses is crucial for maintaining transcriptional and genomic integrity of cells and is maintained by histone H3K9 methylation and/or DNA methylation in various cell types. Here the authors show that loss of DNA methyltransferase DNMT1 in endoderm results in ERV derepression while H3K9me3 is unaltered.

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.

Biochemical and biophysical analyses of eye lenses from mouse strains that develop cataract due to mutations in α-, β-, or γ-crystallin proteins reveal that the mutant protein levels are largely reduced, but other crystallin proteins, including α-crystallins, precipitate.

Using stereolithography 3D printers, a silica nanocomposite is shaped and then fused to produce non-porous, very smooth, highly transparent fused silica glass components.

Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

The phase behavior of grain boundaries can influence the interfacial properties. Here the authors demonstrate nanoscale patterning of a grain boundary by two alternating phases in Cu that exhibit a congruent, diffusionless transition between the two phases.

Proteomics can be used to refine cancer classification. Here, the authors characterise chronic lymphocytic leukaemia patients by proteogenomics, and identified a subtype of patients with poor prognosis associated with aberrant B cell receptor signalling.

Liet al. study degradation in organic photovoltaics from a morphological perspective. They find that donor and acceptor phases undergo excessive demixing via spinodal decomposition resulting in a reduction of charge generation. Demixing is due to the inherently low miscibility of both materials.