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The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

The order in which driver mutations of colorectal cancer occur in intestinal epithelium can determine whether clones are positively or negatively selected and can shape subsequent tumour development.

How age affect the immune response to malaria is not fully understood. Here, the authors characterise the transcriptome and serum inflammatory cytokines in children and adults in response to malaria, showing that there is an increase of inflammatory chemokine and cellular responses in adults compared to children.

Axonal injury, induced in the white matter by expansion of early tumour cells, is a key driver of glioblastoma progression.

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.

Al-Hilal, Chrysovergi et al. identify a role for durotaxis in lung fibrosis and metastatic pancreatic cancer, mediated by the FAK–paxillin mechanosensor complex, and demonstrate therapeutic targeting of this pathway using the small molecule JP-153.

This study uses single-cell DNA sequencing to analyze genomic evolution in pancreatic cancer using a cohort of multiregionally and longitudinally sampled patients’ tissues across various clinical contexts.

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.

Sebaceous tumours are a rare skin tumour which have highly variable outcomes. Here, the authors analyse tumours from 222 patients to identify genomic mutations to assess the molecular portrait of the spectrum of tumours.

Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

Energetic electron precipitation (EEP) from the Earth's outer radiation belt can lead to ozone loss in the mesosphere, yet long-term variability has not been quantified. Here, the authors present satellite observations and show that on solar cycle timescales EEP causes ozone to vary by up to 34%.

Analysis of medulloblastomas in humans and mice shows that the functional consequences of ZIC1 mutations are exquisitely dependent on the cells of origin that give rise to different subgroups of medulloblastoma.

Patients with myelodysplastic syndromes (MDS) have limited therapeutic options. Here the authors show that functionally impaired NK cells contribute to immune escape of pre-malignant clones in early stage MDS and that NK adoptive cell therapy can be considered to prevent or delay the development of MDS.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Li et al. reveal projection neuron-type-specific dynamics that coordinate corticothalamic communication during reach-to-consume behavior in mice.

Jonaitis et al demonstrate that serotonin differentially modulates feedforward inhibitory neurons in the olfactory system of Drosophila which likely reflects odor categorization in higher order brain regions.

In cancer, associations between mutational signatures and driver mutations have been proposed but not fully explored. Here, the authors develop sigDriver to find associations between mutational signatures and mutation hotspots in order to predict coding and non-coding driver mutations in pan-cancer genomics data.

In many strongly correlated systems the coupling of electronic and lattice degrees of freedom leads to ambiguity over the mechanism driving electronic phase transitions. Here the authors show that inter-layer effects play an important role in the charge ordering transition of 1T-TaS₂.

This study finds that flood insurance policy design affects economic development in floodplains and, consequently, flood risk in Europe. Therefore, the authors advocate for flood insurance design to be integrated in climate change adaptation policy.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

A mathematical framework to estimate the fitness of cancer driver mutations by integrating mutational bias, oncogenicity and immunogenicity finds fundamental trade-offs in cancer evolution.

The authors analyze 162 primary mismatch-repair-deficient gliomas and identify three subgroups underpinned by distinct somatic mutations in replicative DNA polymerases and IDH1.

Many premalignant colorectal polyps in familial adenomatous polyposis arise polyclonally rather than from a single mutated cell, showing diverse early evolutionary trajectories that frequently occur without clonal APC or KRAS driver events.

A wide survey of pesticide effects on soil biodiversity across 373 sites in Europe reveals that pesticide residues occur in 70% of sites and have major effects on soil biodiversity and functional ecology.

By integrating DNA genotype and RNA sequencing data from human samples, d’Escamard et al. identify a gene regulatory co-expression supernetwork that plays an important role in fibromuscular dysplasia, a poorly understood disease affecting 3–5% of adult females.

In glioblastoma (GBM), tumour microtubes (TM) connect tumour cells to a broader cellular network, with roles in tumour progression and therapy resistance. Here, the authors combine a dye uptake method in GBM xenograft models with subsequent scRNA-seq to infer a TM connectivity signature, finding CHI3L1 as a marker of connectivity.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

Spiradenoma and cylindroma are skin adnexal tumors that can behave aggressively and undergo malignant transformation. Here, the authors genetically assess a cohort of these adnexal tumours, highlighting recurrent ALPK1 mutations and revealing the genomic landscape of these rare tumours.

Analysis of whole-genome sequencing data from over 10,000 tumor samples spanning 35 cancer types identifies putative driver genes and highlights new therapeutic opportunities.

Single-cell multi-omic analyses show that chronic inflammation contributes to myeloproliferative neoplasm transformation to secondary acute myeloid leukemia by enhancing tumor protein 53 (TP53) mutant cell fitness and genetic evolution.

Cerebral organoids can be used to gain insights into neuropsychiatric disorders. Here the authors carry out RNAseq characterization from organoids derived from donors with autism spectrum disorder to identify associated cell type specific driver genes.

It is difficult to identify cancer driver genes in cancers, for instance BRCA1 mutated breast cancer, that are characterised by large scale genomic alterations. Here, the authors develop genetically engineered mouse models of BRCA1-deficient breast cancer that allow highthroughput in vivo perturbation of candidate driver genes, validating drivers Myc, Met, Pten and Rb1, and identifying MCL1 as a collaborating driver whose targeting can impact efficacy of PARP inhibition.

The accumulation and subsequent recycling of carbonate in the crust may have helped to drive the oxygenation of the early Earth, according to an ocean and atmosphere box model incorporating the inorganic carbon cycle.

Somatic mutations in blood cells (CHIP) are linked to diseases like heart disease, but the mechanisms are unclear. Here, the authors show that different CHIP driver genes alter unique sets of plasma proteins, some of which are validated in mouse models.

Metagenomics and metabolomics analysis of a longitudinal cohort of 123 very preterm infants reveals multiple drivers of gut microbiome development and indicates that there are strain-specific effects of probiotic products.

Magnetotail reconnection plays a crucial role in explosive energy conversion in geospace. Here, the authors show that magnetotail reconnection starts from electron reconnection in the presence of a strong external driver, which then develops into ion reconnection.

Seegren et al. demonstrate that the mitochondrial calcium uptake complex is a key molecular apparatus that links age-related changes in mitochondrial physiology to systemic macrophage-mediated age-associated inflammation.

Identification of cancer driver genes, especially those that can act as tumour suppressors or oncogenes depending on context, remains a challenge. Here, the authors introduce Moonlight, a tool that integrates multi-omic data to address this challenge and identify numerous dual-role cancer genes.

It is currently unclear if cell-free DNA samples from metastatic cancers are as informative as tissue ones for cancer profiling. Here the authors show that cell-free DNA samples from rapid autopsies capture clonal and subclonal alterations of metastatic tumours and reveal more driver alterations than single tissue samples.

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.

Of 248 marine heatwaves between 1993 and 2019 in North American and European seas, the effects on fish biomass were often minimal, and the heatwaves were not consistently associated with tropicalization or deborealization.

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.

Acute myeloid leukaemia (AML) is maintained by self-renewing leukemic stem cells. Here the authors show that Heat Shock Transcription Factor 1 (HSF1) is specifically required for the maintenance of AML stem cells, while sparing steady-state and stressed haematopoiesis and that pharmacologically targeting HSF1 may have broad anti-leukemic effects.

Saturation genome editing of a cancer mutation hotspot in CTNNB1, the gene encoding β-catenin, reveals a gradient of effects of missense mutations on Wnt signaling.

The accumulation of genetic and epigenetic mutations in cancer cells can drive malignant growth. Here, the authors model the evolution of intratumoral diversity and examine the classification of driver and passenger mutations, heterogeneity within tumours, and the dynamics of tumour response to targeted therapies.