Uncovering cancer-immunesystem interactions could inform how patients respond to immunotherapy thecrick
Canonical and candidate drivers damaged in 7,730 TCGA samples.Predicted TIME drivers using Lasso regularised ordinal regression.Frequency of TIME and non-TIME driver alterations per cancer type.Comparison of clonality between TIME and non-TIME drivers.Comparison of TIME levels between HNSC molecular subtypes.Components of HNSC TIME drivers - TIME TFs functional networks.Rights and permissionsThis article is licensed under a Creative Commons Attribution 4.
0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material.
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Genomic hallmarks and therapeutic implications of G0 cell cycle arrest in cancer - Genome BiologyBackground Therapy resistance in cancer is often driven by a subpopulation of cells that are temporarily arrested in a non-proliferative G0 state, which is difficult to capture and whose mutational drivers remain largely unknown. Results We develop methodology to robustly identify this state from transcriptomic signals and characterise its prevalence and genomic constraints in solid primary tumours. We show that G0 arrest preferentially emerges in the context of more stable, less mutated genomes which maintain TP53 integrity and lack the hallmarks of DNA damage repair deficiency, while presenting increased APOBEC mutagenesis. We employ machine learning to uncover novel genomic dependencies of this process and validate the role of the centrosomal gene CEP89 as a modulator of proliferation and G0 arrest capacity. Lastly, we demonstrate that G0 arrest underlies unfavourable responses to various therapies exploiting cell cycle, kinase signalling and epigenetic mechanisms in single-cell data. Conclusions We propose a G0 arrest transcriptional signature that is linked with therapeutic resistance and can be used to further study and clinically track this state.
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Newborn genome sequencing project identifies unanticipated disease risksGenomic sequencing of newborns reveals unanticipated genetic risks, prompting actionable medical interventions and potential life-saving care for infants and their families. This study highlights the value of comprehensive sequencing in newborns for early detection and management of genetic conditions.
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Mechanistic insights into how the SARS-CoV-2 virus affects the nervous system, alters its function, and causes neuropathologyMechanistic insights into how the SARS-CoV-2 virus affects the nervous system, alters its function, and causes neuropathology ScienceAdvances UQ_News covid COVID19 SARSCoV2 nervoussystem function neuropathology
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Conor Daly loses full-time Ed Carpenter Racing IndyCar drive🗣️'This is the most difficult decision I have made as a team owner because I respect ConorDaly22 and know what he means to IndyCar and its fans.' Daly and ECRIndy have parted company ⬇️
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Conor Daly loses full-time Ed Carpenter Racing IndyCar driveIndyCar fan favourite Conor Daly has lost his full-time IndyCar Series ride with Ed Carpenter Racing, with a new driver set to replace him for the next race.\u00a0
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