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http://dx.doi.org/10.1016/j.ejim.2024.09.010 | DOI Listing |
Nat Genet
September 2025
Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK.
Aberrant DNA methylation has been described in nearly all human cancers, yet its interplay with genomic alterations during tumor evolution is poorly understood. To explore this, we performed reduced representation bisulfite sequencing on 217 tumor and matched normal regions from 59 patients with non-small cell lung cancer from the TRACERx study to deconvolve tumor methylation. We developed two metrics for integrative evolutionary analysis with DNA and RNA sequencing data.
View Article and Find Full Text PDFBr J Cancer
September 2025
Department of Genetics, Institut Curie, PSL Research University, Paris, France.
Background: Identifying molecular alterations specific to advanced lung adenocarcinomas could provide insights into tumour progression and dissemination mechanisms.
Method: We analysed tumour samples, either from locoregional lesions or distant metastases, from patients with advanced lung adenocarcinoma from the SAFIR02-Lung trial by targeted sequencing of 45 cancer genes and comparative genomic hybridisation array and compared them to early tumours samples from The Cancer Genome Atlas.
Results: Differences in copy-number alterations frequencies suggest the involvement in tumour progression of LAMB3, TNN/KIAA0040/TNR, KRAS, DAB2, MYC, EPHA3 and VIPR2, and in metastatic dissemination of AREG, ZNF503, PAX8, MMP13, JAM3, and MTURN.
Nature
September 2025
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.
View Article and Find Full Text PDFLife Sci Alliance
November 2025
Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan
Mass-based fingerprinting can characterize microorganisms; however, expansion of these methods to predict specific gene functions is lacking. Therefore, mass fingerprinting was developed to functionally profile a yeast knockout library. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) fingerprints of 3,238 knockouts were digitized for correlation with gene ontology (GO).
View Article and Find Full Text PDFJ Neurotrauma
September 2025
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
Mean apparent propagator MRI (MAP-MRI) quantifies subtle alterations in tissue microstructure noninvasively and provides a more nuanced and comprehensive assessment of tissue architectural and structural integrity compared with other diffusion MRI techniques. We investigate the sensitivity of MAP-MRI-derived quantitative imaging biomarkers to detect previously unseen microstructural damage in patients with mild traumatic brain injuries (mTBI), whose clinical scans otherwise appeared normal. We developed and validated an MAP-MRI data processing pipeline for analyzing diffusion-weighted images for use in healthy controls and mTBI patients whose longitudinal scans were obtained from the GE/NFL/mTBI MRI database.
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