Clonal driver neoantigen loss under EGFR TKI and immune selection pressures.

Neoantigen vaccines are under investigation for various cancers, including epidermal growth factor receptor (EGFR)-driven lung cancers. We tracked the phylogenetic history of an EGFR mutant lung cancer treated with erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine (NPV) targeting ten somatic mutations, including EGFR exon 19 deletion (ex19del). The ex19del mutation was clonal, but is likely to have appeared after a whole-genome doubling (WGD) event.

Establishing a Pan-European, multi-disciplinary taphonomic research Infrastructure: The 'UK-Netherlands decomposition experimental research (UNDER) Group'.

This study unveils the establishment of the United Kingdom-Netherlands Decomposition Experimental Research (UNDER) working group, marking a pioneering initiative in practical Forensic Taphonomy within the UK. Our primary objective was to craft a cohesive multidisciplinary framework, designed to ethically orchestrate, execute, and assess human decomposition. Concurrently, we aimed to amass data through human burials, fostering collaboration among diverse forensic experts across Europe.

Deep cell phenotyping and spatial analysis of multiplexed imaging with TRACERx-PHLEX.

The growing scale and dimensionality of multiplexed imaging require reproducible and comprehensive yet user-friendly computational pipelines. TRACERx-PHLEX performs deep learning-based cell segmentation (deep-imcyto), automated cell-type annotation (TYPEx) and interpretable spatial analysis (Spatial-PHLEX) as three independent but interoperable modules. PHLEX generates single-cell identities, cell densities within tissue compartments, marker positivity calls and spatial metrics such as cellular barrier scores, along with summary graphs and spatial visualisations.

Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling.

The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone.