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New preprint: Spatial structure governs the mode of tumour evolution
Characterizing the mode – the way, manner, or pattern – of evolution in tumours is important for clinical forecasting and optimizing cancer treatment. DNA sequencing studies have inferred various modes, including branching, punctuated and neutral evolution, but it is unclear why a particular pattern predominates in any given tumour.1, 2 Here we propose that differences in tumour architecture alone can explain the variety of observed patterns. We examine this hypothesis using spatially explicit population genetic models and demonstrate that, within biologically relevant parameter ranges, human tumours are expected to exhibit four distinct onco-evolutionary modes (oncoevotypes): rapid clonal expansion (predicted in leukaemia); progressive diversification (in colorectal adenomas and early-stage colorectal carcinomas); branching evolution (in invasive glandular tumours); and effectively almost neutral evolution (in certain non-glandular and poorly differentiated solid tumours).
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Paper published in Nature Medicine: Deep learning can predict microsatellite instability directly from histology in gastrointestinal cancer
Microsatellite instability determines whether patients with gastrointestinal cancer respond exceptionally well to immunotherapy. However, in clinical practice, not every patient is tested for MSI, because this requires additional genetic or immunohistochemical tests. Here we show that deep residual learning can predict MSI directly from H&E histology, which is ubiquitously available. This approach has the potential to provide immunotherapy to a much broader subset of patients with gastrointestinal cancer.
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