Predicting subclonal TP53 mutations from tumor spatial transcriptomics data using a graph convolutional neural network

Luijts, T.; Hoogstoel, S.; Pappaert, E.; De Meester, E.; Van Nieuwerburgh, F.; Van Hamme, E.; De Schepper, S.; Willaert, W.; Vral, A.; Hoorens, I.; Van den Eynden, J.

doi:10.64898/2026.07.08.737173

bioRxiv · 10.64898/2026.07.08.737173

Predicting subclonal TP53 mutations from tumor spatial transcriptomics data using a graph convolutional neural network

Luijts, T.·Hoogstoel, S.·Pappaert, E.·De Meester, E.·Van Nieuwerburgh, F.·Van Hamme, E.·De Schepper, S.·Willaert, W.·Vral, A.·Hoorens, I.·Van den Eynden, J.

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Abstract

Spatial transcriptomics (ST) has revolutionized our understanding of tumor biology but inherently lacks information on the upstream somatic driver mutations. We developed a spatially-aware graph convolutional neural network (MuT-GCNN) that infers TP53 clones directly from ST data. MuT-GCNN was trained on virtual ST slides with clones simulated from a large collection of existing RNA and matched DNA sequencing data. The model is highly performant with precision and recall values exceeding 95% in most analysed cancer types. It is sensitive for single hit mutations and is primarily informed by the expression of p53 signalling genes in cancer cells. After demonstrating the potential of the model on publicly available squamous cell carcinoma (SCC) data, a direct validation was performed using ST and matched DNA sequencing from serial slices obtained from 4 cutaneous SCC samples. With the increasing availability of ST data and upcoming ST atlases, MuT-GCNN can unveil the location of (sub)clonal alterations in TP53, the most frequently mutated gene in human cancer.

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Luijts, T., Hoogstoel, S., Pappaert, E., De Meester, E., Van Nieuwerburgh, F., Van Hamme, E., De Schepper, S., Willaert, W., Vral, A., Hoorens, I., Van den Eynden, J.. 2026-07-09. Predicting subclonal TP53 mutations from tumor spatial transcriptomics data using a graph convolutional neural network. https://doi.org/10.64898/2026.07.08.737173

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