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arXiv · 2408.00200

UnPaSt: unsupervised patient stratification by biclustering of omics data

Michael Hartung·Andreas Maier·Yuliya Burankova·Fernando Delgado-Chaves·Olga I. Isaeva·Alexey Savchik·Fábio Malta de Sá Patroni·Jens J. G. Lohmann·Daniel He·Casey Shannon·Jan-Ole Schulze·Katharina Kaufmann·Zoe Chervontseva·Farzaneh Firoozbakht·Anne Hartebrodt·Niklas Probul·Olga Tsoy·Alexandra Abisheva·Evgenia Zotova·Kavya Singh·Kristel Van Steen·Malte Kuehl·Victor G. Puelles·David B. Blumenthal·Martin Ester·Tanja Laske·Jan Baumbach·Olga Zolotareva
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Abstract

Unsupervised patient stratification is essential for disease subtype discovery, yet, despite growing evidence of molecular heterogeneity of non-oncological diseases, popular methods are benchmarked primarily using cancers with mutually exclusive molecular subtypes well-differentiated by numerous biomarkers. Evaluating 22 unsupervised methods, including clustering and biclustering, using simulated and real transcriptomics data revealed their inefficiency in scenarios with non-mutually exclusive subtypes or subtypes discriminated only by few biomarkers. To address these limitations and advance precision medicine, we developed UnPaSt, a novel biclustering algorithm for unsupervised patient stratification based on differentially expressed biclusters. UnPaSt outperformed widely used patient stratification approaches in the de novo identification of known subtypes of breast cancer and asthma. In addition, it detected many biologically insightful patterns across bulk transcriptomics, proteomics, single-cell, spatial transcriptomics, and multi-omics datasets, enabling a more nuanced and interpretable view of high-throughput data heterogeneity than traditionally used methods.

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Michael Hartung, Andreas Maier, Yuliya Burankova, Fernando Delgado-Chaves, Olga I. Isaeva, Alexey Savchik, Fábio Malta de Sá Patroni, Jens J. G. Lohmann, Daniel He, Casey Shannon, Jan-Ole Schulze, Katharina Kaufmann, Zoe Chervontseva, Farzaneh Firoozbakht, Anne Hartebrodt, Niklas Probul, Olga Tsoy, Alexandra Abisheva, Evgenia Zotova, Kavya Singh, Kristel Van Steen, Malte Kuehl, Victor G. Puelles, David B. Blumenthal, Martin Ester, Tanja Laske, Jan Baumbach, Olga Zolotareva. 2024-07-31. UnPaSt: unsupervised patient stratification by biclustering of omics data. https://arxiv.org/abs/2408.00200

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