Victor G. Puelles

Michael Hartung, Andreas Maier, Yuliya Burankova et al.

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.

Ann-Katrin Thebille, Esther Dietrich, Martin Klaus et al.

The automated analysis of medical images is currently limited by technical and biological noise and bias. The same source tissue can be represented by vastly different images if the image acquisition or processing protocols vary. For an image analysis pipeline, it is crucial to compensate such biases to avoid misinterpretations. Here, we evaluate, compare, and improve existing generative model architectures to overcome domain shifts for immunofluorescence (IF) and Hematoxylin and Eosin (H&E) stained microscopy images. To determine the performance of the generative models, the original and transformed images were segmented or classified by deep neural networks that were trained only on images of the target bias. In the scope of our analysis, U-Net cycleGANs trained with an additional identity and an MS-SSIM-based loss and Fixed-Point GANs trained with an additional structure loss led to the best results for the IF and H&E stained samples, respectively. Adapting the bias of the samples significantly improved the pixel-level segmentation for human kidney glomeruli and podocytes and improved the classification accuracy for human prostate biopsies by up to 14%.