Precision medicine is a paradigm shift in healthcare relying heavily on genomics data. However, the complexity of biological interactions, the large number of genes as well as the lack of comparisons on the analysis of data, remain a tremendous bottleneck regarding clinical adoption. In this paper, we introduce a novel, automatic and unsupervised framework to discover low-dimensional gene biomarkers. Our method is based on the LP-Stability algorithm, a high dimensional center-based unsupervised clustering algorithm. It offers modularity as concerns metric functions and scalability, while being able to automatically determine the best number of clusters. Our evaluation includes both mathematical and biological criteria to define a quantitative metric. The recovered signature is applied to a variety of biological tasks, including screening of biological pathways and functions, and characterization relevance on tumor types and subtypes. Quantitative comparisons among different distance metrics, commonly used clustering methods and a referential gene signature used in the literature, confirm state of the art performance of our approach. In particular, our signature, based on 27 genes, reports at least 30 times better mathematical significance (average Dunn's Index) and 25% better biological significance (average Enrichment in Protein-Protein Interaction) than those produced by other referential clustering methods. Finally, our signature reports promising results on distinguishing immune inflammatory and immune desert tumors, while reporting a high balanced accuracy of 92% on tumor types classification and averaged balanced accuracy of 68% on tumor subtypes classification, which represents, respectively 7% and 9% higher performance compared to the referential signature.

In this study, we propose a 3D deep neural network called U-ReSNet, a joint framework that can accurately register and segment medical volumes. The proposed network learns to automatically generate linear and elastic deformation models, trained by minimizing the mean square error and the local cross correlation similarity metrics. In parallel, a coupled architecture is integrated, seeking to provide segmentation maps for anatomies or tissue patterns using an additional decoder part trained with the dice coefficient metric. U-ReSNet is trained in an end to end fashion, while due to this joint optimization the generated network features are more informative leading to promising results compared to other deep learning-based methods existing in the literature. We evaluated the proposed architecture using the publicly available OASIS 3 dataset, measuring the dice coefficient metric for both registration and segmentation tasks. Our promising results indicate the potentials of our method which is composed from a convolutional architecture that is extremely simple and light in terms of parameters.