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This thesis develops an Artificial Intelligence (AI) approach intended for accurate patient stratification and precise diagnostics/prognostics in clinical and preclinical applications. The rapid advance in high throughput technologies and bioinformatics tools is still far from linking precisely the genome-phenotype interactions with the biological mechanisms that underlie pathophysiological conditions. In practice, the incomplete knowledge on individual heterogeneity in complex diseases keeps forcing clinicians to settle for surrogate endpoints and therapies based on a generic one-size-fits-all approach. The working hypothesis is that AI can add new tools to elaborate and integrate together in new features or structures the rich information now available from high-throughput omics and bioimaging data, and that such re- structured information can be applied through predictive models for the precision medicine paradigm, thus favoring the creation of safer tailored treatments for specific patient subgroups. The computational techniques in this thesis are based on the combination of dimensionality reduction methods with Deep Learning (DL) architectures to learn meaningful transformations between the input and the predictive endpoint space. The rationale is that such transformations can introduce intermediate spaces offering more succinct representations, where data from different sources are summarized. The research goal was attacked at increasing levels of complexity, starting from single input modalities (omics and bioimaging of different types and scales), to their multimodal integration. The approach also deals with the key challenges for machine learning (ML) on biomedical data, i.e. reproducibility, stability, and interpretability of the models. Along this path, the thesis contribution is thus the development of a set of specialized AI models and a core framework of three tools of general applicability: i. A Data Analysis Plan (DAP) for model selection and evaluation of classifiers on omics and imaging data to avoid selection bias. ii. The histolab Python package that standardizes the reproducible pre-processing of Whole Slide Images (WSIs), supported by automated testing and easily integrable in DL pipelines for Digital Pathology. iii. Unsupervised and dimensionality reduction techniques based on the UMAP and TDA frameworks for patient subtyping. The framework has been successfully applied on public as well as original data in precision oncology and predictive toxicology. In the clinical setting, this thesis has developed1: 1. (DAPPER) A deep learning framework for evaluation of predictive models in Digital Pathology that controls for selection bias through properly designed data partitioning schemes. 2. (RADLER) A unified deep learning framework that combines radiomics fea- tures and imaging on PET-CT images for prognostic biomarker development in head and neck squamous cell carcinoma. The mixed deep learning/radiomics approach is more accurate than using only one feature type. 3. An ML framework for automated quantification tumor infiltrating lymphocytes (TILs) in onco-immunology, validated on original pathology Neuroblastoma data of the Bambino Gesu’ Children’s Hospital, with high agreement with trained pathologists. The network-based INF pipeline, which applies machine learning models over the combination of multiple omics layers, also providing compact biomarker signatures. INF was validated on three TCGA oncogenomic datasets. In the preclinical setting the framework has been applied for: 1. Deep and machine learning algorithms to predict DILI status from gene expression (GE) data derived from cancer cell lines on the CMap Drug Safety dataset. 2. (ML4TOX) Deep Learning and Support Vector Machine models to predict potential endocrine disruption of environmental chemicals on the CERAPP dataset. 3. (PathologAI) A deep learning pipeline combining generative and convolutional models for preclinical digital pathology. Developed as an internal project within the FDA/NCTR AIRForce initiative and applied to predict necrosis on images from the TG-GATEs project, PathologAI aims to improve accuracy and reduce labor in the identification of lesions in predictive toxicology. Furthermore, GE microarray data were integrated with histology features in a unified multi-modal scheme combining imaging and omics data. The solutions were developed in collaboration with domain experts and considered promising for application.

Yes / Recovering high-quality 3D point clouds from monocular endoscopic images is a challenging task. This paper proposes a novel deep learning-based computational framework for 3D point cloud reconstruction from single monocular endoscopic images. An unsupervised mono-depth learning network is used to generate depth information from monocular images. Given a single mono endoscopic image, the network is capable of depicting a depth map. The depth map is then used to recover a dense 3D point cloud. A generative Endo-AE network based on an auto-encoder is trained to repair defects of the dense point cloud by generating the best representation from the incomplete data. The performance of the proposed framework is evaluated against state-of-the-art learning-based methods. The results are also compared with non-learning based stereo 3D reconstruction algorithms. Our proposed methods outperform both the state-of-the-art learning-based and non-learning based methods for 3D point cloud reconstruction. The Endo-AE model for point cloud completion can generate high-quality, dense 3D endoscopic point clouds from incomplete point clouds with holes. Our framework is able to recover complete 3D point clouds with the missing rate of information up to 60%. Five large medical in-vivo databases of 3D point clouds of real endoscopic scenes have been generated and two synthetic 3D medical datasets are created. We have made these datasets publicly available for researchers free of charge. The proposed computational framework can produce high-quality and dense 3D point clouds from single mono-endoscopy images for augmented reality, virtual reality and other computer-mediated medical applications.

Master's thesis deals with multiclass image segmentation using convolutional neural networks. The theoretical part of the Master's thesis focuses on image segmentation. There are basics principles of neural networks and image segmentation with more types of approaches. In practical part the Unet architecture is choosen and is described for image segmentation more. U-net was applied for medicine dataset. There is processing procedure which is more described for image proccesing of three-dimmensional data. There are also methods for data preproccessing which were applied for image multiclass segmentation. Final part of current master's thesis evaluates results.