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We are rapidly approaching a future in which cancer patient digital twins will reach their potential to predict cancer prevention, diagnosis, and treatment in individual patients. This will be realized based on advances in high performance computing, computational modeling, and an expanding repertoire of observational data across multiple scales and modalities. In 2020, the US National Cancer Institute, and the US Department of Energy, through a trans-disciplinary research community at the intersection of advanced computing and cancer research, initiated team science collaborative projects to explore the development and implementation of predictive Cancer Patient Digital Twins. Several diverse pilot projects were launched to provide key insights into important features of this emerging landscape and to determine the requirements for the development and adoption of cancer patient digital twins. Projects included exploring approaches to using a large cohort of digital twins to perform deep phenotyping and plan treatments at the individual level, prototyping self-learning digital twin platforms, using adaptive digital twin approaches to monitor treatment response and resistance, developing methods to integrate and fuse data and observations across multiple scales, and personalizing treatment based on cancer type. Collectively these efforts have yielded increased insights into the opportunities and challenges facing cancer patient digital twin approaches and helped define a path forward. Given the rapidly growing interest in patient digital twins, this manuscript provides a valuable early progress report of several CPDT pilot projects commenced in common, their overall aims, early progress, lessons learned and future directions that will increasingly involve the broader research community. 

This paper presents a new algorithm, Reinforced and Informed Network-based Clustering (RINC), for finding unknown groups of similar data objects in sparse and largely non-overlapping feature space where a network structure among features can be observed. Sparse and non-overlapping unlabeled data become increasingly common and available especially in text mining and biomedical data mining. RINC inserts a domain informed model into a modelless neural network. In particular, our approach integrates physically meaningful feature dependencies into the neural network architecture and soft computational constraint. Our learning algorithm efficiently clusters sparse data through integrated smoothing and sparse auto-encoder learning. The informed design requires fewer samples for training and at least part of the model becomes explainable. The architecture of the reinforced network layers smooths sparse data over the network dependency in the feature space. Most importantly, through back-propagation, the weights of the reinforced smoothing layers are simultaneously constrained by the remaining sparse auto-encoder layers that set the target values to be equal to the raw inputs. Empirical results demonstrate that RINC achieves improved accuracy and renders physically meaningful clustering results.