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Network modeling methods for precision medicine

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 Added by Victor Popescu
 Publication date 2021
and research's language is English




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We discuss in this survey several network modeling methods and their applicability to precision medicine. We review several network centrality methods (degree centrality, closeness centrality, eccentricity centrality, betweenness centrality, and eigenvector-based prestige) and two systems controllability methods (minimum dominating sets and network structural controllability). We demonstrate their applicability to precision medicine on three multiple myeloma patient disease networks. Each network consists of protein-protein interactions built around a specific patients mutated genes, around the targets of the drugs used in the standard of care in multiple myeloma, and around multiple myeloma-specific essential genes. For each network we demonstrate how the network methods we discuss can be used to identify personalized, targeted drug combinations uniquely suited to that patient.



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The Oxford English Dictionary defines precision medicine as medical care designed to optimize efficiency or therapeutic benefit for particular groups of patients, especially by using genetic or molecular profiling. It is not an entirely new idea: physicians from ancient times have recognized that medical treatment needs to consider individual variations in patient characteristics. However, the modern precision medicine movement has been enabled by a confluence of events: scientific advances in fields such as genetics and pharmacology, technological advances in mobile devices and wearable sensors, and methodological advances in computing and data sciences. This chapter is about bandit algorithms: an area of data science of special relevance to precision medicine. With their roots in the seminal work of Bellman, Robbins, Lai and others, bandit algorithms have come to occupy a central place in modern data science ( Lattimore and Szepesvari, 2020). Bandit algorithms can be used in any situation where treatment decisions need to be made to optimize some health outcome. Since precision medicine focuses on the use of patient characteristics to guide treatment, contextual bandit algorithms are especially useful since they are designed to take such information into account. The role of bandit algorithms in areas of precision medicine such as mobile health and digital phenotyping has been reviewed before (Tewari and Murphy, 2017; Rabbi et al., 2019). Since these reviews were published, bandit algorithms have continued to find uses in mobile health and several new topics have emerged in the research on bandit algorithms. This chapter is written for quantitative researchers in fields such as statistics, machine learning, and operations research who might be interested in knowing more about the algorithmic and mathematical details of bandit algorithms that have been used in mobile health.
Often questions arise about old or extinct networks. What proteins interacted in a long-extinct ancestor species of yeast? Who were the central players in the Last.fm social network 3 years ago? Our ability to answer such questions has been limited by the unavailability of pa
Quantitative studies of cell metabolism are often based on large chemical reaction network models. A steady state approach is suited to analyze phenomena on the timescale of cell growth and circumvents the problem of incomplete experimental knowledge on kinetic laws and parameters, but it shall be supported by a correct implementation of thermodynamic constraints. In this article we review the latter aspect highlighting its computational challenges and physical insights. The simple introduction of Gibbs inequalities avoids the presence of unfeasible loops allowing for correct timescale analysis but leads to possibly non-convex feasible flux spaces, whose exploration needs efficient algorithms. We shorty review on the implementation of thermodynamics through variational principles in constraints based models of metabolic networks.
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Learning representations for graphs plays a critical role in a wide spectrum of downstream applications. In this paper, we summarize the limitations of the prior works in three folds: representation space, modeling dynamics and modeling uncertainty. To bridge this gap, we propose to learn dynamic graph representation in hyperbolic space, for the first time, which aims to infer stochastic node representations. Working with hyperbolic space, we present a novel Hyperbolic Variational Graph Neural Network, referred to as HVGNN. In particular, to model the dynamics, we introduce a Temporal GNN (TGNN) based on a theoretically grounded time encoding approach. To model the uncertainty, we devise a hyperbolic graph variational autoencoder built upon the proposed TGNN to generate stochastic node representations of hyperbolic normal distributions. Furthermore, we introduce a reparameterisable sampling algorithm for the hyperbolic normal distribution to enable the gradient-based learning of HVGNN. Extensive experiments show that HVGNN outperforms state-of-the-art baselines on real-world datasets.
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