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## Learning from Metabolic Networks: Current Trends and Future Directions for Precision Medicine

Purpose: Systems biology and network modeling represent, nowadays, the hallmark approaches for the development of predictive and targeted-treatment based precision medicine. The study of health and disease as properties of the human body system allows the understanding of the genotype-phenotype relationship through the definition of molecular interactions and dependencies. In this scenario, metabolism plays a central role as its interactions are well characterized and it is considered an important indicator of the genotype-phenotype associations. In metabolic systems biology, the genome-scale metabolic models are the primary scaffolds to integrate multi-omics data as well as cell-, tissue-, condition-specific information. Modeling the metabolism has both investigative and predictive values. Several methods have been proposed to model systems, which involve steady-state or kinetic approaches, and to extract knowledge through machine and deep learning.

Method: This review collects, analyzes, and compares the suitable data and computational approaches for the exploration of metabolic networks as tools for the development of precision medicine. To this extent, we organized it into three main sections: "Data and Databases", "Methods and Tools", and "Metabolic Networks for medicine". In the first one, we have collected the most used data and relative databases to build and annotate metabolic models. In the second section, we have reported the state-of-the-art methods and relative tools to reconstruct, simulate, and interpret metabolic systems. Finally, we have reported the most recent and innovative studies which exploited metabolic networks for the study of several pathological conditions, not only those directly related to the metabolism.

Conclusion: We think that this review can be a guide to researchers of different disciplines, from computer science to biology and medicine, in exploring the power, challenges and future promises of the metabolism as predictor and target of the so-called P4 medicine (predictive, preventive, personalized and participatory).

In this paper we consider the analysis of an M/D[y] /1 vacation queue with periodically gated discipline. The motivation of introducing the new periodically gated discipline lies in modeling a kind of contention-based bandwidth reservation mechanism applied in wireless networks. The analysis approach applied here consists of two steps and it is based on appropriately chosen characteristic epochs of the system. We provide approximate expressions for the probability-generating function of the number of customers at arbitrary epoch as well as for the Laplace–Stieljes transform and for the mean of the steady-state waiting time. Several numerical examples are also provided. In the second part of the paper we discuss how to apply the periodically gated vacation model to the non real-time uplink traffic in IEEE 802.16-based wireless broadband networks.

The methods of biomechanical systems design with artificial elements are analyzed. The data of high-precision measurements of all set of the biometric characteristics, determining of biomechanical system is a basis of mathematical model. The calculations allows to predict complications at denture installation.

The law of accelerating returns can be viewed as a concept that describes acceleration of technological progress. The idea is that tools are used for developing more advanced tools that are applied for creating even more advanced tools etc. A similar idea has been implemented in algorithms for advancing artificial intelligence. In this paper, the results of applying these algorithms in games are discussed. Nevertheless, real life tasks seem more complicated. The game theoretic approach can be applied for transition from theoretical and unrealistic games to more complex and practical tasks. Applications of the game theoretic approach to advance artificial intelligence in solving tasks in the credit industry are proposed.

The Conference “Mathematical Modeling and Computational Physics 2015” is jointly organized by the Joint Institute for Nuclear Research (JINR), Dubna, Russia, the Technical University (TU), Institute of Experimental Physics SAS, the Pavol Jozef Šafárik University (UPJŠ), Košice, Slovakia, and the IFIN-HH, Bucharest, Romania.

The Conference follows the rich traditions of the previous conferences on mathematical modeling, numerical methods and computational physics that have been held in Dubna, Russia and also in Slovakia since 1964, e.g., Computational Modeling and Computing in Physics 1996, Modern Trends in Computational Physics 1998, V. International Congress on Mathematical Modeling 2002, Mathematical Modeling and Computational Physics 2006, 2009, 2011, and 2013. This year Conference is dedicated to the 60th anniversary of JINR.

We propose a novel multi-texture synthesis model based on generative adversarial networks (GANs) with a user-controllable mechanism. The user control ability allows to explicitly specify the texture which should be generated by the model. This property follows from using an encoder part which learns a latent representation for each texture from the dataset. To ensure a dataset coverage, we use an adversarial loss function that penalizes for incorrect reproductions of a given texture. In experiments, we show that our model can learn descriptive texture manifolds for large datasets and from raw data such as a collection of high-resolution photos. We show our unsupervised learning pipeline may help segmentation models. Moreover, we apply our method to produce 3D textures and show that it outperforms existing baselines.

This paper is devoted to mathematical modelling of the progression and stages of breast cancer. The Consolidated mathematical growth Model of primary tumor (PT) and secondary distant metastases (MTS) in patients with lymph nodes MTS (Stage III) (CoM-III) is proposed as a new research tool. The CoM-III rests on an exponential tumor growth model and consists of a system of determinate nonlinear and linear equations. The CoM-III describes correctly primary tumor growth (parameter T) and distant metastases growth (parameter M, parameter N). The CoM-III model and predictive software: a) detect di erent growth periods of primary tumor and distant metastases in patients with lymph nodes MTS; b) make forecast of the period of the distant metastases appearance in patients with lymph nodes MTS; c) have higher average prediction accuracy than the other tools; d) can improve forecasts on survival of breast cancer and facilitate optimisation of diagnostic tests. The CoM-III enables us, for the rst time, to predict the whole natural history of PT and secondary distant MTS growth of patients with/without lymph nodes MTS on each stage relying only on PT sizes.

A model for organizing cargo transportation between two node stations connected by a railway line which contains a certain number of intermediate stations is considered. The movement of cargo is in one direction. Such a situation may occur, for example, if one of the node stations is located in a region which produce raw material for manufacturing industry located in another region, and there is another node station. The organization of freight traﬃc is performed by means of a number of technologies. These technologies determine the rules for taking on cargo at the initial node station, the rules of interaction between neighboring stations, as well as the rule of distribution of cargo to the ﬁnal node stations. The process of cargo transportation is followed by the set rule of control. For such a model, one must determine possible modes of cargo transportation and describe their properties. This model is described by a ﬁnite-dimensional system of diﬀerential equations with nonlocal linear restrictions. The class of the solution satisfying nonlocal linear restrictions is extremely narrow. It results in the need for the “correct” extension of solutions of a system of diﬀerential equations to a class of quasi-solutions having the distinctive feature of gaps in a countable number of points. It was possible numerically using the Runge–Kutta method of the fourth order to build these quasi-solutions and determine their rate of growth. Let us note that in the technical plan the main complexity consisted in obtaining quasi-solutions satisfying the nonlocal linear restrictions. Furthermore, we investigated the dependence of quasi-solutions and, in particular, sizes of gaps (jumps) of solutions on a number of parameters of the model characterizing a rule of control, technologies for transportation of cargo and intensity of giving of cargo on a node station.

Event logs collected by modern information and technical systems usually contain enough data for automated process models discovery. A variety of algorithms was developed for process models discovery, conformance checking, log to model alignment, comparison of process models, etc., nevertheless a quick analysis of ad-hoc selected parts of a journal still have not get a full-fledged implementation. This paper describes an ROLAP-based method of multidimensional event logs storage for process mining. The result of the analysis of the journal is visualized as directed graph representing the union of all possible event sequences, ranked by their occurrence probability. Our implementation allows the analyst to discover process models for sublogs defined by ad-hoc selection of criteria and value of occurrence probability

Existing approaches suggest that IT strategy should be a reflection of business strategy. However, actually organisations do not often follow business strategy even if it is formally declared. In these conditions, IT strategy can be viewed not as a plan, but as an organisational shared view on the role of information systems. This approach generally reflects only a top-down perspective of IT strategy. So, it can be supplemented by a strategic behaviour pattern (i.e., more or less standard response to a changes that is formed as result of previous experience) to implement bottom-up approach. Two components that can help to establish effective reaction regarding new initiatives in IT are proposed here: model of IT-related decision making, and efficiency measurement metric to estimate maturity of business processes and appropriate IT. Usage of proposed tools is demonstrated in practical cases.