Analysis of complex diseases. A mathematical perspective

DOI10.1201/B16259MaRDI QIDQ2871230zbMATH OpenOpenAlexFDO

Publication date 22 January 2014

Full work available at URL https://doi.org/10.1201/b16259

differential equations modeling complex disease PI3K-AKT-TOR pathway systems biology

Research exposition (monographs, survey articles) pertaining to operations research and mathematical programming (90-02) Research exposition (monographs, survey articles) pertaining to biology (92-02) General biology and biomathematics (92B05) Physiology (general) (92C30) Systems biology, networks (92C42) Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) (92C45) Medical applications (general) (92C50)

Review text

The book with a total of 200 pages is subdivided into three parts describing normal physiology (Part I, chapters 1--4), organizing principles and molecular circuits (Part II, chapters 5--7) and complex diseases combining the two first parts from a unifying perspective (Part III, chapters 8--13). The requirements at the organismal level of the four chapters of Part I are food intake and energy metabolism, glucose homoestasis, and bioavailability. What molecular levels can provide is described in the three chapters in Part II which are about molecular biology, biomolecular networks, and on the key chapter on the PI3K-AKT-TOR (phosphoinositide 3 kinase-proteinkinase B-target of rapamycin) pathway with its almost 20 pages. Part III ``Mathematical analysis of complex diseases considers diseases related to metabolism, the modeling of the PI3K-AKT-TOR pathway, and the analytical technique of decomposition to simplify the analysis corresponding. This corresponds to the three key elements (and parameters) of the pathway. Finally, the methods are shown to describe the normal and the disease phenotypes. The book has 38 references and an index of 4 pages.NEWLINENEWLINE The author's approach is based on what he calls a ``holistic method which aims to integrate information from multiple levels such that he can conclude that some disease phenotypes ``correspond to well-evolved control mechanisms that worked optimally in ancient times and has been disturbed by acute changes of the environment and lifestyle, caused by ``industrialization and agriculture deteriorating control mechanisms leading ``to the epidemics of complex diseases such as diabetes and cancer, but also Alzheimer's and Parkinsons's diseases. The ``holistic approach taken claims that one ``must think fundamentally and seek overarching mechanisms that govern the complex biological phenomena underlying complex disease and is based on two rather philosophical ways of thinking: (i) to quantify ``aberration associated with a disease as a deviation from normality of the organism using physical principles to handle small/infinitesimal variations and their mathematical analysis; (ii) recurring to Tao in Chinese philosophy assuming that ``a person's well-being depends on a well-balanced Yin and Yang that may ``interact to convert into each other detailed in the last chapter 13.NEWLINENEWLINE Independent of those fundamental and philosophical considerations, a number of deterministic mathematical models is developed in the three parts supplemented by five Appendices, e.g., on the insulin action, singularity theory and what the authors calls ``Master Equation. It is this system of differential equations built to characterize the PI3K-AKT-TOR pathway which appears as the most visible and relevant feature and novelty of the book.

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