Building SuperModels: emerging patient avatars for use in precision and systems medicine.

Abstract

The era is approaching when each individual can be mapped to a patient avatar—not a life-sized 3D blue form of the patient filled with physical substance (as in the movie “Avatar”), but a hologram of the patient that simulates key medical components. Patient avatars will be composed of computational models combined with various data types and analytics to form what might be called SuperModels (Figure ​(Figure1).1). These SuperModels (comprehensive virtual representations of the patient, not fashion models) will be important to help realize visionary precision medicine initiatives that have recently been announced (Collins and Varmus, 2015; Nature Biotechnology, 2015). Figure 1 Building SuperModels for precision and systems medicine, with incorporation of computational avatars. Input: A feedforward loop (top left panel X connects to patient avatar Z both indirectly via bottom left panel Y and also directly, by large blue arrows) ... Precision medicine tailors prevention, diagnosis, therapeutics, and prognosis for each patient (Garay and Gray, 2012; Highnam and Mittelman, 2012; Mirnezami et al., 2012). Related to precision medicine is systems medicine (Auffray et al., 2009; Capobianco, 2012; Emmert-Streib and Dehmer, 2013; Wolkenhauer, 2013), which leverages systems biology (Noble, 2008) for clinical application, with resulting data termed “systems medicine data” (Brown et al., 2015b). Systems biology studies the behavior of organisms or cells as whole systems, and uses various advances in biotechnology, including genomics, transcriptomics, proteomics, metabolomics, methylomics, microbiomics, and elucidation of cellular interaction networks by network biology (Figure ​(Figure1,1, top left panel labeled X). Often, systems medicine data from these various advances can be modeled and simulated with complementary computer science, mathematics, chemistry, physics, and engineering concepts in computational biology. A variety of fields have used computational models as virtual surrogates of specific portions of patient physiology. These individual models can be considered computational avatars of a subset of the patient's organic identity. This is akin to cancer avatars in mice, which involve mouse models mapped to individual patients, for example, by injection of tumor cells from a particular individual. These cancer avatars facilitate personalized study of the pathophysiology and response to drugs of a particular patient's cancer cells. Similarly, biomathematical or computational cancer avatars simulate the micro-environment of individualized cancer cells. Beyond such in silico exemplars, a computational avatar may also be thought of as any finite representation of a specific portion of the patient, that harnesses computing power. This includes electronic health records (EHR), patient portals, and a variety of other precision medicine tools. However, this paper focuses on individual biomathematical models as computational avatars that can be incorporated into comprehensive patient avatars for use in precision and systems medicine. The following section describes a non-exhaustive sample of biomathematical models, including genome-scale metabolic models (GEMs) that use computational approaches to integrate omics data (Yizhak et al., 2015). These computational avatars can serve as ingredients for SuperModels, forming the first portion (X → Z) of a positive feedback loop in Figure ​Figure11.