Requirements for the formal representation of pathophysiology mechanisms by clinicians

Abstract

Knowledge of multiscale mechanisms in pathophysiology is the bedrock of clinical practice. If quantitative methods, predicting patient-specific behaviour of these pathophysiology mechanisms, are to be brought to bear on clinical decision-making, the Human Physiome community and Clinical community must share a common computational blueprint for pathophysiology mechanisms. A number of obstacles stand in the way of this sharing—not least the technical and operational challenges that must be overcome to ensure that (i) the explicit biological meanings of the Physiome's quantitative methods to represent mechanisms are open to articulation, verification and study by clinicians, and that (ii) clinicians are given the tools and training to explicitly express disease manifestations in direct contribution to modelling. To this end, the Physiome and Clinical communities must co-develop a common computational toolkit, based on this blueprint, to bridge the representation of knowledge of pathophysiology mechanisms (a) that is implicitly depicted in electronic health records and the literature, with (b) that found in mathematical models explicitly describing mechanisms. In particular, this paper makes use of a step-wise description of a specific disease mechanism as a means to elicit the requirements of representing pathophysiological meaning explicitly. The computational blueprint developed from these requirements addresses the Clinical community goals to (i) organize and manage healthcare resources in terms of relevant disease-related knowledge of mechanisms and (ii) train the next generation of physicians in the application of quantitative methods relevant to their research and practice.

Representing Normal and Abnormal Physiology as Routes of Flow in ApiNATOMY

“…extending the definition of conduit to any topologically-cylindrical biological structure (immaterial of scale) that conveys fluid flow (i.e., the subcellular sodium pump, as well as an unbranched segment of the thoracic aorta, are both considered as conduits in ApiNATOMY) ( de Bono et al, 2015 , 2016a );…”

“…the second part of the Methods (section 3.2) outlines the annotation of the TOO map with disease mechanism terms defined as altered flow between body compartments, as originally envisioned in our earlier work ( de Bono et al, 2016a );…”

Epithelial Modelling Platform: A Tool for Model Discovery and Assembly with the Physiome Model Repository

“…For example, biomedical engineers and clinicians often utilize computational models to investigate experimental or clinical hypotheses that are difficult or expensive to achieve experimentally using animal or human subjects. Modern tools and technologies help them to quickly and precisely test such hypotheses which may involve disparate biophysical symptoms and/or mechanisms such as clinical observations, diseases, and drug actions through physiology pathways (de Bono et al, 2016).…”

The Human Physiome: a necessary key for the creative destruction of medicine

“…Strategies for linking the variables and parameters of these models down to molecular biology and bioinformatics databases in order to produce formal representations of pathophysiology mechanisms for clinicians are considered by de Bono et al [14]. Issues associated with the development and use of Human Physiome models of the heart and the musculo-skeletal system in the clinic and for industry are discussed by Chabiniok et al [15] and Fernandez et al [16], respectively.…”

“…The second theme component, on the methodology for establishing a clinically relevant Human Physiome, begins with a discussion of modelling and data standards and their associated Web-accessible repositories and open source multiscale modelling tools, since standards for reproducible modelling and modular approaches to handling are essential if we are to use quantitative physiological models in clinical workflows [13]. Strategies for linking the variables and parameters of these models down to molecular biology and bioinformatics databases in order to produce formal representations of pathophysiology mechanisms for clinicians are considered by de Bono et al [14]. Issues associated with the development and use of Human Physiome models of the heart and the musculo-skeletal system in the clinic and for industry are discussed by Chabiniok et al [15] and Fernandez et al [16], respectively.…”