Click here to read some interesting recently published papers from our community. If you have published an article in the field of in silico medicine, send it to us: we will include it in this section of the newsletter!
J Theor Biol: "A Theoretical Analysis of the Scale Separation in a Model to Predict Solid Tumour Growth"
Bárbara de Melo Quintela et al
Solid tumour growth depends on a host of factors which affect the cell life cycle and extracellular matrix vascularization that leads to a favourable environment. The whole solid tumour can either grow or wither in response to the action of the immune system and therapeutics. A personalised mathematical model of such behaviour must consider both the intra- and inter-cellular dynamics and the mechanics of the solid tumour and its microenvironment. However, such wide range of spatial and temporal scales can hardly be modelled in a single model, and require the so-called multiscale models, defined as orchestrations of single-scale component models, connected by relation models that transform the data for one scale to another. While multiscale models are becoming common, there is a well-established engineering approach to the definition of the scale separation, e.g., how the spatiotemporal continuum is split in the various component models. In most studies scale separation is defined as natural, linked to anatomical concepts such as organ, tissue, or cell; but these do not provide reliable definition of scales: for examples skeletal organs can be as large as 500 mm (femur), or as small as 3 mm (stapes). Here we apply a recently proposed scale-separation approach based on the actual experimental and computational limitations to a patient-specific model of the growth of neuroblastoma. The resulting multiscale model can be properly informed with the available experimental data and solved in a reasonable timeframe with the available computational resources.
BMC Bioinformatics: "Model verification tools: a computational framework for verification assessment of mechanistic agent-based models"
Giulia Russo et al
Nowadays, the inception of computer modeling and simulation in life science is a matter of fact. This is one of the reasons why regulatory authorities are open in considering in silico trials evidence for the assessment of safeness and efficacy of medicinal products. In this context, mechanistic Agent-Based Models are increasingly used. Unfortunately, there is still a lack of consensus in the verification assessment of Agent-Based Models for regulatory approval needs. VV&UQ is an ASME standard specifically suited for the verification, validation, and uncertainty quantification of medical devices. However, it can also be adapted for the verification assessment of in silico trials for medicinal products.
Comput Struct Biotechnol J: "Translatability and transferability of in silico models: Context of use switching to predict the effects of environmental chemicals on the immune system"
Francesco Pappalardo et al
Immunotoxicity hazard identification of chemicals aims to evaluate the potential for unintended effects of chemical exposure on the immune system. Perfluorinated alkylate substances (PFAS), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are persistent, globally disseminated environmental contaminants known to be immunotoxic. Elevated PFAS exposure is associated with lower antibody responses to vaccinations in children and in adults. In addition, some studies have reported a correlation between PFAS levels in the body and lower resistance to disease, in other words an increased risk of infections or cancers. In this context, modelling and simulation platforms could be used to simulate the human immune system with the aim to evaluate the adverse effects that immunotoxicants may have. Here, we show the conditions under which a mathematical model developed for one purpose and application (e.g., in the pharmaceutical domain) can be successfully translated and transferred to another (e.g., in the chemicals domain) without undergoing significant adaptation. In particular, we demonstrate that the Universal Immune System Simulator was able to simulate the effects of PFAS on the immune system, introducing entities and new interactions that are biologically involved in the phenomenon. This also revealed a potentially exploitable pathway for assessing immunotoxicity through a computational model.
Comput Struct Biotechnol J: "Inverse problems in blood flow modeling: A review"
David Nolte, Cristóbal Bertoglio
Mathematical and computational modeling of the cardiovascular system is increasingly providing non-invasive alternatives to traditional invasive clinical procedures. Moreover, it has the potential for generating additional diagnostic markers. In blood flow computations, the personalization of spatially distributed (i.e., 3D) models is a key step which relies on the formulation and numerical solution of inverse problems using clinical data, typically medical images for measuring both anatomy and function of the vasculature. In the last years, the development and application of inverse methods has rapidly expanded most likely due to the increased availability of data in clinical centers and the growing interest of modelers and clinicians in collaborating. Therefore, this work aims to provide a wide and comparative overview of literature within the last decade. We review the current state of the art of inverse problems in blood flows, focusing on studies considering fully dimensional fluid and fluid-solid models. The relevant physical models and hemodynamic measurement techniques are introduced, followed by a survey of mathematical data assimilation approaches used to solve different kinds of inverse problems, namely state and parameter estimation. An exhaustive discussion of the literature of the last decade is presented, structured by types of problems, models and available data.