Sbalzarini Ivo F, Greber Urs F
Faculty of Computer Science, TU Dresden, Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Methods Mol Biol. 2018;1836:609-631. doi: 10.1007/978-1-4939-8678-1_30.
An implicit aim in cellular infection biology is to understand the mechanisms how viruses, microbes, eukaryotic parasites, and fungi usurp the functions of host cells and cause disease. Mechanistic insight is a deep understanding of the biophysical and biochemical processes that give rise to an observable phenomenon. It is typically subject to falsification, that is, it is accessible to experimentation and empirical data acquisition. This is different from logic and mathematics, which are not empirical, but built on systems of inherently consistent axioms. Here, we argue that modeling and computer simulation, combined with mechanistic insights, yields unprecedented deep understanding of phenomena in biology and especially in virus infections by providing a way of showing sufficiency of a hypothetical mechanism. This ideally complements the necessity statements accessible to empirical falsification by additional positive evidence. We discuss how computational implementations of mathematical models can assist and enhance the quantitative measurements of infection dynamics of enveloped and non-enveloped viruses and thereby help generating causal insights into virus infection biology.
细胞感染生物学的一个隐含目标是了解病毒、微生物、真核寄生虫和真菌如何篡夺宿主细胞功能并引发疾病的机制。机制性见解是对产生可观察现象的生物物理和生化过程的深入理解。它通常容易被证伪,也就是说,它可以通过实验和实证数据获取来检验。这与逻辑和数学不同,逻辑和数学不是实证性的,而是建立在内在一致的公理系统之上。在此,我们认为,建模和计算机模拟与机制性见解相结合,通过提供一种展示假设机制充分性的方式,能对生物学现象,尤其是病毒感染现象产生前所未有的深入理解。这理想地补充了通过额外的正面证据进行实证证伪时可获得的必要性陈述。我们讨论了数学模型的计算实现如何协助并增强对包膜病毒和非包膜病毒感染动态的定量测量,从而有助于对病毒感染生物学产生因果性见解。