Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future.

Cancer is a complex disease, responsible for a significant portion of global deaths. The increasing prioritisation of know-why over know-how approaches in biological research has favoured the rising use of both white- and black-box mathematical techniques for cancer modelling, seeking to better grasp the multi-scale mechanistic workings of its complex phenomena (such as tumour-immune interactions, drug resistance, tumour growth and diffusion, etc.). In light of this wide-ranging use of mathematics in cancer modelling, the unique memory and non-local properties of Fractional Calculus (FC) have been sought after in the last decade to replace ordinary differentiation in the hypothesising of FC’s superior modelling of complex oncological phenomena, which has been shown to possess an accumulated knowledge of its past states. As such, this review aims to present a thorough and structured survey about the main guiding trends and modelling categories in cancer research, emphasising in the field of oncology FC’s increasing employment in mathematical modelling as a whole. The most pivotal research questions, challenges and future perspectives are also outlined.

Objective: Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate comprehensive models of complex cells. Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in the Systems Biology Markup Language. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose several new WC modeling standards, software, and databases. Significance: We anticipate that these new standards and software will enable more comprehensive models.