A blueprint for human whole-cell modeling

Abstract

Whole-cell dynamical models of human cells are a central goal of systems biology. Such models could help researchers understand cell biology and help physicians treat disease. Despite significant challenges, we believe that human whole-cell models are rapidly becoming feasible. To develop a plan for achieving human whole-cell models, we analyzed the existing models of individual cellular pathways, surveyed the biomodeling community, and reflected on our experience developing whole-cell models of bacteria. Based on these analyses, we propose a plan for a project, termed the Human Whole-Cell Modeling Project, to achieve human whole-cell models. The foundations of the plan include technology development, standards development, and interdisciplinary collaboration.

Figure 1

WC models can be built by leveraging existing models of well-studied pathways (yellow bubbles) and developing new models of other known (blue bubbles) and unknown (bullseyes) pathways.

Figure 2

A survey of the biomodeling community indicated that WC models can be achieved by collaborating on a common goal, developing scalable modeling tools, sharing data and models, adopting modeling standards, and training new researchers. (A) Fields of the 214 respondents. (B) Major bottlenecks to biomodeling and the major methods, tools, and resources needed to advance biomodeling reported by the respondents.

Figure 3

The proposed Human Whole-Cell Modeling Project would achieve human WC models in three phases: (1) demonstrating the feasibility of human WC models by developing scalable modeling tools and using them to model several core pathways, (2) demonstrating the feasibility of collaborative modeling by developing a collaborative modeling platform and using it to model additional pathways, and (3) developing a comprehensive model as a community.