HillTau: A fast, compact abstraction for model reduction in biochemical signaling networks

PLoS Comput Biol. 2021 Nov 29;17(11):e1009621. doi: 10.1371/journal.pcbi.1009621. eCollection 2021 Nov.

Abstract

Signaling networks mediate many aspects of cellular function. The conventional, mechanistically motivated approach to modeling such networks is through mass-action chemistry, which maps directly to biological entities and facilitates experimental tests and predictions. However such models are complex, need many parameters, and are computationally costly. Here we introduce the HillTau form for signaling models. HillTau retains the direct mapping to biological observables, but it uses far fewer parameters, and is 100 to over 1000 times faster than ODE-based methods. In the HillTau formalism, the steady-state concentration of signaling molecules is approximated by the Hill equation, and the dynamics by a time-course tau. We demonstrate its use in implementing several biochemical motifs, including association, inhibition, feedforward and feedback inhibition, bistability, oscillations, and a synaptic switch obeying the BCM rule. The major use-cases for HillTau are system abstraction, model reduction, scaffolds for data-driven optimization, and fast approximations to complex cellular signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Feedback, Physiological
  • Models, Biological*
  • Signal Transduction*

Grants and funding

USB received support from NCBS-TIFR which is supported by the Department of Atomic Energy, Government of India, under project identification No. RTI 4006. USB also received grant support from Department of Science and Technology, project No. DST/INT/SWD/VR/P-09/2016. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.