SWITCHES: Searchable Web Interface for Topologies of CHEmical Switches.

G V Harsharani,N Ramakrishnan,U S Bhalla,S Moza,Peter Robinson

doi:10.1093/bioinformatics/btab006

Abstract

Bistable biochemical switches are key motifs in cellular state decisions and long-term storage of cellular 'memory'. There are a few known biological switches that have been well characterized, however, these examples are insufficient for systematic surveys of properties of these important systems. Here we present a resource of all possible bistable biochemical reaction networks with up to six reactions between three molecules, and three reactions between four molecules. Over 35000 reaction topologies were constructed by identifying unique combinations of reactions between a fixed number of molecules. Then, these topologies were populated with rates within a biologically realistic range. The Searchable Web Interface for Topologies of CHEmical Switches (SWITCHES, https://switches.ncbs.res.in) provides a bistability and parameter analysis of over seven million models from this systematic survey of chemical reaction space. This database will be useful for theoreticians interested in analyzing stability in chemical systems and also experimentalists for creating robust synthetic biological switches. Freely available on the web at https://switches.ncbs.res.in. Website implemented in PHP, MariaDB, Graphviz and Apache, with all major browsers supported.

Highlights

Biochemical switches are key motifs in cellular state decisions and long-term storage of cellular 'memory' (Angeli et al, 2004, Craciun et al, 2006, Markevich et al, 2004, Tyson et al, 2003)
We previously conducted a systematic survey of chemical kinetic models to generate all possible reaction topologies up to a certain size, and assess their ability to form bistable switches (Ramakrishnan and Bhalla, 2008)
There are over 33,000 bistable models, all of which have been encoded in SBML (Systems Biology Markup Language, Hucka et al, 2003)

Summary

Introduction

Biochemical switches are key motifs in cellular state decisions and long-term storage of cellular 'memory' (Angeli et al, 2004, Craciun et al, 2006, Markevich et al, 2004, Tyson et al, 2003). That is, they have the property that they can exist stably in either of two states, with a third state acting as a transition or saddle point. Two broad strategies to characterize bistable systems are the theory-based (e.g., Soranzo and Altafini, 2009, Craciun and Feinberg, 2006) and the catalog/database approach (Ramakrishnan and Bhalla, 2008). Fully defined chemical networks using linear algebra criteria for bistability, that is, two stable states and a saddle point.

Results

Conclusion