SWITCHES: Searchable Web Interface for Topologies of CHEmical Switches.

SUMMARY: 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 35 000 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. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at https://switches.ncbs.res.in. Website implemented in PHP, MariaDB, Graphviz and Apache, with all major browsers supported.

Electronic data sources for kinetic models of cell signaling.

Functional understanding of signaling pathways requires detailed information about the constituent molecules and their interactions. Simulations of signaling pathways therefore build upon a great deal of data from various sources. We first survey electronic data resources for cell signaling modeling and then based on the type of data representation the data sources are broadly classified into five groups. None of the data sources surveyed provide all required data in a ready-to-be-modeled fashion. We then put forward a "wish list" for the desired attributes for an ideal modeling centric database. Finally, we close with perspectives on how electronic data sources for cell signaling modeling have developed. We suggest that future directions in such data sources are largely model-driven and are hinged on interoperability of data sources.