Jump to main content
Jump to site search
PLANNED MAINTENANCE Close the message box

Scheduled maintenance upgrade on Thursday 4th of May 2017 from 8.00am to 9.00am (BST).

During this time our websites will be offline temporarily. If you have any questions please use the feedback button on this page. We apologise for any inconvenience this might cause and thank you for your patience.


Issue 4, 2017
Previous Article Next Article

Steady state statistical correlations predict bistability in reaction motifs

Author affiliations

Abstract

Various cellular decision making processes are regulated by bistable switches that take graded input signals and convert them to binary all-or-none responses. Traditionally, a bistable switch generated by a positive feedback loop is characterized either by a hysteretic signal response curve with two distinct signaling thresholds or by characterizing the bimodality of the response distribution in the bistable region. To identify the intrinsic bistability of a feedback regulated network, here we propose that bistability can be determined by correlating higher order moments and cumulants (≥2) of the joint steady state distributions of two components connected in a positive feedback loop. We performed stochastic simulations of four feedback regulated models with intrinsic bistability and we show that for a bistable switch with variation of the signal dose, the steady state variance vs. covariance adopts a signatory cusp-shaped curve. Further, we find that the (n + 1)th order cross-cumulant vs. nth order cross-cumulant adopts a closed loop structure for at least n = 3. We also propose that our method is capable of identifying systems without intrinsic bistability even though the system may show bimodality in the marginal response distribution. The proposed method can be used to analyze single cell protein data measured at steady state from experiments such as flow cytometry.

Graphical abstract: Steady state statistical correlations predict bistability in reaction motifs

Back to tab navigation
Please wait while Download options loads

Supplementary files

Publication details

The article was received on 20 Jan 2017, accepted on 19 Feb 2017 and first published on 21 Feb 2017


Article type: Paper
DOI: 10.1039/C7MB00052A
Citation: Mol. BioSyst., 2017,13, 775-784
  •   Request permissions

    Steady state statistical correlations predict bistability in reaction motifs

    S. Chakravarty and D. Barik, Mol. BioSyst., 2017, 13, 775
    DOI: 10.1039/C7MB00052A

Search articles by author