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PLoS Comput Biol. 2017 Apr 5;13(4):e1005436. doi: 10.1371/journal.pcbi.1005436. eCollection 2017 Apr.

Computation and measurement of cell decision making errors using single cell data.

Author information

1
Center for Wireless Information Processing, Department of Electrical and Computer Engineering, New Jersey Institute of Technology, Newark, NJ, United States of America.
2
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States of America.
3
Institute of Fundamental Technological Research, Polish Academy of Sciences, Pawinskiego 5B, Warsaw, Poland.
4
Yale Systems Biology Institute and Department of Biomedical Engineering, Yale University, New Haven, CT, United States of America.
5
Advanced Technologies for Novel Therapeutics, Enterprise Development Center, New Jersey Institute of Technology, Newark, NJ, United States of America.
6
Department of Biological Sciences, New Jersey Institute of Technology, Newark, NJ, United States of America.

Abstract

In this study a new computational method is developed to quantify decision making errors in cells, caused by noise and signaling failures. Analysis of tumor necrosis factor (TNF) signaling pathway which regulates the transcription factor Nuclear Factor κB (NF-κB) using this method identifies two types of incorrect cell decisions called false alarm and miss. These two events represent, respectively, declaring a signal which is not present and missing a signal that does exist. Using single cell experimental data and the developed method, we compute false alarm and miss error probabilities in wild-type cells and provide a formulation which shows how these metrics depend on the signal transduction noise level. We also show that in the presence of abnormalities in a cell, decision making processes can be significantly affected, compared to a wild-type cell, and the method is able to model and measure such effects. In the TNF-NF-κB pathway, the method computes and reveals changes in false alarm and miss probabilities in A20-deficient cells, caused by cell's inability to inhibit TNF-induced NF-κB response. In biological terms, a higher false alarm metric in this abnormal TNF signaling system indicates perceiving more cytokine signals which in fact do not exist at the system input, whereas a higher miss metric indicates that it is highly likely to miss signals that actually exist. Overall, this study demonstrates the ability of the developed method for modeling cell decision making errors under normal and abnormal conditions, and in the presence of transduction noise uncertainty. Compared to the previously reported pathway capacity metric, our results suggest that the introduced decision error metrics characterize signaling failures more accurately. This is mainly because while capacity is a useful metric to study information transmission in signaling pathways, it does not capture the overlap between TNF-induced noisy response curves.

PMID:
28379950
PMCID:
PMC5397092
DOI:
10.1371/journal.pcbi.1005436
[Indexed for MEDLINE]
Free PMC Article

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