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

• Published in: PLoS computational biology 2017-04, Vol.13 (4), p.e1005436-e1005436
• Main Authors: Habibi, Iman, Cheong, Raymond, Lipniacki, Tomasz, Levchenko, Andre, Emamian, Effat S, Abdi, Ali
• Format: Article
• Language: English
• Subjects: A20 protein; Abnormalities; Alarm systems; Animal models; Apoptosis; Autoimmune diseases; B-cell lymphoma; Biochemistry; Biology; Biology and Life Sciences; Biomedical engineering; Bivariate analysis; Cancer; Cell Communication - physiology; Cell death; Cell interactions; Cell survival; Computation; Computational Biology - methods; Computer and Information Sciences; Computer applications; Computer engineering; Computer simulation; Data acquisition; Data collection; Data processing; Decision making; Decision Theory; Decisions; Decomposition; Drug development; Engineering; Engineering and Technology; Experimental data; Failure analysis; False alarms; Hepatocytes; Inactivation; Information processing; Integration; Intracellular signalling; Liver; Lymphocytes B; Mathematical models; Mice; Models, Biological; Models, Statistical; Mortality; NF-kappa B - metabolism; Noise; Noise levels; Nuclear capture; Observations; Physical Sciences; Physiological aspects; Probability theory; Radar; Random variables; Science; Signal processing; Signal Processing, Computer-Assisted; Signal transduction; Signal Transduction - physiology; Single-Cell Analysis; Social Sciences; Sonar; Statistics; Stochastic processes; Technology; Transcription factors; Translocation; Tumor necrosis factor; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumors
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1005436

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.