Partner: A. Abdi

New Jersey Institute of Technology (US)

Ostatnie publikacje
1.Habibi I., Cheong R., Lipniacki T., Levchenko A., Emamian E.S., Abdi A., Computation and measurement of cell decision making errors using single cell data, PLOS COMPUTATIONAL BIOLOGY, ISSN: 1553-734X, DOI: 10.1371/journal.pcbi.1005436, Vol.13, No.4, pp.e1005436-1-17, 2017

Streszczenie:

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.

Słowa kluczowe:

Decision making, Radar, Probability distribution, Transcription factors, Signal processing, Signal transduction, Signaling networks, Statistical signal processing

Afiliacje autorów:

Habibi I.-New Jersey Institute of Technology (US)
Cheong R.-Johns Hopkins University (US)
Lipniacki T.-IPPT PAN
Levchenko A.-Yale University (US)
Emamian E.S.-New Jersey Institute of Technology (US)
Abdi A.-New Jersey Institute of Technology (US)
45p.
2.Tudelska K., Markiewicz J., Kochańczyk M., Czerkies M., Prus W., Korwek Z., Abdi A., Błoński S., Kaźmierczak B., Lipniacki T., Information processing in the NF-κB pathway, Scientific Reports, ISSN: 2045-2322, DOI: 10.1038/s41598-017-16166-y, Vol.7, pp.15926-15926, 2017

Streszczenie:

The NF-κB pathway is known to transmit merely 1 bit of information about stimulus level. We combined experimentation with mathematical modeling to elucidate how information about TNF concentration is turned into a binary decision. Using Kolmogorov-Smirnov distance, we quantified the cell’s ability to discern 8 TNF concentrations at each step of the NF-κB pathway, to find that input discernibility decreases as signal propagates along the pathway. Discernibility of low TNF concentrations is restricted by noise at the TNF receptor level, whereas discernibility of high TNF concentrations it is restricted by saturation/depletion of downstream signaling components. Consequently, signal discernibility is highest between 0.03 and 1 ng/ml TNF. Simultaneous exposure to TNF or LPS and a translation inhibitor, cycloheximide, leads to prolonged NF-κB activation and a marked increase of transcript levels of NF-κB inhibitors, IκBα and A20. The impact of cycloheximide becomes apparent after the first peak of nuclear NF-κB translocation, meaning that the NF-κB network not only relays 1 bit of information to coordinate the all-or-nothing expression of early genes, but also over a longer time course integrates information about other stimuli. The NF-κB system should be thus perceived as a feedback-controlled decision-making module rather than a simple information transmission channel.

Słowa kluczowe:

cellular signaling networks, innate immunity, stress signaling

Afiliacje autorów:

Tudelska K.-IPPT PAN
Markiewicz J.-IPPT PAN
Kochańczyk M.-IPPT PAN
Czerkies M.-IPPT PAN
Prus W.-IPPT PAN
Korwek Z.-IPPT PAN
Abdi A.-New Jersey Institute of Technology (US)
Błoński S.-IPPT PAN
Kaźmierczak B.-IPPT PAN
Lipniacki T.-IPPT PAN
40p.