NDLI: Moment-based inference predicts bimodality in transient gene expression

Content Provider	PubMed Central
Author	Zechner, Christoph Ruess, Jakob Krenn, Peter Pelet, Serge Peter, Matthias John, Lygeros Koeppl, Heinz
Abstract	Recent computational studies indicate that the molecular noise of a cellular process may be a rich source of information about process dynamics and parameters. However, accessing this source requires stochastic models that are usually difficult to analyze. Therefore, parameter estimation for stochastic systems using distribution measurements, as provided for instance by flow cytometry, currently remains limited to very small and simple systems. Here we propose a new method that makes use of low-order moments of the measured distribution and thereby keeps the essential parts of the provided information, while still staying applicable to systems of realistic size. We demonstrate how cell-to-cell variability can be incorporated into the analysis obviating the need for the ubiquitous assumption that the measurements stem from a homogeneous cell population. We demonstrate the method for a simple example of gene expression using synthetic data generated by stochastic simulation. Subsequently, we use time-lapsed flow cytometry data for the osmo-stress induced transcriptional response in budding yeast to calibrate a stochastic model, which is then used as a basis for predictions. Our results show that measurements of the mean and the variance can be enough to determine the model parameters, even if the measured distributions are not well-characterized by low-order moments only—e.g., if they are bimodal.
Related Links	http://dx.doi.org/10.1073/pnas.1200161109
Ending Page	8345
Page Count	6
Starting Page	8340
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	21
Volume Number	109
Language	English
Publisher	National Academy of Sciences
Publisher Date	2012-05-22
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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