Universität zu Köln

Loos, Carolin ORCID: 0000-0003-3680-0627, Moeller, Katharina, Froehlich, Fabian, Hucho, Tim ORCID: 0000-0002-4147-9308 and Hasenauer, Jan ORCID: 0000-0002-4935-3312 (2018). A Hierarchical, Data-Driven Approach to Modeling Single-Cell Populations Predicts Latent Causes of Cell-To-Cell Variability. Cell Syst., 6 (5). S. 593 - 617. CAMBRIDGE: CELL PRESS. ISSN 2405-4720

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Abstract

All biological systems exhibit cell-to-cell variability. Frameworks exist for understanding how stochastic fluctuations and transient differences in cell state contribute to experimentally observable variations in cellular responses. However, current methods do not allow identification of the sources of variability between and within stable subpopulations of cells. We present a data-driven modeling framework for the analysis of populations comprising heterogeneous subpopulations. Our approach combines mixture modeling with frameworks for distribution approximation, facilitating the integration of multiple single-cell datasets and the detection of causal differences between and within subpopulations. The computational efficiency of our framework allows hundreds of competing hypotheses to be compared. We initially validate our method using simulated data with an understood ground truth, then we analyze data collected using quantitative single-cell microscopy of cultured sensory neurons involved in pain initiation. This approach allows us to quantify the relative contribution of neuronal subpopulations, culture conditions, and expression levels of signaling proteins to the observed cell-to-cell variability in NGF/TrkA-initiated Erk1/2 signaling.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Loos, Carolin UNSPECIFIED orcid.org/0000-0003-3680-0627 UNSPECIFIED Moeller, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Froehlich, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucho, Tim UNSPECIFIED orcid.org/0000-0002-4147-9308 UNSPECIFIED Hasenauer, Jan UNSPECIFIED orcid.org/0000-0002-4935-3312 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-186022
DOI:	10.1016/j.cels.2018.04.008
Journal or Publication Title:	Cell Syst.
Volume:	6
Number:	5
Page Range:	S. 593 - 617
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2405-4720
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BAYES FACTORS; DIFFERENTIAL EXPRESSION; PARAMETER-ESTIMATION; GENE-EXPRESSION; CYTOMETRY DATA; HETEROGENEITY; DYNAMICS; SUBPOPULATIONS; SELECTION; BIOLOGY Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18602