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Abstract:

Background: Cell biology research is fundamentally limited by the number of intracellular components, particularly proteins, that can be co-measured in the same cell. Therefore, cell-to-cell heterogeneity in unmeasured proteins can lead to completely different observed relations between the same measured proteins. Attempts to infer such relations in a heterogeneous cell population can yield uninformative average relations if only one underlying biochemical network is assumed. To address this, we developed a method that recursively couples an iterative unmixing process with a Bayesian analysis of each unmixed subpopulation. Results: Our approach enables to identify the number of distinct cell subpopulations, unmix their corresponding observations and resolve the network structure of each subpopulation. Using simulations of the MAPK pathway upon EGF and NGF stimulations we assess the performance of the method. We demonstrate that the presented method can identify better than clustering approaches the number of subpopulations within a mixture of observations, thus resolving correctly the statistical relations between the proteins. Conclusions: Coupling the unmixing of multiplexed observations with the inference of statistical relations between the measured parameters is essential for the success of both of these processes. Here we present a conceptual and algorithmic solution to achieve such coupling and hence to analyze data obtained from a natural mixture of cell populations. As the technologies and necessity for multiplexed measurements are rising in the systems biology era, this work addresses an important current challenge in the analysis of the derived data. © 2015 Wieczorek et al.

Registro:

Documento: Artículo
Título:Uncovering distinct protein-network topologies in heterogeneous cell populations
Autor:Wieczorek, J.; Malik-Sheriff, R.S.; Fermin, Y.; Grecco, H.E.; Zamir, E.; Ickstadt, K.
Filiación:TU Dortmund University, Faculty of Statistics, Dortmund, Germany
Max-Planck Institute of Molecular Physiology, Department of Systemic Cell Biology, Dortmund, Germany
European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, Cambridge, United Kingdom
Imperial College London, MRC Clinical Sciences Centre, London, United Kingdom
University of Buenos Aires and IFIBA, Department of Physics, FCEN, CONICET, Buenos Aires, Argentina
Palabras clave:Bayesian analysis; Cluster analysis; Intercellular variability; Network analysis; Protein networks; Reverse engineering; Unmixing; epidermal growth factor; mitogen activated protein kinase; nerve growth factor; Raf protein; animal; Bayes theorem; biological model; biology; drug effects; metabolism; PC12 cell line; procedures; protein protein interaction; rat; Animals; Bayes Theorem; Computational Biology; Epidermal Growth Factor; Mitogen-Activated Protein Kinases; Models, Biological; Nerve Growth Factor; PC12 Cells; Protein Interaction Maps; raf Kinases; Rats
Año:2015
Volumen:9
Número:1
DOI: http://dx.doi.org/10.1186/s12918-015-0170-2
Título revista:BMC Systems Biology
Título revista abreviado:BMC Syst. Biol.
ISSN:17520509
CAS:epidermal growth factor, 59459-45-9, 62229-50-9; mitogen activated protein kinase, 142243-02-5; nerve growth factor, 9061-61-4; Epidermal Growth Factor; Mitogen-Activated Protein Kinases; Nerve Growth Factor; raf Kinases
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17520509_v9_n1_p_Wieczorek

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Citas:

---------- APA ----------
Wieczorek, J., Malik-Sheriff, R.S., Fermin, Y., Grecco, H.E., Zamir, E. & Ickstadt, K. (2015) . Uncovering distinct protein-network topologies in heterogeneous cell populations. BMC Systems Biology, 9(1).
http://dx.doi.org/10.1186/s12918-015-0170-2
---------- CHICAGO ----------
Wieczorek, J., Malik-Sheriff, R.S., Fermin, Y., Grecco, H.E., Zamir, E., Ickstadt, K. "Uncovering distinct protein-network topologies in heterogeneous cell populations" . BMC Systems Biology 9, no. 1 (2015).
http://dx.doi.org/10.1186/s12918-015-0170-2
---------- MLA ----------
Wieczorek, J., Malik-Sheriff, R.S., Fermin, Y., Grecco, H.E., Zamir, E., Ickstadt, K. "Uncovering distinct protein-network topologies in heterogeneous cell populations" . BMC Systems Biology, vol. 9, no. 1, 2015.
http://dx.doi.org/10.1186/s12918-015-0170-2
---------- VANCOUVER ----------
Wieczorek, J., Malik-Sheriff, R.S., Fermin, Y., Grecco, H.E., Zamir, E., Ickstadt, K. Uncovering distinct protein-network topologies in heterogeneous cell populations. BMC Syst. Biol. 2015;9(1).
http://dx.doi.org/10.1186/s12918-015-0170-2