Simultaneous Reconstruction of Multiple Signaling Pathways via the Prize-Collecting Steiner Forest Problem

Download

Date

2013-02-01

Author

Tunçbağ, Nurcan
PAGNANI, Andrea
Huang, Shao-Shan Carol
CHAYES, Jennifer
BORGS, Christian
Zecchina, Riccardo
FRAENKEL, Ernest

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

173
views

0
downloads

Signaling and regulatory networks are essential for cells to control processes such as growth, differentiation, and response to stimuli. Although many "omic'' data sources are available to probe signaling pathways, these data are typically sparse and noisy. Thus, it has been difficult to use these data to discover the cause of the diseases and to propose new therapeutic strategies. We overcome these problems and use "omic'' data to reconstruct simultaneously multiple pathways that are altered in a particular condition by solving the prize-collecting Steiner forest problem. To evaluate this approach, we use the well-characterized yeast pheromone response. We then apply the method to human glioblastoma data, searching for a forest of trees, each of which is rooted in a different cell-surface receptor. This approach discovers both overlapping and independent signaling pathways that are enriched in functionally and clinically relevant proteins, which could provide the basis for new therapeutic strategies. Although the algorithm was not provided with any information about the phosphorylation status of receptors, it identifies a small set of clinically relevant receptors among hundreds present in the interactome.

Subject Keywords

Multiple network reconstruction, Prize-collecting Steiner forest, Signaling pathways

URI

https://hdl.handle.net/11511/31736

Journal

JOURNAL OF COMPUTATIONAL BIOLOGY

DOI

https://doi.org/10.1089/cmb.2012.0092

Collections

Graduate School of Informatics, Article

Suggestions

OpenMETU
Core

Simultaneous reconstruction of multiple signaling pathways via the prize collecting Steiner forest problem Tunçbağ, Nurcan; PAGNANI, ANDREA; HUANG, SHAO SHAN CAROL; CHAYES, JENNIFER; BORGS, CHRISTIAN; ZECCHINA, RICCARDO; FRAENKEL, ERNEST (2012-04-13) Signaling networks are essential for cells to control processes such as growth and response to stimuli. Although many “omic” data sources are available to probe signaling pathways, these data are typically sparse and noisy. Thus, it has been difficult to use these data to discover the cause of the diseases. We overcome these problems and use “omic” data to simultaneously reconstruct multiple pathways that are altered in a particular condition by solving the prize-collecting Steiner forest problem. To evalua...
Combining Multiple Types of Biological Data in Constraint-Based Learning of Gene Regulatory Networks Tan, Mehmet; AlShalalfa, Mohammed; Alhajj, Reda; Polat, Faruk (2008-09-17) Due to the complex structure and scale of gene regulatory networks, we support the argument that combination of multiple types of biological data to derive satisfactory network structures is necessary to understand the regulatory mechanisms of cellular systems. In this paper, we propose a simple but effective method of combining two types of biological data, namely microarray and transcription factor (TF) binding data, to construct gene regulatory networks. The proposed algorithm is based on and extends the...
Quantitative Analysis of MAP-Mediated Regulation of Microtubule Dynamic Instability In Vitro—Focus on Tau Kiriş, Erkan; Feinstein, Stuart C. (Elsevier Science, 2010-05-01) The regulation of microtubule growing and shortening dynamics is essential for proper cell function and viability, and microtubule-associated proteins (MAPs) such as the neural protein tau are critical regulators of these dynamic processes. Further, we and our colleagues have proposed that misregulation of microtubule dynamics may contribute to tau-mediated neuronal cell death and dementia in Alzheimer's and related diseases. In the first part of this chapter, we present a general background on microtubule ...
Quantitative Analysis of MAP-Mediated Regulation of Microtubule Dynamic Instability In Vitro: Focus on Tau Kiriş, Erkan; Feinstein, Stuart C (Elsevier, 2010-01-01) The regulation of microtubule growing and shortening dynamics is essential for proper cell function and viability, and microtubule-associated proteins (MAPs) such as the neural protein tau are critical regulators of these dynamic processes. Further, we and our colleagues have proposed that misregulation of microtubule dynamics may contribute to tau-mediated neuronal cell death and dementia in Alzheimer’s and related diseases. In the first part of this chapter, we present a general background on microtubule ...
Stochastic modelling of the MAPK signalling pathway Purutçuoğlu Gazi, Vilda (null; 2006-06-01) The MAPK (mitogen-activated protein kinase) or its synonymous ERK (extracellular signal regulated kinase) pathway whose components are Ras, Raf, and MEK proteins with many biochemical links, is one of the major signalling systems involved in cellular growth control of eukaryotes including cell proliferation, transformation, differentiation, and apoptosis. Because of its diverse functionality, it is also activated in a variety of hormone activation and many illnesses, which have multi-complex gene structure ...

Citation Formats

N. Tunçbağ et al., “Simultaneous Reconstruction of Multiple Signaling Pathways via the Prize-Collecting Steiner Forest Problem,” JOURNAL OF COMPUTATIONAL BIOLOGY, pp. 124–136, 2013, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/31736.