PATHWAY ENRICHMENT SYSTEM
Current approaches integrating large scale data and information from a variety of sources to reveal molecular basis of cellular events do not adequately benefit from pathway information.
Computational analysis of high-throughput technologies usually generates significant gene lists specific to experimental conditions.
In order to explore a biological interpretation for such gene lists, the next step of the analysis is the association of these genes with known molecular or signaling pathways.
Determination of the response of signaling pathways for a specific condition or drug treatment is very crucial to understand underlying phenomena of pathological conditions.
We portray a novel approach that fuses and exploits pathway model and experimental data from signaling pathways.
Our model- and data-driven hybrid approach allows for quantitatively assessing the biological activity of a cyclic cellular pathway and simultaneous enrichment of the significant paths leading to the ultimate cellular response.
High-throughput, microarray and ChIP-sequencing, data sources are associated to compute an integrated gene score corresponding each node of a signaling pathway.
The fundamental constituent of our approach is the Signal Transduction Score Flow (SiTSFlow) Algorithm.
SiTSFlow algorithm converts each pathway into a cascaded graph and then integrated gene scores are mapped onto the protein nodes.
Gene scores are transferred to en route of the pathway to form a final activity score describing behaviour of a specific process in the pathway while enriching the gene node scores.
Because of cyclic pathways, the algorithm runs in an iterative manner and it terminates when the node scores converge.
The converged final activity score provides a quantitative measure to assess the biological significance of a process under the given experimental conditions.
The developed approach was experimented on both KEGG and manually generated pathways with a Cytoscape plug-in by using several transcriptome datasets.
The biological results obtained by assessing of experimental data by developed approach were in correlation with the expected cellular behaviour under the given experimental conditions.
Keywords: pathway enrichment, signal transduction score flow algorithm, cyclic signaling pathways, microarray, chip-sequencing
Members i-cancer Research Group
- Volkan Atalay
- Rengul Atalay
- Zerrin Isik (Sokmen), PhD
- Tulin Ersahin, MSc
- Sokmen Z., Ozturk M., Atalay V., and Cetin-Atalay R., “A Hybrid Method For The Identification of Expression Patterns From Microarray Data”, 15th Annual International Conference on Intelligent Systems for Molecular Biology (ISMB) and 6th European Conference on Computational Biology (ECCB), Vienna - Austria, (2007).
- Sokmen Z., Yuzugullu O., Atalay V., and Cetin-Atalay R., “Short Time Series Microarray Data Analysis for Resistance to Selenium DeficiencyÓ, International Symposium on Health Informatics and Bioinformatics (HIBIT 2008), Turkey, (2008).
- Sokmen Z., Atalay V., and Cetin-Atalay R., “Short Time Series Microarray Data Analysis and Biological Annotation”, IEEE 16. Sinyal Isleme, Iletisim ve Uygulamalari Kurultayi (SIU 2008), Turkey, ISBN: 978-1-4244-1998-2, (2008).
- Sokmen Z., Atalay V., and Cetin-Atalay R., “Progressive Clustering by Integration of Heterogeneous Data From Multiple Sources for Target Gene Identification”, Second International Workshop on Machine Learning in Systems Biology (MLSB 2008), Brussels, (2008).
- Sokmen Z., Atalay V., and Cetin-Atalay R., “Integration of ChIP-seq and microarray gene expression data”, International Symposium on Health Informatics and Bioinformatics (HIBIT 2009), Turkey, (2009).
- Isik Z., Atalay V., and Cetin-Atalay R., “Evaluation of Signaling Cascades Based on the Weights from Microarray and ChIP-seq Data”, Journal of Machine Learning Research W&C Proceedings, MIT Press, Vol.8, pp.44-54, (2010).
- Isik Z., Atalay V., Aykanat C., and Cetin-Atalay R., “Data and Model Driven Hybrid Approach to Activity Scoring of Cyclic Pathway”, Lecture Notes in Electrical Engineering, Proceedings of the 25th International Symposium on Computer and Information Sciences (ISCIS 2010), Vol. 62, pp.91-94, (2010).
- Isik Z., Atalay V., and Cetin-Atalay R., “Integrated Transcriptome Data Unified into the En Route of the Cell Signaling Pathways”, International Symposium on Health Informatics and Bioinformatics (HIBIT 2010), Turkey, (2010).
- Isik Z., Ersahin T., Atalay V., Aykanat C., and Cetin-Atalay R., “Cyclic Cellular Pathway Activities Analyzed by a Novel Signal Transduction Score Flow Algorithm”, submitted to Nucleic Acids Research Journal, (2011).
Theses:
- Zerrin Isik, “Network Structure Based Pathway Enrichment System to Analyze Pathway Activities”, Dept. of Computer Engineering, METU, February 2011.