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A data integration method for exploring gene regulatory mechanisms

Published:30 October 2008Publication History

ABSTRACT

Systems biology aims to understand the behavior of and interaction between various components of the living cell, such as genes, proteins, and metabolites. A large number of components are involved in these complex systems and the diversity of relationships between the components can be overwhelming, and there is therefore a need for analysis methods incorporating data integration. We here present a method for exploring gene regulatory mechanisms which integrates various types of data to assist the identification of important components in gene regulation mechanisms. By first analyzing gene expression data, a set of differentially expressed genes is selected. These genes are then further investigated by combining various types of biological information, such as clustering results, promoter sequences, binding sites, transcription factors and other previously published information regarding the selected genes. Inspired by Information Fusion research, we also mapped functions of the proposed method to the well-known OODA-model to facilitate application of this data integration method in other research communities. We have successfully applied the method to genes identified as differentially expressed in human embryonic stem cells at different stages of differentiation towards cardiac cells. We identified 15 novel motifs that may represent important binding sites in the cardiac cell linage.

References

  1. GuhaThakurta, D. Computational identification of transcriptional regulatory elements in DNA sequence. 2006. Nucleic Acids Res. 34, 3585--3598Google ScholarGoogle Scholar
  2. Rani, V. 2007. Computational methods to dissect cis-regulatory transcriptional network. J. Biosci. 32, 1325--1330.Google ScholarGoogle ScholarCross RefCross Ref
  3. Datta, S., Sokhansanj, B. A. 2007. Accelerated search for biomolecular network models to interpret high-throughput experimental data. BMC Bioinformatics. 8, 258.Google ScholarGoogle ScholarCross RefCross Ref
  4. Wang, Y., Joshi, T., Zhang, X. S., Xu, D., and Chen L. 2006. Inferring gene regulatory networks from multiple microarray datasets. Bioinformatics. 22 (19), 2413--2420. Google ScholarGoogle ScholarDigital LibraryDigital Library
  5. Laurent, L. C., Chen, J., Ulitsky, I., Mueller, F. J., Lu, C., Shamir, R., Fan, J. B., and Loring, J. F. 2008. Comprehensive MicroRNA Profiling Reveals a Unique Human Embryonic Stem Cell Signature Dominated by a Single Seed Sequence. Stem Cells, 26, 1506--1516.Google ScholarGoogle ScholarCross RefCross Ref
  6. Stark, C., Breitkreutz, B. J., Reguly, T., Boucher, L., Breitkreutz, A., Tyers, M. 2006. BioGRID: a general repository for interaction datasets. Nucleic Acids Res. 34, 535--539.Google ScholarGoogle ScholarCross RefCross Ref
  7. Kanehisa, M., Goto, S., Hattori, M., Aoki-Kinoshita, K. F., Itoh, M., Kawashima, S., Katayama, T., Araki, M., Hirakawa, M. 2006. From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res. 34, 354--357.Google ScholarGoogle ScholarCross RefCross Ref
  8. Eisen, M., Spellman, P. L., Brown, P. O., Botsein, D. 1998. Cluster analysis and display of genomewide expression patterns. Proc Natl Acad Sci USA 95. 14863--14868.Google ScholarGoogle Scholar
  9. Tamayo, P., Slonim, D., Mesirov, J., Zhu, Q., Kitareewan, S., Dmitrovsky, E., Launder, E. S., Golub, T. R. 1999. Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoetic differentiation. Proc Natl Acad Sci USA 96. 2907--2912.Google ScholarGoogle ScholarCross RefCross Ref
  10. The Gene Ontology Consortium. 2000. Gene Ontology: tool for the unification of biology. Nature Genet. 25, 25--29.Google ScholarGoogle ScholarCross RefCross Ref
  11. Gawronska, B., Erlendsson, B., Olsson., B. 2006. Towards an Automated Analysis of Biomedical Abstracts. DILS 2006, 50--65. Google ScholarGoogle ScholarDigital LibraryDigital Library
  12. McNeish J. 2004. Embryonic stem cells in drug discovery. Nat Rev Drug Discov. 3, 70--80.Google ScholarGoogle ScholarCross RefCross Ref
  13. Beqqali, A., Kloots, J., Ward-van Oostwaard, D., Mummery, C., Passier, R. 2006. Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes. Stem Cells. 24, 1956--1967.Google ScholarGoogle ScholarCross RefCross Ref
  14. Synnergren, J., Adak, S., Englund, M. C., Giesler, T. L., Noaksson, K., Lindahl, A., Nilsson, P., Nelson, D., Abbot, S., Olsson, B., and Sartipy, P. 2008. Cardiomyogenic gene expression profiling of differentiating human embryonic stem cells. J Biotechnol. 134, 162--170.Google ScholarGoogle ScholarCross RefCross Ref
  15. Ernst, J., Nau, G., Bar-Joseph, Z. 2005. Clustering short time series gene expression data. Bioinformatics. 21, 59--68. Google ScholarGoogle ScholarDigital LibraryDigital Library
  16. Birnbaum, K., Benfey, P. N. and Shasha, D. E. 2001. Cis element/transcription factor analysis (cis/TF): a method for discovering transcription factor/cis element relationships. Genome Res. 11, 1583--1590.Google ScholarGoogle ScholarCross RefCross Ref
  17. Zhu, Z., Yitzhak, P. and George, M. C. 2002. Computational identification of transcription factor binding sites via a transcription-factorcentric clustering (TFCC) algorithm. J. Mol. Biol. 318, 71--81.Google ScholarGoogle ScholarCross RefCross Ref
  18. Han J. D, Bertin N., Hao T., et al. Evidence for dynamically organized modularity in the yeast protein-protein interaction network. Nature. 2004;430:88--93.Google ScholarGoogle Scholar
  19. Harris, B.,S., Jay, P., Y., Rackley, M., S., et al. Transcriptional regulation of cardiac conduction system development: 2004 FASEB cardiac conduction system minimeeting, Washington, DC. Anat Rec A Discov Mol Cell Evol Biol. 2004;280:1036--1045.Google ScholarGoogle ScholarCross RefCross Ref
  20. Firouzi, M., Bierhuizen, M.,F., Kok, B., et al. The human Cx40 promoter polymorphism -44G->A differentially affects transcriptional regulation by Sp1 and GATA4. Biochim Biophys Acta. 2006;1759:491--496.Google ScholarGoogle Scholar
  21. Linhares, V.,L., Almeida, N.,A., Menezes, D., C., et al. Transcriptional regulation of the murine Connexin40 promoter by cardiac factors Nkx2-5, GATA4 and Tbx5. Cardiovasc Res. 2004;64:402--411.Google ScholarGoogle Scholar
  22. Yang, W., M., Inouye, C., J., Seto, E. Cyclophilin A and FKBP12 interact with YY1 and alter its transcriptional activity.J Biol Chem. 1995;270:15187--1519.Google ScholarGoogle Scholar
  23. Coram, R. 2002. Boyd: The Fighter Pilot Who changed the Art of War. ISBN 0-316-88146-5. Little Brown.Google ScholarGoogle Scholar

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  1. A data integration method for exploring gene regulatory mechanisms

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        Tommaso Mazza

        The problem of understanding the behavior of the constituting components of living beings is of great interest. Many steps have been taken in this direction, but most "cellular intelligence" is still being ignored by our sciences. Experimental findings have confirmed many theoretical assumptions, and databases have been populated to permanently store and make information further available. Redundancy and overlapped bio-concepts are key factors for such repositories. Consequently, cross references have been established between them. From this perspective, the main challenge lies in mining knowledge from them. Synnergren et al. address this problem by proposing an integration method for exploring gene regulatory mechanisms. They give short descriptions of some types of data-and data sources-generally used in gene regulation studies. They discuss pure biological and "derived" information, without providing clear distinctions between these two classes. Then, they claim a methodology to explore gene regulatory mechanisms by integrating such data sources. Unfortunately, what it comes down to is a series of well-known tasks and tools that are individually presented; they are not described from a global cooperative perspective. Possible ways to combine them would have been of great interest. The biological description of the use case changes the tone of the paper, as it quickly becomes unnecessarily complex and detailed; then, the reader gets lost and his or her attention drops. Hence, even though the results seem interesting, it is hard to appreciate and evaluate them. Some grammatical errors and misspelled words also decrease the paper's readability. Online Computing Reviews Service

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        • Published in

          cover image ACM Conferences
          DTMBIO '08: Proceedings of the 2nd international workshop on Data and text mining in bioinformatics
          October 2008
          92 pages
          ISBN:9781605582511
          DOI:10.1145/1458449

          Copyright © 2008 ACM

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          Publication History

          • Published: 30 October 2008

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