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Properties of Interaction Networks

Properties of Interaction Networks. Jason Turner-Maier May 1st. Systems Biology Review. Lots of data about biological systems Need to approach data in a structured way to understand it. Protein Interaction Networks. Proteins in a biological system interact in a complex web Model as a graph

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Properties of Interaction Networks

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  1. Properties of Interaction Networks Jason Turner-Maier May 1st

  2. Systems Biology Review • Lots of data about biological systems • Need to approach data in a structured way to understand it

  3. Protein Interaction Networks • Proteins in a biological system interact in a complex web • Model as a graph • If model is accurate, can deduce additional features of system Source: http://www.nature.com/ng/journal/v35/n2/images/ng1003-118-F1.gif

  4. Example: Iterative Improvement • Marc’s Talk on Tuesday • Use model of protein-protein interactions to infer additional information about the signaling network: new links Source: Schaub, M., Bezdek, A., Henzinger, T., Radtke, F., and Fisher, J. Qualitative Crosstalk Analysis of Wnt and Notch Signaling in Mamalian Skin. RECOMB Satelite Conference on Systems Biology (2007).

  5. Problem: Data Availability • While in for some organisms lots of interaction data, most very little • However: Generally abundant sequence data

  6. Annotation Transfer Between Genomes • Yu, H., Luscombe, N.M., Lu, H.X, Zhu, X., Xia, Y., Han, J.J., Bertin, N., Chung, S., Vidal, M., and Gerstein, M. Annotation Transfer Between Genomes: Protein-Protein Interologs and Protein-DNA Regulogs. Genome Research14(6), 1107-18 (2004).

  7. Terminology • Ortholog - Two sequences which derived from a common ancestor sequence A1 A A2 A3

  8. Terminology • Homolog - Two sequences with significant similarity A1 A’1 A A A’ A2 A’2

  9. Idea: Relationship Mapping • Problem: Some organisms lots of interaction data, some very little • Interaction data hard to generate • Idea: If proteins are orthologs, might they have similar interactions?

  10. Interolog • Interolog - A pair of interacting proteins which are orthologous • Orthology difficult to determine, use homology

  11. Similarity Metric • How to measure similarity between protein pairs? • JI = sqrrt(IA x IB) • JE = sqrrt(EA x EB) • JAB = min(SA, SB) • Result suggest exact metric doesn’t change results much

  12. Interolog Mapping • Unidirectional Best Hit Mapping • Bidirectional Best Hit Mapping • Generalized Interolog Mapping

  13. Data Sets • Gold Standards • Positive - MIPS Complex Catalog (S. cerevisiae ) • Negative - Proteins in different subcellular compartments • Source Data Sets • C. elegans, D. melanogaster, H. pylori

  14. Validation

  15. Results: TP vs. J

  16. Results: Total vs. J

  17. Results: Interolog Mapping Comparison • Unidirectional Best Hit • 84 predictions, 30% verified • Bidirectional Best Hit • 33 predictions, 54% verified • Generalized Interolog Mapping • 9317 predictions, 2% verified • Only use top 5% pairs: 112 predictions, 31% verified

  18. Interolog Database

  19. Sampling Properties of Networks • Stumpf, M.P.H., Wiuf, C., May, R.M. Subnets of scale-free networks are not scale-free: Sampling properties of networks. PNAS 102(12), 4221-4224 (2005).

  20. Entire Graph

  21. Sampled Graph Scale-Free!

  22. Therefore…

  23. Entire Graph Scale-Free!

  24. Sampled Graph != Full Graph • In general case, properties in the sampled graph do not hold for the full graph • More of the graph you have, more likely they are to hold • Need to be careful when dealing with portions of an unknown graph

  25. Questions?

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