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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 If model is accurate,
can deduce additional features of system
Source: http://www.nature.com/ng/journal/v35/n2/images/ng1003-118-F1.gif
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).
Problem: Data Availability While in for some organisms lots of
interaction data, most very little However: Generally abundant sequence
data
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 Research 14(6), 1107-18 (2004).
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?
Interolog Interolog - A pair of
interacting proteins which are orthologous
Orthology difficult to determine, use homology
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
Interolog Mapping Unidirectional Best
Hit Mapping Bidirectional Best Hit
Mapping Generalized
Interolog Mapping
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
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
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).
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