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 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).

Terminology Ortholog - Two sequences which

derived from a common ancestor sequence

A

A1

A2

A3

Terminology Homolog - Two sequences with

significant similarity

A A

A’

A1

A’1

A2

A’2

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

Validation

Results: TP vs. J

Results: Total vs. J

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

Interolog Database

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).

Entire Graph

Sampled Graph

Scale-Free!

Therefore…

Entire Graph

Scale-Free!

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

Questions?