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T. Przytycka's Research Group

Teresa M. Przytycka’s research group

Algorithmic and Graph Theoretical methods in

Computational and Systems Biology

Predicting domain-domain interactions using a

parsimony approach

Group members:

References:

Katia Guimares, Raja Jothi, Elena Zotenko, and Teresa Przytycka, Predicting Domain-Domain Interactions Using a Parsimony Approach

Genome Biology 2006, 7:R104 (9 November 2006) pdf

Katia Guimares and Teresa Przytycka, Interrogating domain-domain interactions with parsimony based approaches. BMC Bioinformatics. 2008 Mar 26;9:171.

Assumption: Protein interactions are mediated by domain interactions

Hypothesis: Interactions evolved in most parsimonious way

Method: Find the smallest set of putative domain-domain interactions that explain all protein-protein interactions in the network

For each domain pair D_i D_j : variable x_ij in [0,1] (contribution of domain pair in explaining the network)

Modeling noise in the network

• Select constraints randomly with probability equal to the reliability of protein interaction network (5o%)

• Repeat the random selection process 103 times and solve each instance of such randomized LP program

• Average the results

Particular strength

Ability to difficult domain interaction defined as domain interactions that have not been observed in the context of single interactions between single domain proteins

DATA FILES

ORIGINAL INPUT FILES

Protein annotation

(obtained from Additional data file 4 in http://genomebiology.com/2005/6/10/R89)

Protein-protein Interaction

(obtained from Additional data file 3 in http://genomebiology.com/2005/6/10/R89)

Crystal Structure Pairs

(3074 domain-domain pairs obtained from iPFAM's ftp site in December/2005)

SUBSETS SELECTED FOR EXPERIMENTS

iPFAM Crystal Structure Pairs that occur between different proteins or different chains

(Our golden standard set, with 2612 domain-domain pairs)

Protein-protein pairs with multiple potentially interacting domain-domain pairs and at least one pair in the golden standard set

OUTPUT DATA

>> Data collected assuming network reliability of 60% (error rate of 40%)

>> Domain-domain pairs in each file are ordered by LP-scores.

4100 domain-domain pairs with LP-score ≥ 0.5

3499 dom-dom pairs with LP-score ≥ 0.5 and 0.0 ≤ p-score≤ 0.1

> 50 topmost LP-score NOVEL dom-dom pairs with 0.0 ≤ p-score ≤ 0.1

(Novel pairs are those without crystal structure or witness)

ANALYSIS TABLES

Table 1. Top 50 LP-score (NOVEL) domain-domain pairs with p-score ≤ 0.1 (pdf file)

Table 2. Ras Partners with LP-score ≥0.5 (pdf file)

Table 3. Comparative Results for Set of Protein Pairs containing at least one potentially interacting pair among the DPEA method’s high-scoring domain pairs (pdf file)

READ ME FILE

Read Me text file with format and contents of all other files available

All pairs from 2008 paper