Biological Network Inference


Protein-Protein interactions (PPIs)


We have developed a new technique to predict PPIs using the signature descriptor described in the QSAR pages. The signature of a protein sequence (or DNA sequence) is a vector of occurence numbers of the sequence k-mers (or k-words). To predict protein binding pairs a new type of QSAR was developed where the signagture is a product of the signagtures of both the bait (target) and the prey (ligand). The QSAR, which is trained using SVM compares well in term of accuracy/precision/sensitivity with other existing techniques. Our method is not specific to a particular type of experimental dataset, does not require knowledge of protein domains or physico-chemical parameters, it just uses as input a list of sequences and binding pairs. More information can be found in the following papers:

  1. Brown W. M., Martin S., Chabarek J.P., Strauss C, Faulon J.L. Prediction of β-Strand Packing Interactions using the Signature Product, Journal of Molecular Modeling, in press. [PMID: 16365772]   (link to journal)
  2. Martin S., Roe D., Faulon J.L. Predicting Protein-Protein Interactions using Signature Products, Bioinformatics, 21, 218-26, 2005. [PMID: 15319262]. (.pdf manuscript).
    Protein-Protein Interaction Predictor Downloads



Regulatory interactions

Regulatory interactions are probed using a combinatorial  technique that enumerates all the possible regulators of a given gene/protein from hight throughput expression profiles. The technique takes as input time series expression profiles under experimental perturbations (knock-out for instance), and outputs all the possible networks, where relationships between genes/proteins are represented by activation/inhibition rules. The activation/inhibition rules are implemented by Boolean functions, which allows one to study the steady state dynamics of the infered networks. The computational efficiency of the technique relies of the assumption that the number of regulator per gene/protein is bounded by some constant.  Our combinatorial enumeration has been applied to infer gene regulatory networks for Yeast cell cycle, and IL2 stimulated T cell regulatory response. More information can be found in the following papers:

  1. Faulon J.L.,, Zhang Z., Martino A., Timlin J.A., Haaland D.M.,, Martin S., Davidson G.,  May E., Slepoy A. Reverse Engineering Biological Networks: T-cell response to IL-2 stimulation. SANDIA Report 2005- 5238379, Sandia National Laboratories, Albuquerque, NM. (.pdf manuscript).
  2. Martin S, Davidson G, May E, Werner-Washburne M., Faulon J.L. Inferring Genetic Networks from Microarray Data. Proceedings IEEE CSB2004, 3, 566-569, 2004. (.pdf manuscript).
  3. Faulon J.L., Martin S., Carr RD.  Dynamical Robustness in Gene Regulatory Networks. Proceedings IEEE CSB2004, 3, 626-627, 2004. (.pdf manuscript).




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jfaulon@sandia.gov
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