Dataset Information

QPath: a method for querying pathways in a protein-protein interaction network.

ABSTRACT:

Background

Sequence comparison is one of the most prominent tools in biological research, and is instrumental in studying gene function and evolution. The rapid development of high-throughput technologies for measuring protein interactions calls for extending this fundamental operation to the level of pathways in protein networks.

Results

We present a comprehensive framework for protein network searches using pathway queries. Given a linear query pathway and a network of interest, our algorithm, QPath, efficiently searches the network for homologous pathways, allowing both insertions and deletions of proteins in the identified pathways. Matched pathways are automatically scored according to their variation from the query pathway in terms of the protein insertions and deletions they employ, the sequence similarity of their constituent proteins to the query proteins, and the reliability of their constituent interactions. We applied QPath to systematically infer protein pathways in fly using an extensive collection of 271 putative pathways from yeast. QPath identified 69 conserved pathways whose members were both functionally enriched and coherently expressed. The resulting pathways tended to preserve the function of the original query pathways, allowing us to derive a first annotated map of conserved protein pathways in fly.

Conclusion

Pathway homology searches using QPath provide a powerful approach for identifying biologically significant pathways and inferring their function. The growing amounts of protein interactions in public databases underscore the importance of our network querying framework for mining protein network data.

SUBMITTER: Shlomi T

PROVIDER: S-EPMC1458361 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature

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Publications

QPath: a method for querying pathways in a protein-protein interaction network.

Shlomi Tomer T Segal Daniel D Ruppin Eytan E Sharan Roded R

BMC bioinformatics 20060410

<h4>Background</h4>Sequence comparison is one of the most prominent tools in biological research, and is instrumental in studying gene function and evolution. The rapid development of high-throughput technologies for measuring protein interactions calls for extending this fundamental operation to the level of pathways in protein networks.<h4>Results</h4>We present a comprehensive framework for protein network searches using pathway queries. Given a linear query pathway and a network of interest, ...[more]

PMID: 16606460

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Project description:BACKGROUND: Searching for structural motifs across known protein structures can be useful for identifying unrelated proteins with similar function and characterising secondary structures such as ?-sheets. This is infeasible using conventional sequence alignment because linear protein sequences do not contain spatial information. ?-residue motifs are ?-sheet substructures that can be represented as graphs and queried using existing graph indexing methods, however, these approaches are designed for general graphs that do not incorporate the inherent structural constraints of ?-sheets and require computationally-expensive filtering and verification procedures. 3D substructure search methods, on the other hand, allow ?-residue motifs to be queried in a three-dimensional context but at significant computational costs. FINDINGS: We developed a new method for querying ?-residue motifs, called BetaSearch, which leverages the natural planar constraints of ?-sheets by indexing them as 2D matrices, thus avoiding much of the computational complexities involved with structural and graph querying. BetaSearch exhibits faster filtering, verification, and overall query time than existing graph indexing approaches whilst producing comparable index sizes. Compared to 3D substructure search methods, BetaSearch achieves 33 and 240 times speedups over index-based and pairwise alignment-based approaches, respectively. Furthermore, we have presented case-studies to demonstrate its capability of motif matching in sequentially dissimilar proteins and described a method for using BetaSearch to predict ?-strand pairing. CONCLUSIONS: We have demonstrated that BetaSearch is a fast method for querying substructure motifs. The improvements in speed over existing approaches make it useful for efficiently performing high-volume exploratory querying of possible protein substructural motifs or conformations. BetaSearch was used to identify a nearly identical ?-residue motif between an entirely synthetic (Top7) and a naturally-occurring protein (Charcot-Leyden crystal protein), as well as identifying structural similarities between biotin-binding domains of avidin, streptavidin and the lipocalin gamma subunit of human C8.

Project description:Identification of central genes and proteins in biomolecular networks provides credible candidates for pathway analysis, functional analysis, and essentiality prediction. The DiffSLC centrality measure predicts central and essential genes and proteins using a protein-protein interaction network. Network centrality measures prioritize nodes and edges based on their importance to the network topology. These measures helped identify critical genes and proteins in biomolecular networks. The proposed centrality measure, DiffSLC, combines the number of interactions of a protein and the gene coexpression values of genes from which those proteins were translated, as a weighting factor to bias the identification of essential proteins in a protein interaction network. Potentially essential proteins with low node degree are promoted through eigenvector centrality. Thus, the gene coexpression values are used in conjunction with the eigenvector of the network's adjacency matrix and edge clustering coefficient to improve essentiality prediction. The outcome of this prediction is shown using three variations: (1) inclusion or exclusion of gene co-expression data, (2) impact of different coexpression measures, and (3) impact of different gene expression data sets. For a total of seven networks, DiffSLC is compared to other centrality measures using Saccharomyces cerevisiae protein interaction networks and gene expression data. Comparisons are also performed for the top ranked proteins against the known essential genes from the Saccharomyces Gene Deletion Project, which show that DiffSLC detects more essential proteins and has a higher area under the ROC curve than other compared methods. This makes DiffSLC a stronger alternative to other centrality methods for detecting essential genes using a protein-protein interaction network that obeys centrality-lethality principle. DiffSLC is implemented using the igraph package in R, and networkx package in Python. The python package can be obtained from git.io/diffslcpy. The R implementation and code to reproduce the analysis is available via git.io/diffslc.

Project description:BACKGROUND:Functional modules in biological networks consist of numerous biomolecules and their complicated interactions. Recent studies have shown that biomolecules in a functional module tend to have similar interaction patterns and that such modules are often conserved across biological networks of different species. As a result, such conserved functional modules can be identified through comparative analysis of biological networks. RESULTS:In this work, we propose a novel network querying algorithm based on the CUFID (Comparative network analysis Using the steady-state network Flow to IDentify orthologous proteins) framework combined with an efficient seed-and-extension approach. The proposed algorithm, CUFID-query, can accurately detect conserved functional modules as small subnetworks in the target network that are expected to perform similar functions to the given query functional module. The CUFID framework was recently developed for probabilistic pairwise global comparison of biological networks, and it has been applied to pairwise global network alignment, where the framework was shown to yield accurate network alignment results. In the proposed CUFID-query algorithm, we adopt the CUFID framework and extend it for local network alignment, specifically to solve network querying problems. First, in the seed selection phase, the proposed method utilizes the CUFID framework to compare the query and the target networks and to predict the probabilistic node-to-node correspondence between the networks. Next, the algorithm selects and greedily extends the seed in the target network by iteratively adding nodes that have frequent interactions with other nodes in the seed network, in a way that the conductance of the extended network is maximally reduced. Finally, CUFID-query removes irrelevant nodes from the querying results based on the personalized PageRank vector for the induced network that includes the fully extended network and its neighboring nodes. CONCLUSIONS:Through extensive performance evaluation based on biological networks with known functional modules, we show that CUFID-query outperforms the existing state-of-the-art algorithms in terms of prediction accuracy and biological significance of the predictions.

Dataset Information

QPath: a method for querying pathways in a protein-protein interaction network.

Background

Results

Conclusion

Publications

QPath: a method for querying pathways in a protein-protein interaction network.

Similar Datasets

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