Finding Occurrences of Protein Complexes in Protein-Protein Interaction Graphs

International audienceIn the context of comparative analysis of protein-protein interaction graphs, we use a graph-based formalism to detect the preservation of a given protein complex G in the protein-protein interaction graph H of another species with respect to (w.r.t.) orthologous proteins. Two problems are considered: the Exact-($\mu$G; $\mu$H)-Matching problem and the Max-($\mu$G; $\mu$H)-Matching problems, where $\mu$G (resp. $\mu$H) denotes in both problems the maximum number of orthologous proteins in H (resp. G) of a protein in G (resp. H). Following [10], the Exact-($\mu$G; $\mu$H)-Matching problem asks for an injective homomorphism of G to H w.r.t. orthologous proteins. The optimization version is called the Max-($\mu$G; $\mu$H)-Matching problem and is concerned with finding an injective mapping of a graph G to a graph H w.r.t. orthologous proteins that matches as many edges of G as possible. For both problems, we essentially focus on bounded degree graphs and extremal small values of parameters $\mu$G and $\mu$H

Finding and counting vertex-colored subtrees

The problems studied in this article originate from the Graph Motif problem introduced by Lacroix et al. in the context of biological networks. The problem is to decide if a vertex-colored graph has a connected subgraph whose colors equal a given multiset of colors $M$. It is a graph pattern-matching problem variant, where the structure of the occurrence of the pattern is not of interest but the only requirement is the connectedness. Using an algebraic framework recently introduced by Koutis et al., we obtain new FPT algorithms for Graph Motif and variants, with improved running times. We also obtain results on the counting versions of this problem, proving that the counting problem is FPT if M is a set, but becomes W[1]-hard if M is a multiset with two colors. Finally, we present an experimental evaluation of this approach on real datasets, showing that its performance compares favorably with existing software.Comment: Conference version in International Symposium on Mathematical Foundations of Computer Science (MFCS), Brno : Czech Republic (2010) Journal Version in Algorithmic

Frequent Pattern Finding in Integrated Biological Networks

Biomedical research is undergoing a revolution with the advance of high-throughput technologies. A major challenge in the post-genomic era is to understand how genes, proteins and small molecules are organized into signaling pathways and regulatory networks. To simplify the analysis of large complex molecular networks, strategies are sought to break them down into small yet relatively independent network modules, e.g. pathways and protein complexes. In fulfillment of the motivation to find evolutionary origins of network modules, a novel strategy has been developed to uncover duplicated pathways and protein complexes. This search was first formulated into a computational problem which finds frequent patterns in integrated graphs. The whole framework was then successfully implemented as the software package BLUNT, which includes a parallelized version. To evaluate the biological significance of the work, several large datasets were chosen, with each dataset targeting a different biological question. An application of BLUNT was performed on the yeast protein-protein interaction network, which is described. A large number of frequent patterns were discovered and predicted to be duplicated pathways. To explore how these pathways may have diverged since duplication, the differential regulation of duplicated pathways was studied at the transcriptional level, both in terms of time and location. As demonstrated, this algorithm can be used as new data mining tool for large scale biological data in general. It also provides a novel strategy to study the evolution of pathways and protein complexes in a systematic way. Understanding how pathways and protein complexes evolve will greatly benefit the fundamentals of biomedical research

APPAGATO: an APproximate PArallel and stochastic GrAph querying TOol for biological networks

Motivation: Biological network querying is a problem requiring a considerable computational effort tobe solved. Given a target and a query network, it aims to find occurrences of the query in the target byconsidering topological and node similarities (i.e. mismatches between nodes, edges, or node labels).Querying tools that deal with similarities are crucial in biological network analysis since they providemeaningful results also in case of noisy data. In addition, since the size of available networks increasessteadily, existing algorithms and tools are becoming unsuitable. This is rising new challenges for the designof more efficient and accurate solutions.Results: This paper presents APPAGATO, a stochastic and parallel algorithm to find approximateoccurrences of a query network in biological networks. APPAGATO handles node, edge, and node labelmismatches. Thanks to its randomic and parallel nature, it applies to large networks and, compared toexisting tools, it provides higher performance as well as statistically significant more accurate results.Tests have been performed on protein-protein interaction networks annotated with synthetic and real geneontology terms. Case studies have been done by querying protein complexes among different species andtissue

Some results on more flexible versions of Graph Motif

The problems studied in this paper originate from Graph Motif, a problem introduced in 2006 in the context of biological networks. Informally speaking, it consists in deciding if a multiset of colors occurs in a connected subgraph of a vertex-colored graph. Due to the high rate of noise in the biological data, more flexible definitions of the problem have been outlined. We present in this paper two inapproximability results for two different optimization variants of Graph Motif: one where the size of the solution is maximized, the other when the number of substitutions of colors to obtain the motif from the solution is minimized. We also study a decision version of Graph Motif where the connectivity constraint is replaced by the well known notion of graph modularity. While the problem remains NP-complete, it allows algorithms in FPT for biologically relevant parameterizations

Accuracy improvement in protein complex prediction from protein interaction networks by refining cluster overlaps

<p>Abstract</p> <p>Background</p> <p>Recent computational techniques have facilitated analyzing genome-wide protein-protein interaction data for several model organisms. Various graph-clustering algorithms have been applied to protein interaction networks on the genomic scale for predicting the entire set of potential protein complexes. In particular, the density-based clustering algorithms which are able to generate overlapping clusters, i.e. the clusters sharing a set of nodes, are well-suited to protein complex detection because each protein could be a member of multiple complexes. However, their accuracy is still limited because of complex overlap patterns of their output clusters.</p> <p><b>Results</b></p> <p>We present a systematic approach of refining the overlapping clusters identified from protein interaction networks. We have designed novel metrics to assess cluster overlaps: overlap coverage and overlapping consistency. We then propose an overlap refinement algorithm. It takes as input the clusters produced by existing density-based graph-clustering methods and generates a set of refined clusters by parameterizing the metrics. To evaluate protein complex prediction accuracy, we used the <it>f</it>-measure by comparing each refined cluster to known protein complexes. The experimental results with the yeast protein-protein interaction data sets from BioGRID and DIP demonstrate that accuracy on protein complex prediction has increased significantly after refining cluster overlaps.</p> <p><b>Conclusions</b></p> <p>The effectiveness of the proposed cluster overlap refinement approach for protein complex detection has been validated in this study. Analyzing overlaps of the clusters from protein interaction networks is a crucial task for understanding of functional roles of proteins and topological characteristics of the functional systems.</p

Graph theoretic methods for the analysis of structural relationships in biological macromolecules

Subgraph isomorphism and maximum common subgraph isomorphism algorithms from graph theory provide an effective and an efficient way of identifying structural relationships between biological macromolecules. They thus provide a natural complement to the pattern matching algorithms that are used in bioinformatics to identify sequence relationships. Examples are provided of the use of graph theory to analyze proteins for which three-dimensional crystallographic or NMR structures are available, focusing on the use of the Bron-Kerbosch clique detection algorithm to identify common folding motifs and of the Ullmann subgraph isomorphism algorithm to identify patterns of amino acid residues. Our methods are also applicable to other types of biological macromolecule, such as carbohydrate and nucleic acid structures