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Topological network alignment uncovers biological function and phylogeny.

ABSTRACT: Sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology and disease. Comparison and alignment of biological networks will probably have a similar impact. Existing network alignments use information external to the networks, such as sequence, because no good algorithm for purely topological alignment has yet been devised. In this paper, we present a novel algorithm based solely on network topology, that can be used to align any two networks. We apply it to biological networks to produce by far the most complete topological alignments of biological networks to date. We demonstrate that both species phylogeny and detailed biological function of individual proteins can be extracted from our alignments. Topology-based alignments have the potential to provide a completely new, independent source of phylogenetic information. Our alignment of the protein-protein interaction networks of two very different species-yeast and human-indicate that even distant species share a surprising amount of network topology, suggesting broad similarities in internal cellular wiring across all life on Earth.

SUBMITTER: Kuchaiev O

PROVIDER: S-EPMC2894889 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Topological network alignment uncovers biological function and phylogeny.

Kuchaiev Oleksii O Milenkovic Tijana T Memisevic Vesna V Hayes Wayne W Przulj Natasa N

Journal of the Royal Society, Interface 20100317 50

Sequence comparison and alignment has had an enormous impact on our understanding of evolution, biology and disease. Comparison and alignment of biological networks will probably have a similar impact. Existing network alignments use information external to the networks, such as sequence, because no good algorithm for purely topological alignment has yet been devised. In this paper, we present a novel algorithm based solely on network topology, that can be used to align any two networks. We appl ...[more]

PMID: 20236959

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Project description:MotivationSignificant efforts have been made to acquire data under different conditions and to construct static networks that can explain various gene regulation mechanisms. However, gene regulatory networks are dynamic and condition-specific; under different conditions, networks exhibit different regulation patterns accompanied by different transcriptional network topologies. Thus, an investigation on the topological changes in transcriptional networks can facilitate the understanding of cell development or provide novel insights into the pathophysiology of certain diseases, and help identify the key genetic players that could serve as biomarkers or drug targets.ResultsHere, we report a differential dependency network (DDN) analysis to detect statistically significant topological changes in the transcriptional networks between two biological conditions. We propose a local dependency model to represent the local structures of a network by a set of conditional probabilities. We develop an efficient learning algorithm to learn the local dependency model using the Lasso technique. A permutation test is subsequently performed to estimate the statistical significance of each learned local structure. In testing on a simulation dataset, the proposed algorithm accurately detected all the genes with network topological changes. The method was then applied to the estrogen-dependent T-47D estrogen receptor-positive (ER+) breast cancer cell line datasets and human and mouse embryonic stem cell datasets. In both experiments using real microarray datasets, the proposed method produced biologically meaningful results. We expect DDN to emerge as an important bioinformatics tool in transcriptional network analyses. While we focus specifically on transcriptional networks, the DDN method we introduce here is generally applicable to other biological networks with similar characteristics.AvailabilityThe DDN MATLAB toolbox and experiment data are available at http://www.cbil.ece.vt.edu/software.htm.

Project description:BACKGROUND:Recent advances in genome sequencing technologies and the cost drop in high-throughput sequencing continue to give rise to a deluge of data available for downstream analyses. Among others, evolutionary biologists often make use of genomic data to uncover phenotypic diversity and adaptive evolution in protein-coding genes. Therefore, multiple sequence alignments (MSA) and phylogenetic trees (PT) need to be estimated with optimal results. However, the preparation of an initial dataset of multiple sequence file(s) (MSF) and the steps involved can be challenging when considering extensive amount of data. Thus, it becomes necessary the development of a tool that removes the potential source of error and automates the time-consuming steps of a typical workflow with high-throughput and optimal MSA and PT estimations. RESULTS:We introduce LMAP_S (Lightweight Multigene Alignment and Phylogeny eStimation), a user-friendly command-line and interactive package, designed to handle an improved alignment and phylogeny estimation workflow: MSF preparation, MSA estimation, outlier detection, refinement, consensus, phylogeny estimation, comparison and editing, among which file and directory organization, execution, manipulation of information are automated, with minimal manual user intervention. LMAP_S was developed for the workstation multi-core environment and provides a unique advantage for processing multiple datasets. Our software, proved to be efficient throughout the workflow, including, the (unlimited) handling of more than 20 datasets. CONCLUSIONS:We have developed a simple and versatile LMAP_S package enabling researchers to effectively estimate multiple datasets MSAs and PTs in a high-throughput fashion. LMAP_S integrates more than 25 software providing overall more than 65 algorithm choices distributed in five stages. At minimum, one FASTA file is required within a single input directory. To our knowledge, no other software combines MSA and phylogeny estimation with as many alternatives and provides means to find optimal MSAs and phylogenies. Moreover, we used a case study comparing methodologies that highlighted the usefulness of our software. LMAP_S has been developed as an open-source package, allowing its integration into more complex open-source bioinformatics pipelines. LMAP_S package is released under GPLv3 license and is freely available at https://lmap-s.sourceforge.io/.

Dataset Information

Topological network alignment uncovers biological function and phylogeny.

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Topological network alignment uncovers biological function and phylogeny.

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