Network-based Similarity Research Articles

Measuring semantic similarities by combining gene ontology annotations and gene co-function networks.

BackgroundGene Ontology (GO) has been used widely to study functional relationships between genes. The current semantic similarity measures rely only on GO annotations and GO structure. This limits the power of GO-based similarity because of the limited proportion of genes that are annotated to GO in most organisms.ResultsWe introduce a novel approach called NETSIM (network-based similarity measure) that incorporates information from gene co-function networks in addition to using the GO structure and annotations. Using metabolic reaction maps of yeast, Arabidopsis, and human, we demonstrate that NETSIM can improve the accuracy of GO term similarities. We also demonstrate that NETSIM works well even for genomes with sparser gene annotation data. We applied NETSIM on large Arabidopsis gene families such as cytochrome P450 monooxygenases to group the members functionally and show that this grouping could facilitate functional characterization of genes in these families.ConclusionsUsing NETSIM as an example, we demonstrated that the performance of a semantic similarity measure could be significantly improved after incorporating genome-specific information. NETSIM incorporates both GO annotations and gene co-function network data as a priori knowledge in the model. Therefore, functional similarities of GO terms that are not explicitly encoded in GO but are relevant in a taxon-specific manner become measurable when GO annotations are limited. Supplementary information and software are available at http://www.msu.edu/~jinchen/NETSIM.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0474-7) contains supplementary material, which is available to authorized users.

EPSILON: an eQTL prioritization framework using similarity measures derived from local networks

When genomic data are associated with gene expression data, the resulting expression quantitative trait loci (eQTL) will likely span multiple genes. eQTL prioritization techniques can be used to select the most likely causal gene affecting the expression of a target gene from a list of candidates. As an input, these techniques use physical interaction networks that often contain highly connected genes and unreliable or irrelevant interactions that can interfere with the prioritization process. We present EPSILON, an extendable framework for eQTL prioritization, which mitigates the effect of highly connected genes and unreliable interactions by constructing a local network before a network-based similarity measure is applied to select the true causal gene. We tested the new method on three eQTL datasets derived from yeast data using three different association techniques. A physical interaction network was constructed, and each eQTL in each dataset was prioritized using the EPSILON approach: first, a local network was constructed using a k-trials shortest path algorithm, followed by the calculation of a network-based similarity measure. Three similarity measures were evaluated: random walks, the Laplacian Exponential Diffusion kernel and the Regularized Commute-Time kernel. The aim was to predict knockout interactions from a yeast knockout compendium. EPSILON outperformed two reference prioritization methods, random assignment and shortest path prioritization. Next, we found that using a local network significantly increased prioritization performance in terms of predicted knockout pairs when compared with using exactly the same network similarity measures on the global network, with an average increase in prioritization performance of 8 percentage points (P < 10(-5)). The physical interaction network and the source code (Matlab/C++) of our implementation can be downloaded from http://bioinformatics.intec.ugent.be/epsilon. lieven.verbeke@intec.ugent.be, kamar@psb.ugent.be, jan.fostier@intec.ugent.be Supplementary data are available at Bioinformatics online.

PathSim

Similarity search is a primitive operation in database and Web search engines. With the advent of large-scale heterogeneous information networks that consist of multi-typed, interconnected objects, such as the bibliographic networks and social media networks, it is important to study similarity search in such networks. Intuitively, two objects are similar if they are linked by many paths in the network. However, most existing similarity measures are defined for homogeneous networks. Different semantic meanings behind paths are not taken into consideration. Thus they cannot be directly applied to heterogeneous networks. In this paper, we study similarity search that is defined among the same type of objects in heterogeneous networks. Moreover, by considering different linkage paths in a network, one could derive various similarity semantics. Therefore, we introduce the concept of meta path-based similarity , where a meta path is a path consisting of a sequence of relations defined between different object types ( i.e. , structural paths at the meta level). No matter whether a user would like to explicitly specify a path combination given sufficient domain knowledge, or choose the best path by experimental trials, or simply provide training examples to learn it, meta path forms a common base for a network-based similarity search engine. In particular, under the meta path framework we define a novel similarity measure called PathSim that is able to find peer objects in the network ( e.g. , find authors in the similar field and with similar reputation), which turns out to be more meaningful in many scenarios compared with random-walk based similarity measures. In order to support fast online query processing for PathSim queries, we develop an efficient solution that partially materializes short meta paths and then concatenates them online to compute top- k results. Experiments on real data sets demonstrate the effectiveness and efficiency of our proposed paradigm.

A neural network-based similarity index for clustering DNA microarray data

A common approach to the analysis of gene expression data is to define clusters of genes that have similar expression. A critical step in cluster analysis is the determination of similarity between the expression levels of two genes. We introduce a neural network-based similarity index as a non-linear similarity index and compare the results with other proximity measures for Saccharomyces cerevisiae gene expression data. We show that the clusters obtained using Euclidean distance, correlation coefficients, and mutual information were not significantly different. The clusters formed with the neural network-based index were more in agreement with those defined by functional categories and common regulatory motifs.