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Graph ranking for exploratory gene data analysis.

ABSTRACT: BACKGROUND: Microarray technology has made it possible to simultaneously monitor the expression levels of thousands of genes in a single experiment. However, the large number of genes greatly increases the challenges of analyzing, comprehending and interpreting the resulting mass of data. Selecting a subset of important genes is inevitable to address the challenge. Gene selection has been investigated extensively over the last decade. Most selection procedures, however, are not sufficient for accurate inference of underlying biology, because biological significance does not necessarily have to be statistically significant. Additional biological knowledge needs to be integrated into the gene selection procedure. RESULTS: We propose a general framework for gene ranking. We construct a bipartite graph from the Gene Ontology (GO) and gene expression data. The graph describes the relationship between genes and their associated molecular functions. Under a species condition, edge weights of the graph are assigned to be gene expression level. Such a graph provides a mathematical means to represent both species-independent and species-dependent biological information. We also develop a new ranking algorithm to analyze the weighted graph via a kernelized spatial depth (KSD) approach. Consequently, the importance of gene and molecular function can be simultaneously ranked by a real-valued measure, KSD, which incorporates the global and local structure of the graph. Over-expressed and under-regulated genes also can be separately ranked. CONCLUSION: The gene-function bigraph integrates molecular function annotations into gene expression data. The relevance of genes is described in the graph (through a common function). The proposed method provides an exploratory framework for gene data analysis.

SUBMITTER: Gao C

PROVIDER: S-EPMC3226190 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Graph ranking for exploratory gene data analysis.

Gao Cuilan C Dang Xin X Chen Yixin Y Wilkins Dawn D

BMC bioinformatics 20091008

<h4>Background</h4>Microarray technology has made it possible to simultaneously monitor the expression levels of thousands of genes in a single experiment. However, the large number of genes greatly increases the challenges of analyzing, comprehending and interpreting the resulting mass of data. Selecting a subset of important genes is inevitable to address the challenge. Gene selection has been investigated extensively over the last decade. Most selection procedures, however, are not sufficient ...[more]

PMID: 19811684

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Project description:BackgroundThe internet has become an increasingly important resource for health information. However, with a growing amount of web pages, it is nearly impossible for humans to manually keep track of evolving and continuously changing content in the health domain. To better understand the nature of all web-based health information as given in a specific language, it is important to identify (1) information hubs for the health domain, (2) content providers of high prestige, and (3) important topics and trends in the health-related web. In this context, an automatic web crawling approach can provide the necessary data for a computational and statistical analysis to answer (1) to (3).ObjectiveThis study demonstrates the suitability of a focused crawler for the acquisition of the German Health Web (GHW) which includes all health-related web content of the three mostly German speaking countries Germany, Austria and Switzerland. Based on the gathered data, we provide a preliminary analysis of the GHW's graph structure covering its size, most important content providers and a ratio of public to private stakeholders. In addition, we provide our experiences in building and operating such a highly scalable crawler.MethodsA support vector machine classifier was trained on a large data set acquired from various German content providers to distinguish between health-related and non-health-related web pages. The classifier was evaluated using accuracy, recall and precision on an 80/20 training/test split (TD1) and against a crowd-validated data set (TD2). To implement the crawler, we extended the open-source framework StormCrawler. The actual crawl was conducted for 227 days. The crawler was evaluated by using harvest rate and its recall was estimated using a seed-target approach.ResultsIn total, n=22,405 seed URLs with country-code top level domains .de: 85.36% (19,126/22,405), .at: 6.83% (1530/22,405), .ch: 7.81% (1749/22,405), were collected from Curlie and a previous crawl. The text classifier achieved an accuracy on TD1 of 0.937 (TD2=0.966), a precision on TD1 of 0.934 (TD2=0.954) and a recall on TD1 of 0.944 (TD2=0.989). The crawl yields 13.5 million presumably relevant and 119.5 million nonrelevant web pages. The average harvest rate was 19.76%; recall was 0.821 (4105/5000 targets found). The resulting host-aggregated graph contains 215,372 nodes and 403,175 edges (network diameter=25; average path length=6.466; average degree=1.872; average in-degree=1.892; average out-degree=1.845; modularity=0.723). Among the 25 top-ranked pages for each country (according to PageRank), 40% (30/75) were web sites published by public institutions. 25% (19/75) were published by nonprofit organizations and 35% (26/75) by private organizations or individuals.ConclusionsThe results indicate, that the presented crawler is a suitable method for acquiring a large fraction of the GHW. As desired, the computed statistical data allows for determining major information hubs and important content providers on the GHW. In the future, the acquired data may be used to assess important topics and trends but also to build health-specific search engines.

Project description:In cancer, gene networks and pathways often exhibit dynamic behavior, particularly during the process of carcinogenesis. Thus, it is important to prioritize those genes that are strongly associated with the functionality of a network. Traditional statistical methods are often inept to identify biologically relevant member genes, motivating researchers to incorporate biological knowledge into gene ranking methods. However, current integration strategies are often heuristic and fail to incorporate fully the true interplay between biological knowledge and gene expression data.To improve knowledge-guided gene ranking, we propose a novel method called coordinative component analysis (COCA) in this paper. COCA explicitly captures those genes within a specific biological context that are likely to be expressed in a coordinative manner. Formulated as an optimization problem to maximize the coordinative effort, COCA is designed to first extract the coordinative components based on a partial guidance from knowledge genes and then rank the genes according to their participation strengths. An embedded bootstrapping procedure is implemented to improve statistical robustness of the solutions. COCA was initially tested on simulation data and then on published gene expression microarray data to demonstrate its improved performance as compared to traditional statistical methods. Finally, the COCA approach has been applied to stem cell data to identify biologically relevant genes in signaling pathways. As a result, the COCA approach uncovers novel pathway members that may shed light into the pathway deregulation in cancers.We have developed a new integrative strategy to combine biological knowledge and microarray data for gene ranking. The method utilizes knowledge genes for a guidance to first extract coordinative components, and then rank the genes according to their contribution related to a network or pathway. The experimental results show that such a knowledge-guided strategy can provide context-specific gene ranking with an improved performance in pathway member identification.

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Graph ranking for exploratory gene data analysis.

Publications

Graph ranking for exploratory gene data analysis.

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