62
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A Comparison of Gene Set Analysis Methods in Terms of Sensitivity, Prioritization and Specificity

      research-article
      1 , 2 , * , 2 , 2 , 3 , 4
      PLoS ONE
      Public Library of Science

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Identification of functional sets of genes associated with conditions of interest from omics data was first reported in 1999, and since, a plethora of enrichment methods were published for systematic analysis of gene sets collections including Gene Ontology and biological pathways. Despite their widespread usage in reducing the complexity of omics experiment results, their performance is poorly understood. Leveraging the existence of disease specific gene sets in KEGG and Metacore® databases, we compared the performance of sixteen methods under relaxed assumptions while using 42 real datasets (over 1,400 samples). Most of the methods ranked high the gene sets designed for specific diseases whenever samples from affected individuals were compared against controls via microarrays. The top methods for gene set prioritization were different from the top ones in terms of sensitivity, and four of the sixteen methods had large false positives rates assessed by permuting the phenotype of the samples. The best overall methods among those that generated reasonably low false positive rates, when permuting phenotypes, were PLAGE, GLOBALTEST, and PADOG. The best method in the category that generated higher than expected false positives was MRGSE.

          Related collections

          Most cited references9

          • Record: found
          • Abstract: found
          • Article: not found

          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Quantitative monitoring of gene expression patterns with a complementary DNA microarray.

            A high-capacity system was developed to monitor the expression of many genes in parallel. Microarrays prepared by high-speed robotic printing of complementary DNAs on glass were used for quantitative expression measurements of the corresponding genes. Because of the small format and high density of the arrays, hybridization volumes of 2 microliters could be used that enabled detection of rare transcripts in probe mixtures derived from 2 micrograms of total cellular messenger RNA. Differential expression measurements of 45 Arabidopsis genes were made by means of simultaneous, two-color fluorescence hybridization.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Systematic determination of genetic network architecture.

              Technologies to measure whole-genome mRNA abundances and methods to organize and display such data are emerging as valuable tools for systems-level exploration of transcriptional regulatory networks. For instance, it has been shown that mRNA data from 118 genes, measured at several time points in the developing hindbrain of mice, can be hierarchically clustered into various patterns (or 'waves') whose members tend to participate in common processes. We have previously shown that hierarchical clustering can group together genes whose cis-regulatory elements are bound by the same proteins in vivo. Hierarchical clustering has also been used to organize genes into hierarchical dendograms on the basis of their expression across multiple growth conditions. The application of Fourier analysis to synchronized yeast mRNA expression data has identified cell-cycle periodic genes, many of which have expected cis-regulatory elements. Here we apply a systematic set of statistical algorithms, based on whole-genome mRNA data, partitional clustering and motif discovery, to identify transcriptional regulatory sub-networks in yeast-without any a priori knowledge of their structure or any assumptions about their dynamics. This approach uncovered new regulons (sets of co-regulated genes) and their putative cis-regulatory elements. We used statistical characterization of known regulons and motifs to derive criteria by which we infer the biological significance of newly discovered regulons and motifs. Our approach holds promise for the rapid elucidation of genetic network architecture in sequenced organisms in which little biology is known.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                15 November 2013
                : 8
                : 11
                : e79217
                Affiliations
                [1 ]Department of Computer Science, Wayne State University, Detroit, Michigan, United States of America
                [2 ]Perinatology Research Branch, National Institute of Child Health and Human Development/National Institutes of Health, Rockville, Maryland, United States of America
                [3 ]Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, United States of America
                [4 ]Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, United States of America
                The University of Chicago, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AT. Performed the experiments: AT. Analyzed the data: AT RR. Contributed reagents/materials/analysis tools: GB. Wrote the paper: AT RR.

                Article
                PONE-D-13-31980
                10.1371/journal.pone.0079217
                3829842
                24260172
                1ea0b3c4-84c3-4b6d-b896-eeba532f28b0
                Copyright @ 2013

                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 4 August 2013
                : 26 September 2013
                Page count
                Pages: 10
                Funding
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AT, GB, and RR were supported, in part, by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services.
                Categories
                Research Article

                Uncategorized
                Uncategorized

                Comments

                Comment on this article