Cross-species microarray analysis with the OSCAR system suggests an INSR->Pax6->NQO1 neuro-protective pathway in aging and Alzheimer's disease - PubMed (original) (raw)

. 2007 Jul;35(Web Server issue):W105-14.

doi: 10.1093/nar/gkm408. Epub 2007 Jun 1.

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Cross-species microarray analysis with the OSCAR system suggests an INSR->Pax6->NQO1 neuro-protective pathway in aging and Alzheimer's disease

Yue Lu et al. Nucleic Acids Res. 2007 Jul.

Abstract

OSCAR is a web platform for cluster and cross-species analysis of microarray data. It provides a comprehensive but friendly environment to both users and algorithm developers. For users, OSCAR provides cluster tools for both single and multiple species data, together with interactive analysis features. For single species data, OSCAR currently provides Hierarchical Clustering, K-means, partition around medoids (PAM), Self-Organizing Map (SOM), Tight Clustering and a novel algorithm called 'Consensus Tight-clustering'. The new Consensus Tight-clustering algorithm delivers robust gene clusters and its result is more resistant to false positives than other state-of-the-art algorithms. For cross-species data analysis, OSCAR provides two novel computational tools: 'coherentCluster', 'coherentSubset' and a novel visualization tool: 'comparative heatmap'. Applying the coherentCluster algorithm to human and fly aging data, we identified several coherent clusters of genes, which share co-regulation patterns that are highly correlated with the aging process in both of the two species. One coherent cluster suggests insulin receptor (INSR) may regulate Pax6 in both species and across different tissues. Further analysis with human brain expression and pathological data suggests an INSR->Pax6->quinone oxidoreductase (NQO1)->detoxification neuro-protective pathway might be present in aging or diseased brain. For algorithm developers, OSCAR is a plug-and-play platform. With little effort, developers can plug their own algorithms into the OSCAR server without revealing the source codes, which will equip their command line executables with user-friendly interface and interactive analysis capability. In summary, OSCAR initiates an open platform for development and application of clustering and cross-species analysis programs. OSCAR stands for an open system for cluster analysis of microarray data. It is available at: http://biocomp.bioen.uiuc.edu/oscar.

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Figures

Figure 1.

Figure 1.

Screenshot of the main web page for users.

Figure 2.

Figure 2.

Screenshot of a heatmap output. The heatmap is interactive. Hovering mouse cursor over each spot on the heatmap will dynamically retrieve the gene expression values. Hovering cursor over sample numbers will retrieve full sample names. Blue represents lower expression and yellow represents higher expression. The color scheme can be changed by clicking the ‘Change Color’ button. The figure can be saved by clicking the disk button.

Figure 3.

Figure 3.

Flowchart of the coherentClustering algorithm.

Figure 4.

Figure 4.

The ‘comparative heatmap’ showing the result from an analysis of aging data in two species. The displayed probe sets and gene names are retrieved from the second input species. The expression patterns of the homologous genes in the two species are displayed side by side, separated by a vertical bar. Each cluster represents a subset of genes that show coherent expression in both of the two species. The figure is interactive and sample information will appear in a pop-up window if the user hovers the cursor on the sample IDs. Only 3 of the 46 coherent clusters are displayed. See Supplementary Figure S6 for all the 46 coherent clusters.

Figure 5.

Figure 5.

The insulin receptor containing coherent cluster.

Figure 6.

Figure 6.

A hypothetical model for the dual roles of insulin signaling in human brain.

References

    1. Schena M, et al. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 1995;270:467–470. - PubMed
    1. Brown PO, Botstein D. Exploring the new world of the genome with DNA microarrays. Nat. Genet. 1999;21(Suppl. 1):33–37. - PubMed
    1. Lee HK, et al. Coexpression analysis of human genes across many microarray data sets. Genome Res. 2004;14:1085–1094. - PMC - PubMed
    1. Eisen MB, et al. Cluster analysis and display of genome-wide expression patterns. Proc. Natl Acad. Sci. USA. 1998;95:14863–14868. - PMC - PubMed
    1. Ramaswamy S, et al. A molecular signature of metastasis in primary solid tumors. Nat. Genet. 2003;33:49–54. - PubMed

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