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High-Throughput GoMiner, an 'industrial-strength'
integrative Gene Ontology tool for interpretation of multiple-microarray experiments,
with application to studies of Common Variable Immune Deficiency (CVID)
Barry R Zeeberg, Haiying Qin, Sudarshan Narasimhan,
Margot Sunshine, Hong Cao, David W Kane, Mark Reimers, Robert Stephens, David Bryant,
Stanley K Burt, Eldad Elnekave, Danielle M Hari, Thomas A Wynn, Charlotte Cunningham-Rundles,
Donn M Stewart, David Nelson and John N Weinstein
BMC Bioinformatics. 2005 Jul 5;6(1):168 [Epub ahead of print]
Abstract:
Background
We previously developed GoMiner, an application that organizes lists of 'interesting' genes
(for example, under- and overexpressed genes from a microarray experiment) for biological interpretation
in the context of the Gene Ontology. The original version of GoMiner was oriented toward visualization and
interpretation of the results from a single microarray (or other high-throughput experimental platform),
using a graphical user interface. Although that version can be used to examine the results from a number
of microarrays one at a time, that is a rather tedious task, and original GoMiner includes no apparatus for
obtaining a global picture of results from an experiment that consists of multiple microarrays. We wanted
to provide a computational resource that automates the analysis of multiple microarrays and then integrates
the results across all of them in useful exportable output files and visualizations.
Results
We now introduce a new tool, High-Throughput GoMiner, that has those capabilities and a number
of others: It (i) efficiently performs the computationally-intensive task of automated batch processing of an
arbitrary number of microarrays, (ii) produces a human- or computer-readable report that rank-orders the multiple
microarray results according to the number of significant GO categories, (iii) integrates the multiple microarray
results by providing organized, global clustered image map visualizations of the relationships of significant GO
categories, (iv) provides a fast form of 'false discovery rate' multiple comparisons calculation, and (v) provides
annotations and visualizations for relating transcription factor binding sites to genes and GO categories.
Conclusions
High-Throughput GoMiner achieves the desired goal of providing a computational resource that
automates the analysis of multiple microarrays and integrates results across all of the microarrays. For
illustration, we show an application of this new tool to the interpretation of altered gene expression patterns
in Common Variable Immune Deficiency (CVID). High-Throughput GoMiner will be useful in a wide range of applications,
including the study of time-courses, evaluation of multiple drug treatments, comparison of multiple gene knock-outs
or knock-downs, and screening of large numbers of chemical derivatives generated from a promising lead compound.
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