ReviewComprehensive post-genomic data analysis approaches integrating biochemical pathway maps
Graphical abstract
This review provides an overview of currently available bioinformatic tools for the analyses of complex post-genomic data sets using biochemical pathway maps and introduces a novel tool, termed BioPathAt, which is particularly useful for scientists interested in the regulation of metabolic pathways in the model plant Arabidopsis thaliana.
Introduction
Owing to their obligate phototrophic and sessile lifestyle, plants have evolved numerous unique adaptations to help cope with unavoidable stresses that are imposed upon them. Developmental, abiotic and biotic signals can directly or indirectly influence changes in biochemical pathways leading to the production of bioactive primary and secondary metabolites (Croteau et al., 2000). Post-genomic technologies provide an unprecedented opportunity to acquire measurements that can accurately describe the complex networks regulating such biochemical pathways in plants. The results from post-genomic experiments investigating biochemical processes should provide researchers with quantitative information regarding global transcript, protein and metabolite patterns, transcriptional and translational modifications, protein–DNA and protein–protein interactions, and enzymatic activities (Burbulis and Winkel-Shirley, 1999, Koller et al., 2002, MacCoss et al., 2002, Conrads et al., 2003, Hendricks et al., 2003, Aebersold and Mann, 2003, Tao and Aebersold, 2003, Cutler, 2003, Weckwerth, 2003). Combined with experimental information regarding plant phenotype, the subcellular localization and tissue specific-accumulation of transcripts, proteins and metabolites, a high-resolution network of biochemical processes would emerge. However, the toolbox for the knowledge-based analysis of post-genomic experiments is still in its infancy. Thus, strategies need to be developed that allow visualizing and processing the complexity of post-genomic data sets that are obtained today and also leave room for future expansion. Biochemical pathway maps are a powerful tool to provide a biological context for the display of post-genomic data sets.
Section snippets
Kyoto Encyclopedia of Genes and Genomes (KEGG)
The most prominent examples of generic maps are the Roche Applied Science Wall Charts (“Biochemical Pathways” and “Cellular and Molecular Processes” at http://www.expasy.org/cgi-bin/search-biochem-index) and the Kyoto Encyclopedia of Genes and Genomes maps (KEGG; available at http://www.genome.ad.jp/kegg/; Kanehisa et al., 2002). With the advent of the post-genomic era the KEGG maps have been integrated into a software that allows the visualization of mRNA expression data in a biochemical map
BioPathAt, a novel tool for post-genomic data integration
Although several bioinformatic tools for the analysis of genome-scale data sets in a biochemical pathway context have been developed over the last couple of years, we felt that the currently available tools have critical limitations in providing details about the role of specific isogenes/isozymes in the regulation of biochemical networks. Ideally, bioinformatic tools and gene function databases are integrated into one common software package, thus allowing a holistic analysis of data generated
Future directions
Transcriptome analyses, which use microarray technology to assess transcriptional activity across a large number of genes, can yield important insights into the regulation of metabolic pathways at the transcriptional level. However, in plant cells, numerous posttranscriptional modifications take place that can not be studied with microarrays. Among these, mRNA stability and translatability, posttranslational protein modifications and the impact of modulators on enzyme activities play important
Note added in proof
During the final stages of the revision of this article, a new analysis tool for microarray data was published (Zimmermann et al., 2004). The GENEVESTIGATOR toolbox is available at http://www.genevestigator.ethz.ch.
Acknowledgement
This work was supported by the Agricultural Research Center at Washington State University.
Bernd Markus Lange is an Assistant Professor at the Institute of Biological Chemistry and the Center for Integrated Biotechnology at Washington State University. He received his Bachelor’s and Master’s degrees in Chemistry from the University of Bonn and his Doctoral degree in Botany from the University of Munich. Upon graduation, Dr. Lange held postdoctoral positions with Lutz Heide at the University of Tübingen and Rodney Croteau at Washington State University. Subsequently, he led research
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Bernd Markus Lange is an Assistant Professor at the Institute of Biological Chemistry and the Center for Integrated Biotechnology at Washington State University. He received his Bachelor’s and Master’s degrees in Chemistry from the University of Bonn and his Doctoral degree in Botany from the University of Munich. Upon graduation, Dr. Lange held postdoctoral positions with Lutz Heide at the University of Tübingen and Rodney Croteau at Washington State University. Subsequently, he led research groups in the biotechnology industry (Novartis Agricultural Research Institute Inc., Torrey Mesa Research Institute of Syngenta and Diversa Inc.). His research interests center on using post-genomic technologies to characterize the regulation of biochemical pathways with particular emphasis on the crosstalk of pathways involved in isoprenoid biosynthesis.
Majid Ghassemian is a Staff Scientist at Diversa Corporation (San Diego, CA). He received his honors Bachelor of Science, Master’s (cyanobacterial molecular biology and physiology) and Ph.D. (genetics and molecular biology) from the Department of Botany, University of Toronto, Canada. Upon graduation he has held an NSERC postdoctoral fellowship at the University of California, San Diego and the Torrey Mesa Research Institute. His research interests revolve around systems biology and functional genomic approaches to enhance the understanding of biochemical processes.
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Present address: Diversa Corporation, 4955 Directors Place, San Diego, CA 92121, USA.