Dataset Information

Metabolomic correlation-network modules in Arabidopsis based on a graph-clustering approach.

ABSTRACT:

Background

Deciphering the metabolome is essential for a better understanding of the cellular metabolism as a system. Typical metabolomics data show a few but significant correlations among metabolite levels when data sampling is repeated across individuals grown under strictly controlled conditions. Although several studies have assessed topologies in metabolomic correlation networks, it remains unclear whether highly connected metabolites in these networks have specific functions in known tissue- and/or genotype-dependent biochemical pathways.

Results

In our study of metabolite profiles we subjected root tissues to gas chromatography-time-of-flight/mass spectrometry (GC-TOF/MS) and used published information on the aerial parts of 3 Arabidopsis genotypes, Col-0 wild-type, methionine over-accumulation 1 (mto1), and transparent testa4 (tt4) to compare systematically the metabolomic correlations in samples of roots and aerial parts. We then applied graph clustering to the constructed correlation networks to extract densely connected metabolites and evaluated the clusters by biochemical-pathway enrichment analysis. We found that the number of significant correlations varied by tissue and genotype and that the obtained clusters were significantly enriched for metabolites included in biochemical pathways.

Conclusions

We demonstrate that the graph-clustering approach identifies tissue- and/or genotype-dependent metabolomic clusters related to the biochemical pathway. Metabolomic correlations complement information about changes in mean metabolite levels and may help to elucidate the organization of metabolically functional modules.

SUBMITTER: Fukushima A

PROVIDER: S-EPMC3030539 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Publications

Metabolomic correlation-network modules in Arabidopsis based on a graph-clustering approach.

Fukushima Atsushi A Kusano Miyako M Redestig Henning H Arita Masanori M Saito Kazuki K

BMC systems biology 20110101

<h4>Background</h4>Deciphering the metabolome is essential for a better understanding of the cellular metabolism as a system. Typical metabolomics data show a few but significant correlations among metabolite levels when data sampling is repeated across individuals grown under strictly controlled conditions. Although several studies have assessed topologies in metabolomic correlation networks, it remains unclear whether highly connected metabolites in these networks have specific functions in kn ...[more]

PMID: 21194489

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Project description:BackgroundGlucosinolates (GSLs) are plant secondary metabolites that contain nitrogen-containing compounds. They are important in the plant defense system and known to provide protection against cancer in humans. Currently, increasing the amount of data generated from various omics technologies serves as a hotspot for new gene discovery. However, sometimes sequence similarity searching approach is not sufficiently effective to find these genes; hence, we adapted a network clustering approach to search for potential GSLs genes from the Arabidopsis thaliana co-expression dataset.MethodsWe used known GSL genes to construct a comprehensive GSL co-expression network. This network was analyzed with the DPClusOST algorithm using a density of 0.5. 0.6. 0.7, 0.8, and 0.9. Generating clusters were evaluated using Fisher's exact test to identify GSL gene co-expression clusters. A significance score (SScore) was calculated for each gene based on the generated p-value of Fisher's exact test. SScore was used to perform a receiver operating characteristic (ROC) study to classify possible GSL genes using the ROCR package. ROCR was used in determining the AUC that measured the suitable density value of the cluster for further analysis. Finally, pathway enrichment analysis was conducted using ClueGO to identify significant pathways associated with the GSL clusters.ResultsThe density value of 0.8 showed the highest area under the curve (AUC) leading to the selection of thirteen potential GSL genes from the top six significant clusters that include IMDH3, MVP1, T19K24.17, MRSA2, SIR, ASP4, MTO1, At1g21440, HMT3, At3g47420, PS1, SAL1, and At3g14220. A total of Four potential genes (MTO1, SIR, SAL1, and IMDH3) were identified from the pathway enrichment analysis on the significant clusters. These genes are directly related to GSL-associated pathways such as sulfur metabolism and valine, leucine, and isoleucine biosynthesis. This approach demonstrates the ability of the network clustering approach in identifying potential GSL genes which cannot be found from the standard similarity search.

Project description:In pharmacogenomic studies, the biological context of cell lines influences the predictive ability of drug-response models and the discovery of biomarkers. Thus, similar cell lines are often studied together based on prior knowledge of biological annotations. However, this selection approach is not scalable with the number of annotations, and the relationship between gene-drug association patterns and biological context may not be obvious. We present a procedure to compare cell lines based on their gene-drug association patterns. Starting with a grouping of cell lines from biological annotation, we model gene-drug association patterns for each group as a bipartite graph between genes and drugs. This is accomplished by applying sparse canonical correlation analysis (SCCA) to extract the gene-drug associations, and using the canonical vectors to construct the edge weights. Then, we introduce a nuclear norm-based dissimilarity measure to compare the bipartite graphs. Accompanying our procedure is a permutation test to evaluate the significance of similarity of cell line groups in terms of gene-drug associations. In the pharmacogenomics datasets CTRP2, GDSC2, and CCLE, hierarchical clustering of carcinoma groups based on this dissimilarity measure uniquely reveals clustering patterns driven by carcinoma subtype rather than primary site. Next, we show that the top associated drugs or genes from SCCA can be used to characterize the clustering patterns of haematopoietic and lymphoid malignancies. Finally, we confirm by simulation that when drug responses are linearly-dependent on expression, our approach is the only one that can effectively infer the true hierarchy compared to existing approaches. Bipartite graph-based hierarchical clustering is implemented in R and can be obtained from CRAN: https://CRAN.R-project.org/package=hierBipartite. The source code is available at https://github.com/CalvinTChi/hierBipartite. Supplementary data are available at Bioinformatics online.

Dataset Information

Metabolomic correlation-network modules in Arabidopsis based on a graph-clustering approach.

Background

Results

Conclusions

Publications

Metabolomic correlation-network modules in Arabidopsis based on a graph-clustering approach.

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