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Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes.

Kastenmüller G, Schenk ME, Gasteiger J, Mewes HW - Genome Biol. (2009)

Bottom Line: Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics.Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale.Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse, Neuherberg, Germany. g.kastenmueller@helmholtz-muenchen.de

ABSTRACT
Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics. Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale. Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.

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Pathway scores of the relevant pathways for the periodontal species. Plotting the pathway scores of the relevant pathways (from Table 6), the differences of A. actinomycetemcomitans (black) compared to F. nucleatum (red), P. gingivalis (green), and T. denticola (blue) become apparent. In contrast, the scores for F. nucleatum, P. gingivalis, and T. denticola are very similar.
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Figure 7: Pathway scores of the relevant pathways for the periodontal species. Plotting the pathway scores of the relevant pathways (from Table 6), the differences of A. actinomycetemcomitans (black) compared to F. nucleatum (red), P. gingivalis (green), and T. denticola (blue) become apparent. In contrast, the scores for F. nucleatum, P. gingivalis, and T. denticola are very similar.

Mentions: The classification quality did not reach 1.00 for any combination of attribute selection method and classifier because A. actinomycetemcomitans was always misclassified. Plotting the pathway scores of the relevant pathways, the differences of A. actinomycetemcomitans compared to F. nucleatum, P. gingivalis, and T. denticola become apparent (Figure 7). In contrast, the scores for F. nucleatum, P. gingivalis, and T. denticola are very similar. This 'outlier' role of A. actinomycetemcomitans agrees with studies of Socransky et al. [52]. They investigated the co-occurrence of bacterial species in a large number of subgingival plaque samples (collected from hundreds of patients) and identified five major clusters of bacteria, which they designated by the colors red, orange, green, yellow, and purple. A. actinomycetemcomitans (serotype b) did not fall in one of these clusters. The cluster holding P. gingivalis, T. denticola, and T. forsythensis (called the 'red' cluster in [52]) and the cluster consisting of F. nucleatum and some Prevotella and not yet sequenced Centruroides species (called the 'orange' cluster in [52]), were associated with clinical measures of periodontal disease. A. actinomycetemcomitans, however, was not found to be significantly enhanced for periodontal disease in Socransky et al. [52]. Nonetheless, according to several studies, a high-toxic JP2 clone of A. actinomycetemcomitans (serotype b) (strain HK1651 is a representative of this clone) is strongly associated with localized juvenile periodontitis in adolescents of African origin [53]. Based on the major differences of A. actinomycetemcomitans compared to the other pathogens in our analyses, one could speculate that the mechanisms causing the disease might also differ.


Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes.

Kastenmüller G, Schenk ME, Gasteiger J, Mewes HW - Genome Biol. (2009)

Pathway scores of the relevant pathways for the periodontal species. Plotting the pathway scores of the relevant pathways (from Table 6), the differences of A. actinomycetemcomitans (black) compared to F. nucleatum (red), P. gingivalis (green), and T. denticola (blue) become apparent. In contrast, the scores for F. nucleatum, P. gingivalis, and T. denticola are very similar.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2690999&req=5

Figure 7: Pathway scores of the relevant pathways for the periodontal species. Plotting the pathway scores of the relevant pathways (from Table 6), the differences of A. actinomycetemcomitans (black) compared to F. nucleatum (red), P. gingivalis (green), and T. denticola (blue) become apparent. In contrast, the scores for F. nucleatum, P. gingivalis, and T. denticola are very similar.
Mentions: The classification quality did not reach 1.00 for any combination of attribute selection method and classifier because A. actinomycetemcomitans was always misclassified. Plotting the pathway scores of the relevant pathways, the differences of A. actinomycetemcomitans compared to F. nucleatum, P. gingivalis, and T. denticola become apparent (Figure 7). In contrast, the scores for F. nucleatum, P. gingivalis, and T. denticola are very similar. This 'outlier' role of A. actinomycetemcomitans agrees with studies of Socransky et al. [52]. They investigated the co-occurrence of bacterial species in a large number of subgingival plaque samples (collected from hundreds of patients) and identified five major clusters of bacteria, which they designated by the colors red, orange, green, yellow, and purple. A. actinomycetemcomitans (serotype b) did not fall in one of these clusters. The cluster holding P. gingivalis, T. denticola, and T. forsythensis (called the 'red' cluster in [52]) and the cluster consisting of F. nucleatum and some Prevotella and not yet sequenced Centruroides species (called the 'orange' cluster in [52]), were associated with clinical measures of periodontal disease. A. actinomycetemcomitans, however, was not found to be significantly enhanced for periodontal disease in Socransky et al. [52]. Nonetheless, according to several studies, a high-toxic JP2 clone of A. actinomycetemcomitans (serotype b) (strain HK1651 is a representative of this clone) is strongly associated with localized juvenile periodontitis in adolescents of African origin [53]. Based on the major differences of A. actinomycetemcomitans compared to the other pathogens in our analyses, one could speculate that the mechanisms causing the disease might also differ.

Bottom Line: Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics.Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale.Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse, Neuherberg, Germany. g.kastenmueller@helmholtz-muenchen.de

ABSTRACT
Identifying the biochemical basis of microbial phenotypes is a main objective of comparative genomics. Here we present a novel method using multivariate machine learning techniques for comparing automatically derived metabolic reconstructions of sequenced genomes on a large scale. Applying our method to 266 genomes directly led to testable hypotheses such as the link between the potential of microorganisms to cause periodontal disease and their ability to degrade histidine, a link also supported by clinical studies.

Show MeSH
Related in: MedlinePlus