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Unified and isomer-specific NMR metabolomics database for the accurate analysis of (13)C-(1)H HSQC spectra.

Bingol K, Li DW, Bruschweiler-Li L, Cabrera OA, Megraw T, Zhang F, Brüschweiler R - ACS Chem. Biol. (2014)

Bottom Line: The performance of our new database and query web server compares favorably with the one of existing web servers, especially for spectra of samples of high complexity, including metabolite mixtures from the model organisms Drosophila melanogaster and Escherichia coli.For such samples, our web server has on average a 37% higher accuracy (true positive rate) and a 82% lower false positive rate, which makes it a useful tool for the rapid and accurate identification of metabolites from (13)C-(1)H HSQC spectra at natural abundance.This information can be combined and validated with NMR data from 2D TOCSY-type spectra that provide connectivity information not present in HSQC spectra.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, ‡Campus Chemical Instrument Center, The Ohio State University , Columbus, Ohio 43210, United States.

ABSTRACT
A new metabolomics database and query algorithm for the analysis of (13)C-(1)H HSQC spectra is introduced, which unifies NMR spectroscopic information on 555 metabolites from both the Biological Magnetic Resonance Data Bank (BMRB) and Human Metabolome Database (HMDB). The new database, termed Complex Mixture Analysis by NMR (COLMAR) (13)C-(1)H HSQC database, can be queried via an interactive, easy to use web interface at http://spin.ccic.ohio-state.edu/index.php/hsqc/index . Our new HSQC database separately treats slowly exchanging isomers that belong to the same metabolite, which permits improved query in cases where lowly populated isomers are below the HSQC detection limit. The performance of our new database and query web server compares favorably with the one of existing web servers, especially for spectra of samples of high complexity, including metabolite mixtures from the model organisms Drosophila melanogaster and Escherichia coli. For such samples, our web server has on average a 37% higher accuracy (true positive rate) and a 82% lower false positive rate, which makes it a useful tool for the rapid and accurate identification of metabolites from (13)C-(1)H HSQC spectra at natural abundance. This information can be combined and validated with NMR data from 2D TOCSY-type spectra that provide connectivity information not present in HSQC spectra.

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Screenshots taken fromthe interactive COLMAR 13C–1H HSQC webserver. (A) The HSQC peak list with 165 cross-peaksof Drosophila melanogaster metabolite extract (upperleft) is queried against the database. The lower left shows the cross-peakpositions (blue circles and black crosses) in a 2D plane correspondingto the 2D HSQC spectrum. The thin blue circles correspond to HSQCcross-peaks that match a single compound in the database, the thickblue circles correspond cross-peaks that match multiple compounds,and the black crosses correspond to cross-peaks that do not matchany compound in the database. (B) List of matching compounds returnedby the query. The results served as input for Supporting Information Table S-3.
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fig4: Screenshots taken fromthe interactive COLMAR 13C–1H HSQC webserver. (A) The HSQC peak list with 165 cross-peaksof Drosophila melanogaster metabolite extract (upperleft) is queried against the database. The lower left shows the cross-peakpositions (blue circles and black crosses) in a 2D plane correspondingto the 2D HSQC spectrum. The thin blue circles correspond to HSQCcross-peaks that match a single compound in the database, the thickblue circles correspond cross-peaks that match multiple compounds,and the black crosses correspond to cross-peaks that do not matchany compound in the database. (B) List of matching compounds returnedby the query. The results served as input for Supporting Information Table S-3.

Mentions: A specifically designed web portal at http://spin.ccic.ohio-state.edu/index.php/hsqc/index allowsquerying of the 2D 13C–1H HSQCspectra of metabolic mixtures in batch mode as well as querying ofthe 2D 13C–1H HSQC spectra against individualmetabolites in the COLMAR 13C–1H HSQCdatabase. As an example, the 165 peaks of Drosophila were queried against the COLMAR in batch mode on the web server(Figure 4A). The query successfully returnedthe list of compounds in the sample (Figure 4B). The interactive user interface based on a JavaScript allowedoverlaying of 13C–1H HSQC peaks of individualcompounds in the database with the experimental peaks upon clickingthe “Show Me” button (Figure 4B) of the matched compound, which allows direct visual inspectionof the presence of the matched compound in the experimental 2D spectrum.To our knowledge, this is the first 13C–1H HSQC metabolomics database allowing such quick visual checks online,which is very useful to maximize confidence of identifications. Matchedcompounds are always shown in ‘Number_Metabolite Name’format, where the integer in front of the metabolite name is usedto denote different isomeric states of the metabolite. Metaboliteswith only one isomeric state are always shown as ‘1_Metabolite-name’,such as ‘1_Alanine’, whereas metabolites with more thanone isomeric state are shown as ‘n_Metabolite-name’,where n = 1, 2, 3, ... are different isomers of themetabolite (e.g., 1_Maltose and 2_Maltose).


Unified and isomer-specific NMR metabolomics database for the accurate analysis of (13)C-(1)H HSQC spectra.

Bingol K, Li DW, Bruschweiler-Li L, Cabrera OA, Megraw T, Zhang F, Brüschweiler R - ACS Chem. Biol. (2014)

Screenshots taken fromthe interactive COLMAR 13C–1H HSQC webserver. (A) The HSQC peak list with 165 cross-peaksof Drosophila melanogaster metabolite extract (upperleft) is queried against the database. The lower left shows the cross-peakpositions (blue circles and black crosses) in a 2D plane correspondingto the 2D HSQC spectrum. The thin blue circles correspond to HSQCcross-peaks that match a single compound in the database, the thickblue circles correspond cross-peaks that match multiple compounds,and the black crosses correspond to cross-peaks that do not matchany compound in the database. (B) List of matching compounds returnedby the query. The results served as input for Supporting Information Table S-3.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4340359&req=5

fig4: Screenshots taken fromthe interactive COLMAR 13C–1H HSQC webserver. (A) The HSQC peak list with 165 cross-peaksof Drosophila melanogaster metabolite extract (upperleft) is queried against the database. The lower left shows the cross-peakpositions (blue circles and black crosses) in a 2D plane correspondingto the 2D HSQC spectrum. The thin blue circles correspond to HSQCcross-peaks that match a single compound in the database, the thickblue circles correspond cross-peaks that match multiple compounds,and the black crosses correspond to cross-peaks that do not matchany compound in the database. (B) List of matching compounds returnedby the query. The results served as input for Supporting Information Table S-3.
Mentions: A specifically designed web portal at http://spin.ccic.ohio-state.edu/index.php/hsqc/index allowsquerying of the 2D 13C–1H HSQCspectra of metabolic mixtures in batch mode as well as querying ofthe 2D 13C–1H HSQC spectra against individualmetabolites in the COLMAR 13C–1H HSQCdatabase. As an example, the 165 peaks of Drosophila were queried against the COLMAR in batch mode on the web server(Figure 4A). The query successfully returnedthe list of compounds in the sample (Figure 4B). The interactive user interface based on a JavaScript allowedoverlaying of 13C–1H HSQC peaks of individualcompounds in the database with the experimental peaks upon clickingthe “Show Me” button (Figure 4B) of the matched compound, which allows direct visual inspectionof the presence of the matched compound in the experimental 2D spectrum.To our knowledge, this is the first 13C–1H HSQC metabolomics database allowing such quick visual checks online,which is very useful to maximize confidence of identifications. Matchedcompounds are always shown in ‘Number_Metabolite Name’format, where the integer in front of the metabolite name is usedto denote different isomeric states of the metabolite. Metaboliteswith only one isomeric state are always shown as ‘1_Metabolite-name’,such as ‘1_Alanine’, whereas metabolites with more thanone isomeric state are shown as ‘n_Metabolite-name’,where n = 1, 2, 3, ... are different isomers of themetabolite (e.g., 1_Maltose and 2_Maltose).

Bottom Line: The performance of our new database and query web server compares favorably with the one of existing web servers, especially for spectra of samples of high complexity, including metabolite mixtures from the model organisms Drosophila melanogaster and Escherichia coli.For such samples, our web server has on average a 37% higher accuracy (true positive rate) and a 82% lower false positive rate, which makes it a useful tool for the rapid and accurate identification of metabolites from (13)C-(1)H HSQC spectra at natural abundance.This information can be combined and validated with NMR data from 2D TOCSY-type spectra that provide connectivity information not present in HSQC spectra.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, ‡Campus Chemical Instrument Center, The Ohio State University , Columbus, Ohio 43210, United States.

ABSTRACT
A new metabolomics database and query algorithm for the analysis of (13)C-(1)H HSQC spectra is introduced, which unifies NMR spectroscopic information on 555 metabolites from both the Biological Magnetic Resonance Data Bank (BMRB) and Human Metabolome Database (HMDB). The new database, termed Complex Mixture Analysis by NMR (COLMAR) (13)C-(1)H HSQC database, can be queried via an interactive, easy to use web interface at http://spin.ccic.ohio-state.edu/index.php/hsqc/index . Our new HSQC database separately treats slowly exchanging isomers that belong to the same metabolite, which permits improved query in cases where lowly populated isomers are below the HSQC detection limit. The performance of our new database and query web server compares favorably with the one of existing web servers, especially for spectra of samples of high complexity, including metabolite mixtures from the model organisms Drosophila melanogaster and Escherichia coli. For such samples, our web server has on average a 37% higher accuracy (true positive rate) and a 82% lower false positive rate, which makes it a useful tool for the rapid and accurate identification of metabolites from (13)C-(1)H HSQC spectra at natural abundance. This information can be combined and validated with NMR data from 2D TOCSY-type spectra that provide connectivity information not present in HSQC spectra.

Show MeSH
Related in: MedlinePlus