Identity elucidation of unknown metabolites
View Patent ↗A method of elucidating the identity of an unknown metabolite comprising measuring amounts of known and unknown metabolites in subjects; associating the unknown metabolite with a specific gene from a gene association study; determining a protein associated with the specific gene and analyzing information for the protein; associating the unknown metabolite with concentrations and/or ratios of other metabolites in subjects; obtaining chemical structural data for the unknown metabolite; and using the information obtained to elucidate the identity of the unknown metabolite.
1. A method of determining the structure of an unknown metabolite when the accurate mass of the metabolite is known, comprising:
(a) measuring amounts of known and unknown metabolites in subjects;
(b) associating an unknown metabolite with a specific gene using a genome wide association study;
(c) determining a protein associated with the specific gene and analyzing information for the protein;
(d) associating the unknown metabolite with concentrations and/or ratios of other metabolites in the subjects using a partial correlation network;
(e) obtaining chemical structural data for the unknown metabolite using a mass spectrometer; and
(f) correlating the results obtained from steps (a) through (e) to determine the structure of the unknown metabolite.
2. The method of claim 1 , wherein the specific gene comprises a genetic polymorphism.
3. The method of claim 1 , further comprising reviewing the structure and/or characteristics of other metabolites associated with the specific gene from the genome wide association study and/or identifying the biochemical pathway with which at least a portion of the other metabolites associated with the specific gene are involved prior to performing step (f).
4. The method of claim 1 , further comprising reviewing the structure and/or characteristics of the other metabolites associated with the unknown metabolite using the partial correlation network and/or identifying the biochemical pathway with which at least a portion of the other metabolites are involved prior to performing step (f).
5. The method of claim 1 , wherein the mass spectrometric data of the unknown metabolite comprises mass, molecular formula, or fragmentation spectra.
6. The method of claim 1 , wherein the information concerning the protein known to be associated with the gene includes function of the protein.
7. The method of claim 1 , wherein the protein performs a metabolic function.
8. The method of claim 1 , wherein the protein is an enzyme.
9. The method of claim 8 , wherein the substrate of the enzyme is identified.
10. The method of claim 9 , wherein the information includes the biochemical pathway for the substrate.
11. The method of claim 9 , wherein the information includes alternative biochemical pathways for the substrate.
12. The method of claim 8 , wherein an alternative substrate of the enzyme is determined.
13. The method of claim 12 , wherein the information includes the biochemical pathway for the substrate.
14. The method of claim 1 , wherein the protein is a transporter.
15. The method of claim 3 , wherein reviewing the structure and/or characteristics of the other metabolites associated with the specific gene from the genome wide association study and/or metabolites associated using the partial correlation network includes reviewing mass, class of compound, retention time, isotope patterns, fragments, and functionality of the other metabolites.
16. The method of claim 1 , wherein the association between the protein and the specific gene is the protein being encoded by the gene.
17. A method of determining the structure of an unknown metabolite when the accurate mass of the metabolite is known, comprising:
(a) measuring amounts of known and unknown metabolites in subjects;
(b) associating an unknown metabolite with a specific gene from a genome wide association study;
(c) determining a protein associated with the specific gene and analyzing information for the protein;
(d) reviewing the structure and/or characteristics of other metabolites associated with the specific gene from the genome wide association study;
and/or identifying the biochemical pathway with which at least a portion of the other metabolites associated with the specific gene are involved;
(e) obtaining chemical structural data for the unknown metabolite using a mass spectrometer; and
(f) correlating results obtained from steps (a) through (e) to determine the structure of the unknown metabolite.
18. A method of determining the structure of an unknown metabolite when the accurate mass of the metabolite is known, comprising:
(a) measuring amounts of known and unknown metabolites in subjects;
(b) associating an unknown metabolite with concentrations and/or ratios of other metabolites in the subjects using a partial correlation network;
(c) reviewing the structure and/or characteristics of the other metabolites associated with the unknown metabolite; and/or identifying the biochemical pathway with which at least a portion of the other metabolites associated with the unknown metabolite are involved;
(d) obtaining chemical structural data for the unknown metabolite using a mass spectrometer; and
(e) correlating the results obtained from steps (a) through (d) to determine the structure of the unknown metabolite.
19. The method of claim 18 , further comprising associating the unknown metabolite with a specific gene from a genome wide association study and determining a protein associated with the specific gene and analyzing information for the protein.