Interactive analysis of mass spectrometry data

• US 10,199,206 B2
• Filed: 05/01/2017
• Issued: 02/05/2019
• Est. Priority Date: 06/16/2014
• Status: Active Grant

• Current Assignee: Protein Metrics LLC
• Original Assignee: Protein Metrics Inc. (Insightful Science LLC)
• Inventors: Becker, Christopher, Bern, Marshall, Kil, Yong Joo, Kim, Michael Taejong, Zhang, Boyan
• Primary Examiner(s): Nguyen, Vu
• Application Number:
  US15/583,752
• Publication Number:
  US 20170236697A1
• Time in Patent Office: 645 Days
• Field of Search: None
• CPC Class Codes: G06T 11/206 Drawing of charts or graphs
• CPC Class Codes: H01J 49/0036 Step by step routines describing the handling of the data generated during a measurement
• CPC Class Codes: H01J 49/02 Details

Abstract

This invention relates to graphical user-interactive displays for use in MS-based analysis of protein impurities, as well as methods and software for generating and using such. One aspect provides a user-interactive display comprising an extracted mass chromatogram (XIC), an MS1 spectrum and an MS2 spectrum, all simultaneously representing a user-selected peptide. Another aspect provides a user interactive display simultaneously presenting paired spectra (XIC, MS1 and/or MS2) for a variant peptide and its corresponding wildtype counterpart.

Claims

1. A non-transitory machine-readable medium that stores instructions, which, when performed by a machine, cause the machine to perform operations comprising:

receiving a data file comprising mass spectrometry (MS) data for a sample comprising a reference molecule and one or more variant molecules, wherein each variant molecule has a chemical modification relative to the reference molecule;

providing an assembly of molecular identifications, wherein each molecular identification correlates a spectral representation with the reference molecule and a modification state for a variant molecule relative to the reference molecule;

selecting a molecular identification based on user-input; and

simultaneously and interactively displaying a first arrangement of a plurality of spectral representations, wherein a first spectral representation of the first arrangement is correlated to the selected molecular identification and a second spectral representation of the first arrangement is correlated to a first molecular identification having the same reference molecule but different modification state;

wherein a user selection or modification in the first spectral representation is automatically made in the second spectral representation and a user selection or modification in the second spectral representation is automatically made in the first spectral representation.

2. The non-transitory machine-readable medium of claim 1, wherein the reference molecule is a protein.

3. The non-transitory machine-readable medium of claim 1, wherein the reference molecule is one peptide from a plurality of peptides that are a product of enzymatic digestion of a protein.

4. The non-transitory machine-readable medium of claim 3, wherein the assembly of molecular identifications is a graphical representation of the protein, wherein the graphical representation of the protein comprises an amino acid sequence for the protein and a plurality of markers mapped to the amino acid sequence and representing the plurality of peptides, and further wherein the step of selecting a molecular identification comprises user selection of a marker in the graphical representation.

5. The non-transitory machine-readable medium of claim 3, wherein the modification state of the selected molecular identification is a sequence variant and the modification state of the first molecular identification is null.

6. The non-transitory machine-readable medium of claim 1, wherein the assembly of molecular identifications is presented in tabular form, wherein each line of the tabular form represents the reference molecule or a single variant molecule, and wherein the step of selecting a molecular identification comprises selecting a line of the tabular form.

7. The non-transitory machine-readable medium of claim 6, wherein the assembly of molecular identifications is populated from results of a computational search of observed spectra with respect to a molecular database or library of recorded spectra.

8. The non-transitory machine-readable medium of claim 1, wherein the modification state is selected from the group consisting of unmodified, sequence variant, insertion, deletion, extension, oxidation, deamidation, conjugate, glycation, sulfation, and glycosylation.

9. The non-transitory machine-readable medium of claim 1, wherein the plurality of spectral representations of the first arrangement are selected from the group consisting of a first stage of mass spectrometry (MS1) spectra, a second stage of mass spectrometry (MS2) spectra and extracted ion chromatograms (XIC).

10. The non-transitory machine-readable medium of claim 1, wherein a third spectral representation of the first arrangement is correlated to a second molecular identification having the same reference molecule as the selected and first molecular identifications but a different modification state from both the selected and first molecular identifications.

11. The non-transitory machine-readable medium of claim 1, wherein the operations further comprise:

simultaneously displaying a second arrangement of a plurality of spectral representations, wherein a first spectral representation of the second arrangement is correlated to the selected molecular identification and a second spectral representation of the second arrangement is correlated to the first molecular identification.

12. The non-transitory machine-readable medium of claim 11, wherein the spectral representations of the first arrangement are a first stage of mass spectrometry (MS1) spectra, and the spectral representations of the second arrangement are a second stage of mass spectrometry (MS2) spectra.

13. The non-transitory machine-readable medium of claim 11, wherein the spectral representations of the first arrangement are a first stage of mass spectrometry (MS1) spectra, and the spectral representations of the second arrangement are extracted ion chromatograms (XIC).

14. The non-transitory machine-readable medium of claim 11, wherein the spectral representations of the first arrangement are a second stage of mass spectrometry (MS2) spectra, and the spectral representations of the second arrangement are extracted ion chromatograms (XIC).

15. The non-transitory machine-readable medium of claim 1, wherein the first spectral representation is displayed immediately above, immediately below or immediately beside the second spectral representation.

16. The non-transitory machine-readable medium of claim 1, wherein the first spectral representation and second spectral representation are displayed sharing a single horizontal axis.

17. The non-transitory machine-readable medium of claim 1, wherein the reference molecule is selected from the group consisting of polypeptides, oligonucleotides, lipids, and organic polymers.

18. A method for displaying mass spectrometry data comprising:

receiving a data file comprising mass spectrometry (MS) data for a sample comprising a reference molecule and one or more variant molecules, wherein each variant molecule has a chemical modification relative to the reference molecule;

providing an assembly of molecular identifications, wherein each molecular identification correlates a spectral representation with the reference molecule and a modification state for a variant molecule relative to the reference molecule;

selecting a molecular identification based on user-input; and

simultaneously and interactively displaying a first arrangement of a plurality of spectral representations, wherein a first spectral representation of the first arrangement is correlated to the selected molecular identification and a second spectral representation of the first arrangement is correlated to a first molecular identification having the same reference molecule but different modification state;

wherein a user selection or modification in the first spectral representation is automatically made in the second spectral representation and a user selection or modification in the second spectral representation is automatically made in the first spectral representation.