Apparatuses and methods for annotated peptide mapping

• US 10,354,421 B2
• Filed: 03/10/2016
• Issued: 07/16/2019
• Est. Priority Date: 03/10/2015
• Status: Active Grant

• Current Assignee: Protein Metrics LLC
• Original Assignee: Protein Metrics Inc. (Insightful Science LLC)
• Inventors: Becker, Christopher, Bern, Marshall, Bern, Nicholas, Kil, Yong Joo, Seipert, Richard, Kim, Michael Taejong
• Primary Examiner(s): Riggs, II, Larry D
• Application Number:
  US15/066,871
• Publication Number:
  US 20160267220A1
• Time in Patent Office: 1,223 Days
• Field of Search: None
• CPC Class Codes: G06T 11/206 Drawing of charts or graphs
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/10 Signal processing, e.g. from mass spectrometry [MS] or from PCR
• CPC Class Codes: G16B 45/00 ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks

Abstract

Methods and apparatuses for the analysis of mass spectroscopic (MS) data as well as ultraviolet (UV) absorption data. In particular, described herein are tools and methods to assist in generating annotated peptide maps from a raw MS data.

Claims

1. A method for the automated analysis and annotation of a peptide map, the method comprising:

importing candidate peptides related to a target protein;

concurrently displaying a chromatographic trace, a listing of candidate peptides, and a mass over charge (m/z) trace;

automatically annotating peaks of the chromatographic trace using the listing of candidate peptides; and

displaying the annotated peaks concurrently with the chromatographic trace, the listing of candidate peptides and the m/z trace;

receiving, from a user, a selected time period from the chromatographic trace comprising a region of peak signal intensity;

determining intensity values at one or more m/z segment for each of a plurality of times within the selected time period;

comparing a time course of the intensity values for the m/z segment over the time period to the time course of the chromatographic trace signal intensity over the region of peak signal intensity to determine a score of the comparison; and

annotating the m/z trace with a visual representation of the score of the comparison.

2. The method of claim 1, further comprising concurrently displaying a plurality of additional chromatographic traces.

3. The method of claim 2, further comprising aligning the plurality of additional chromatographic traces with a reference chromatographic trace.

4. The method of claim 1, wherein automatically annotating the peaks comprises applying a user-definable threshold of the candidate peptides based on accuracy scores associated with each candidate.

5. The method of claim 1, further comprising allowing a user to manually annotate peaks of the chromatographic trace.

6. The method of claim 1, further comprising allowing the user to modify the chromatographic trace display.

7. The method of claim 1, further comprising adjusting a baseline of the chromatographic trace.

8. The method of claim 7, further comprising allowing the user to manually adjust the baseline.

9. The method of claim 1, further comprising generating a report including the annotations.

10. A method of displaying a correlation between a candidate molecule and a candidate chromatographic peak, the method comprising:

concurrently displaying a chromatographic trace and a mass/charge (m/z) trace;

receiving a user-selected time period from the display of the chromatographic trace that includes a region of peak signal intensity;

determining intensity values at a m/z segment for each of a plurality of times within the time period;

comparing a time course of the intensity values for the m/z segment over the time period to the time course of the chromatographic trace signal intensity over the region of peak signal intensity; and

concurrently updating the m/z trace with a visual representation of an indicator of a score of the comparison.

11. The method of claim 10, further comprising selecting the m/z segment from within a mass/charge region having an intensity that is greater than a threshold.

12. The method of claim 10, further comprising selecting the m/z segment from within a m/z region having an intensity that is greater than a threshold percentage of a maximum value of the intensity within the region of m/z.

13. The method of claim 10, further comprising labeling a visual representation of the m/z segment in a mass spectrogram with an indicator of the score of the comparison that comprises coloring the visual representation of the m/z segment with a color indicating the score.

14. The method of claim 10, further comprising labeling a visual representation of the m/z segment in a mass spectrogram with an indicator of the score of the comparison that comprises coloring the visual representation of the m/z segment with a numeric value of the score.

15. A non-transitory computer-readable storage medium storing a set of instructions capable of being executed by a processor, that when executed by the processor causes the processor to:

concurrently display a chromatographic trace and a mass/charge (m/z) trace;

receive a user-selected time period from the display of the chromatographic trace that includes a region of peak signal intensity;

determine intensity values at a m/z segment for each of a plurality of times within the time period;

compare a time course of the intensity values for the m/z segment over the time period to the time course of the chromatographic trace signal intensity over the region of peak signal intensity; and

update the m/z trace with a visual representation of an indicator of a score of the comparison.