APPARATUSES AND METHODS FOR ANNOTATED PEPTIDE MAPPING

• US 20160267220A1
• Filed: 03/10/2016
• Published: 09/15/2016
• Est. Priority Date: 03/10/2015
• Status: Active Grant

• Current Assignee: Protein Metrics LLC
• Original Assignee: Christopher Becker, Marshall Bern, Yong Joo Kil
• Inventors: BECKER, Christopher, BERN, Marshall, BERN, Nicholas, KIL, Yong Joo, SEIPERT, Richard, KIM, Michael Taejong
• Granted Patent: US 10,354,421 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 listing of peaks from the chromatographic trace;

automatically annotating peaks of the chromatograph using the candidate peptides; and

displaying the annotated peaks concurrently with the chromatographic trace, listing of candidate peptides and listing of peaks from the chromatographic trace.

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 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 chromatograph.

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 the 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:

defining a time period from a chromatograph corresponding to a region of peak signal intensity;

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

comparing a time course of the intensity values for the mass/charge segment over the time period to the time course of the signal intensity over the region of peak signal intensity; and

labeling a visual representation of the mass/charge segment in a mass spectrogram with an indicator of a score of the comparison.

11. The method of claim 10, wherein defining the time period is automatically defined.

12. The method of claim 10, wherein defining the time period is manually defined.

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

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

15. The method of claim 10, wherein labeling the visual representation of the mass/charge segment in a mass spectrogram with an indicator of a score of the comparison comprises coloring the visual representation of the mass/charge segment with a color indicating the score.

16. The method of claim 10, wherein labeling the visual representation of the mass/charge segment in a mass spectrogram with an indicator of a score of the comparison comprises coloring the visual representation of the mass/charge segment with a numeric value of the score.

17. 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:

define a time period from a chromatograph corresponding to a region of peak signal intensity;

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

compare a time course of the intensity values for the mass/charge segment over the time period to the time course of the signal intensity over the region of peak signal intensity; and

label a visual representation of the mass/charge segment in a mass spectrogram with an indicator of a score of the comparison.

18. A method of displaying a plurality of chromatographic traces to allow visual inspection of the traces, the method comprising:

generating a first time transformed trace of a first chromatographic trace by comparing signal intensities from the first chromatographic trace with signal intensities of a reference chromatographic trace and adjusting the time values from the first chromatographic trace to correspond to time values of similar signal intensities of the reference chromatographic trace;

identifying a plurality of reference anchor points from the reference chromatographic trace, wherein the reference anchor points include one or more points of peak signal intensity;

determining a corresponding anchor point for each of the reference anchor points from the first time transformed trace;

generating a second transformed first chromatographic trace from the time values for each of the corresponding anchor points by scaling time values from the first chromatographic trace between time-adjacent pairs of corresponding anchor points; and

displaying the second transformed first chromatographic trace aligned with the reference chromatographic trace.

19. The method of claim 18, wherein generating the first time transformed trace comprises comparing dividing the first chromatographic trace and the reference chromatographic trace into a plurality of sub-regions for comparison.

20. The method of claim 18, wherein generating the second transformed first chromatographic trace from the time values for each of the corresponding anchor points comprises linearly scaling time values from the first chromatographic trace between time-adjacent pairs of corresponding anchor points.

21. The method of claim 18, wherein identifying the plurality of anchor points comprises identifying local maximum and flanking minimum intensity values from the reference chromatographic trace forming a peak in the reference chromatographic trace.

22. The method of claim 18, wherein determining the corresponding anchor point comprises using the first transformed first chromatographic trace as a map to identify the corresponding anchor points in the first chromatographic trace.

23. The method of claim 18, wherein displaying comprises presenting the second transformed first chromatographic trace immediately above or below the reference chromatographic trace.

24. The method of claim 18, wherein displaying comprises presenting the second transformed first chromatographic trace on top of the reference chromatographic trace.

25. The method of claim 18, wherein displaying comprises displaying the reference chromatographic trace in a different color than the second transformed first chromatographic trace.

26. 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:

generate a first time transformed trace of a first chromatographic trace by comparing signal intensities from the first chromatographic trace with signal intensities of a reference chromatographic trace and adjusting the time values from the first chromatographic trace to correspond to time values of similar signal intensities of the reference chromatographic trace;

identify a plurality of reference anchor points from the reference chromatographic trace, wherein the reference anchor points include one or more points of peak signal intensity;

determine a corresponding anchor point for each of the reference anchor points from the first time transformed trace;

generate a second transformed first chromatographic trace from the time values for each of the corresponding anchor points by scaling time values from the first chromatographic trace between time-adjacent pairs of corresponding anchor points; and

display the second transformed first chromatographic trace aligned with the reference chromatographic trace.