Comparing a modeled molecule fragmentation to an experimental molecule fragmentation
Exemplary embodiments described herein provide improved techniques for matching an experimental mass spectrometry fragmentation against a known or predicted fragmentation from a library. Among other improvements, exemplary embodiments provide more accessible interfaces that are easier to interpret, thus allowing for more accurate and faster matches. They also may automatically accumulate multiple experimental results to determine whether several runs of a given sample cumulatively represent a library fragmentation pattern. Furthermore, exemplary embodiments provide simplified techniques for identifying and accounting for molecule variants.
1 . A computer implemented method comprising:
receiving, by a processor, input data from a mass spectrometry apparatus, the input data representing a fragmentation of a molecule into a plurality of experimental fragments, where the input data comprises mass-to-charge ratios and intensity values for detected ions;
comparing, by the processor, the fragmentation to a library of modeled fragmentations to identify a candidate match comprising a plurality of modeled fragments, the comparing comprising:
selecting, by the processor, a model fragmentation pattern in the library of modeled fragmentations,
calculating, using the processor, a coverage score for the selected model fragmentation pattern by determining a closeness of a match of at least one fragment corresponding to a first mass peak in the model fragmentation pattern to at least one fragment corresponding to a second mass peak in the plurality of modeled fragments, and
selecting, with the processor, the selected model fragmentation pattern as the candidate match based on the coverage score; and
displaying, via a graphical user interface, a graphical representation of the candidate match, the graphical representation comprising a graphical element corresponding to each of the modeled fragments, wherein
each graphical element is capable of being in an on state or an off state, and
a respective graphical element is in the on state if the graphical element's modeled fragment matches a corresponding experimental fragment in the input data based on the experimental fragment having a mass-to-charge ratio matching within a predetermined mass tolerance window of the modeled fragment and having an intensity value above a predetermined minimum threshold.
2 . The computer-implemented method of claim 1 , wherein the molecule is an oligonucleotide and the experimental fragments represent monomers in the oligonucleotide.
3 . The computer-implemented method of claim 1 , further comprising:
receiving second input data representing a second fragmentation of the molecule into a second plurality of experimental fragments; and
aggregating at least the plurality of experimental fragments and the second plurality of experimental fragments into cumulative input data, wherein
the respective graphical element is in the on state if the modeled fragment corresponding to the graphical element matches at least one of the corresponding experimental fragment in the input data or a second corresponding experimental fragment from the second input data.
4 . The computer-implemented method of claim 3 , wherein each graphical element displays a score representing how often the modeled fragment corresponding to the graphical element was found in the cumulative input data.
5 . The computer-implemented method of claim 3 , further comprising:
receiving a selection of a selected graphical element in the graphical representation of the candidate match; and
highlighting corresponding graphical elements in graphical representations of the cumulative input data.
6 . The computer-implemented method of claim 1 , further comprising:
identifying a second candidate match; and
displaying a graphical representation of the second candidate match aligned to a graphical representation of the candidate match.
7 . The computer-implemented method of claim 1 , further comprising:
identifying that a specified experimental fragment is associated with one or more variant configurations; and
modifying the graphical element corresponding to the specified experimental fragment with a variant identifier.
8 . The computer-implemented method of claim 7 , further comprising:
identifying that a plurality of experimental fragments are each associated with one or more variant configurations, and that at least one of the experimental fragments is in a variant state; and
modifying the graphical elements corresponding to the plurality of experimental fragments associated with the variant configurations with a potential variant identifier.
9 . The computer-implemented method of claim 7 , further comprising:
receiving a selection of the graphical element corresponding to the specified experimental fragment;
receiving a selection of a selected variant configuration; and
modifying the display of the graphical representation based on the selected variant configuration.
10 . The computer-implemented method of claim 1 , further comprising:
receiving a selection of a selected graphical element in the graphical representation of the candidate match; and
displaying a mass spectrum from the input data corresponding to the experimental fragment associated with the selected graphical element.
11 . The method of claim 1 , wherein the comparing comprises:
retrieving a hypothetical fragmentation for one of the modeled fragmentations in the library into constituent ions;
identifying, for each experimental fragment in the input data, an experimental mass peak;
identifying, for each constituent ion in the hypothetical fragmentation, a predicted mass-to-charge ratio value for the constituent ion;
establishing a predetermined window around the predicted mass-to-charge ratio value for the constituent ion; and
determining that the constituent ion in the hypothetical fragmentation is a match for the experimental fragment in the input data when the experimental mass peak falls within the predetermined window.
12 . A non-transitory computer-readable storage medium, the computer-readable storage medium including instructions that when executed by a computer, cause the computer to:
receive, using a processor, input data representing a fragmentation of a molecule into a plurality of experimental fragments, where the input data comprises mass-to-charge ratios and intensity values for detected ions;
compare, using the processor, the fragmentation to a library of modeled fragmentations to identify a candidate match comprising a plurality of modeled fragments, the comparing comprising:
selecting, by the processor, a model fragmentation pattern in the library of modeled fragmentations,
calculating, using the processor, a coverage score for the selected model fragmentation pattern by determining a closeness of a match of at least one fragment corresponding to a first mass peak in the model fragmentation pattern to at least one fragment corresponding to a second mass peak in the plurality of modeled fragments, and
selecting, with the processor, the selected model fragmentation pattern as the candidate match based on the coverage score; and
display, via a graphical user interface, a graphical representation of the candidate match, the graphical representation comprising a graphical element corresponding to each of the modeled fragments, wherein
each graphical element is capable of being in an on state or an off state, and
a respective graphical element is in the on state if the graphical element's modeled fragment matches a corresponding experimental fragment in the input data based on the experimental fragment having a mass-to-charge ratio matching within a predetermined mass tolerance window of the modeled fragment and having an intensity value above a predetermined minimum threshold.
13 . The computer-readable storage medium of claim 12 , wherein the molecule is an oligonucleotide and the experimental fragments represent monomers in the oligonucleotide.
14 . The computer-readable storage medium of claim 12 , wherein the instructions further configure the computer to:
receive second input data representing a second fragmentation of the molecule into a second plurality of experimental fragments; and
aggregate at least the plurality of experimental fragments and the second plurality of experimental fragments into cumulative input data, wherein
the respective graphical element is in the on state if the modeled fragment corresponding to the graphical element matches at least one of the corresponding experimental fragment in the input data or a second corresponding experimental fragment from the second input data.
15 . The computer-readable storage medium of claim 14 , wherein each graphical element displays a score represent how often the modeled fragment corresponding to the graphical element was found in the cumulative input data.
16 . The computer-readable storage medium of claim 14 , wherein the instructions further configure the computer to:
receive a selection of a selected graphical element in the graphical representation of the candidate match; and
highlight corresponding graphical elements in graphical representations of the cumulative input data.
17 . The computer-readable storage medium of claim 12 , wherein the instructions further configure the computer to:
identify a second candidate match; and
display a graphical representation of the second candidate match aligned to a graphical representation of the candidate match.
18 . The computer-readable storage medium of claim 12 , wherein the instructions further configure the computer to:
identify that a specified experimental fragment is associated with one or more variant configurations; and
modify the graphical element corresponding to the specified experimental fragment with a variant identifier.
19 . The computer-readable storage medium of claim 18 , wherein the instructions further configure the computer to:
identify that a plurality of experimental fragments are each associated with one or more variant configurations, and that at least one of the experimental fragments is in a variant state; and
modify the graphical elements corresponding to the plurality of experimental fragments associated with the variant configurations with a potential variant identifier.
20 . The computer-readable storage medium of claim 18 , wherein the instructions further configure the computer to:
receive a selection of the graphical element corresponding to the specified experimental fragment;
receive a selection of a selected variant configuration; and
modify the display of the graphical representation based on the selected variant configuration.
21 . The computer-readable storage medium of claim 12 , wherein the instructions further configure the computer to:
receive a selection of a selected graphical element in the graphical representation of the candidate match; and
display a mass spectrum from the input data corresponding to the experimental fragment associated with the selected graphical element.