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US 8,620,588 B2Granted
Method, system, and computer program product for determining a putative amino acid sequence
AssigneeShimadzu Research Laboratory (Europe) Ltd.
InventorsMichael May, Jing Wen Yao
Life of this patent
Estimating the term…
Abstract
The present invention is concerned with methods for the de novo sequencing of polypeptides from data obtained from mass spectrometry devices, particularly from (MS)n devices.
Claims21
A system for determining at least one putative amino acid sequence for a sample polypeptide, said sample polypeptide being partially degraded, said system comprising:
- (a) a memory storing processor readable instructions;
- and
- (b) a processor arranged to read and execute instructions stored in said memory;
- wherein said processor readable instructions contain instructions to:
- (i) control the processor to store in said memory a set of m/z peaks obtained from a soft ionization mass spectrum of said sample polypeptide giving said set of m/z peaks of ion species obtained from said partially degraded sample polypeptide and determine from said set of m/z peaks a plurality of candidate m/z peak sets, each m/z peak in each candidate m/z peak set differing from its at least one neighbor by the mass of an amino acid residue;
- (ii) control the processor to store in said memory each candidate m/z peak set determined at step (i);
- for each candidate m/z peak set stored in said memory:
- determine an associated sequence of mass differences between each m/z peak in the set and its at least one neighbor;
- and
- determine an associated sequence of mass differences in reverse order;
- process the determined sequences of mass differences and determined sequences of mass differences in reverse order using a reflective predicate filter to determine a plurality of candidate m/z peak sets in which each m/z peak set has an associated sequence of mass differences in reverse order that forms at least part of the sequence of mass differences of another of said candidate m/z peak sets determined at step (i);
- and
- discard any candidate m/z peaks not in the determined plurality of candidate m/z peak sets;
- (iii) control the processor to:
- identify candidate m/z peak sets in which mass differences between each m/z peak and at least one peak in the candidate m/z peak set having a closest m/z value above and/or below the peak correspond to that of a daughter ion or an end ion cluster;
- and
- discard any identified candidate m/z peak sets from the plurality of candidate m/z peak sets;
- (iv) control the processor to process the plurality of candidate m/z peak sets to:
- identify any candidate m/z peak set which is a contiguous subsequence of another candidate m/z peak set;
- and
- discard the identified candidate m/z peak sets from the plurality of candidate m/z peak sets;
- and
- (v) control the processor to determine an amino acid sequence for each remaining candidate m/z peak set, each amino acid sequence being that of the amino acids which correspond to the mass differences between each m/z peak and its at least one neighbor, said at least one putative amino acid sequence of said sample polypeptide being made up of one or more of said determined amino acid sequences.
20 more elements
A computer program product for determining at least one putative amino acid sequence for a sample polypeptide, said sample polypeptide being partially degraded and a soft ionization mass spectrum of said sample polypeptide having been obtained giving a set of m/z peaks of ion species obtained from said partially degraded sample polypeptide, the computer program product comprising a non-transient computer usable medium having a computer readable program code, said computer readable program code comprising:
- (i) program code for determining a plurality of candidate m/z peak sets, from said set of m/z peaks, each m/z peak in each candidate m/z peak set differing from its at least one neighbor by the mass of an amino acid residue;
- (ii) program code for determining from each candidate m/z peak set determined at step (i) a sequence of mass differences between each m/z peak in the set and its at least one neighbor, and
- determining an associated sequence of mass differences in reverse order;
- processing the determined sequences of mass differences and determined sequences of mass differences in reverse order using a reflective predicate filter to determine a plurality of candidate m/z peak sets in which each m/z peak set has an associated sequence of mass differences in reverse order that forms at least part of the sequence of mass differences of another of said candidate m/z peak sets determined at step (i);
- and
- discard any candidate m/z peak sets not in the determined plurality of candidate m/z peak sets;
- (iv) program code for:
- identifying candidate m/z peak sets in which mass differences between each m/z peak and at least one peak in the candidate m/z peak set having a closest m/z value above and/or below the peak correspond to that of a daughter ion or an end ion cluster;
- and
- discarding any candidate m/z peak sets from the plurality of candidate m/z peak sets;
- (v) program code for:
- processing the plurality of candidate m/z peak sets to identify any candidate m/z peak set which is a contiguous subsequence of another candidate m/z peak set;
- and
- discarding the identified candidate m/z peak sets from the plurality of candidate m/z peak sets;
- and
- (vi) program code for determining an amino acid sequence for each remaining candidate m/z peak set, each amino acid sequence being that of the amino acids which correspond to the mass differences between each m/z peak and its at least one neighbor, each putative amino acid sequence comprising an at least partial putative amino acid sequence of said sample polypeptide and outputting the results to the user in any desired tangible form, to allow said user to putatively identify the amino acid sequence for said sample polypeptide.
13 more elements
A method for determining at least one putative amino acid sequence for a sample polypeptide with a computer program using (a) a memory storing processor readable instructions, and (b) a processor arranged to read and execute instructions stored in said memory, said sample polypeptide being partially degraded, said method comprising causing a suitably programmed computer comprising machine readable instructions to perform the steps of:
- (i) obtaining a soft ionization mass spectrum of said partially degraded sample polypeptide giving a set of m/z peaks of ion species obtained from said partially degraded sample polypeptide and storing said set of m/z peaks in said memory using said processor;
- (ii) with said set of m/z peaks obtained in step (i), using said processor in determining a plurality of candidate m/z peak sets, each m/z peak in each candidate m/z peak set differing from its at least one neighbor by the mass of an amino acid residue;
- (iii) with each candidate m/z peak set determined at step (ii), using said processor in:
- determining an associated sequence of mass differences between each m/z peak in the set and its at least one neighbor;
- determining an associated sequence of mass differences in reverse order;
- processing the determined sequences of mass differences and determined sequences of mass differences in reverse order using a reflective predicate filter to determine a plurality of candidate m/z peak sets in which each m/z peak set has an associated sequence of mass differences in reverse order that forms at least part of the sequence of mass differences of another of said candidate m/z peak sets determined at step (ii);
- and
- discarding any candidate m/z peak sets not in the determined plurality of candidate m/z peak sets;
- (iv) controlling said processor to:
- identify candidate m/z peak sets in which mass differences between each m/z peak and at least one peak in the candidate m/z peak set having a closest m/z value above and/or below the peak correspond to that of a daughter ion or an end ion cluster;
- and
- discard any candidate m/z peak sets from the plurality of candidate m/z peak sets;
- (v) controlling said processor to process the plurality of candidate m/z peak sets to:
- identify any candidate m/z peak set which is a contiguous subsequence of another candidate m/z peak set;
- and
- discard the identified candidate m/z peak sets from the plurality of candidate m/z peak sets;
- (vi) determining a putative amino acid sequence for each remaining candidate m/z peak set, each amino acid sequence being that of the amino acids which correspond to the mass differences between each m/z peak and its at least one neighbor, each putative amino acid sequence comprising an at least partial putative amino acid sequence of said sample polypeptide and outputting the results to the user in any desired tangible form, to allow said user to putatively identify the amino acid sequence for said sample polypeptide.
14 more elements
A system for determining at least one putative amino acid sequence for a sample polypeptide, said sample polypeptide being partially degraded, said system comprising a processor and a non-transitory computer-readable storage medium encoded with computer-executable instructions which, when executed by said processor, cause the processor to execute a method comprising the steps of:
- (a) obtaining a set of m/z peaks from a soft ionization mass spectrum of said sample polypeptide
- (b) determining from said set of m/z peaks a plurality of candidate m/z peak sets, each m/z peak in each candidate m/z peak set differing from its adjacent m/z peaks by the mass of an amino acid residue;
- (c) determining a sequence of mass differences associated with each of the plurality of candidate m/z peak sets based upon mass differences between each m/z peak in the set and its adjacent m/z peaks;
- (d) filtering the plurality of candidate m/z peak sets by:
- (i) for each candidate m/z peak set, analyzing the determined sequence of mass differences associated with the candidate ink peak set determined at step (c) using a reflective predicate filter and discarding the candidate m/z peak set if the sequence of mass differences associated with the candidate m/z peak set in reverse order does not form at least part of a sequence of mass differences of another of said candidate m/z peak sets determined at step (c);
- (ii) identifying and discarding any candidate m/z peak sets in which a mass difference between a m/z peak of the candidate m/z peak set and an adjacent m/z peak of the candidate m/z peak set corresponds to that of a daughter ion or an end ion cluster;
- (iii) identifying and discarding any candidate m/z peak set which is a contiguous subsequence of another candidate m/z peak set;
- and
- (e) determining an amino acid sequence for each remaining candidate m/z peak set that has not been discarded, each amino acid sequence being determined based upon the mass differences between adjacent m/z peaks in a respective candidate m/z peak set and the associated amino acid residues used to determine the candidate m/z peak set at step (b), wherein said at least one putative amino acid sequence of said sample polypeptide comprises one or more of said determined amino acid sequences.
6 more elements
A computer program product for determining at least one putative amino acid sequence for a sample polypeptide, said sample polypeptide being partially degraded, the computer program product comprising a non-transient computer usable medium having a computer readable program code, said computer readable program code comprising instructions arranged to cause a computer to:
- (a) obtain a set of m/z peaks from a soft ionization mass spectrum of said sample polypeptide
- (b) determine from said set of m/z peaks a plurality of candidate m/z peak sets, each m/z peak in each candidate m/z peak set differing from its adjacent m/z peaks by the mass of an amino acid residue;
- (c) determine a sequence of mass differences associated with each of the plurality of candidate m/z peak sets based upon mass differences between each m/z peak in the set and its adjacent m/z peaks;
- (d) filter the plurality of candidate m/z peak sets by:
- (i) for each candidate m/z peak set, analyzing the determined sequence of mass differences associated with the candidate m/z peak set determined at step (c) using a reflective predicate filter and discarding the candidate m/z peak set if the sequence of mass differences associated with the candidate m/z peak set in reverse order does not form at least part of a sequence of mass differences of another of said candidate m/z peak sets determined at step (c);
- (ii) identifying and discarding any candidate m/z peak sets in which a mass difference between a m/z peak of the candidate m/z peak set and an adjacent m/z peak of the candidate m/z peak set corresponds to that of a daughter ion or an end ion cluster;
- (iii) identifying and discarding any candidate m/z peak set which is a contiguous subsequence of another candidate m/z peak set;
- and
- (e) determine an amino acid sequence for each remaining candidate m/z peak set that has not been discarded, each amino acid sequence being determined based upon the mass differences between adjacent m/z peaks in a respective candidate m/z peak set and the associated amino acid residues used to determine the candidate m/z peak set at step (b), wherein said at least one putative amino acid sequence of said sample polypeptide comprises one or more of said determined amino acid sequences.
6 more elements
A method for causing a computer to determine at least one putative amino acid sequence for a sample polypeptide with a computer program using (a) a memory storing processor readable instructions, and (b) a processor arranged to read and execute instructions stored in said memory, said sample polypeptide being partially degraded, said method comprising causing a suitably programmed computer comprising machine readable instructions to perform the steps of:
- (i) obtaining a soft ionization mass spectrum of said partially degraded sample polypeptide giving a set of m/z peaks of ion species obtained from said partially degraded sample polypeptide and storing said set of m/z peaks in said memory using said processor;
- (ii) with said set of m/z peaks obtained in step (i), using said processor in determining a plurality of candidate m/z peak sets, each m/z peak in each candidate m/z peak set differing from its at least one neighbor by the mass of an amino acid residue;
- (iii) with each candidate m/z peak set determined at step (ii), using said processor in:
- determining an associated sequence of mass differences between each m/z peak in the set and its at least one neighbor;
- determining an associated sequence of mass differences in reverse order;
- processing the determined sequences of mass differences and determined sequences of mass differences in reverse order using a reflective predicate filter to determine a plurality of candidate m/z peak sets in which each m/z peak set has an associated sequence of mass differences in reverse order that forms at least part of the sequence of mass differences of another of said candidate m/z peak sets determined at step (ii);
- and
- discarding any candidate m/z peak sets not in the determined plurality of candidate m/z peak sets;
- (iv) controlling said processor to:
- identify candidate m/z peak sets in which mass differences between each m/z peak and at least one peak in the candidate m/z peak set having a closest m/z value above and/or below the peak correspond to that of a daughter ion or an end ion cluster;
- and
- discard any candidate m/z peak sets from the plurality of candidate m/z peak sets;
- (v) controlling said processor to process the plurality of candidate m/z peak sets to:
- identify any candidate m/z peak set which is a contiguous subsequence of another candidate m/z peak set;
- and
- discard the identified candidate m/z peak sets from the plurality of candidate m/z peak sets;
- (vi) determining a putative amino acid sequence for each remaining candidate m/z peak set, each amino acid sequence being that of the amino acids which correspond to the mass differences between each m/z peak and its at least one neighbor, each putative amino acid sequence comprising an at least partial putative amino acid sequence of said sample polypeptide and outputting the results to the user in any desired tangible form, to allow said user to putatively identify the amino acid sequence for said sample polypeptide.
14 more elements
Dependencies are inferred from the claim text.