Method of identifying spliced peptide

Patent metadata

Field	Value
Publication number	US-2024345096-A1
Application number	US-202218292641-A
Country	US
Kind code	A1
Filing date	Jul 22, 2022
Priority date	Jul 28, 2021
Publication date	Oct 17, 2024
Grant date	—

Abstract

A method of identifying an unknown spliced peptide derived from a known parent peptide contained in a biological sample, the method comprising: (1) a first step involving performing mass spectrometry on the sample to obtain mass spectrometry data regarding a peptide contained in the sample; (2) a second step involving searching a primary library, which is a database of known amino acid sequences, for an amino acid sequence that matches the mass spectrometry data, to identify a parent peptide contained in the sample, (3) a third step involving creating a secondary library including a candidate group of spliced peptides obtainable from the identified parent peptide; and (4) a fourth step involving searching the secondary library for an amino acid sequence that matches the mass spectrometry data, to identify a spliced peptide contained in the sample.

First claim

1 . A method of identifying an unknown spliced peptide derived from a known parent peptide contained in a biological sample, the method comprising:
(1) a first step involving performing mass spectrometry on the sample to obtain mass spectrometry data regarding a peptide contained in the sample; (2) a second step involving searching a primary library, which is a database of known amino acid sequences, for an amino acid sequence that matches the mass spectrometry data, to identify a parent peptide contained in the sample; (3) a third step involving creating a secondary library including a candidate group of spliced peptides obtainable from the identified parent peptide; and (4) a fourth step involving searching the secondary library for an amino acid sequence that matches the mass spectrometry data, to identify a spliced peptide contained in the sample.

2 . The method according to claim 1 , wherein the candidate group consists of spliced peptides that are highly likely obtainable from the parent peptide.

3 . The method according to claim 1 , wherein the candidate group consists of variant peptides to be obtained from the parent peptide through at least one of the following: deletion of a predetermined number or less of amino acid residues from at least one of the C-terminus and the N-terminus; and addition of a predetermined number or less of amino acid residues to the C-terminus and the N-terminus.

4 . The method according to claim 3 , wherein the predetermined number for residues is two.

5 . The method according to claim 1 , wherein
the mass spectrometry data is a mass spectrometry spectrum, and the amino acid sequence that matches the mass spectrometry data is an amino acid sequence corresponding to a mass spectrometry spectrum having a peak at the same m/z value as or at an m/z value within a predetermined deviation range from an m/z value for at least one peak in the mass spectrometry spectrum.

6 . The method according to claim 1 , wherein the parent peptide is a known HLA-binding peptide.

7 . The method according to claim 1 , wherein the parent peptide is a known peptide derived from a cancer cell.

8 . The method according to claim 1 , wherein the parent peptide is a known HLA-binding peptide derived from a cancer cell.

Assignees

• Providence Health & Services Oregon
• Shimadzu Corp

Inventors

• Koguchi Yoshinobu
• Iwamoto Noriko
• Shimada Takashi

Classifications

• G16B15/30

  Drug targeting using structural data; Docking or binding prediction · CPC title

• G16B40/10

  Signal processing, e.g. from mass spectrometry [MS] or from PCR · CPC title

• G16B35/20

  Screening of libraries · CPC title

• G01N2333/70539

  MHC-molecules, e.g. HLA-molecules · CPC title

• C07K5/101

  the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu · CPC title