Development of an information/hypothesis-driven proteogenomics strategy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K21386
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Niigata University
• Principal Investigator: Matsumoto Masaki 新潟大学, 医歯学系, 教授 (60380531)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Keywords: プロテオミクス / プロテオゲノミクス / 質量分析

Outline of Final Research Achievements

In this study, we developed a technology to link nucleic acid information and proteome information through "information/hypothesis-driven proteogenomics," a strategy that is opposite to existing proteogenomics research. We created an isotope-labeled internal standard production system using E. coli, and developed QuantiCode, an ultra-multiplex quantitative tag system for large-scale absolute quantification, and Quantimer, which functions as an internal standard. Furthermore, we developed the SLiM method, a new ultra-sensitive mass spectrometry technique that seamlessly links two mass spectrometry techniques called DIA and PRM, and conducted a proof-of-concept experiment for proteogenomics using this method.

Free Research Field

機能ゲノミクス

Academic Significance and Societal Importance of the Research Achievements

本研究によって、任意のペプチド配列の存在を確定的に検証することが可能となり、プロテオームに存在する多数の未確認タンパク質を同定あるいは定量が可能となった。これらの新規タンパク質の発見や機能解析は、ゲノム機能の注釈やタンパク質のミスセンス変異やスプライシング異常などがタンパク質発現への影響を知る手段となるため、学術的な意義はとても大きい。また、真のプロテオームの把握は、基礎生物学的な意義だけでなく、疾患研究や創薬における基盤的情報となるため、将来的に人類の健康等に貢献できると期待される。