Mass spectrometry-based proteomics for advancing solid organ transplantation research.

Area of Science:

• Biomarker discovery
• Proteomics
• Solid organ transplantation

Background:

• Solid organ transplantation (SOT) faces challenges including organ scarcity, quality assessment, and poor long-term survival.
• Accurate biomarkers are crucial for predicting graft injury, rejection, and dysfunction to personalize patient treatment.
• Proteins and their specific molecular forms, proteoforms, are ideal candidates for biomarkers and therapeutic targets due to their direct link to biological function.

Purpose of the Study:

• To highlight the limitations of current "bottom-up" proteomics (BUP) in SOT research.
• To introduce "top-down" proteomics (TDP) as a superior method for analyzing intact proteins and proteoforms.
• To emphasize the potential of TDP, combined with advanced techniques, for future biomarker and therapeutic target discovery in SOT.

Main Methods:

• Utilizing mass spectrometry-based proteomics, specifically comparing "bottom-up" (BUP) and "top-down" (TDP) approaches.
• Analyzing intact proteins with TDP to retain proteoform-level information, unlike BUP which analyzes peptides.
• Exploring the integration of TDP with single-cell and spatial proteomics technologies.

Main Results:

• BUP provides incomplete information by analyzing peptides rather than intact proteins.
• TDP has recently been applied to transplantation studies, successfully identifying promising proteoforms as biomarkers for organ rejection and dysfunction.
• TDP offers a more accurate basis for connecting molecular changes to complex phenotypes.

Conclusions:

• Top-down proteomics (TDP) is a valuable tool for identifying proteoform biomarkers in solid organ transplantation.
• TDP provides more comprehensive information than traditional BUP, leading to better identification of disease markers.
• Future advancements in TDP and related technologies promise significant breakthroughs in SOT research for improved patient care.