Plasma Proteome Signature of Sepsis: a Functionally Connected Protein Network

Area of Science:

• Proteomics
• Systems Biology
• Infectious Disease Research

Background:

• Sepsis is a life-threatening condition characterized by organ dysfunction and cardiovascular compromise.
• Rising mortality rates highlight the urgent need for improved sepsis diagnostics and therapeutics.
• Current diagnostic approaches rely on clinical symptoms, often leading to delayed treatment.

Purpose of the Study:

• To investigate the plasma proteome in mouse models of sepsis using quantitative proteomics.
• To identify a molecular signature for sepsis diagnosis and understanding disease progression.
• To establish a basis for developing novel sepsis diagnostic and therapeutic strategies.

Main Methods:

• Utilized label-free quantification (LFQ) and tandem mass tag (TMT)-based quantitative proteomics.
• Analyzed plasma samples from five distinct mouse models of sepsis.
• Applied knowledge-based interpretation to identify protein-protein interactions and functional networks.

Main Results:

• Identified a highly interconnected protein network in the plasma of septic mice.
• Confirmed that proteins within this network have documented roles in sepsis and are extracellular.
• Observed protein abundance changes consistent with human sepsis literature, establishing the Plasma Proteome Signature of Sepsis (PPSS).

Conclusions:

• The Plasma Proteome Signature of Sepsis (PPSS) offers a quantifiable molecular readout for sepsis.
• PPSS has the potential to replace current symptom-based diagnostic methods.
• This molecular approach advances understanding of sepsis, aiding in the discovery and evaluation of new therapies.