Label-free LC-MS/MS quantitative proteomics for large-scale biomarker discovery in complex samples

Area of Science:

• Biochemistry
• Proteomics
• Biomarker Discovery

Background:

• High-throughput proteomic platforms are crucial for identifying biomarkers in complex biological samples.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers a label-free approach for analyzing numerous samples without protein labeling.
• Ensuring consistent system performance is vital for sequential analyses in large-scale proteomic studies.

Purpose of the Study:

• To evaluate the reproducibility and accuracy of a label-free quantitative proteomics approach for biomarker discovery.
• To assess the suitability of LC-MS/MS for analyzing large cohorts of clinical serum samples.
• To identify serum proteins and assess the dynamic range achievable with this methodology.

Main Methods:

• Utilized a label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic platform.
• Analyzed spiked serum samples to assess method performance.
• Examined 55 clinical serum samples from schizophrenia patients and healthy controls.

Main Results:

• Demonstrated reproducible results across a large number of serum samples using the label-free approach.
• Confirmed the accurate measurement of relative protein abundance.
• Identified 1709 serum proteins, covering a dynamic range exceeding three orders of magnitude.

Conclusions:

• Label-free quantitative proteomics is a robust and reproducible method suitable for biomarker discovery in large sample sets.
• The LC-MS/MS approach accurately quantifies protein levels and is effective for clinical sample analysis.
• This methodology holds significant potential for identifying novel biomarkers in complex diseases like schizophrenia.