Label-free mass spectrometry-based proteomics for biomarker discovery and validation

Abstract

For most diseases, better biomarkers are urgently needed to enable (early) detection, diagnosis, prognosis, stratification for therapy and response monitoring. Proteomics delineates gene products that carry out the majority of cellular functions, and thereby may not only yield insight into altered signaling pathways in disease, but also yield novel biomarkers. In recent years, great progress has been made in mass spectrometry-based analysis of clinical tissues and biofluids, with identification and quantification of thousands of proteins now becoming increasingly routine. However, biomarker validation and clinical translation has turned out to be challenging. In this review, we summarize current mass spectrometry-based proteomics strategies for biomarker discovery and verification using selected reaction monitoring, with a focus on progress and recent applications in clinical material using label-free approaches.

Methylcrotonyl-CoA Carboxylase Regulates Triacylglycerol Accumulation in the Model Diatom Phaeodactylum tricornutum

“…With recent advances in mass spectrometry, label-free quantitative proteomic approaches have progressed and are now considered to be reliable, robust, and efficient methods to study changes in protein abundance in complex mixtures (Geetha et al, 2011;Megger et al, 2013). These approaches are based either on measuring a peptide's response (intensity) in the mass spectrometer as a quantitative method, or counting and comparing the number of peptide-to-spectrum matches obtained for each protein (Pham et al, 2012;Nahnsen et al, 2013). Although considered less accurate than the isotope labeling methods, they have the advantage of generating higher proteome coverage, higher dynamic range, and a simpler experimental protocol.…”

Biomarkers in Malignant Melanoma: Recent Trends and Critical Perspective

“…In contrast, a cluster of biomarkers for one disease would be a better diagnostic tool with much higher sensitivity, specificity, and clinical accuracy. Therefore, new investigations called "proteomic profiling" or "multimarker profiling" focus on the identification of multiple co-expressed biomarkers or signature biomarker patterns which allow early detection, staging, therapeutic monitoring, and prognostic predictions (7,(84)(85)(86)(87)(88). This approach can be adopted for both serum and tissue specimens.…”

Proteomic analysis of post translational modifications in cyanobacteria

“…It is applicable to any source material and allows direct comparison of MS signals between any numbers of samples [123]. Label-free approaches are generally considered less accurate than the isotope labeling methods [124]. However, remarkably improved MS performance and algorithms make label-free quantification extremely attractive in the PTM field in the near future [125].…”