The challenges of peptidomics in complementing proteomics in a clinical context

Abstract

Naturally occurring peptides, including growth factors, hormones, and neurotransmitters, represent an important class of biomolecules and have crucial roles in human physiology. The study of these peptides in clinical samples is therefore as relevant as ever. Compared to more routine proteomics applications in clinical research, peptidomics research questions are more challenging and have special requirements with regard to sample handling, experimental design, and bioinformatics. In this review, we describe the issues that confront peptidomics in a clinical context. After these hurdles are (partially) overcome, peptidomics will be ready for a successful translation into medical practice.

Detecting single amino acids and small peptides by combining isobaric tags and peptidomics

“…The addition of the TMT tag is vital in order to detect and quantify the small molecules in question, though it should be noted that a potential downside of the TMT tag is that it attaches to the n-terminal, where active peptides often already are modified. 2 Amino acids and small peptides with such modifications will thus not be detectable with the suggested approach. On the other hand, the inclusion of the TMT tag on the n-terminal also increases the likelihood of observing small b-ions, given the TMT tag's high chance of retaining a charge.…”

“…naturally occurring) peptides in biological samples. 1,2 Such peptides can either be produced from RNA or be products of proteolysis. For the latter, differences in peptide abundance can potentially be an indication of dysfunctional proteases, peptidases or proteolytic pathways.…”

Proteome Analysis of Molecular Events in Oral Pathogenesis and Virus: A Review with a Particular Focus on Periodontitis

“…MS technology has become significantly robust and sophisticated and, as a result, has been increasingly adopted in various subdisciplines of laboratory medicine ( Table 1 ). Identification of peptides and proteins or of proteomic differential displays in body fluids and other clinical samples has applications in proteomics [ 59 , 60 , 61 ]. Technical developments in proteomics have progressed for the purpose of identifying all proteins expressed in a cell line, tissue, or body.…”

Hexagonal Mesoporous Silica as a Rapid, Efficient and Versatile Tool for MALDI-TOF MS Sample Preparation in Clinical Peptidomics Analysis: A Pilot Study

“…The study of these peptides in biological matrices such as bodily fluids is, therefore, more significant than ever in clinical peptidomics [1]. However, the complexity and the high dynamic range of biological samples makes peptidomics even more challenging than proteomics [2]. In general, peptides are expressed in quite low abundance; moreover, they are frequently subjected to various post-translational processing, among which site-specific proteolysis by proteases and also proteasome degradation, making their detection challenging [3].…”

“…Abundant protein components (e.g., albumin in serum or plasma; mucins in induced sputum, hyaluronic acid polymers in synovial fluid) typically interfere with peptidomic analysis. Additionally, the presence in biological fluid of lipids, carbohydrates and salts gives rise to suppression effects, reducing the ionization efficiency of peptides [2]. Therefore, sample pretreatment is necessary prior to MS analysis for peptidomics-based investigations.…”