Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics

Abstract

Accurate diagnosis of predominantly colonic inflammatory bowel disease (IBD) is not possible in 30% of patients. For decades, scientists have worked to find a solution to improve diagnostic accuracy for IBD, encompassing Crohn's colitis and ulcerative colitis. Evaluating protein patterns in surgical pathology colectomy specimens of colonic mucosal and submucosal compartments, individually, has potential for diagnostic medicine by identifying integrally independent, phenotype-specific cellular and molecular characteristics. Mass spectrometry (MS) and imaging (I) MS are analytical technologies that directly measure molecular species in clinical specimens, contributing to the in-depth understanding of biological molecules. The biometric-system complexity and functional diversity is well suited to proteomic and diagnostic studies. The direct analysis of cells and tissues by Matrix-Assisted-Laser Desorption/Ionization (MALDI) MS/IMS has relevant medical diagnostic potential. MALDI-MS/IMS detection generates molecular signatures obtained from specific cell types within tissue sections. Herein discussed is a perspective on the use of MALDI-MS/IMS and bioinformatics technologies for detection of molecular-biometric patterns and identification of differentiating proteins. I also discuss a perspective on the global challenge of transferring technologies to clinical laboratories dealing with IBD issues. The significance of serologic-immunometric advances is also discussed.

Keywords: Advances and challenges; Diagnosis; Immunometrics; Inflammatory bowel disease; MALDI-MS/IMS; Molecular biometrics.

Figures

Figure 1

Human colon cross section depicts layers for mining proteomic patterns that delineates untreated ulcerative and Crohn’s colitis phenotype. The colon is comprised of four distinct layers: (1) the mucosa; (2) the submucosa; (3) the muscularis (two thick bands of muscle); and (4) the serosa. Comparable proteomic patterns that are mined from these layers are analyzed, based on the diagnosis [untreated ulcerative and Crohn’s colitis, (with no ambiguity)], disease activity and tissue layer.

Figure 2

Histology-directed tissue layer profiling for matrix-assisted-laser desorption/ionization mass spectrometry. Digital photomicrographs acquired from histology and matrix-assisted-laser desorption/ionization sections were used to identify and designate sites of interest for profiling. Comparisons were performed in both the training and independent test set samples between inflamed mucosa Crohn’s colitis (CC) vs ulcerative colitis (UC) and inflamed submucosa CC vs UC. Tissue section showing marked areas of pathological interest. Rings demonstrate matrix spots in mucosal and sub-mucosal layers (unpublished figure).

Figure 3

Show averaged mass spectrum proteomic pattern spectra from Crohn’s colitis (blue) and ulcerative colitis (red). Differential distribution of three selected proteomic pattern peaks (m/z) obtained from colonic mucosal and/or submucosal tissue sections that were part of the Support Vector Machine model. They are denoted by “a” symbol in the full spectra. Reproduced with permission from the publisher: Seeley et al[50].