Proteomic analysis of ascending colon biopsies from a paediatric inflammatory bowel disease inception cohort identifies protein biomarkers that differentiate Crohn's disease from UC

Abstract

ObjectiveAccurate differentiation between Crohn's disease (CD) and UC is important to ensure early and appropriate therapeutic intervention. We sought to identify proteins that enable differentiation between CD and UC in children with new onset IBD.DesignMucosal biopsies were obtained from children undergoing baseline diagnostic endoscopy prior to therapeutic interventions. Using a super-stable isotope labeling with amino acids in cell culture (SILAC)-based approach, the proteomes of 99 paediatric control and biopsies of patients with CD and UC were compared. Multivariate analysis of a subset of these (n=50) was applied to identify novel biomarkers, which were validated in a second subset (n=49).ResultsIn the discovery cohort, a panel of five proteins was sufficient to distinguish control from IBD-affected tissue biopsies with an AUC of 1.0 (95% CI 0.99 to 1.0); a second panel of 12 proteins segregated inflamed CD from UC within an AUC of 0.95 (95% CI 0.86 to 1.0). Application of the two panels to the validation cohort resulted in accurate classification of 95.9% (IBD from control) and 80% (CD from UC) of patients. 116 proteins were identified to have correlation with the severity of disease, four of which were components of the two panels, including visfatin and metallothionein-2.ConclusionsThis study has identified two panels of candidate biomarkers for the diagnosis of IBD and the differentiation of IBD subtypes to guide appropriate therapeutic interventions in paediatric patients.

Singular manifolds of proteomic drivers to model the evolution of inflammatory bowel disease status

“…These graphs were constructed based on high-throughput proteome screenings of the two samples of IBD patients, i.e., discovery and validation cohorts. Then to make this methodology more biological meaningful, we can test our predictions by means of experiments that study how specific interventions influence the reprogramming of IBD status, either via high-throughput sequencing surveys of validation populations (18) or by immunofluorescence specific to given antibodies (19). The comparison between theory and experiment will provide insight into the functional constraints of immune system in the recognition of bio-drivers varying when facing an intestinal chronic inflammatory threat.…”

Peripheral blood miR‑372 as a biomarker for ulcerative colitis via direct targeting of NLRP12

“…However, CRP can be challenging to use as a biomarker due to its low specificity and high expression heterogeneity (22,23). It is difficult to screen and monitor the progression of UC and therefore necessary to invest the use of other novel noninvasive biomarkers for patients with UC (24). Increasing evidence suggests that miRs are involved in the progression of a number of diseases, which include cancer and inflammatory diseases (25,26).…”

A synthetic non-histone substrate to study substrate targeting by the Gcn5 HAT and sirtuin HDACs

“…ELITE LC-MS/MS was completed as described previously with minor modifications (65). Briefly, our analysis employed an Ekspert nanoLC 400 (Eksigent, Dublin, CA) and an Orbitrap ELITE MS (Thermo Fisher Scientific, San Jose, CA).…”