Computational Analysis Identifies Putative Prognostic Biomarkers of Pathological Scarring in Skin Wounds
Abstract
Background: Pathological scarring in wounds is a prevalent clinical outcome with limited prognostic options. The objective of this study was to investigate whether cellular signaling proteins could be used as prognostic biomarkers of pathological scarring in traumatic skin wounds. Methods: We used our previously developed and validated computational model of injury-initiated wound healing to simulate the time courses for platelets, 6 cell types, and 21 proteins involved in the inflammatory and proliferative phases of wound healing. Next, we analysed thousands of simulated wound-healing scenarios to identify those that resulted in pathological (i.e., excessive) scarring. Then, we identified candidate proteins that were levated (or decreased) at the early stages of wound healing in those simulations and could therefore serve as predictive biomarkers of pathological scarring outcomes. Finally, we performed logistic regression analysis and calculated the area under the receiver operating characteristic curve to quantitatively assess the predictive accuracy of the model-identified putative biomarkers. Results: We identified three proteins (interleukin-10, tissue inhibitor of matrix metalloproteinase-1, and fibronectin) whose levels were elevated in pathological scars as early as 2 weeks post-wounding and could predict a pathological scarring outcome occurring 40 days after wounding with 80 accuracy. Conclusion: Our method for predicting putative prognostic wound-outcome biomarkers may serve as an effective means to guide the identification of proteins predictive of pathological scarring.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 20, 2018
- Accession Number
- AD1047544
Entities
People
- Alexander Mitrophanov
- Jaques Reifman
- Lin Chen
- Luisa Dipietro
- Sridevi Nagaraja
Organizations
- Biotechnology High Performance Computing Software Applications Institute
- University of Illinois Urbana–Champaign