title: Optimal reaction coordinate as a biomarker for the dynamics of recovery from kidney transplant.
abstract: The evolution of disease or the progress of recovery of a patient is a complex process, which depends on many factors. A quantitative description of this process in real-time by a single, clinically measurable parameter (biomarker) would be helpful for early, informed and targeted treatment. Organ transplantation is an eminent case in which the evolution of the post-operative clinical condition is highly dependent on the individual case. The quality of management and monitoring of patients after kidney transplant often determines the long-term outcome of the graft. Using NMR spectra of blood samples, taken at different time points from just before to a week after surgery, we have shown that a biomarker can be found that quantitatively monitors the evolution of a clinical condition. We demonstrate that this is possible if the dynamics of the process is considered explicitly: the biomarker is defined and determined as an optimal reaction coordinate that provides a quantitatively accurate description of the stochastic recovery dynamics. The method, originally developed for the analysis of protein folding dynamics, is rigorous, robust and general, i.e., it can be applied in principle to analyze any type of biological dynamics. Such predictive biomarkers will promote improvement of long-term graft survival after renal transplantation, and have potentially unlimited applications as diagnostic tools.
authors: School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
authors: Sergei V
authors: SV
authors: Krivov
authors: School of Chemistry, University of Leeds, Leeds, United Kingdom.
authors: Hayley
authors: H
authors: Fenton
authors: Hepatopancreatobiliary Transplant Unit, St. James's University Hospital, Leeds, United Kingdom.
authors: Paul J
authors: PJ
authors: Goldsmith
authors: Hepatopancreatobiliary Transplant Unit, St. James's University Hospital, Leeds, United Kingdom.
authors: Rajendra K
authors: RK
authors: Prasad
authors: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom; School of Chemistry, University of Leeds, Leeds, United Kingdom.
authors: Julie
authors: J
authors: Fisher
authors: School of Molecular and Cellular Biology, University of Leeds, Leeds, United Kingdom; Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.
authors: Emanuele
authors: E
authors: Paci
mesh_terms: D015415:Biomarkers / Q000097:blood*; D019295:Computational Biology; D006801:Humans; D007668:Kidney / Q000502:physiology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000706:statistics & numerical data*; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D020127:Recovery of Function / Q000502:physiology
chemical_list: D015415:Biomarkers