Equations defined using gene expression and histological data resolve coeliac disease biopsies within the Marsh score continuum

Charlesworth, Richard P G; Agnew, Linda L; Scott, David R; Andronicos, Nicholas M

doi:10.1016/j.compbiomed.2018.10.036

Author(s)

Charlesworth, Richard P G

Agnew, Linda L

Scott, David R

Andronicos, Nicholas M

Publication Date

2019-01

Abstract

Background/Aim: The gold standard diagnostic for coeliac disease (CD) is subjective histological assignment of biopsies into the Marsh score categories. It is hypothesized that discrete Marsh score categories can be quantitatively resolved into a continuum using discriminant equations defined using histological and gene expression data. Therefore, the aim of this study was to use a combination of histological and gene expression data to develop equations that classify CD patient biopsies into a quantitative Marsh score continuum which could be used by clinicians to monitor CD treatment efficacy. Methods: Both empirical and simulated gene expression and histological data were used to define predictive Marsh score equations. The distances of treated sample biopsies from the Marsh score standards were determined using the Mahalanobis distance calculation. Results: Three function, high resolution discriminant equations derived from simulated data were used to accurately classify 99.6% of simulated and empirically derived biopsy data. The first function resolved active (Marsh type 3) CD from mild (Marsh type 1) CD. The second function resolved normal (no specific pathology) biopsies from mild CD. The third function resolved active Marsh score 3 into a and b subcategories. Finally, measuring the Mahalanobis distance enabled the conversion of discrete Marsh score categories into a continuum. Conclusions: This proof-of-concept study successfully demonstrated that the discrete Marsh score scale can be converted into a quantitative continuum capable of high resolution monitoring of patient treatment efficacy using equations defined by gene expression and histology data.

Citation

Computers in Biology and Medicine, v.104, p. 183-196

ISSN

1879-0534

0010-4825

Link

https://hdl.handle.net/1959.11/26556

Language

en

Publisher

Elsevier Ltd

Title

Equations defined using gene expression and histological data resolve coeliac disease biopsies within the Marsh score continuum

Type of document

Journal Article

Entity Type

Publication

Author(s)	Charlesworth, Richard P G Agnew, Linda L Scott, David R Andronicos, Nicholas M
Publication Date	2019-01
Abstract	Background/Aim: The gold standard diagnostic for coeliac disease (CD) is subjective histological assignment of biopsies into the Marsh score categories. It is hypothesized that discrete Marsh score categories can be quantitatively resolved into a continuum using discriminant equations defined using histological and gene expression data. Therefore, the aim of this study was to use a combination of histological and gene expression data to develop equations that classify CD patient biopsies into a quantitative Marsh score continuum which could be used by clinicians to monitor CD treatment efficacy. Methods: Both empirical and simulated gene expression and histological data were used to define predictive Marsh score equations. The distances of treated sample biopsies from the Marsh score standards were determined using the Mahalanobis distance calculation. Results: Three function, high resolution discriminant equations derived from simulated data were used to accurately classify 99.6% of simulated and empirically derived biopsy data. The first function resolved active (Marsh type 3) CD from mild (Marsh type 1) CD. The second function resolved normal (no specific pathology) biopsies from mild CD. The third function resolved active Marsh score 3 into a and b subcategories. Finally, measuring the Mahalanobis distance enabled the conversion of discrete Marsh score categories into a continuum. Conclusions: This proof-of-concept study successfully demonstrated that the discrete Marsh score scale can be converted into a quantitative continuum capable of high resolution monitoring of patient treatment efficacy using equations defined by gene expression and histology data.
Citation	Computers in Biology and Medicine, v.104, p. 183-196
ISSN	1879-0534 0010-4825
Link	https://hdl.handle.net/1959.11/26556
Language	en
Publisher	Elsevier Ltd
Title	Equations defined using gene expression and histological data resolve coeliac disease biopsies within the Marsh score continuum
Type of document	Journal Article
Entity Type	Publication

Equations defined using gene expression and histological data resolve coeliac disease biopsies within the Marsh score continuum

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