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

Title
Equations defined using gene expression and histological data resolve coeliac disease biopsies within the Marsh score continuum
Publication Date
2019-01
Author(s)
Charlesworth, Richard P G
( author )
OrcID: https://orcid.org/0000-0002-4557-1419
Email: rcharle3@une.edu.au
UNE Id une-id:rcharle3
Agnew, Linda L
( author )
OrcID: https://orcid.org/0000-0002-2803-0995
Email: lagnew2@une.edu.au
UNE Id une-id:lagnew2
Scott, David R
Andronicos, Nicholas M
( author )
OrcID: https://orcid.org/0000-0001-5881-2296
Email: nandroni@une.edu.au
UNE Id une-id:nandroni
Type of document
Journal Article
Language
en
Entity Type
Publication
Publisher
Elsevier Ltd
Place of publication
United Kingdom
DOI
10.1016/j.compbiomed.2018.10.036
UNE publication id
une:1959.11/26556
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.
Link
Citation
Computers in Biology and Medicine, v.104, p. 183-196
ISSN
1879-0534
0010-4825
Start page
183
End page
196

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