A Pathway Based Classification Method for Analyzing Gene Expression for Alzheimer's Disease Diagnosis.
Journal of Alzheimer's Disease
Copyright © 2016 – IOS Press and the authors. All rights reserved. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License.
BACKGROUND: Recent studies indicate that gene expression levels in blood may be able to differentiate subjects with Alzheimer's disease (AD) from normal elderly controls and mild cognitively impaired (MCI) subjects. However, there is limited replicability at the single marker level. A pathway-based interpretation of gene expression may prove more robust. OBJECTIVES: This study aimed to investigate whether a case/control classification model built on pathway level data was more robust than a gene level model and may consequently perform better in test data. The study used two batches of gene expression data from the AddNeuroMed (ANM) and Dementia Case Registry (DCR) cohorts. METHODS: Our study used Illumina Human HT-12 Expression BeadChips to collect gene expression from blood samples. Random forest modeling with recursive feature elimination was used to predict case/control status. Age and APOE ɛ4 status were used as covariates for all analysis. RESULTS: Gene and pathway level models performed similarly to each other and to a model based on demographic information only. CONCLUSIONS: Any potential increase in concordance from the novel pathway level approach used here has not lead to a greater predictive ability in these datasets. However, we have only tested one method for creating pathway level scores. Further, we have been able to benchmark pathways against genes in datasets that had been extensively harmonized. Further work should focus on the use of alternative methods for creating pathway level scores, in particular those that incorporate pathway topology, and the use of an endophenotype based approach.
InnoMed, European Union of the Sixth Framework program priority
Alzheimer’s Research Trust UK
John and Lucille van Geest Foundation
NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at the South London, Maudsley NHS Foundation Trust
Kings College London
Guy’s and St Thomas’ Charity
European Union’s Seventh Framework Program
Kuopio University Hospital (HS)
MRC Career Development Award in Biostatistics
Vol. 49, Iss. 3, pp. 659 - 669
UEF- BRAIN (HS)
Place of publication