Bayesian graphical network analyses reveal complex biological interactions specific to Alzheimer's disease
Authors
Alan Rembach
Francesco C. Stingo
Christine Peterson
Marina Vannucci
Kim-Anh Do
William J. Wilson
Lance S. Macaulay
Timothy M. Ryan
Ralph Martins, Edith Cowan UniversityFollow
David Ames
Colin L. Masters
James D. Doecke
Document Type
Journal Article
Publisher
I O S Press
Place of Publication
Netherlands
Faculty
Faculty of Health, Engineering and Science
School
School of Medical and Health Sciences
RAS ID
18814
Abstract
With different approaches to finding prognostic or diagnostic biomarkers for Alzheimer's disease (AD), many studies pursue only brief lists of biomarkers or disease specific pathways, potentially dismissing information from groups of correlated biomarkers. Using a novel Bayesian graphical network method, with data from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging, the aim of this study was to assess the biological connectivity between AD associated blood-based proteins. Briefly, three groups of protein markers (18, 37, and 48 proteins, respectively) were assessed for the posterior probability of biological connection both within and between clinical classifications. Clinical classification was defined in four groups: high performance healthy controls (hpHC), healthy controls (HC), participants with mild cognitive impairment (MCI), and participants with AD. Using the smaller group of proteins, posterior probabilities of network similarity between clinical classifications were very high, indicating no difference in biological connections between groups. Increasing the number of proteins increased the capacity to separate both hpHC and HC apart from the AD group (0 for complete separation, 1 for complete similarity), with posterior probabilities shifting from 0.89 for the 18 protein group, through to 0.54 for the 37 protein group, and finally 0.28 for the 48 protein group. Using this approach, we identified beta-2 microglobulin (β2M) as a potential master regulator of multiple proteins across all classifications, demonstrating that this approach can be used across many data sets to identify novel insights into diseases like AD.
DOI
10.3233/JAD-141497
Access Rights
free_to_read
Comments
Rembach, A., Stingo, F. C., Peterson, C., Vannucci, M., Do, K., Macaulay, S. L., ... Doecke, J. D. (2015). Bayesian graphical network analyses reveal complex biological interactions specific to Alzheimer's disease. Journal of Alzheimer's Disease, 44(3) 917-925. Available here