title: Bayesian graphical network analyses reveal complex biological interactions specific to Alzheimer's disease.
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.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Rembach
authors.affiliation: The MD Anderson Cancer Center, Texas, Houston, USA.
authors.forename: Francesco C
authors.initials: FC
authors.lastname: Stingo
authors.affiliation: Stanford University, Stanford, California, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Peterson
authors.affiliation: Rice University, Texas, Houston, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Vannucci
authors.affiliation: The MD Anderson Cancer Center, Texas, Houston, USA.
authors.forename: Kim-Anh
authors.initials: KA
authors.lastname: Do
authors.affiliation: CSIRO Digital Productivity and Services/Australian e-Health Research Centre, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia Cooperative Research Centre for Mental Health, Parkville, VIC, Australia.
authors.forename: William J
authors.initials: WJ
authors.lastname: Wilson
authors.affiliation: Department of Psychiatry, St George's Hospital, University of Melbourne, VIC, Australia.
authors.forename: S Lance
authors.initials: SL
authors.lastname: Macaulay
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Ryan
authors.affiliation: Sir James McCusker Alzheimer's Disease Research Unit, Health Department of WA, Perth, WA, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: National Ageing Research Institute, Parkville, VIC, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, VIC, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.affiliation: CSIRO Digital Productivity and Services/Australian e-Health Research Centre, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia Cooperative Research Centre for Mental Health, Parkville, VIC, Australia.
authors.forename: James D
authors.initials: JD
authors.lastname: Doecke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis* / Q000523:psychology; D001315:Australia; D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood*; D060825:Cognitive Dysfunction; D005260:Female; D006801:Humans; D008019:Life Style; D008297:Male; D053858:Metabolic Networks and Pathways; D008875:Middle Aged; D009483:Neuropsychological Tests; D040081:Protein Array Analysis
chemical_list: D015415:Biomarkers
keywords: Alzheimer's disease; Bayesian; biomarkers; graphical networks; imputation