P4‐110: Differential Co‐expression Analysis Reveals Early Stage Gene Dis‐coordination in Alzheimer's Disease
Year: 2019
Type: article
Abstract: Alzheimer's disease (AD) is one of the leading cause of death in the US. Despite significant progress in biomarker discovery, existing findings are mostly individual biomarkers and provide limited insights into the dis-coordination of genes during the progression of AD. We propose to explore the differential co-expression patterns across multiple AD stages, including cognitively normal (CN), early mild cognitive impairment (EMCI), late MCI and AD. The plasma microarray data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Detailed quality control steps can be found in (http://adni.loni.usc.edu). We focused our analysis on 75 genes of AD-enriched pathways highlighted in[1] and chose the probe with the maximum mean expression to represent the gene. Gene expression was adjusted for RIN, baseline age and sex. Finally, 662 subjects without missing data were included(Table. 1). Assuming that the co-expression networks in consecutive disease stages are largely similar with critical differences, we modified joint graphical lasso[2] to infer the co-expression networks of multiple groups simultaneously. We did 1000 permutation and removed insignificant edges in all groups. Finally, we performed network comparison analysis to identify stage specific differential co-expression patterns. With permuted data, JGL generated much less false positives than graphical lasso (GL), which estimates one network at a time. The network comparison result shows that the global clustering coefficient remains stable from CN to LMCI but drops significantly from LMCI to AD, suggesting structural resilience of the co-expression network in the early development of AD. Fig. 1(a-b) show the gene clusters with continuous correlation and nodal centrality change during AD progression. In (a), 5 of 8 clusters show early co-expression change from CN to EMCI and in Fig.1(c) is the gene module with these 5 clusters.
Source: Alzheimer s & Dementia
Authors: Linhui Xie, Yurika Upadhyaya, Paul Salama, Kwangsik Nho, Andrew J. Saykin, Jingwen Yan
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2980960318