Poster abstracts

Poster number 4 submitted by Prabhakar Sairam Andhey

Novel AD risk genes identified through a tissue-specific transcriptome-wide differential expression and co-expression analysis

Prabhakar Sairam Andhey (Department of BioHealth, IUPUI), Jingwen Yan (Department of BioHealth, IUPUI)

Abstract:
Alzheimer’s disease (AD) is the most type of brain dementia characterized by gradual impairment of cognitive functions and it usually starts in the hippocampus, deep within and part of the temporal lobe of the brain. Understanding the biological alterations inside these brain regions are essential for more insights of disease mechanism. In this study, we analyzed the gene expression profiles collected in temporal cortex of both AD and health controls to investigate the tissue-specific transcriptional changes associated with AD. By adjusting for age, gender, RIN and post mortem interval (PMI) effect, 39 genes ( >2 fold changes) were identified to be differentially expressed between AD patients and normal controls with FDR corrected p value smaller than 0.05. Top ones include NPNT (p=3.1e-17), VGF (p=2.28e-09), SLC7A2 (p=4.51e-9), AC026691.1 (p=1.51e-8) and METTL7B (2.63e-8). When adding APOE group as an extra covariate, 24 out of 39 genes remain to be statistically significant. We further map these genes to Reactome functional interaction network and found that many of them are located very closely to known AD-risk genes, e.g. APOE, CLU, BIN1, CD40 and PICALM. This study paves the way for investigating the tissue-specific biological activities underlying the progression of AD.

References:
1.Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009, 25(8):1091-3.

Keywords: Alzheimer disease, differential expression, network analysis