Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks.

Genome Medicine
Aaron M NewmanMonte J Radeke

Abstract

Please see related commentary: http://www.biomedcentral.com/1741-7015/10/21/abstract Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent dono...Continue Reading

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Datasets Mentioned

BETA
GSE29801

Methods Mentioned

BETA
dissection

Software Mentioned

Cytoscape
Ingenuity Pathway Analyzer
Ingenuity Pathway Analyzer ( IPA
SplitDatasetTrainTest
IPA
AutoSOME
ToppFun
DAVID
IPA Core Analysis
STRING

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