Systems Biology Profiling of AMD on the Basis of Gene Expression

Genetic pathways underlying the initiation and progression of age-related macular degeneration (AMD) have not been yet sufficiently revealed, and the correlations of AMD’s genotypes, phenotypes, and disease spectrum are still awaiting resolution. We are tackling both problems with systems biology ph...

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Main Authors: Mones S. Abu-Asab, Jose Salazar, Jingsheng Tuo, Chi-Chao Chan
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Journal of Ophthalmology
Online Access:http://dx.doi.org/10.1155/2013/453934
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author Mones S. Abu-Asab
Jose Salazar
Jingsheng Tuo
Chi-Chao Chan
author_facet Mones S. Abu-Asab
Jose Salazar
Jingsheng Tuo
Chi-Chao Chan
author_sort Mones S. Abu-Asab
collection DOAJ
description Genetic pathways underlying the initiation and progression of age-related macular degeneration (AMD) have not been yet sufficiently revealed, and the correlations of AMD’s genotypes, phenotypes, and disease spectrum are still awaiting resolution. We are tackling both problems with systems biology phylogenetic parsimony analysis. Gene expression data (GSE29801: NCBI, Geo) of macular and extramacular specimens of the retinas and retinal pigment epithelium (RPE) choroid complexes representing dry AMD without geographic atrophy (GA), choroidal neovascularization (CNV), GA, as well as pre-AMD and subclinical pre-AMD were polarized against their respective normal specimens and then processed through the parsimony program MIX to produce phylogenetic cladograms. Gene lists from cladograms’ nodes were processed in Genomatix GePS to reveal the affected signaling pathway networks. Cladograms exposed a highly heterogeneous transcriptomic profiles within all the conventional phenotypes. Moreover, clades and nodal synapomorphies did not support the classical AMD phenotypes as valid transcriptomal genotypes. Gene lists defined by cladogram nodes showed that the AMD-related deregulations occurring in the neural retina were different from those in RPE-choroidal tissue. Our analysis suggests a more complex transcriptional profile of the phenotypes than expected. Evaluation of the disease in much earlier stages is needed to elucidate the initial events of AMD.
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spelling doaj-art-dbeba200d8e942dfadd17a46f90c63992025-02-03T01:31:28ZengWileyJournal of Ophthalmology2090-004X2090-00582013-01-01201310.1155/2013/453934453934Systems Biology Profiling of AMD on the Basis of Gene ExpressionMones S. Abu-Asab0Jose Salazar1Jingsheng Tuo2Chi-Chao Chan3Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USAGenetic pathways underlying the initiation and progression of age-related macular degeneration (AMD) have not been yet sufficiently revealed, and the correlations of AMD’s genotypes, phenotypes, and disease spectrum are still awaiting resolution. We are tackling both problems with systems biology phylogenetic parsimony analysis. Gene expression data (GSE29801: NCBI, Geo) of macular and extramacular specimens of the retinas and retinal pigment epithelium (RPE) choroid complexes representing dry AMD without geographic atrophy (GA), choroidal neovascularization (CNV), GA, as well as pre-AMD and subclinical pre-AMD were polarized against their respective normal specimens and then processed through the parsimony program MIX to produce phylogenetic cladograms. Gene lists from cladograms’ nodes were processed in Genomatix GePS to reveal the affected signaling pathway networks. Cladograms exposed a highly heterogeneous transcriptomic profiles within all the conventional phenotypes. Moreover, clades and nodal synapomorphies did not support the classical AMD phenotypes as valid transcriptomal genotypes. Gene lists defined by cladogram nodes showed that the AMD-related deregulations occurring in the neural retina were different from those in RPE-choroidal tissue. Our analysis suggests a more complex transcriptional profile of the phenotypes than expected. Evaluation of the disease in much earlier stages is needed to elucidate the initial events of AMD.http://dx.doi.org/10.1155/2013/453934
spellingShingle Mones S. Abu-Asab
Jose Salazar
Jingsheng Tuo
Chi-Chao Chan
Systems Biology Profiling of AMD on the Basis of Gene Expression
Journal of Ophthalmology
title Systems Biology Profiling of AMD on the Basis of Gene Expression
title_full Systems Biology Profiling of AMD on the Basis of Gene Expression
title_fullStr Systems Biology Profiling of AMD on the Basis of Gene Expression
title_full_unstemmed Systems Biology Profiling of AMD on the Basis of Gene Expression
title_short Systems Biology Profiling of AMD on the Basis of Gene Expression
title_sort systems biology profiling of amd on the basis of gene expression
url http://dx.doi.org/10.1155/2013/453934
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