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Atul Kakrana, Deepti Anand, Salil Anil Lachke; Integration of cornea expression microarrays in iSyTE to expedite eye gene discovery. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4894.
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© ARVO (1962-2015); The Authors (2016-present)
We recently described a web-based open access resource called iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE) for expediting gene discovery in the eye. iSyTE applies a unique normalization method to prioritize genes based on their enriched expression in ocular-tissues. The present version of iSyTE is focused on lens tissue, and has led to the characterization of several new cataract-linked genes, such as Tdrd7, Sep15, Pvrl3, etc. Here, we have processed high-throughput mouse cornea gene expression data by this approach to prioritize genes that potentially function in corneal tissue.
We obtained microarray datasets on mouse corneal epithelium, corneal limbal cells and isolated cornea tissue from the NCBI Gene Expression Omnibus (GEO) database (GSE6676, GSE36229, GSE9743, GSE14270, GSE4098). These microarrays were performed using the Affymetrix 430 2.0 platform and represented corneal cell/tissue at mouse postnatal (P) days P11, P14, P56 and P121. Mouse embryonic whole body tissue (WB) microarray datasets, which were used as a reference dataset for the in silico subtraction comparative analysis, were obtained from GEO (GSE32334).
Cornea microarray datasets were processed by "in silico WB subtraction", which compares gene expression data on a specific tissue with a WB microarray reference dataset to score for tissue-enriched genes based on t-statistic or fold-change p-values. This approach effectively identifies genes that are related to corneal biology. For example, gene ontology analysis of the top 200 minRank genes identified by this normalization method are significantly enriched for gene ontology (GO) categories such as “keratinocyte differentiation”, “epithelial cell differentiation”, “eye morphogenesis” and “ectoderm development”. In contrast, without in silico WB subtraction, the top 200 minRank genes are primarily enriched for GO categories representing housekeeping genes. Further, genes with known function in the cornea, such as Aldh3a1, Aqp5, A2m, Col12a1, Dsc2, Elf3, Krt12, Krt6b and Muc4 are among the top most-highly enriched genes identified by this approach.
Application of in silico WB subtraction on cornea microarray datasets effectively enriches for genes relevant to corneal biology. Thus, integration of these curated datasets into iSyTE will expedite discovery of new genes in corneal development and disease.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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