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Marc R J Carlson

Publications and source records attributed to Marc R J Carlson.

2 recordsLinked to original sources

Gene connectivity, function, and sequence conservation: predictions from modular yeast co-expression networks.

BACKGROUND: Genes and proteins are organized into functional modular networks in which the network context of a gene or protein has implications for cellular function. Highly connected hub proteins, largely responsible for maintaining network connectivity, have been found to be much more likely to be essential for yeast survival. RESULTS: Here we investigate the properties of weighted gene co-expression networks formed from multiple microarray datasets. The constructed networks approximate scale-free topology, but this is not universal across all datasets. We show strong positive correlations between gene connectivity within the whole network and gene essentiality as well as gene sequence conservation. We demonstrate the preservation of a modular structure of the networks formed, and demonstrate that, within some of these modules, it is possible to observe a strong correlation between connectivity and essentiality or between connectivity and conservation within the modules particularly within modules containing larger numbers of essential genes. CONCLUSION: Application of these techniques can allow a finer scale prediction of relative gene importance for a particular process within a group of similarly expressed genes.

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Proteinase and growth factor alterations revealed by gene microarray analysis of human diabetic corneas.

PURPOSE: To identify proteinases and growth factors abnormally expressed in human corneas of donors with diabetic retinopathy (DR), additional to previously described matrix metalloproteinase (MMP)-10 and -3 and insulin-like growth factor (IGF)-I. METHODS: RNA was isolated from 35 normal, diabetic, and DR autopsy human corneas ex vivo or after organ culture. Amplified cRNA was analyzed using 22,000-gene microarrays (Agilent Technologies, Palo Alto, CA). Gene expression in each diabetic corneal cRNA was assessed against pooled cRNA from 7 to 9 normal corneas. Select differentially expressed genes were validated by quantitative real-time RT-PCR (QPCR) and immunohistochemistry. Organ cultures were treated with a cathepsin inhibitor, cystatin C, or MMP-10. RESULTS: More than 100 genes were upregulated and 2200 were downregulated in DR corneas. Expression of cathepsin F and hepatocyte growth factor (HGF) genes was increased in ex vivo and organ-cultured DR corneas compared with normal corneas. HGF receptor c-met, fibroblast growth factor (FGF)-3, its receptor FGFR3, tissue inhibitor of metalloproteinase (TIMP)-4, laminin alpha4 chain, and thymosin beta(4) genes were downregulated. The data were corroborated by QPCR and immunohistochemistry analyses; main changes of these components occurred in corneal epithelium. In organ-cultured DR corneas, cystatin C increased laminin-10 and integrin alpha(3)beta(1), whereas in normal corneas MMP-10 decreased laminin-10 and integrin alpha(3)beta(1) expression. CONCLUSIONS: Elevated cathepsin F and the ability of its inhibitor to produce a more normal phenotype in diabetic corneas suggest increased proteolysis in these corneas. Proteinase changes may result from abnormalities of growth factors, such as HGF and FGF-3, in DR corneas. Specific modulation of proteinases and growth factors could reduce diabetic corneal epitheliopathy.

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