dorsal/arxiv
View SchemaCorrelated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis
| Authors | A. Re, D. Cora, A. M. Puliti, M. Caselle, I. Sbrana |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0610047 |
| URL | https://arxiv.org/abs/q-bio/0610047 |
| Journal | BMC Bioinformatics 2006, 7:413 |
Abstract
Common fragile sites (cfs) are specific regions in the human genome that are particularly prone to genomic instability under conditions of replicative stress. Several investigations support the view that common fragile sites play a role in carcinogenesis. We discuss a genome-wide approach based on graph theory and Gene Ontology vocabulary for the functional characterization of common fragile sites and for the identification of genes that contribute to tumour cell biology. CFS were assembled in a network based on a simple measure of correlation among common fragile site patterns of expression. By applying robust measurements to capture in quantitative terms the non triviality of the network, we identified several topological features clearly indicating departure from the Erdos-Renyi random graph model. The most important outcome was the presence of an unexpected large connected component far below the percolation threshold. Most of the best characterized common fragile sites belonged to this connected component. By filtering this connected component with Gene Ontology, statistically significant shared functional features were detected. Common fragile sites were found to be enriched for genes associated to the immune response and to mechanisms involved in tumour progression such as extracellular space remodeling and angiogenesis. Our results support the hypothesis that fragile sites serve a function; we propose that fragility is linked to a coordinated regulation of fragile genes expression.
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"abstract": "Common fragile sites (cfs) are specific regions in the human genome that are\nparticularly prone to genomic instability under conditions of replicative\nstress. Several investigations support the view that common fragile sites play\na role in carcinogenesis. We discuss a genome-wide approach based on graph\ntheory and Gene Ontology vocabulary for the functional characterization of\ncommon fragile sites and for the identification of genes that contribute to\ntumour cell biology. CFS were assembled in a network based on a simple measure\nof correlation among common fragile site patterns of expression. By applying\nrobust measurements to capture in quantitative terms the non triviality of the\nnetwork, we identified several topological features clearly indicating\ndeparture from the Erdos-Renyi random graph model. The most important outcome\nwas the presence of an unexpected large connected component far below the\npercolation threshold. Most of the best characterized common fragile sites\nbelonged to this connected component. By filtering this connected component\nwith Gene Ontology, statistically significant shared functional features were\ndetected. Common fragile sites were found to be enriched for genes associated\nto the immune response and to mechanisms involved in tumour progression such as\nextracellular space remodeling and angiogenesis. Our results support the\nhypothesis that fragile sites serve a function; we propose that fragility is\nlinked to a coordinated regulation of fragile genes expression.",
"arxiv_id": "q-bio/0610047",
"authors": [
"A. Re",
"D. Cora",
"A. M. Puliti",
"M. Caselle",
"I. Sbrana"
],
"categories": [
"q-bio.GN"
],
"journal_ref": "BMC Bioinformatics 2006, 7:413",
"title": "Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis",
"url": "https://arxiv.org/abs/q-bio/0610047"
},
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