rSNP Guide

Database Description

We have earlier developed the computer system and the database, rSNP_Guide, devoted to prediction of transcription factor (TF) binding sites, alterations of which are responsible for disease phenotype [Nucleic Acids Res. 29(1):312-316]. Then, with this system, the prediction results were obtained and, also, confirmed by 70 known relationships between TF sites and diseases, as well as by site-directed mutagenesis data. So that, for this current release presented, the rSNP_Guide is next considered as a tool for TF site annotation. Previously analyzed and characterized cases of altered TF sites are used to annotate potential sites of the same type and at the same location in homologous genes. Based on 20 TF sites with known alterations in TF binding to DNA, we have localized 245 potential TF sites in homologous genes. For these potential TF sites, rSNP_Guide estimates TF-DNA interaction according to three categories: 'present', 'weak', and 'absent'. The significance of each assignment is statistically measured. The present rSNP_Guide issue is at URL=http://util.bionet.nsc.ru/databases/rsnp.html.

Recent Developments

We have adapted our earlier developed system rSNP_Guide to genome annotation. The main idea of our approach is to involve into TF site annotation both sequences of known TF-sites different types, not only of the type investigated, and available experimental data on alterations in binding of mutated DNA to unknown TFs. The focus of this resent annotation is on annotation of potential TF sites using models of experimentally characterized altered TF sites derived by rSNP_Guide system for recognizing TFs relevant to the known TF site. A set of known transcription factors is theoretically evaluated for their ability to bind altered DNA thus resulting in vectors of scores. Experimental data describing mutation-caused alteration in DNA binding to unknown TF are formalized thus resulting in vectors of values. Theoretical and experimental vectors of values are compared using Euclidian distance measure. Assignment of the TF from the theoretical set is then performed, for the binding site under study, which has been altered by mutation(s). For a given TF site with known SNP-disease association, when it is correctly predicted by rSNP_Guide, all the theoretical and experimental vectors are documented in the database rSNP_Report. From this report-entry, in this work, the corresponding Java applet addressed to examining the phylogenetic footprints of only this known TF site is automatically generated and stored in the knowledge-base rSNP_Tuning. So that, the final results of annotation of potential TF sites are documented in TFsite_Annotations database. Based on 20 TF sites with known alterations in TF binding to DNA, we have localized 245 potential TF sites in homologous genes. For these potential TF sites rSNP_Guide estimates TF-DNA interaction according to three categories: 'present', 'weak', and 'absent'. The significance of each assignment is statistically measured. The rSNP_Guide is available through the Web, http://util.bionet.nsc.ru/databases/rsnp.html.

Acknowledgements

The work is supported by Russian Foundation for Basic Research, 01-04-49860 and 02-04-49485.

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