wangqian Pokročilý
Počet príspevkov : 115 Registration date : 28.11.2013
| Predmet: No deletions or duplications were found in the 15 USH2 families or in the 11 at St február 19, 2014 8:20 am | |
| More advanced therapies that target focused pathways and reduce but do not eliminate this type of side effect are extremely costly, whereas traditional approaches receive controversial favour JNJ-7706621 structure and lack molecular evidence, To gain more insight into the basic mechanisms of action of the disease and to develop more specific and useful drugs, molecular data have been collected and combined so that the whole structure of the molecular networks involved in RA can be studied, Specifically, gene microarray data have contributed greatly to pathogenesis and to the identification of biomarkers for diagnosis, to pa tient stratification and prognostication of RA, Other methods such as Genome Wide Association Studies have been used to scan the whole genome in search of loci susceptible to carry mutations related to RA and in some cases information from these 2 approaches are joined to better predict candidate suscepti bility genes of the disease, Furthermore, some signal transduction pathways have also been identified as being involved in the disease and have been recommended as drug targets to treat RA, Where possible, these data have already been combined and analysed in, in which a comprehensive map for RA was built to combine together the molecules and path ways that were so far found to be associated with RA, based on systemic, high throughput data and made avail able following the CellDesigner standard, Expanding on this work, here we present the outcome of further investigation into one of the most important results from the aforementioned publication.<br><br><br><br> Specifically, we investigate further the potential of CRKL like and its close network, as a drug tar get for RA. CRKL is believed to activate a number of signal ling LDN193189 溶解度 pathways and m supplier LY2228820 ay also be involved in tumour growth. As CRKL is currently not a known drug target for RA, it is potentially interesting for further research, In the present study, the hypothesis that CRKL could act as a potential drug target has been tested using computa tional methods to simulate the likely effect that perturbing CRKL will have on the rest of the molecular interaction network presented in, In order to achieve this, the up and down regulation of CRKL have been simulated using the computational software BioLayout Express and a biological interpretation of the results is discussed.<br><br> By add ing here dynamics and regulations to a sub network of the static reconstruction of the global molecular network in, the current study allows us to show how, in time, perturbation of the expression of molecules of interest in the network can lead to a novel state of up or down regu lation of other molecules in the network. Methods Network reconstruction In the first instance, a directional network of molecular interactions between components involved in RA, including CRKL, was extracted from the RA map publi cally available at, Where necessary, Disease Atlas was used to clarify or disambiguate the literature regarding the known state of the maps molecules in RA.<br><br> As the original map contained some nodes that were not connected to CRKL, the aforementioned static interaction map was trimmed using Cytoscape, Specifically, using Tarjans algorithm, available in the Cytoscape plug in BiNoM, all nodes that were strongly connected to CRKL were identified, forming the core of the CRKL sub network. Nodes that were weakly connected to the CRKL core network were identified and added back to the network using a clustering algorithm in Cytoscape that considers node overlap, In this way, isolated clusters of nodes and pathways that were part of the original RA map but did not contain CRKL and or could not be affected by perturbation of CRKL were removed. | |
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