Specific Connectivity And Its Effect On A Growing Network

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“Specific connectivity” is used to prioritize the molecule to add to a growing network. As the network grows, IPA evaluates how much a new gene’s neighborhood overlaps the current network and selects the molecule that overlaps the most. “Overlap” is the number of molecules that are similar compared to the total number of molecules. “Specific connectivity” is computed by dividing the number of molecules found in the intersection of the neighborhood and the network by the number of molecules in their union If specific connectivity (SC) = (number of genes in intersection of the neighborhood and network) / (number of genes in union of the neighborhood and network) Then: SC for the red molecule = 3/16 = 0.1875 SC for the green molecule =…show more content…
They can aid in identifying biological pathways affected by mutated genes. By projecting lists consisting of deleted, amplified and mutated genes onto biological pathways, a statistical improbable subset of unrelated genes would turn out to be closely clustered in ‘reaction space’. Pathway analysis can therefore reveal valuable insight into the underling biological causes of a disease. [Wu, Feng and Stein, 2010] Different mutations found in different genes can cause the same Mendelian disease. [Gilissen et al., 2011] For example, in Fanconi anemia, a condition that causes renal, cardiac and limb malformations, mutations in many genes leads to one phenotype. [Neveling et al., 2009] On the other hand, different mutations in the same gene can lead to different phenotypes as is observed in tumor protein p63. Different mutations lead to a number of monogenic malformation syndromes [Brunner, Hamel and Bokhoven, 2002] suggesting that the mutations affect different biological pathways. [Gilissen et al., 2011] In patients with dilated cardiomyopathy Norton et al. 2011 identified missense and truncated mutations in Bcl2-associated athanogene 3 (BAG3). A missense mutation in the BAG3 gene was also found to cause a different condition, myofibrillar myopathy. [Norton et al., 2011] Thus, our rationale is that identifying and understanding how genes (variants) interact and in what biological pathways putative mutations occupy will reveal a more
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