NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap(4)A) and Down-Regulates Immune Response and Cancer Promotion Genes

Marriott, Andrew S.; Vasieva, Olga; Fang, Yongxiang; Copeland, Nikki A.; McLennan, Alexander G.; Jones, Nigel J.

Genes showing 2-fold up-or down-regulation with an FDR-adjusted P value < 0.05 were analyzed through the use of QIAGEN Ingenuity 1 Pathway Analysis software (IPA 1 , QIA-GEN, Redwood City, http://www.ingenuity.com) in order to assign them to different functional networks. IPA 1 uses the manually curated Ingenuity1 Knowledge Base, which contains information from several gene and protein expression, interaction and annotation databases such as IntACT, BIND and MiPs, as well as from the published literature [46] . We also used IPA to identify functionally related genes that correspond to specific canonical pathways that were most significant to the data set from a collection of 200 curated metabolic, cell-signaling cascade and disease-associated pathways. Fisher's exact test of independence was used to calculate the probability that the association between the genes in the dataset and the canonical pathway can be explained by chance alone. Finally, we used the IPA upstream regulator analysis to identify factors that may control the genes and pathways highlighted by network analysis to provide testable hypotheses for gene regulation by Ap 4 A.