PMC:4307189 / 23793-26976 JSONTXT

{"project":"2_test","denotations":[{"id":"25599599-24243840-14868130","span":{"begin":1574,"end":1576},"obj":"24243840"},{"id":"25599599-12539951-14868131","span":{"begin":1612,"end":1614},"obj":"12539951"},{"id":"25599599-22096230-14868132","span":{"begin":1664,"end":1666},"obj":"22096230"}],"text":"Bayesian analysis\nFor the two gene-gene relationship networks YkR and YkP, Bayesian inference of the parameters of the p1-model for an undirected network was applied. We used WinBUGS for scripting this inference and our scripts were inspired by Adams et al. [30]. We used 6000 MCMC iterations for parameter estimation with the first 5000 as ‘burn-in’. All the parameters in the p1-model appeared to converge rapidly during the burn-in iterations (data not shown). With the above settings, we estimated the posterior probabilities of each edge (gene-gene relationship) Pr(Yij1=1) in the two networks YkR and YkP. For each edge, the proportion of the 1000 sampled networks containing the edge was considered as the posterior probability of that edge being present in the network.\nNext, for each edge we calculated the odds ratio of their posterior probabilities as defined above. The rationale behind this calculation was that the edges (gene-pairs) found with high probabilities in resistant conditions but lower probabilities in parental conditions are more likely to be due to acquired resistance in cell lines. Therefore, we chose only gene-pairs with high odds ratio (≥ 10.0) and high posterior probabilities (≥ 0.5) of occurring in resistant conditions. We found 11,515 such gene-pairs (Additional file 2: Table S1) among all 68,265 [=(370×369)÷2] possibilities.\nWe then observed whether the above gene-pairs overlap with the list of potential cross-talks between EGFR/ErbB signaling and other signaling pathways. Here, we collected 24 signaling pathways from Reactome [32], 35 signaling pathways from KEGG [33,34], and 63 signaling pathways from WikiPathway [35] databases, and respectively identified 1,083 (841 distinct), 2,179 (1,050 distinct) and 3,084 (876 distinct) gene-pairs (Additional file 3: Table S2, Additionalfile 4: Table S3 and Additional file 5: Table S4) between EGFR/ErbB and other signaling pathways (seeMaterials and method). Of the 11,515 gene-pairs identified above, we found 104 (97 distinct), 188 (99 distinct) and 299 (96 distinct) gene-pairs overlap with the potential EGFR cross-talks identified using Reactome, KEGG and WikiPathway, respectively. Note the number of potential cross-talks and the number of distinct gene-pairs are different because the same gene-pair can form cross-talks between multiple pathway-pairs (pathways are overlapping). We consider these overlapping gene-pairs as putative drug-resistant cross-talks between EGFR/ErbB and other signaling pathways. In these 104, 188 and 299 cross-talks, we found candidate EGFR/ErbB cross-talks with 13, 26 and 51 other signaling pathways, respectively. Moreover, among all 104, 188 and 299 cross-talks from Reactome, KEGG and WikiPathway, respectively, we found 32 distinct gene-pairs in at least two of these sets. Primary findings and detailed descriptions of all these putative cross-talks from the analyses of all three pathway sources are listed in Table 1, and Additional file 6: Table S5, Additional file 7: Table S6 and Additional file 8: Table S7, respectively. The network views of all these cross-talk sets from the analyses of individual pathway sources are shown in Figure 2."}