MOESM9 of An integrative methodology based on protein-protein interaction networks for identification and functional annotation of disease-relevant genes applied to channelopathies

Additional file 9 Quantitative validation by significance analysis of DAVID search against other phenotype-oriented resources. We searched the nine relevant genes resulted from the workflow in PheGenI [56], ToppGene [57] and g:Profiler [58]. We quantitatively evaluated this search selecting those terms with a significance less than 0.05 using Benjamini-Hochberg FDR statistic. We obtained a minor result in DAVID search (OMIM search did not offer the phenotypes p-values, unlike GAP DISEASE database). Even so, results are useful to develop a quantitative comparison between semiautomatic platforms and bibliographic search systems (sheet 1). From these results we represented the genotype-phenotype association networks to compare easily each p-value phenotype obtained (sheet 2). It should be noted that p-values of clinical phenotypes could be only obtained from one of the two databases explored through DAVID (GAP DISEASE database), and so the genotype-phenotype association network is sparser than the network of the manuscript (section A in Figs. 5, 6, 7). Yet, it is demonstrated that the workflow results are statistically significant and are as valid as or even better than systematic or exhaustive reviews. Then, we created three Boolean tables (in sheets 3, 4, 5) comparing each phenotype obtained from each search; these tables were then converted to binary matrices and clustering multivariate statistical analyses and bootstrap validations were carried out. This approach demonstrated that the results provided in the manuscript, obtained from DAVID (DAVID_m) and systematic and exhaustive reviews, clustered together in a robust and significant way (sheets 3, 4, 5). Hence, this workflow builds as productive results as a non-automatic research but in a quicker way allowing the extraction of information which a priori might not seem relevant when the starting point is a very large group of genes in disease. Moreover, the results obtained using just significant FDR corrected p-values also cluster in particular branches.