DINA Network Similarity Validations

validation for p value calculation and null distributions the validation analysis described under docid\ m3ywqj3arjsy4zaf7wthc incorporates deltacon similarities and their corresponding p values within the pipeline therefore, they can be considered as part of the deltacon similarity p value validation to further ensure that our implementation of deltacon and null distributions give expected relative similarities between comparisons, and that the p values are significant where expected, comparative analyses of a known function across different subnetworks were performed we analyzed subnetworks centered on the zap70 gene, which is associated with t cell development and lymphocyte activation, and compared these subnetworks across multiple tissues cd8 anchored (zap70) deltacon validation across tissues to evaluate the performance of the deltacon based network similarity method, we compared gene subnetworks derived from multiple tissue specific networks, namely multi tissue – cd8+ t cells, multi tissue – cd4+ t cells, blood – general, pbmc – general, lung – general, breast – general, bone marrow – general, and pancreas – general the objective was to verify that biologically related networks exhibit higher similarity, while unrelated networks show lower similarity, with statistically significant p values in the expected comparisons in this validation, the multi tissue – cd8+ t cells network served as the reference (anchor), constructed around genes associated with t lymphocytes receptor signaling and activation, centered on zap70 the hypothesis is that network similarity to the cd8 + t lymphocytes reference should decrease with increasing biological dissimilarity a detailed description of the expected relations between the networks is given in table 1 table 1 expected similarities between the networks from different tissues and the cd8+ t lymphocytes as reference compared to multi tissue – cd8+ t cells expected similarity rationale multi tissue – cd4+ t cells very high closely related t cell lineage; shared signaling (e g , tcr/zap70), many co expressed immune genes blood – general high mixed compartment that includes circulating cd8+ t lymphocytes pbmc – general high enriched for lymphocytes (including cd8+), but still a mixture of cell types lung – general moderate contains tissue resident or infiltrating cd8+ t lymphocytes, especially during inflammation or in tumors bone marrow – general low–moderate fewer mature cd8+ t lymphocytes; presence of precursors and diverse hematopoietic cells dilutes the t cell signal breast – general low–moderate limited cd8+ infiltration, typically in tumor adjacent or immune active regions only pancreas – general low generally low immune infiltration, particularly of cd8+ t lymphocytes, in non inflamed tissue observed deltacon similarities follow the expected biological gradient cd4+ t lymphocytes show the highest similarity to cd8+ t lymphocytes (0 0385; p = 0 0216), followed by blood (0 0258; p = 0 0905) and pbmc (0 0249; p = 0 1042) (table 2) more dissimilar tissues show progressively lower similarity—bone marrow (0 0194), lung (0 0190), breast (0 0152), and pancreas (0 0139)—all non significant (p > 0 05) overall, the results match the hypothesis biologically related networks are more similar to cd8+ t lymphocytes, and unrelated tissues are less similar, with significance where expected (cd4+ t lymphocytes) table 2 observed similarities between the networks from different tissues and the cd8+ t lymphocytes as reference multi tissue – cd8+ t cells vs size number of edges average degree observed deltacon similarity p value –log10 p value multi tissue – cd4+ t cells 20 54 5 4 0 0385 0 0214 1 666 blood – general 20 39 3 9 0 0258 0 0905 1 043 pbmc – general 20 41 4 1 0 0249 0 1042 0 982 bone marrow – general 20 31 3 1 0 0194 0 3072 0 513 lung – general 20 25 2 5 0 0110 0 3398 0 469