---
title: DINA Network Similarity Validations
slug: dina-network-similarity-validations
createdAt: 2026-01-20T12:29:30.901Z
---

# Validation for P-Value Calculation and Null Distributions

The validation analysis described under [Biological Relevance](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          |
| Breast **–** General           | 20   | 15              | 1,5            | 0,0152                       | 0,7596  | 0,119          |
| Pancreas **–** General         | 20   | 8               | 0,8            | 0,0139                       | 0,8727  | 0,059          |