This Hypophosphatasia network was generated for the Rare Disease AI Hackathon in 2024.

To build this network, expression data was used to define a proxy embedding for the disease. The source study involved stem cells from periodontic ligament undergoing osteogenic differentiation (in vitro) two weeks with or without the TNAP inhibitor levamisole (1 mM), mimicking mutated ALPL. Raw RNA-seq data was re-processed from GSE131338 using QIAGEN's RNA-seq Analysis Portal.

The following description of the network was generated by the Large Language Model (LLM) Gemini-1.5-flash. Please consider with the same caveats as any LLM text:

This biological network describes a complex interplay of various molecules and their effects on bone development, inflammation, and immune responses. Here's a simplified summary:

Key Themes:

• Bone Development: Many molecules influence bone formation and resorption, including ALPL, PTH, TNFSF11, IL17A, and IL1B. Decreases in ALPL, PTH, and TNFSF11 lead to reduced bone formation and increased bone resorption.
• Inflammation: Several molecules, particularly cytokines like IL17A, IL1B, TNF, and CXCL5, are involved in inflammatory processes. Decreases in these molecules generally reduce inflammation.
• Immune Response: The network highlights the role of various molecules in regulating immune cell activity, including neutrophil transmigration (CXCL5, GNA13), B lymphocyte interaction (IL17A), and osteoclast activation (IL17A, IL1B).

Overall, the network suggests that:

• Decreasing ALPL leads to increased pyrophosphate and Hypophosphatasia, a condition affecting bone mineralization.
• Decreasing CAMP reduces inflammation and immune responses, potentially impacting wound healing and tissue repair.
• Decreasing IL17A has a broad impact, reducing inflammation, bone resorption, and immune cell activity.
• Decreasing IL1B reduces inflammation, bone resorption, and immune cell activity, but also impacts bone development.
• Decreasing TNF reduces inflammation, bone resorption, and immune cell activity, but also impacts bone development.
• Increasing CCR3 negatively affects bone formation.

Important Note: This is a simplified summary. The network is complex and involves many interconnected pathways. Further research is needed to fully understand the implications of these interactions.