This Ehlers-Danlos Syndrome 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. Data was derived by merging RNA-seq data from dermal fibroblasts from patients with Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorder. Cells 2022 Dec 14;11(24):4040. doi:10.3390/cells11244040. Differentially expressed genes from the supplementary tables

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 disease network highlights the complex interplay of genes, proteins, and biological processes involved in the pathogenesis of Ehlers-Danlos syndrome and related conditions.

Here's a breakdown of the key points related to Ehlers-Danlos:
Direct Impact on Ehlers-Danlos:

• A decrease in SMAD3 leads to an increase in Ehlers-Danlos syndrome. This suggests that SMAD3 plays a crucial role in preventing or mitigating the development of Ehlers-Danlos.
• A decrease in NOTCH1 leads to an increase in Ehlers-Danlos syndrome. This indicates that NOTCH1 is also involved in regulating the development of Ehlers-Danlos.
• An increase in COL3A1 leads to an increase in Ehlers-Danlos syndrome. This highlights the importance of COL3A1 in the development of the disease, likely due to its role in collagen synthesis.
• An increase in TGFBR2 leads to an increase in Ehlers-Danlos syndrome. This suggests that TGFBR2, a receptor involved in transforming growth factor beta signaling, might contribute to the development of Ehlers-Danlos.

Indirect Impact on Ehlers-Danlos:

• The network also shows how changes in other genes and proteins can indirectly impact Ehlers-Danlos by influencing related processes like chronic inflammation, accumulation of neutrophils, and collagen synthesis. For example, a decrease in STK11 leads to an increase in the accumulation of neutrophils, which can contribute to inflammation and potentially exacerbate Ehlers-Danlos symptoms.

Overall, this network provides valuable insights into the molecular mechanisms underlying Ehlers-Danlos syndrome. Understanding these relationships can pave the way for developing targeted therapies aimed at preventing or mitigating the disease.