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Finding novel molecular connections between developmental processes and disease.

Jisoo Park1, Heather C Wick1, Daniel E Kee1

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This study introduces a novel method to link human development gene sets with diseases, uncovering unexpected molecular connections. The findings offer new insights into health risks across the lifespan and potential disease origins.

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Area of Science:

  • Genomics
  • Developmental Biology
  • Computational Biology

Background:

  • Identifying molecular links between development and disease is crucial for understanding lifelong health risks.
  • Existing methods face limitations due to incomplete gene-disease association data.

Purpose of the Study:

  • To develop and apply a new computational approach for identifying significant connections between gene sets and disease genes.
  • To explore these connections within human developmental gene sets.
  • To generate novel hypotheses regarding disease pathogenesis and etiology.

Main Methods:

  • Developed a novel approach pooling genes within disease subtrees in the MeSH taxonomy to enhance accuracy.
  • Assessed statistical significance using permutation testing.
  • Created a web-based visualization tool for exploring gene-disease connections.

Main Results:

  • Identified expected links between tissue-specific development and related diseases, as well as developmental disorders and cancers.
  • Discovered novel connections, including dementia with bone development, polycystic ovary syndrome with cardiovascular development, and retinopathy of prematurity with lung development.
  • Provided evidence for TGFB's role in polycystic ovary syndrome and suggested VEGF and NFKB pathways in retinopathy of prematurity and bronchopulmonary dysplasia.

Conclusions:

  • The new approach effectively identifies significant gene-disease associations, improving upon existing methods.
  • The findings reveal both expected and novel molecular links between developmental processes and various diseases.
  • This work offers new hypotheses for disease mechanisms and highlights the interconnectedness of development and disease throughout life.