The extracellular matrix phenome across species

Area of Science:

• Genomics and Systems Biology
• Extracellular Matrix Biology
• Comparative Phenomics

Background:

• Extracellular matrices (ECMs) are crucial for cellular and organismal functions.
• Genome-wide and phenome-wide association studies (GWAS/PheWAS) link genetic variants to phenotypes.
• The full spectrum of phenotypes associated with ECM genes remains largely undefined.

Purpose of the Study:

• To define the extracellular matrix phenome across multiple species.
• To identify key ECM genes and their associated phenotypes.
• To construct interaction networks for predicting novel genotype-to-phenotype relationships.

Main Methods:

• Analysis of over two million genotype-to-phenotype relationships.
• Utilized defined matrisomes from humans, mice, zebrafish, *Drosophila*, and *C. elegans*.
• Constructed interaction networks from identified genotype-to-phenotype relationships.

Main Results:

• The ECM phenome constitutes 3-10% of the total phenome across species.
• Human ECM genes like *COL1A1*, *COL2A1*, and *FBN1* are linked to over 150 phenotypes each.
• Genes such as *MSTN*, *CTSD*, *LAMB2*, *HSPG2*, and *COL11A2* show extensive cross-species phenotypic associations.
• Interaction networks revealed connections between orthologous phenotypes and identified novel phenotype associations.

Conclusions:

• The study successfully defined the extracellular matrix phenome, highlighting its significant contribution to organismal phenotypes.
• Identified key genes and pathways driving ECM-related phenotypes across diverse species.
• Developed interaction networks that serve as a framework for predicting unassessed phenotypes and guiding the selection of appropriate model systems for human disease research.