Structural Changes in Gene Ontology Reveal Modular and Complex Representations of Biological Function.

Area of Science:

• Bioinformatics
• Computational Biology
• Ontology Engineering

Background:

• The Gene Ontology (GO) is a foundational resource for biological knowledge representation.
• Its dynamic evolution and internal structure are often overlooked in computational analyses.
• Understanding GO's changes is crucial for accurate biological data interpretation.

Purpose of the Study:

• To analyze 15 years of Gene Ontology evolution using network-based methods.
• To investigate the impact of curator-driven restructuring on GO's internal organization.
• To assess the implications of GO's evolution for computational biology and data reproducibility.

Main Methods:

• Network-based analysis of Gene Ontology structure over 15 years.
• Examination of specific restructuring events, particularly the 2019 Cellular Component branch reorganization.
• Comparison of GO's modularization with emerging semantic frameworks.

Main Results:

• Gene Ontology evolution is characterized by both incremental growth and significant curator-driven restructurings.
• A major 2019 reorganization of the Cellular Component branch modularized terms into anatomical entities and protein complexes.
• This restructuring impacts similarity metrics and aligns GO with multi-layer semantic network frameworks.

Conclusions:

• Gene Ontology should be treated as a dynamic, multi-layer semantic network, not a static resource.
• Version-aware and multi-layer models are essential for ensuring reproducibility and interpretability in computational analyses.
• Understanding GO's evolution is key to accurately representing biological function across various dimensions.