SDI

SDI quantifies the diversity of protein localization across subcellular compartments to assess gene essentiality using the Gene Ontology-Cellular Component Ontology (GO-CCO) and semantic similarity of GO terms.

Key Features:

• Subcellular Diversity Measurement: Quantifies how proteins encoded by genes are distributed among different subcellular compartments to provide a metric related to gene essentiality.
• GO-CCO semantic similarity: Employs semantic similarity measures of Gene Ontology-Cellular Component Ontology (GO-CCO) terms to compute the SDI.
• Correlation with gene essentiality metrics: SDI correlates with protein-protein interaction (PPI) network topology, dN/dS ratio, homologous gene number, expression levels, and tissue specificity.
• Predictive performance: Demonstrates predictive capability for human essential genes (AUC = 0.702) and drug target genes (AUC = 0.704).
• Drug target association: Higher SDI scores are associated with an increased likelihood of causing side effects when genes are targeted by drugs.

Scientific Applications:

• Gene essentiality studies: Provides insights into the functional importance of genes via the diversity of their protein localizations.
• Drug target identification and optimization: Aids in prioritizing and refining drug targets with consideration of side-effect risk based on SDI.
• Cross-species comparative analysis: Enables comparative studies of SDI scores across eight species for evolutionary and comparative genomics investigations.

Methodology:

SDI is calculated by computing semantic similarity between GO terms within the GO-CCO framework and deriving an index that reflects the distribution of gene products across cellular compartments.