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Mapping Bacterial Functional Networks and Pathways in Escherichia Coli using Synthetic Genetic Arrays
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Quantifying Gene Essentiality Based on the Context of Cellular Components.

Kaiwen Jia1, Yuan Zhou1, Qinghua Cui1

  • 1Department of Biomedical Informatics, Department of Physiology and Pathophysiology, Center for Noncoding RNA Medicine, MOE Key Lab of Cardiovascular Sciences, School of Basic Medical Sciences, Peking University, Beijing, China.

Frontiers in Genetics
|February 11, 2020
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Summary
This summary is machine-generated.

We developed a Subcellular Diversity Index (SDI) to measure gene essentiality based on protein localization. Higher SDI scores correlate with essential genes and can predict drug targets, aiding in side-effect reduction.

Keywords:
cellular componentsdrug targetgene characteristicgene essentialitylocalization diversity

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Area of Science:

  • Genomics
  • Bioinformatics
  • Systems Biology

Background:

  • Protein localization across subcellular compartments is a key gene characteristic.
  • Understanding protein localization diversity can offer insights into gene essentiality.

Purpose of the Study:

  • To introduce and validate a Subcellular Diversity Index (SDI) for measuring gene essentiality.
  • To assess SDI's correlation with existing gene essentiality measures and its predictive power for essential and drug target genes.
  • To explore the relationship between SDI, drug targets, and potential side effects.

Main Methods:

  • Calculated SDI using Gene Ontology-Cellular Component Ontology (GO-CCO) and semantic similarity of GO terms.
  • Correlated SDI with protein-protein interaction (PPI) network topology, dN/dS ratio, homologous gene number, expression level, and tissue specificity.
  • Evaluated SDI's performance in predicting human essential genes and drug target genes using AUC values.

Main Results:

  • SDI showed significant correlations with established gene essentiality measures.
  • SDI effectively predicted human essential genes (AUC = 0.702) and drug target genes (AUC = 0.704).
  • Higher SDI scores in drug targets were associated with increased potential for side effects.

Conclusions:

  • SDI is a valuable metric for assessing gene essentiality from a subcellular localization perspective.
  • SDI can aid in identifying novel drug targets and filtering candidates to minimize potential side effects.
  • An online database for SDI scores across species is available to facilitate research.