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An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
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Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
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A Knowledge Graph Approach to Elucidate the Role of Organellar Pathways in Disease via Biomedical Reports
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HPOFiller: identifying missing protein-phenotype associations by graph convolutional network.

Lizhi Liu1, Hiroshi Mamitsuka2,3, Shanfeng Zhu4,5,6,7,8

  • 1School of Computer Science, Fudan University, Shanghai 200433, China.

Bioinformatics (Oxford, England)
|April 6, 2021
PubMed
Summary
This summary is machine-generated.

HPOFiller, a novel graph convolutional network approach, accurately predicts missing human protein-phenotype associations. This method enhances disease gene discovery by improving Human Phenotype Ontology annotations.

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Area of Science:

  • Genomics
  • Bioinformatics
  • Computational Biology

Background:

  • Understanding human protein-phenotype relationships is crucial for disease research.
  • The Human Phenotype Ontology (HPO) standardizes phenotype abnormalities but has incomplete protein annotations.
  • Identifying missing protein-phenotype associations is vital for advancing disease diagnosis and treatment.

Purpose of the Study:

  • To develop an accurate computational method for predicting missing protein-phenotype associations.
  • To leverage network structures and graph convolutional networks for improved Human Phenotype Ontology annotation.
  • To identify novel disease-gene associations through enhanced protein-phenotype data.

Main Methods:

  • Proposed HPOFiller, a graph convolutional network (GCN)-based approach.
  • Utilized S-GCN on protein-protein interaction and HPO semantic similarity networks.
  • Employed Bi-GCN on the protein-phenotype bipartite graph for message passing.
  • Repeatedly applied GCN modules to refine protein and phenotype embeddings.

Main Results:

  • HPOFiller significantly outperformed existing state-of-the-art methods in predicting missing HPO annotations.
  • Stringent cross-validation and temporal validation confirmed the model's robustness.
  • Ablation studies indicated batch normalization as a key contributor to performance.
  • High-ranking predictions were supported by existing literature evidence.

Conclusions:

  • HPOFiller effectively predicts missing protein-phenotype associations, enhancing the Human Phenotype Ontology.
  • The method successfully identifies potential novel disease-gene associations, offering insights into genetic disorders.
  • This approach provides a valuable tool for disease gene discovery and understanding genetic causes of human disorders.