An integrative C. elegans protein-protein interaction network with reliability assessment based on a probabilistic...

Area of Science:

• Computational Biology
• Systems Biology
• Bioinformatics

Background:

• Protein-protein interactions (PPIs) are crucial for cellular functions, but comprehensive, weighted networks are lacking for model organisms like C. elegans.
• Existing PPI data requires robust methods for reliability assessment and network construction to facilitate downstream analyses like pathway inference.

Purpose of the Study:

• To construct an integrative, weighted protein-protein interaction (PPI) network for C. elegans.
• To develop and validate a novel probabilistic graphical model-based scoring method (RSPGM) for assessing PPI reliability.
• To demonstrate the utility of the weighted PPI network and RSPGM in biological pathway inference.

Main Methods:

• Integrated PPI data from seven databases to build a comprehensive C. elegans PPI network (12,951 interactions, 5039 proteins).
• Developed the Reliability Score based on a Probabilistic Graphical Model (RSPGM) using Bernoulli distribution to evaluate PPI confidence.
• Validated RSPGM against high-confidence yeast datasets and assessed the biological relevance of the constructed network using Gene Ontology, gene expression, and essentiality data.

Main Results:

• The RSPGM score provides a more accurate evaluation of PPIs compared to existing methods.
• The integrated C. elegans PPI network exhibits higher biological relevance than original datasets.
• The weighted network successfully inferred the interaction path of the canonical Wnt/β-catenin pathway, with validated components.

Conclusions:

• RSPGM is an effective method for evaluating PPI reliability and constructing high-quality interaction networks.
• The developed weighted PPI network for C. elegans is a valuable resource for systems biology research and signaling pathway analysis.
• The integrated network and RSPGM scores are accessible via an interactive website for further research.