LocPL

LocPL integrates protein localization data into protein-protein interaction (PPI) networks to improve reconstruction of signaling pathways and produce biologically plausible models of signal transduction.


Key Features:

  • Integration of Protein Localization: Incorporates protein localization information to constrain pathway reconstructions within appropriate cellular compartments.
  • Compartment-aware Signaling Flow: Enforces consistency with known signaling flows (e.g., from membrane to nucleus) when selecting interactions.
  • Dynamic Programming Approach: Employs a dynamic programming algorithm that aligns protein localization with signal transduction pathways to maintain biological relevance.
  • Ambiguity Reduction in PPI Networks: Reduces ambiguities in PPI networks where multiple interactions have similar confidence scores by using localization constraints.
  • Assessment of Accuracy: Evaluates performance using both global and local definitions of accuracy.
  • Applicability to Multiple PPI Networks: Can be applied to different PPI networks to assess versatility and robustness of reconstructions.

Scientific Applications:

  • Signal Transduction Modeling: Reconstructs signaling pathways for systems-level analysis of cellular signal transduction.
  • Hypothesis Generation for Experiments: Produces more biologically plausible pathway models that facilitate generation of testable experimental hypotheses.
  • Comparative Compartmental Signaling Analysis: Enables study and comparison of signaling flow across different cellular compartments and settings.

Methodology:

Implements a dynamic programming framework that integrates protein localization data into PPI networks, enforces spatial constraints from cellular compartmentalization, and assesses reconstructions using global and local accuracy definitions.

Topics

Details

Tool Type:
web application
Added:
1/14/2020
Last Updated:
12/22/2020

Operations

Publications

Youssef I, Law J, Ritz A. Integrating protein localization with automated signaling pathway reconstruction. BMC Bioinformatics. 2019;20(S16). doi:10.1186/s12859-019-3077-x. PMID:31787091. PMCID:PMC6886211.