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Performance assessment of sample-specific network control methods for bulk and single-cell biological data analysis.

Wei-Feng Guo1,2, Xiangtian Yu3, Qian-Qian Shi4

  • 1School of Electrical Engineering, Zhengzhou University, Zhengzhou, China.

Plos Computational Biology
|May 6, 2021
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Summary

This study benchmarks 16 sample-specific network control (SSC) workflows. Cell-Specific Network construction (CSN) and Single-Sample Network (SSN) methods combined with undirected network control are recommended for biological network analysis.

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Area of Science:

  • Systems biology
  • Network science
  • Bioinformatics

Background:

  • Sample-specific network construction and control methods are crucial for identifying driver nodes in biological systems.
  • Existing methods lack comprehensive performance evaluation, hindering optimal application in Sample-Specific network Control (SSC) analysis.

Purpose of the Study:

  • To conduct a comprehensive performance assessment of 16 state-of-the-art SSC analysis workflows.
  • To identify optimal combinations of network construction and control methods for biological network analysis.
  • To provide benchmarked workflows and recommendations for SSC analysis.

Main Methods:

  • Evaluated 16 SSC analysis workflows, combining 4 sample-specific network reconstruction methods (including Cell-Specific Network construction (CSN) and Single-Sample Network (SSN)) with 4 structural control methods.
  • Utilized simulation evaluation on biological networks, personalized driver gene prioritization on TCGA cancer datasets, and cell marker identification on single-cell RNA-seq data.

Main Results:

  • The performance of network control methods is highly dependent on the upstream sample-specific network construction method.
  • Cell-Specific Network construction (CSN) and Single-Sample Network (SSN) methods are identified as preferred network construction approaches.
  • Undirected network-based control methods demonstrated higher effectiveness compared to directed methods post-network construction.

Conclusions:

  • Recommends CSN and SSN methods coupled with undirected network control for robust SSC analysis.
  • Provides a benchmarked evaluation pipeline and data freely available for the research community.
  • Highlights the importance of selecting appropriate upstream methods for effective biological network control.