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Taiji-reprogram: a framework to uncover cell-type specific regulators and predict cellular reprogramming cocktails.
Jun Wang1, Cong Liu1, Yue Chen1
1Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0359, USA.
NAR Genomics and Bioinformatics
|November 11, 2021
Summary
This study introduces Taiji-reprogram, a systems biology method to identify transcription factor (TF) combinations for cellular reprogramming. It efficiently uncovers key TFs for converting between diverse cell types, advancing disease modeling and cell therapies.
Area of Science:
- Systems biology
- Genomics
- Cellular reprogramming
Background:
- Cellular reprogramming holds promise for disease modeling and regenerative medicine.
- Identifying key transcription factors (TFs) is crucial but challenging for efficient cell conversion.
Purpose of the Study:
- To develop an efficient systems biology approach, Taiji-reprogram, for uncovering TF combinations for cell conversion.
- To create a comprehensive catalog of TFs defining cell specialization across diverse cell types.
Main Methods:
- Integration of transcriptomic and epigenomic data to build cell-type specific genetic networks.
- Assessment of TF global importance within these networks.
- Systematic search for TFs with differential importance between source and target cell types.
Main Results:
- Taiji-reprogram successfully identified TF combinations for converting between 154 cell types.
- Comparative analysis revealed cell-type specific TFs linked to specialized functions.
- The method outperformed existing approaches in recovering known reprogramming factors.
Conclusions:
- Taiji-reprogram provides an efficient strategy for discovering TF combinations for direct cell conversion.
- This work offers valuable insights into the genetic regulators of cell specialization.
- The findings facilitate the development of novel cell-based therapies and disease models.
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