Cell fate conversion prediction by group sparse optimization method utilizing single-cell and bulk OMICs data

Jing Qin, Yaohua Hu, Jen Chih Yao, Ricky Wai Tak Leung, Yongqiang Zhou, Yiming Qin, Junwen Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Cell fate conversion by overexpressing defined factors is a powerful tool in regenerative medicine. However, identifying key factors for cell fate conversion requires laborious experimental efforts; thus, many of such conversions have not been achieved yet. Nevertheless, cell fate conversions found in many published studies were incomplete as the expression of important gene sets could not be manipulated thoroughly. Therefore, the identification of master transcription factors for complete and efficient conversion is crucial to render this technology more applicable clinically. In the past decade, systematic analyses on various single-cell and bulk OMICs data have uncovered numerous gene regulatory mechanisms, and made it possible to predict master gene regulators during cell fate conversion. By virtue of the sparse structure of master transcription factors and the group structure of their simultaneous regulatory effects on the cell fate conversion process, this study introduces a novel computational method predicting master transcription factors based on group sparse optimization technique integrating data from multi-OMICs levels, which can be applicable to both single-cell and bulk OMICs data with a high tolerance of data sparsity. When it is compared with current prediction methods by cross-referencing published and validated master transcription factors, it possesses superior performance. In short, this method facilitates fast identification of key regulators, give raise to the possibility of higher successful conversion rate and in the hope of reducing experimental cost.

Original languageEnglish (US)
JournalBriefings in bioinformatics
Volume22
Issue number6
DOIs
StatePublished - Nov 5 2021

Keywords

  • cell fate conversion
  • gene regulatory network
  • group sparse optimization
  • integrative OMICs
  • master transcription factor
  • single-cell genomics

ASJC Scopus subject areas

  • Information Systems
  • Molecular Biology

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