In:
NAR Genomics and Bioinformatics, Oxford University Press (OUP), Vol. 3, No. 4 ( 2021-10-04)
Abstract:
Cellular reprogramming is a promising technology to develop disease models and cell-based therapies. Identification of the key regulators defining the cell type specificity is pivotal to devising reprogramming cocktails for successful cell conversion but remains a great challenge. Here, we present a systems biology approach called Taiji-reprogram to efficiently uncover transcription factor (TF) combinations for conversion between 154 diverse cell types or tissues. This method integrates the transcriptomic and epigenomic data to construct cell-type specific genetic networks and assess the global importance of TFs in the network. Comparative analysis across cell types revealed TFs that are specifically important in a particular cell type and often tightly associated with cell-type specific functions. A systematic search of TFs with differential importance in the source and target cell types uncovered TF combinations for desired cell conversion. We have shown that Taiji-reprogram outperformed the existing methods to better recover the TFs in the experimentally validated reprogramming cocktails. This work not only provides a comprehensive catalog of TFs defining cell specialization but also suggests TF combinations for direct cell conversion.
Type of Medium:
Online Resource
ISSN:
2631-9268
DOI:
10.1093/nargab/lqab100
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2021
detail.hit.zdb_id:
3009998-5
