Decoding transcriptional regulation via a human gene expression predictor

Yuzhou Wang; Yu Zhang; Ning Yu; Bingyan Li; Jiazhen Gong; Yide Mei; Jianqiang Bao; Shisong Ma

doi:10.1016/j.jgg.2023.01.006

Volume 50 Issue 5

May 2023

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Article Navigation > Journal of Genetics and Genomics > 2023 > 50(5): 305-317

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Decoding transcriptional regulation via a human gene expression predictor

doi: 10.1016/j.jgg.2023.01.006

a. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230027, China;
b. MOE Key Laboratory for Cellular Dynamics, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Innovation Academy for Seed Design, Chinese Academy of Sciences, Hefei, Anhui 230027, China;
c. School of Data Science, University of Science and Technology of China, Hefei, Anhui 230027, China

Funds:

The authors thank the USTC Supercomputing Center and USTC School of Life Sciences Bioinformatics Center for providing the computing resources. This work was supported by grants from the National Natural Science Foundation of China (31770268), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA24010303), the Fundamental Research Funds for the Central Universities (WK2070000091), and University of Science and Technology of China (Start-up fund to S.M.).

Received Date: 2022-09-02
Accepted Date: 2023-01-10
Rev Recd Date: 2023-01-04
Publish Date: 2023-01-21

Abstract

Abstract

Transcription factors (TFs) regulate cellular activities by controlling gene expression, but a predictive model describing how TFs quantitatively modulate human transcriptomes is lacking. We construct a universal human gene expression predictor named EXPLICIT-Human and utilize it to decode transcriptional regulation. Using the expression of 1613 TFs, the predictor reconstitutes highly accurate transcriptomes for samples derived from a wide range of tissues and conditions. The broad applicability of the predictor indicates that it recapitulates the quantitative relationships between TFs and target genes ubiquitous across tissues. Significant interacting TF-target gene pairs are extracted from the predictor and enable downstream inference of TF regulators for diverse pathways involved in development, immunity, metabolism, and stress response. A detailed analysis of the hematopoiesis process reveals an atlas of key TFs regulating the development of different hematopoietic cell lineages, and a portion of these TFs are conserved between humans and mice. The results demonstrate that our method is capable of delineating the TFs responsible for fate determination. Compared to other existing tools, EXPLICIT-Human shows a better performance in recovering the correct TF regulators.
- Gene expression predictor,
- Gene regulatory network,
- Graphical Gaussian model,
- Gene module,
- Human,
- Mouse

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References(73)

References

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