Quantifying Waddington's epigenetic landscape: a comparison of single-cell potency measures
2020-01
发表期刊BRIEFINGS IN BIOINFORMATICS (IF:6.8[JCR-2023],7.9[5-Year])
ISSN1467-5463
EISSN1477-4054
卷号21期号:1页码:248-261
发表状态已发表
DOI10.1093/bib/bby093
摘要

Motivation: Estimating differentiation potency of single cells is a task of great biological and clinical significance, as it may allow identification of normal and cancer stem cell phenotypes. However, very few single-cell potency models have been proposed, and their robustness and reliability across independent studies have not yet been fully assessed. Results: Using nine independent single-cell RNA-Seq experiments, we here compare four different single-cell potency models to each other, in their ability to discriminate cells that ought to differ in terms of differentiation potency. Two of the potency models approximate potency via network entropy measures that integrate the single-cell RNA-Seq profile of a cell with a protein interaction network. The comparison between the four models reveals that integration of RNA-Seq data with a protein interaction network dramatically improves the robustness and reliability of single-cell potency estimates. We demonstrate that underlying this robustness is a correlation relationship, according to which high differentiation potency is positively associated with overexpression of network hubs. We further show that overexpressed network hubs are strongly enriched for ribosomal mitochondrial proteins, suggesting that their mRNA levels may provide a universal marker of a cell's potency. Thus, this study provides novel systems-biological insight into cellular potency and may provide a foundation for improved models of differentiation potency with far-reaching implications for the discovery of novel stem cell or progenitor cell phenotypes.

关键词single-cell RNA-Seq entropy differentiation potency network Waddington
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收录类别SCIE
语种英语
WOS研究方向Biochemistry & Molecular Biology ; Mathematical & Computational Biology
WOS类目Biochemical Research Methods ; Mathematical & Computational Biology
WOS记录号WOS:000516610800019
出版者OXFORD UNIV PRESS
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/243343
专题生命科学与技术学院
生命科学与技术学院_特聘教授组_陈洛南组
通讯作者Teschendorff, Andrew E.; Chen, Luonan; Li, Tiejun
作者单位
1.Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China;
2.CAS MPG Partner Inst Computat Biol, Shanghai, Peoples R China;
3.UCL, London, England;
4.Chinese Acad Sci, Key Lab Syst Biol, Shanghai, Peoples R China;
5.Shanghai Inst Biol Sci, Shanghai, Peoples R China
6.School of Life Science and Technology, ShanghaiTech University, Shanghai 20121
通讯作者单位生命科学与技术学院
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Shi, Jifan,Teschendorff, Andrew E.,Chen, Weiyan,et al. Quantifying Waddington's epigenetic landscape: a comparison of single-cell potency measures[J]. BRIEFINGS IN BIOINFORMATICS,2020,21(1):248-261.
APA Shi, Jifan,Teschendorff, Andrew E.,Chen, Weiyan,Chen, Luonan,&Li, Tiejun.(2020).Quantifying Waddington's epigenetic landscape: a comparison of single-cell potency measures.BRIEFINGS IN BIOINFORMATICS,21(1),248-261.
MLA Shi, Jifan,et al."Quantifying Waddington's epigenetic landscape: a comparison of single-cell potency measures".BRIEFINGS IN BIOINFORMATICS 21.1(2020):248-261.
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