Correlated gene modules uncovered by high-precision single-cell transcriptomics
Correlations in gene expression are used to infer functional and regulatory relationships between genes. However, correlations are often calculated across different cell types or perturbations, causing genes with unrelated functions to be correlated. Here, we demonstrate that correlated modules can be better captured by measuring correlations of steady-state gene expression fluctuations in single cells. We report a high-precision single-cell RNA-seq method called MALBAC-DT to measure the correlation between any pair of genes in a homogenous cell population. Using this method, we were able to identify numerous cell-type specific and functionally enriched correlated gene modules. We confirmed through knockdown that a module enriched for p53 signaling predicted p53 regulatory targets more accurately than a consensus of ChIP-seq studies and that steady-state correlations were predictive of transcriptome-wide response patterns to perturbations. This approach provides a powerful way to advance our functional understanding of the genome.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:119 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 119(2022), 51 vom: 20. Dez., Seite e2206938119 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chapman, Alec R [VerfasserIn] |
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| Links: |
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| Themen: |
Correlated gene modules |
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| Anmerkungen: |
Date Completed 14.12.2022 Date Revised 09.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.2206938119 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Correlations in gene expression are used to infer functional and regulatory relationships between genes. However, correlations are often calculated across different cell types or perturbations, causing genes with unrelated functions to be correlated. Here, we demonstrate that correlated modules can be better captured by measuring correlations of steady-state gene expression fluctuations in single cells. We report a high-precision single-cell RNA-seq method called MALBAC-DT to measure the correlation between any pair of genes in a homogenous cell population. Using this method, we were able to identify numerous cell-type specific and functionally enriched correlated gene modules. We confirmed through knockdown that a module enriched for p53 signaling predicted p53 regulatory targets more accurately than a consensus of ChIP-seq studies and that steady-state correlations were predictive of transcriptome-wide response patterns to perturbations. This approach provides a powerful way to advance our functional understanding of the genome | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Lee, David F |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Wenting |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Wenping |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Wenjie |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Xiaoliang Sunney |e verfasserin |4 aut | |
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