Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer
Many recent efforts have been put into the association between expression heterogeneity and different cell types and states using single-cell RNA transcriptome analysis. There is only limited understanding of gene dosage effects for the genetic heterogeneity at the single-cell level. By focusing on...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/1424-8247/14/9/918 |
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| author | Yining Liu Min Zhao |
| author_facet | Yining Liu Min Zhao |
| author_sort | Yining Liu |
| collection | DOAJ |
| description | Many recent efforts have been put into the association between expression heterogeneity and different cell types and states using single-cell RNA transcriptome analysis. There is only limited understanding of gene dosage effects for the genetic heterogeneity at the single-cell level. By focusing on concordant copy number variation (CNV) and expression, we presented a computational framework to explore dosage effect for aggressive metastatic triple-negative breast cancer (TNBC) at the single-cell level. In practice, we collected CNV and single-cell expression data from the same patients with independent technologies. By focusing on 47,198 consistent copy number gains (CNG) and gene up-regulation from 1145 single cells, ribosome proteins with important roles in protein targeting were enriched. Independent validation in another metastatic TNBC dataset further prioritized signal recognition particle-dependent protein targeting as the top functional module. More interesting, the increased ribosome gene copies in TNBC may associate with their enhanced stemness and metastatic potential. Indeed, the prioritization of a well-upregulated functional module confirmed by high copy numbers at the single-cell level and contributing to patient survival may indicate the possibility of targeted therapy based on ribosome proteins for TNBC. |
| first_indexed | 2024-03-10T07:19:47Z |
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| language | English |
| last_indexed | 2024-03-10T07:19:47Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-e866634855bd4a82870f4431eba4943f2023-11-22T14:45:25ZengMDPI AGPharmaceuticals1424-82472021-09-0114991810.3390/ph14090918Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast CancerYining Liu0Min Zhao1The School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, ChinaSchool of Science, Technology and Engineering, University of the Sunshine Coast, Maroochydore, QLD 4558, AustraliaMany recent efforts have been put into the association between expression heterogeneity and different cell types and states using single-cell RNA transcriptome analysis. There is only limited understanding of gene dosage effects for the genetic heterogeneity at the single-cell level. By focusing on concordant copy number variation (CNV) and expression, we presented a computational framework to explore dosage effect for aggressive metastatic triple-negative breast cancer (TNBC) at the single-cell level. In practice, we collected CNV and single-cell expression data from the same patients with independent technologies. By focusing on 47,198 consistent copy number gains (CNG) and gene up-regulation from 1145 single cells, ribosome proteins with important roles in protein targeting were enriched. Independent validation in another metastatic TNBC dataset further prioritized signal recognition particle-dependent protein targeting as the top functional module. More interesting, the increased ribosome gene copies in TNBC may associate with their enhanced stemness and metastatic potential. Indeed, the prioritization of a well-upregulated functional module confirmed by high copy numbers at the single-cell level and contributing to patient survival may indicate the possibility of targeted therapy based on ribosome proteins for TNBC.https://www.mdpi.com/1424-8247/14/9/918single-cell RNA sequencingcopy number variationsignal recognition particledosage effectmetastatic triple-negative breast cancer |
| spellingShingle | Yining Liu Min Zhao Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer Pharmaceuticals single-cell RNA sequencing copy number variation signal recognition particle dosage effect metastatic triple-negative breast cancer |
| title | Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer |
| title_full | Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer |
| title_fullStr | Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer |
| title_full_unstemmed | Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer |
| title_short | Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer |
| title_sort | gene dosage analysis on the single cell transcriptomes linking cotranslational protein targeting to metastatic triple negative breast cancer |
| topic | single-cell RNA sequencing copy number variation signal recognition particle dosage effect metastatic triple-negative breast cancer |
| url | https://www.mdpi.com/1424-8247/14/9/918 |
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