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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472593/ https://www.ncbi.nlm.nih.gov/pubmed/34577617 http://dx.doi.org/10.3390/ph14090918 |
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author | Liu, Yining Zhao, Min |
author_facet | Liu, Yining Zhao, Min |
author_sort | Liu, Yining |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8472593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84725932021-09-28 Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer Liu, Yining Zhao, Min Pharmaceuticals (Basel) Article 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. MDPI 2021-09-10 /pmc/articles/PMC8472593/ /pubmed/34577617 http://dx.doi.org/10.3390/ph14090918 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Liu, Yining Zhao, Min Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to 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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472593/ https://www.ncbi.nlm.nih.gov/pubmed/34577617 http://dx.doi.org/10.3390/ph14090918 |
work_keys_str_mv | AT liuyining genedosageanalysisonthesinglecelltranscriptomeslinkingcotranslationalproteintargetingtometastatictriplenegativebreastcancer AT zhaomin genedosageanalysisonthesinglecelltranscriptomeslinkingcotranslationalproteintargetingtometastatictriplenegativebreastcancer |