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Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq [WES]

ABSTRACT: Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq [WES]

PROVIDER: PRJNA485428 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7666302_1.fastq.gz	Fastqsanger.gz
	SRR7666302_2.fastq.gz	Fastqsanger.gz
	SRR7666303_1.fastq.gz	Fastqsanger.gz
	SRR7666303_2.fastq.gz	Fastqsanger.gz
	SRR7666304_1.fastq.gz	Fastqsanger.gz

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Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq [WES]

Project description:Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conduct single-cell RNA- sequencing (scRNA-seq) of >1500 cells from six primary TNBC, together with whole exome sequencing (WES) for four of the tumors. Intercellular heterogeneity of gene expression programs within each tumor was variable and largely correlated with clonality of inferred genomic copy number changes, suggesting that genotype drives the gene expression phenotype of individual subpopulations. Clustering of gene expression profiles identified distinct subgroups of malignant cells shared by multiple tumors, including a single subpopulation associated with multiple signatures of treatment resistance and metastasis, and characterized functionally by activation of glycosphingolipid metabolism and associated innate immunity pathways. A novel signature defining this subpopulation was predictive of long-term outcomes for TNBC patients in a large patient cohort. Collectively, this analysis reveals the functional heterogeneity and its association with genomic evolution in TNBC, and uncovers unanticipated biological principles dictating poor outcomes in this disease.

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Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq

Project description:Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq

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Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq [RNA-Seq]

Project description:Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq [RNA-Seq]

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Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq [RNA-Seq]

Project description:Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conduct single-cell RNA- sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Intercellular heterogeneity of gene expression programs within each tumor was variable and largely correlated with clonality of inferred genomic copy number changes, suggesting that genotype drives the gene expression phenotype of individual subpopulations. Clustering of gene expression profiles identified distinct subgroups of malignant cells shared by multiple tumors, including a single subpopulation associated with multiple signatures of treatment resistance and metastasis, and characterized functionally by activation of glycosphingolipid metabolism and associated innate immunity pathways. A novel signature defining this subpopulation was predictive of long-term outcomes for TNBC patients in a large patient cohort. Collectively, this analysis reveals the functional heterogeneity and its association with genomic evolution in TNBC, and uncovers unanticipated biological principles dictating poor outcomes in this disease.

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Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq.

Project description:Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conducted single-cell RNA-sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Here, we show that intercellular heterogeneity of gene expression programs within each tumor is variable and largely correlates with clonality of inferred genomic copy number changes, suggesting that genotype drives the gene expression phenotype of individual subpopulations. Clustering of gene expression profiles identified distinct subgroups of malignant cells shared by multiple tumors, including a single subpopulation associated with multiple signatures of treatment resistance and metastasis, and characterized functionally by activation of glycosphingolipid metabolism and associated innate immunity pathways. A novel signature defining this subpopulation predicts long-term outcomes for TNBC patients in a large cohort. Collectively, this analysis reveals the functional heterogeneity and its association with genomic evolution in TNBC, and uncovers unanticipated biological principles dictating poor outcomes in this disease.

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Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq

Project description:This SuperSeries is composed of the SubSeries listed below.

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