sciCNV: high-throughput paired profiling of transcriptomes and DNA copy number variations at single-cell resolution.
Brief Bioinform
; 23(1)2022 01 17.
Article
en En
| MEDLINE
| ID: mdl-34655292
ABSTRACT
Chromosome copy number variations (CNVs) are a near-universal feature of cancer; however, their individual effects on cellular function are often incompletely understood. Single-cell ribonucleic acid (RNA) sequencing (scRNA-seq) might be leveraged to reveal the function of intra-clonal CNVs; however, it cannot directly link cellular gene expression to CNVs. Here, we report a high-throughput scRNA-seq analysis pipeline that provides paired CNV profiles and transcriptomes for single cells, enabling exploration of the effects of CNVs on cellular programs. RTAM1 and -2 normalization methods are described, and are shown to improve transcriptome alignment between cells, increasing the sensitivity of scRNA-seq for CNV detection. We also report single-cell inferred chromosomal copy number variation (sciCNV), a tool for inferring single-cell CNVs from scRNA-seq at 19-46 Mb resolution. Comparison of sciCNV with existing RNA-based CNV methods reveals useful advances in sensitivity and specificity. Using sciCNV, we demonstrate that scRNA-seq can be used to examine the cellular effects of cancer CNVs. As an example, sciCNV is used to identify subclonal multiple myeloma (MM) cells with +8q22-24. Studies of the gene expression of intra-clonal MM cells with and without the CNV demonstrate that +8q22-24 upregulates MYC and MYC-target genes, messenger RNA processing and protein synthesis, which is consistent with established models. In conclusion, we provide new tools for scRNA-seq that enable paired profiling of the CNVs and transcriptomes of single cells, facilitating rapid and accurate deconstruction of the effects of cancer CNVs on cellular programming.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Variaciones en el Número de Copia de ADN
/
Transcriptoma
Idioma:
En
Revista:
Brief Bioinform
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Canadá