scDecouple: decoupling cellular response from infected proportion bias in scCRISPR-seq.
Brief Bioinform
; 25(2)2024 Jan 22.
Article
em En
| MEDLINE
| ID: mdl-38324621
ABSTRACT
Single-cell clustered regularly interspaced short palindromic repeats-sequencing (scCRISPR-seq) is an emerging high-throughput CRISPR screening technology where the true cellular response to perturbation is coupled with infected proportion bias of guide RNAs (gRNAs) across different cell clusters. The mixing of these effects introduces noise into scCRISPR-seq data analysis and thus obstacles to relevant studies. We developed scDecouple to decouple true cellular response of perturbation from the influence of infected proportion bias. scDecouple first models the distribution of gene expression profiles in perturbed cells and then iteratively finds the maximum likelihood of cell cluster proportions as well as the cellular response for each gRNA. We demonstrated its performance in a series of simulation experiments. By applying scDecouple to real scCRISPR-seq data, we found that scDecouple enhances the identification of biologically perturbation-related genes. scDecouple can benefit scCRISPR-seq data analysis, especially in the case of heterogeneous samples or complex gRNA libraries.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ensaios de Triagem em Larga Escala
/
RNA Guia de Sistemas CRISPR-Cas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article