cardelino

cardelino infers clonal structures and assigns single cells to somatic clones from single-cell RNA sequencing (scRNA-seq) data by integrating bulk exome sequencing (exome-seq) clonal trees with sparse variant allele information to characterize phenotypic variation between clones.

Key Features:

• Clonal Tree Configuration Inference: Infers clonal tree configurations that map evolutionary relationships among cell clones using scRNA-seq and exome-seq data.
• Integration of Data Modalities: Integrates imperfect clonal trees derived from bulk exome-seq with sparse variant allele information obtained from scRNA-seq.
• Clone of Origin Identification: Assigns individual cells to their clone of origin based on variant allele evidence from scRNA-seq.
• Phenotypic Variation Characterization: Characterizes phenotypic variation between somatic clones using single-cell transcriptomic profiles.

Scientific Applications:

• Cancer Dataset Analysis: Applied to published cancer datasets to resolve clonal composition and relationships within tumors.
• Matched scRNA-seq and Exome-seq in Fibroblasts: Applied to matched scRNA-seq and exome-seq data from human dermal fibroblast lines to identify clone-specific expression patterns.
• Differential Expression and Pathway Enrichment: Identified hundreds of differentially expressed genes between cells from distinct somatic clones that were frequently enriched in cell cycle and proliferation pathways, informing somatic evolution in healthy skin.

Methodology:

Integrates imperfect clonal trees from bulk exome-seq with sparse variant allele information from scRNA-seq to infer clonal tree configurations and assign cells to clones.