Numbat-multiome

Numbat-multiome extends copy number variation inference to integrate single-cell RNA sequencing and single-cell Assay of Transposase-Accessible Chromatin sequencing data through a unified binning strategy based on common genomic coordinates.

Key Features:

• Multi-modal CNV inference: Performs copy number variation inference from scRNA-seq and scATAC-seq data either separately or in an integrated manner.
• Four running modes: Supports RNA gene, RNA bin, ATAC bin, and Combined bin modes for flexible analysis.
• Unified genomic coordinate system: Uses a binning strategy that relies on common genomic coordinates across modalities to unify data from different assays.
• Clonal evolution tracking: Enables tracking of clonal evolution in serial samples and identification of rare subclones.
• Subclonal epigenomic integration: Allows integration of epigenomic profiles at the subclonal level.

Scientific Applications:

• Cancer genomics: Infers copy number variations in tumors with dynamic expression patterns and copy number heterogeneity, including early-stage multiple myeloma and Richter's syndrome arising from chronic lymphocytic leukemia.
• Clonal evolution studies: Tracks stepwise genetic and epigenetic changes underlying cancer phenotypic shifts through serial sample analysis.
• Subclone identification: Identifies rare subclones to enable subclonal-level epigenomic profiling.
• Validation benchmarking: Performance validated against whole-genome sequencing with median F1 greater than 0.9 across different CNV event types.

Methodology:

Numbat-multiome extends the Numbat algorithm through a binning strategy that relies on a common genomic coordinate system across scRNA-seq and scATAC-seq modalities.