Single cell Multiome

Introduction

Single-cell multiome is another exciting technological advance using which we can measure the transcriptome and epigenome from the same cell. While the quality of each modality is marginally lower than performing these experiments on separate cells, the ability to measure transcriptome + epigenome in the same cells provides an fantastic resolution for analysis and modeling. The 10X description is available here. Plate based technique, Share-seq is described here. An important thing to remember is that in mulitome-seq, nuclear RNA and not cellular RNA is measured.

Analysis

The analysis for the most part follows the same procedure for performing analysis of scRNA and scATAC separately with a few additions:

• Filtering cells: Cells are filtered based on RNA fragments, mitochondrial fractions and ATAC fraction of reads in peaks.
• ATAC analysis is performed using the subset cells from the RNA analysis
• Comparisons to check clustering and diffusion maps are consistent across the different data modalities.

Notebooks

We will use the 10X PBMC dataset as a case study for analysis notebooks

• RNA modality notebook is here
• ATAC modality notebook is here
• Comparative analysis notebook is here

Multi-sample analysis

To analyze multiple sample simultaneously, follow the RNA notebook here and the ArchR script here. ATAC modality notebook can be adopted from the single sample notebook.