# Inferring clonal somatic mutations directed by X chromosome inactivation status in single cells

## TL;DR

This paper introduces a method to better understand cell clones in human tissues by using X chromosome inactivation in female cells.

## Contribution

The novel approach uses X chromosome inactivation to improve the detection of clonal mutations in single cells.

## Key findings

- X chromosome inactivation helps identify informative clonal mutations in female cells.
- The method reveals distinct clonal structures in T cells, including gamma-delta T cells.
- This approach can clarify clonal dynamics in human tissues previously obscured by non-informative mutations.

## Abstract

Analysis of clonal dynamics in human tissues is enabled by somatic genetic variation. Here, we show that analysis of mitochondrial mutations in single cells is dramatically improved in females when using X chromosome inactivation to select informative clonal mutations. Applying this strategy to human peripheral mononuclear blood cells reveals clonal structures within T cells that otherwise are blurred by non-informative mutations, including the separation of gamma-delta T cells, suggesting this approach can be used to decipher clonal dynamics of cells in human tissues.

The online version contains supplementary material available at 10.1186/s13059-024-03360-1.