Genome Biology (Jan 2020)

DENDRO: genetic heterogeneity profiling and subclone detection by single-cell RNA sequencing

  • Zilu Zhou,
  • Bihui Xu,
  • Andy Minn,
  • Nancy R. Zhang

DOI
https://doi.org/10.1186/s13059-019-1922-x
Journal volume & issue
Vol. 21, no. 1
pp. 1 – 15

Abstract

Read online

Abstract Although scRNA-seq is now ubiquitously adopted in studies of intratumor heterogeneity, detection of somatic mutations and inference of clonal membership from scRNA-seq is currently unreliable. We propose DENDRO, an analysis method for scRNA-seq data that clusters single cells into genetically distinct subclones and reconstructs the phylogenetic tree relating the subclones. DENDRO utilizes transcribed point mutations and accounts for technical noise and expression stochasticity. We benchmark DENDRO and demonstrate its application on simulation data and real data from three cancer types. In particular, on a mouse melanoma model in response to immunotherapy, DENDRO delineates the role of neoantigens in treatment response.

Keywords