Abstract

BackgroundSingle-cell sequencing technologies provide unprecedented opportunities to deconvolve the genomic, transcriptomic or epigenomic heterogeneity of complex biological systems. Its application in samples from xenografts of patient-derived biopsies (PDX), however, is limited by the presence of cells originating from both the host and the graft in the analysed samples; in fact, in the bioinformatics workflows it is still a challenge discriminating between host and graft sequence reads obtained in a single-cell experiment.ResultsWe have developed XenoCell, the first stand-alone pre-processing tool that performs fast and reliable classification of host and graft cellular barcodes from single-cell sequencing experiments. We show its application on a mixed species 50:50 cell line experiment from 10× Genomics platform, and on a publicly available PDX dataset obtained by Drop-Seq.ConclusionsXenoCell accurately dissects sequence reads from any host and graft combination of species as well as from a broad range of single-cell experiments and platforms. It is open source and available at https://gitlab.com/XenoCell/XenoCell.

Highlights

  • Single-cell sequencing technologies provide unprecedented opportunities to deconvolve the genomic, transcriptomic or epigenomic heterogeneity of complex biological systems

  • The input to XenoCell consists of paired reads from droplet-based single-cell sequencing experiments of xenograft samples from any proportion of host/graft species

  • To assess the performance of XenoCell, we applied it to a publicly available single-cell gene expression dataset released by 10× Genomics, which is composed of a 1:1 mixture of fresh frozen human (HEK293T) and mouse (NIH3T3) cells

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Summary

Results

We have developed XenoCell, the first stand-alone pre-processing tool that performs fast and reliable classification of host and graft cellular barcodes from single-cell sequencing experiments. We show its application on a mixed species 50:50 cell line experiment from 10× Genomics platform, and on a publicly available PDX dataset obtained by Drop-Seq

Conclusions
Background
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