Seurat Analysis and UMAP Rendering of PDX in Combination Cytarabine and Venetoclax Therapies

R analysis of single cell gene-expression data derived from Bosc et al. “Mitochondrial determinants of response and resistance to venetoclax plus cytarabine duplet therapy in acute myeloid leukemia“.

Patient derived xenograph (PDX) modeling involves the transplantation of patient tissue samples to NGS immunodeficient mice in order to assess in vivo response to different experimental conditions in parallel. In Bosc, viable AML bone marrow cells from Toulouse University Hospital patients "TUH07" and "TUH69" had been xenographed to "PDX1" and "PDX2" respectively. Both PDX models were subjected to three treatments for eight days: venetoclax (VEN), cytarabine (AraC), and venetoclax and cytarabine (VEN+AraC) before sampling. The two PDX models were also sampled at the day of diagnosis without treatment to serve as control group (Ctl). Next generation sequencing of single cell gene expression was performed on each of the four experimental groups per the two PDXs to produce raw FASTQ reads. Gene expression data had been rendered from FASTQ reads using CellRanger software by 10x Genomics.

Here we present the quality control, principle component analysis, and t-SNE/UMAP dimensionality reduction performed using the Seurat 3.0 R package by Satija Lab. Gene expression data from individual PDX samples (1) and (2) were initially processed using files Seuratv3_PDX1.r and Seuratv3_PDX2.r respectively before their final integration and visualization using Seuratv3_PDX1_PDX2.r.