Fig. 5: Inter-patient differences dominates the variability in fitness in PDXs.
From: Accurate determination of CRISPR-mediated gene fitness in transplantable tumours
a Range of gene fitness for 15 PDX lines. Upper panel: circles show the median fitness for all guides targeting a gene in all experiments carried out with each PDX line (n = 135 PDX tumours total). Points are alpha-weighted by the standard error of the mean of fitness values for that guide/PDX line (higher standard error points more transparent). ctl and ctl_t indicate non-targeting controls and non-gene targeting controls respectively. Middle panel: percentage of Cancer DepMap breast cancer cell lines (n = 25) reported with in vitro CRISPR-assayed essentiality for the gene. Lower panel: difference between the gene fitness rank order in PDX lines in vivo and DepMap breast cell lines in vitro (of n = 56 genes). b Relationship between guide fitness (median, bars = 95% CI) and transcript expression, shown for 12 guides in biological replicate series from 16 PDX series (n = 61 PDX tumours total). Transcript expressions are from RNAseq on a tumour from the same PDX line as the fitness measurements. Statistics shown are regression r squared and the p-value testing for zero slope coefficient (highlighted where p < 0.05, two-sided significant within panel: known single-gene breast cancer biomarkers ESR1 and ERBB2; also MDM2). c Relationship between guide fitness (median, bars = 95% CI) and local copy number, shown for 12 guides in biological replicate series from 16 PDX series (n = 61 PDX tumours total). Copy number is derived using TITAN, on WGS from a tumour from the same PDX line as the fitness measurements. Regression statistics as in b (highlighted where p < 0.05: APH1A and MDM2). Source data are provided as Source Data files.
