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. 2022 Aug 4;13:4534. doi: 10.1038/s41467-022-31830-2

Fig. 4. Between-patient variation dominates in vivo gene fitness.

Fig. 4

a Two examples comparing guide fitness measurements (median, bars = 95% CI) between transplants of the same TNBC PDX material into subcutaneous (SQ) or mammary fat pad (MFP) sites. Red, blue: guide outliers between the two conditions satisfying criteria related to both fitness and rank difference, and with more than one outlying guide targeting the same gene (Supplementary Methods). Orange: non-targeting control guides, shown in fitness plots. (PDX tumours: C2271 n = 2, 1 for MFP, SQ; C1368 n = 2, 1 for MFP, SQ.) b Two examples comparing guide fitness measurements (median, bars = 95% CI) between transplants of an early and late passage from the same TNBC PDX line. Criteria for identifying outlying guides as in a. (PDX tumours: C2271 n = 3, 3 for early, late; C1368 n = 3, 2 for early, late.) c Two examples comparing guide fitness measurements (median, bars = 95% CI) between transplants of PDX lines from different patients. Criteria for identifying outlying guides as in a. (PDX tumours: n = 3, 3, 4, 3 for C2271, C1368, C2191, C0331.) d Left panel shows the percentage of guides satisfying outlying criteria for all pairs of datasets that represent biological replicates; site comparisions; early vs late passage comparisons; and comparisions between different patient PDX lines. Right panel shows the Spearman rank correlation of guide fitness for the same sets of comparisons. Bars display mean + /− SEM (p < 0.001 two-sided for all pairs, except for Replicate-Site, in both panels). Both metrics show greatest dissimilarity in fitness for comparisons involving different patients. (n = 249, 30, 496 and 4624 pairwise comparisons for replicate, site, passage, patient). Source data are provided as Source Data files.