Nature - USA (2020-01-16)

(Antfer) #1

Extended Data Fig. 3 | KR AS(G12C)-dependent transcriptional output score
in 10,177 lung cancer cells. a, The distribution of KR AS(G12C)-specific gene-
expression output score across single cells in the three tumour models under
study. The arrows denote cohorts of cells with high output despite treatment.
b, Density plots showing the effect of G12Ci treatment on the KR AS(G12C)
output score (n = 2, 565 single cells from 0 h, n = 3,259 single cells from 4 h,
n = 1,006 single cells from 24 h and n = 3,347 single cells from 72 h). At 72 h the
cells assume an asymmetric distribution, suggesting that a subpopulation of


KR AS(G12C) cells has adapted to treatment by reactivating KR AS(G12C)-
dependent output (arrow). c, The KR AS(G12C) output score as a function of
pseudotime (which was adjusted to allow comparisons between trajectories).
The trend line was derived by fitting a spline to the G12C output score for each
cell (n = 4,759 single cells in path 1, n = 8,653 single cells in path 2 and
n = 4,050 single cells in path 3). d, e, The indicated variables are plotted for each
cell in a two-dimensional t-SNE (d) or diffusion component (e) space. For
simplicity, only the key clusters delineating each trajectory are shown in e.
Free download pdf