a, Dot plots showing the distribution of
MYCN-nonamplified tumors (n = 400) within each of the
clusters based on ranked M-A scores. Tumors from the upper (high M-A) and
lower (low M-A) M-A score quartiles are shown (n = 200 tumors;
P = 0.0011 for C3). Statistical significance assessed
by the two-tailed Fisher’s exact test. b, UMAP
visualization of the distribution of adrenergic, mesenchymal, and M-A scores
among the three tumor clusters derived from 394 NBs in the GSE120572
dataset. Color bar represents normalized z-scores. Values <2.5 and
>2.5 were set to −2.5 and +2.5, respectively, to reduce the
effects of extreme outliers. c, Left, Heat map
of the indicated immune cell signatures in
MYCN-nonamplified tumors (n = 401), ranked by increasing
M-A scores. Log2 gene expression values were z-score transformed
for heat map visualization. Right, violin plots comparing
the quantitative scores of the indicated immune cell signatures in 100
tumors each from the upper (mesenchymal) and lower (adrenergic) quartiles of
the tumor M-A scores using the two-sided K-S test. Box plots within the
violin plots are defined by center lines (medians), box limits
(25th and 75th percentiles) and whiskers (minima
and maxima; 1.5X the interquartile range). d, e, Heat maps depicting IA (d)
and IE (e) signatures in MYCN-nonamplified tumors, ranked
by increasing M-A score. Log2 gene expression values were z-score
transformed for visualization. Violin plots comparing the distribution of IA
(d) and IE (e) signatures in 100 tumors each from upper (mesenchymal) and
lower (adrenergic) quartiles of the tumor M-A scores are shown next to the
heat maps. Significance determined by the two-sided K-S test. Box plots
within the violin plots are defined as in (c). f, Bar diagram
comparing the CIBERSORT-estimated fractional content of the indicated
tumor-infiltrating leukocytes between MYCN-nonamplified
adrenergic and mesenchymal tumors. Adrenergic and mesenchymal tumors were
assigned as in (c). Data represent the mean, n = 100 tumors,
P determined by the two-tailed Welch’s
t-test.