Post on 08-Nov-2020
www.sciencetranslationalmedicine.org/cgi/content/full/7/303/303ra139/DC1
Supplementary Materials for
Magnetic resonance image features identify glioblastoma phenotypic
subtypes with distinct molecular pathway activities
Haruka Itakura, Achal S. Achrol, Lex A. Mitchell, Joshua J. Loya, Tiffany Liu,
Erick M. Westbroek, Abdullah H. Feroze, Scott Rodriguez, Sebastian Echegaray,
Tej D. Azad, Kristen W. Yeom, Sandy Napel, Daniel L. Rubin, Steven D. Chang,
Griffith R. Harsh IV, Olivier Gevaert*
*Corresponding author. E-mail: olivier.gevaert@stanford.edu
Published 2 September 2015, Sci. Transl. Med. 7, 303ra139 (2015)
DOI: 10.1126/scitranslmed.aaa7582
The PDF file includes:
Methods
Fig. S1. Relative contributions of the top 24 imaging features in characterizing
each of the clusters.
Table S1. Clinical characteristics of the Stanford cohort before and after selection
of the development cohort.
Table S2. Clinical characteristics of the TCGA cohort before and after selection
of the validation cohort.
Table S3. All 2D and multislice 2D quantitative MR image features used for
analysis.
Table S4. Two-dimensional and multislice 2D quantitative MR image features
significantly associated with each cluster.
Table S5. Cluster assignment by subjects in the development cohort with and
without midline-crossing lesions.
Table S6. Regulatory signaling pathways significantly associated with each
cluster.
References (45–47)
SUPPLEMENTARY METHODS
Two-dimensional feature representations
To represent 2D features, we computed quantitative image features from the largest slice of
the tumor volume. To represent multislice 2D features, we aggregated 2D features from all
slices within the three-dimensional tumor volume. The quantitative imaging feature
extraction pipeline thus generated separate 2D and multislice 2D features for each patient.
For each subject in each cohort, this generated a feature vector of 193 2D, and 195
multislice 2D quantitative image features, resulting in a total of 388 features (table S3).
Validation of clusters
To validate the reproducibility of the clusters derived from consensus clustering in the
development cohort, we used the IGP analysis to demonstrate the existence of these clusters
in the validation cohort. IGP, which measures the proportion of samples in the group whose
nearest neighbor is also classified to the same group, validated the reproducibility and
robustness of the generated clusters by quantifying how well centroids from the
development cohort predicted test set co-memberships (24).
Statistical significance in IGP denotes low probabilities that the clusters originated
from a null distribution, in which centroids are placed randomly in the data and,
consequently, result in low quality clusters. The p-value of a cluster is the fraction of the null
distribution IGPs that approximate the value of 1 (perfect IGP) more than the actual IGP of
the cluster. The null hypothesis that a cluster is not a high-quality cluster is rejected if the
actual IGP of the group is high enough (i.e. approximates 1). A significant p-value indicates
that a high-quality cluster corresponding to the original cluster was found in an independent
dataset (validation cohort). Hence, the development cohort cluster is deemed reproducible
and validated.
Next we trained a PAM model on the development cohort, fitting a nearest shrunken
centroid classifier on the centroids generated from the development cohort clusters. By
fitting these centroids in the validation cohort, we assigned individual patients to imaging
subtypes defined by the development cohort.
Mapping canonical pathways to imaging subtypes
We used the matched molecular data in the TCGA validation cohort to assign canonical
signaling pathways to the discovered imaging subtypes. TCGA provided CNV and gene
expression data for 560 and 495 subjects, respectively. These data were integrated with
curated pathways from the NCI Pathway Interaction Database using the PARADIGM
algorithm to infer signaling pathway activities (up-regulation or down-regulation) to
generate a molecular signaling pathway consisting of 131 features. Next we used the SAM
algorithm to identify specific regulatory pathways that were significantly associated with
each of the identified imaging subtypes for each of the 144 subjects. We placed the FDR
threshold at <5%.
Evaluating imaging subtypes for traditional risk factors
We examined the subtypes for statistically significant differences in historically associated
risk factors. Such factors included both clinical (age, KPS) (4, 45, 46) and molecular factors,
including previously described gene expression cluster molecular subgroups (8), as well as
CIMP status (10), IDH1 mutation (6, 7), MGMT hypermethylation (47), and EGFR
amplification (9). Tumor volume data were available only for the development cohort. We
compared across-cluster values for all available data, using the Kruskal-Wallis one-way
analysis of variance by ranks test for continuous variables and Fisher’s exact test for
categorical variables.
SUPPLEMENTARY FIGURES
Figure S1. Relative contributions of the top 24 imaging features in characterizing each
of the clusters. The graphic displays the multivariate combination of the top 24
differentially expressed 2D and multislice 2D (2D-MS) imaging features across the three
clusters (table S4). Displacement of colored bars to the right of the central vertical line
demonstrates over-expression, whereas displacement to the left indicates under-expression
of the given imaging feature. The length of the bar signifies magnitude.
-1.5 -0.5 0.5 1.5 -1.5 -0.5 0.5 1.5 -1.5 -0.5 0.5 1.5
2D-MS-LAII2R3.iqr2D-MS-LAII2R3.madmedian2D-MS-LAII2R3.madmean
2D-MS-LAII2R3.var2D-MS-LAII2R3.min2D-MS-LAII2R5.iqr2D-MS-RDS.robustmin2D-MS-RDS.trimmedmean25perc
2D-MS-RDS.mean2D-MS-RDS.min2D-MS-EdgeSharpnessWindow.robustmin2D-MS-EdgeSharpnessWindow.mode2D-MS-EdgeSharpnessWindow.min2D-MS-compactness2dmean2D-LAII2R5.range2D-LAII2R5.madmean
2D-LAII2R8.range2D-RDS.robustmin2D-EdgeSharpnessScale.range2D-EdgeSharpnessScale.iqr2D-EdgeSharpnessScale.madmedian
2D-EdgeSharpnessScale.madmean2D-EdgeSharpnessWindow.min
2D-Compactness2dmean
Cluster1 Cluster2 Cluster3
SUPPLEMENTARY TABLES
Table S1. Clinical characteristics of the Stanford cohort before and after selection of
the development cohort.
Stanford Cohort Stanford Development Cohort
Characteristics (n = 364) (n = 121)
Age, mean (SD) 62.2 (14.1) 64.6 (14.1)
Sex, n male (%) 209 (57) 69 (57)
KPS, n (%)
>70% 192 (53) 65 (54)
50-70% 141 (39) 44 (37)
<50% 28 (8) 11 (9)
Mean ± SD 71.7 ± 16.4 71.7 ± 17
Table S2. Clinical characteristics of the TCGA cohort before and after selection of the
validation cohort. Of the validation cohort, 114 patients had clinical data.
TCGA Cohort TCGA Validation Cohort
Characteristic (n = 575) (n = 144)
Age, mean ± SD 57.9 ± 14.4 58.5 ± 15
Sex, n male (%) 352 (61) 73 (64)
KPS, n (%)
>70% 317 (55) 78 (68)
50-70% 89 (15) 19 (17)
<50% 18 (3) 1 (1)
Missing 151 16
Mean ± SD 77.2 ± 14.6 78.6 ± 12.3
Table S3. All 2D and multislice 2D quantitative MR image features used for analysis. Quantitative image features were extracted using a pipeline previously applied in non–small
cell lung cancer (19) and glioblastoma (15) to characterize intensity, shape, edge sharpness,
and texture of lesions from images.
Number Image feature
1 2D-spherecity
2 2D-volume
3 2D-surfaceArea
4 2D-roughness2dmean
5 2D-compactness2dmean
6 2D-LowIntensityProportion
7 2D-HistogramRaw-min
8 2D-HistogramRaw-mean
9 2D-HistogramRaw-median
10 2D-HistogramRaw-max
11 2D-HistogramRaw-var
12 2D-HistogramRaw-skewness
13 2D-HistogramRaw-kurtosis
14 2D-HistogramRaw-madmean
15 2D-HistogramRaw-madmedian
16 2D-HistogramRaw-iqr
17 2D-HistogramRaw-mode
18 2D-HistogramRaw-range
19 2D-HistogramRaw-trimmedmean25perc
20 2D-HistogramRaw-harmmean
21 2D-HistogramRaw-robustmin
22 2D-HistogramRaw-robustmax
23 2D-HistogramRaw-robustskewness
24 2D-HistogramRaw-robustkurtosis
25 2D-HistogramRaw-entropy
26 2D-EdgeSharpnessWindow-min
27 2D-EdgeSharpnessWindow-mean
28 2D-EdgeSharpnessWindow-median
29 2D-EdgeSharpnessWindow-max
30 2D-EdgeSharpnessWindow-var
31 2D-EdgeSharpnessWindow-skewness
32 2D-EdgeSharpnessWindow-kurtosis
33 2D-EdgeSharpnessWindow-madmean
34 2D-EdgeSharpnessWindow-madmedian
35 2D-EdgeSharpnessWindow-iqr
36 2D-EdgeSharpnessWindow-mode
37 2D-EdgeSharpnessWindow-range
38 2D-EdgeSharpnessWindow-trimmedmean25perc
39 2D-EdgeSharpnessWindow-harmmean
40 2D-EdgeSharpnessWindow-robustmin
41 2D-EdgeSharpnessWindow-robustmax
42 2D-EdgeSharpnessWindow-robustskewness
43 2D-EdgeSharpnessWindow-robustkurtosis
44 2D-EdgeSharpnessWindow-entropy
45 2D-EdgeSharpnessScale-min
46 2D-EdgeSharpnessScale-mean
47 2D-EdgeSharpnessScale-median
48 2D-EdgeSharpnessScale-max
49 2D-EdgeSharpnessScale-var
50 2D-EdgeSharpnessScale-skewness
51 2D-EdgeSharpnessScale-kurtosis
52 2D-EdgeSharpnessScale-madmean
53 2D-EdgeSharpnessScale-madmedian
54 2D-EdgeSharpnessScale-iqr
55 2D-EdgeSharpnessScale-mode
56 2D-EdgeSharpnessScale-range
57 2D-EdgeSharpnessScale-trimmedmean25perc
58 2D-EdgeSharpnessScale-harmmean
59 2D-EdgeSharpnessScale-robustmin
60 2D-EdgeSharpnessScale-robustmax
61 2D-EdgeSharpnessScale-robustskewness
62 2D-EdgeSharpnessScale-robustkurtosis
63 2D-EdgeSharpnessScale-entropy
64 2D-EdgeSharpnessBlurryness-min
65 2D-EdgeSharpnessBlurryness-mean
66 2D-EdgeSharpnessBlurryness-median
67 2D-EdgeSharpnessBlurryness-max
68 2D-EdgeSharpnessBlurryness-var
69 2D-EdgeSharpnessBlurryness-skewness
70 2D-EdgeSharpnessBlurryness-kurtosis
71 2D-EdgeSharpnessBlurryness-madmean
72 2D-EdgeSharpnessBlurryness-madmedian
73 2D-EdgeSharpnessBlurryness-iqr
74 2D-EdgeSharpnessBlurryness-mode
75 2D-EdgeSharpnessBlurryness-range
76 2D-EdgeSharpnessBlurryness-trimmedmean25perc
77 2D-EdgeSharpnessBlurryness-harmmean
78 2D-EdgeSharpnessBlurryness-robustmin
79 2D-EdgeSharpnessBlurryness-robustmax
80 2D-EdgeSharpnessBlurryness-robustskewness
81 2D-EdgeSharpnessBlurryness-robustkurtosis
82 2D-EdgeSharpnessBlurryness-entropy
83 2D-RDS-min
84 2D-RDS-mean
85 2D-RDS-median
86 2D-RDS-var
87 2D-RDS-skewness
88 2D-RDS-kurtosis
89 2D-RDS-madmean
90 2D-RDS-madmedian
91 2D-RDS-iqr
92 2D-RDS-range
93 2D-RDS-trimmedmean25perc
94 2D-RDS-harmmean
95 2D-RDS-robustmin
96 2D-RDS-robustskewness
97 2D-RDS-robustkurtosis
98 2D-RDS-entropy
99 2D-LAII2R10-min
100 2D-LAII2R10-mean
101 2D-LAII2R10-median
102 2D-LAII2R10-max
103 2D-LAII2R10-var
104 2D-LAII2R10-skewness
105 2D-LAII2R10-kurtosis
106 2D-LAII2R10-madmean
107 2D-LAII2R10-madmedian
108 2D-LAII2R10-iqr
109 2D-LAII2R10-mode
110 2D-LAII2R10-range
111 2D-LAII2R10-trimmedmean25perc
112 2D-LAII2R10-harmmean
113 2D-LAII2R10-robustmin
114 2D-LAII2R10-robustmax
115 2D-LAII2R10-robustskewness
116 2D-LAII2R10-robustkurtosis
117 2D-LAII2R10-entropy
118 2D-LAII2R8-min
119 2D-LAII2R8-mean
120 2D-LAII2R8-median
121 2D-LAII2R8-max
122 2D-LAII2R8-var
123 2D-LAII2R8-skewness
124 2D-LAII2R8-kurtosis
125 2D-LAII2R8-madmean
126 2D-LAII2R8-madmedian
127 2D-LAII2R8-iqr
128 2D-LAII2R8-mode
129 2D-LAII2R8-range
130 2D-LAII2R8-trimmedmean25perc
131 2D-LAII2R8-harmmean
132 2D-LAII2R8-robustmin
133 2D-LAII2R8-robustmax
134 2D-LAII2R8-robustskewness
135 2D-LAII2R8-robustkurtosis
136 2D-LAII2R8-entropy
137 2D-LAII2R5-min
138 2D-LAII2R5-mean
139 2D-LAII2R5-median
140 2D-LAII2R5-max
141 2D-LAII2R5-var
142 2D-LAII2R5-skewness
143 2D-LAII2R5-kurtosis
144 2D-LAII2R5-madmean
145 2D-LAII2R5-madmedian
146 2D-LAII2R5-iqr
147 2D-LAII2R5-mode
148 2D-LAII2R5-range
149 2D-LAII2R5-trimmedmean25perc
150 2D-LAII2R5-harmmean
151 2D-LAII2R5-robustmin
152 2D-LAII2R5-robustmax
153 2D-LAII2R5-robustskewness
154 2D-LAII2R5-robustkurtosis
155 2D-LAII2R5-entropy
156 2D-LAII2R3-min
157 2D-LAII2R3-mean
158 2D-LAII2R3-median
159 2D-LAII2R3-max
160 2D-LAII2R3-var
161 2D-LAII2R3-skewness
162 2D-LAII2R3-kurtosis
163 2D-LAII2R3-madmean
164 2D-LAII2R3-madmedian
165 2D-LAII2R3-iqr
166 2D-LAII2R3-mode
167 2D-LAII2R3-range
168 2D-LAII2R3-trimmedmean25perc
169 2D-LAII2R3-harmmean
170 2D-LAII2R3-robustmin
171 2D-LAII2R3-robustmax
172 2D-LAII2R3-robustskewness
173 2D-LAII2R3-robustkurtosis
174 2D-LAII2R3-entropy
175 2D-LAII2R2-min
176 2D-LAII2R2-mean
177 2D-LAII2R2-median
178 2D-LAII2R2-max
179 2D-LAII2R2-var
180 2D-LAII2R2-skewness
181 2D-LAII2R2-kurtosis
182 2D-LAII2R2-madmean
183 2D-LAII2R2-madmedian
184 2D-LAII2R2-iqr
185 2D-LAII2R2-mode
186 2D-LAII2R2-range
187 2D-LAII2R2-trimmedmean25perc
188 2D-LAII2R2-harmmean
189 2D-LAII2R2-robustmin
190 2D-LAII2R2-robustmax
191 2D-LAII2R2-robustskewness
192 2D-LAII2R2-robustkurtosis
193 2D-LAII2R2-entropy
194 2D-MultiSlice-spherecity
195 2D-MultiSlice-volume
196 2D-MultiSlice-surfaceArea
197 2D-MultiSlice-roughness2dmean
198 2D-MultiSlice-roughness2dvar
199 2D-MultiSlice-compactness2dmean
200 2D-MultiSlice-compactness2dvar
201 2D-MultiSlice-LowIntensityProportion
202 2D-MultiSlice-HistogramRaw-min
203 2D-MultiSlice-HistogramRaw-mean
204 2D-MultiSlice-HistogramRaw-median
205 2D-MultiSlice-HistogramRaw-max
206 2D-MultiSlice-HistogramRaw-var
207 2D-MultiSlice-HistogramRaw-skewness
208 2D-MultiSlice-HistogramRaw-kurtosis
209 2D-MultiSlice-HistogramRaw-madmean
210 2D-MultiSlice-HistogramRaw-madmedian
211 2D-MultiSlice-HistogramRaw-iqr
212 2D-MultiSlice-HistogramRaw-mode
213 2D-MultiSlice-HistogramRaw-range
214 2D-MultiSlice-HistogramRaw-trimmedmean25perc
215 2D-MultiSlice-HistogramRaw-harmmean
216 2D-MultiSlice-HistogramRaw-robustmin
217 2D-MultiSlice-HistogramRaw-robustmax
218 2D-MultiSlice-HistogramRaw-robustskewness
219 2D-MultiSlice-HistogramRaw-robustkurtosis
220 2D-MultiSlice-HistogramRaw-entropy
221 2D-MultiSlice-EdgeSharpnessWindow-min
222 2D-MultiSlice-EdgeSharpnessWindow-mean
223 2D-MultiSlice-EdgeSharpnessWindow-median
224 2D-MultiSlice-EdgeSharpnessWindow-max
225 2D-MultiSlice-EdgeSharpnessWindow-var
226 2D-MultiSlice-EdgeSharpnessWindow-skewness
227 2D-MultiSlice-EdgeSharpnessWindow-kurtosis
228 2D-MultiSlice-EdgeSharpnessWindow-madmean
229 2D-MultiSlice-EdgeSharpnessWindow-madmedian
230 2D-MultiSlice-EdgeSharpnessWindow-iqr
231 2D-MultiSlice-EdgeSharpnessWindow-mode
232 2D-MultiSlice-EdgeSharpnessWindow-range
233 2D-MultiSlice-EdgeSharpnessWindow-trimmedmean25perc
234 2D-MultiSlice-EdgeSharpnessWindow-harmmean
235 2D-MultiSlice-EdgeSharpnessWindow-robustmin
236 2D-MultiSlice-EdgeSharpnessWindow-robustmax
237 2D-MultiSlice-EdgeSharpnessWindow-robustskewness
238 2D-MultiSlice-EdgeSharpnessWindow-robustkurtosis
239 2D-MultiSlice-EdgeSharpnessWindow-entropy
240 2D-MultiSlice-EdgeSharpnessScale-min
241 2D-MultiSlice-EdgeSharpnessScale-mean
242 2D-MultiSlice-EdgeSharpnessScale-median
243 2D-MultiSlice-EdgeSharpnessScale-max
244 2D-MultiSlice-EdgeSharpnessScale-var
245 2D-MultiSlice-EdgeSharpnessScale-skewness
246 2D-MultiSlice-EdgeSharpnessScale-kurtosis
247 2D-MultiSlice-EdgeSharpnessScale-madmean
248 2D-MultiSlice-EdgeSharpnessScale-madmedian
249 2D-MultiSlice-EdgeSharpnessScale-iqr
250 2D-MultiSlice-EdgeSharpnessScale-mode
251 2D-MultiSlice-EdgeSharpnessScale-range
252 2D-MultiSlice-EdgeSharpnessScale-trimmedmean25perc
253 2D-MultiSlice-EdgeSharpnessScale-harmmean
254 2D-MultiSlice-EdgeSharpnessScale-robustmin
255 2D-MultiSlice-EdgeSharpnessScale-robustmax
256 2D-MultiSlice-EdgeSharpnessScale-robustskewness
257 2D-MultiSlice-EdgeSharpnessScale-robustkurtosis
258 2D-MultiSlice-EdgeSharpnessScale-entropy
259 2D-MultiSlice-EdgeSharpnessBlurryness-min
260 2D-MultiSlice-EdgeSharpnessBlurryness-mean
261 2D-MultiSlice-EdgeSharpnessBlurryness-median
262 2D-MultiSlice-EdgeSharpnessBlurryness-max
263 2D-MultiSlice-EdgeSharpnessBlurryness-var
264 2D-MultiSlice-EdgeSharpnessBlurryness-skewness
265 2D-MultiSlice-EdgeSharpnessBlurryness-kurtosis
266 2D-MultiSlice-EdgeSharpnessBlurryness-madmean
267 2D-MultiSlice-EdgeSharpnessBlurryness-madmedian
268 2D-MultiSlice-EdgeSharpnessBlurryness-iqr
269 2D-MultiSlice-EdgeSharpnessBlurryness-mode
270 2D-MultiSlice-EdgeSharpnessBlurryness-range
271 2D-MultiSlice-EdgeSharpnessBlurryness-
trimmedmean25perc
272 2D-MultiSlice-EdgeSharpnessBlurryness-harmmean
273 2D-MultiSlice-EdgeSharpnessBlurryness-robustmin
274 2D-MultiSlice-EdgeSharpnessBlurryness-robustmax
275 2D-MultiSlice-EdgeSharpnessBlurryness-robustskewness
276 2D-MultiSlice-EdgeSharpnessBlurryness-robustkurtosis
277 2D-MultiSlice-EdgeSharpnessBlurryness-entropy
278 2D-MultiSlice-RDS-min
279 2D-MultiSlice-RDS-mean
280 2D-MultiSlice-RDS-median
281 2D-MultiSlice-RDS-var
282 2D-MultiSlice-RDS-skewness
283 2D-MultiSlice-RDS-kurtosis
284 2D-MultiSlice-RDS-madmean
285 2D-MultiSlice-RDS-madmedian
286 2D-MultiSlice-RDS-iqr
287 2D-MultiSlice-RDS-range
288 2D-MultiSlice-RDS-trimmedmean25perc
289 2D-MultiSlice-RDS-harmmean
290 2D-MultiSlice-RDS-robustmin
291 2D-MultiSlice-RDS-robustskewness
292 2D-MultiSlice-RDS-robustkurtosis
293 2D-MultiSlice-RDS-entropy
294 2D-MultiSlice-LAII2R10-min
295 2D-MultiSlice-LAII2R10-mean
296 2D-MultiSlice-LAII2R10-median
297 2D-MultiSlice-LAII2R10-max
298 2D-MultiSlice-LAII2R10-var
299 2D-MultiSlice-LAII2R10-skewness
300 2D-MultiSlice-LAII2R10-kurtosis
301 2D-MultiSlice-LAII2R10-madmean
302 2D-MultiSlice-LAII2R10-madmedian
303 2D-MultiSlice-LAII2R10-iqr
304 2D-MultiSlice-LAII2R10-mode
305 2D-MultiSlice-LAII2R10-range
306 2D-MultiSlice-LAII2R10-trimmedmean25perc
307 2D-MultiSlice-LAII2R10-harmmean
308 2D-MultiSlice-LAII2R10-robustmin
309 2D-MultiSlice-LAII2R10-robustmax
310 2D-MultiSlice-LAII2R10-robustskewness
311 2D-MultiSlice-LAII2R10-robustkurtosis
312 2D-MultiSlice-LAII2R10-entropy
313 2D-MultiSlice-LAII2R8-min
314 2D-MultiSlice-LAII2R8-mean
315 2D-MultiSlice-LAII2R8-median
316 2D-MultiSlice-LAII2R8-max
317 2D-MultiSlice-LAII2R8-var
318 2D-MultiSlice-LAII2R8-skewness
319 2D-MultiSlice-LAII2R8-kurtosis
320 2D-MultiSlice-LAII2R8-madmean
321 2D-MultiSlice-LAII2R8-madmedian
322 2D-MultiSlice-LAII2R8-iqr
323 2D-MultiSlice-LAII2R8-mode
324 2D-MultiSlice-LAII2R8-range
325 2D-MultiSlice-LAII2R8-trimmedmean25perc
326 2D-MultiSlice-LAII2R8-harmmean
327 2D-MultiSlice-LAII2R8-robustmin
328 2D-MultiSlice-LAII2R8-robustmax
329 2D-MultiSlice-LAII2R8-robustskewness
330 2D-MultiSlice-LAII2R8-robustkurtosis
331 2D-MultiSlice-LAII2R8-entropy
332 2D-MultiSlice-LAII2R5-min
333 2D-MultiSlice-LAII2R5-mean
334 2D-MultiSlice-LAII2R5-median
335 2D-MultiSlice-LAII2R5-max
336 2D-MultiSlice-LAII2R5-var
337 2D-MultiSlice-LAII2R5-skewness
338 2D-MultiSlice-LAII2R5-kurtosis
339 2D-MultiSlice-LAII2R5-madmean
340 2D-MultiSlice-LAII2R5-madmedian
341 2D-MultiSlice-LAII2R5-iqr
342 2D-MultiSlice-LAII2R5-mode
343 2D-MultiSlice-LAII2R5-range
344 2D-MultiSlice-LAII2R5-trimmedmean25perc
345 2D-MultiSlice-LAII2R5-harmmean
346 2D-MultiSlice-LAII2R5-robustmin
347 2D-MultiSlice-LAII2R5-robustmax
348 2D-MultiSlice-LAII2R5-robustskewness
349 2D-MultiSlice-LAII2R5-robustkurtosis
350 2D-MultiSlice-LAII2R5-entropy
351 2D-MultiSlice-LAII2R3-min
352 2D-MultiSlice-LAII2R3-mean
353 2D-MultiSlice-LAII2R3-median
354 2D-MultiSlice-LAII2R3-max
355 2D-MultiSlice-LAII2R3-var
356 2D-MultiSlice-LAII2R3-skewness
357 2D-MultiSlice-LAII2R3-kurtosis
358 2D-MultiSlice-LAII2R3-madmean
359 2D-MultiSlice-LAII2R3-madmedian
360 2D-MultiSlice-LAII2R3-iqr
361 2D-MultiSlice-LAII2R3-mode
362 2D-MultiSlice-LAII2R3-range
363 2D-MultiSlice-LAII2R3-trimmedmean25perc
364 2D-MultiSlice-LAII2R3-harmmean
365 2D-MultiSlice-LAII2R3-robustmin
366 2D-MultiSlice-LAII2R3-robustmax
367 2D-MultiSlice-LAII2R3-robustskewness
368 2D-MultiSlice-LAII2R3-robustkurtosis
369 2D-MultiSlice-LAII2R3-entropy
370 2D-MultiSlice-LAII2R2-min
371 2D-MultiSlice-LAII2R2-mean
372 2D-MultiSlice-LAII2R2-median
373 2D-MultiSlice-LAII2R2-max
374 2D-MultiSlice-LAII2R2-var
375 2D-MultiSlice-LAII2R2-skewness
376 2D-MultiSlice-LAII2R2-kurtosis
377 2D-MultiSlice-LAII2R2-madmean
378 2D-MultiSlice-LAII2R2-madmedian
379 2D-MultiSlice-LAII2R2-iqr
380 2D-MultiSlice-LAII2R2-mode
381 2D-MultiSlice-LAII2R2-range
382 2D-MultiSlice-LAII2R2-trimmedmean25perc
383 2D-MultiSlice-LAII2R2-harmmean
384 2D-MultiSlice-LAII2R2-robustmin
385 2D-MultiSlice-LAII2R2-robustmax
386 2D-MultiSlice-LAII2R2-robustskewness
387 2D-MultiSlice-LAII2R2-robustkurtosis
388 2D-MultiSlice-LAII2R2-entropy
Table S4. Two-dimensional and multislice 2D quantitative MR image features
significantly associated with each cluster. For each feature the fold change is reported and
defined as the number of times the feature is “expressed” in samples in the cluster versus in
samples not in the cluster. For example, a 3.1-fold increase was observed for the top feature
in Cluster 1 compared with patients not in Cluster 1. The features are ranked by descending
order of fold changes.
Cluster 1 Image feature Fold
change
2D-MultiSlice-LAII2R3-iqr 3.10
2D-MultiSlice-LAII2R3-madmedian 3.09
2D-LAII2R5-madmean 3.08
2D-MultiSlice-LAII2R5-iqr 3.07
2D-MultiSlice-LAII2R5-madmedian 3.03
2D-LAII2R3-madmean 3.03
2D-LAII2R5-iqr 2.96
2D-LAII2R3-iqr 2.96
2D-MultiSlice-LAII2R8-robustmax 2.96
2D-MultiSlice-LAII2R3-robustmax 2.96
2D-LAII2R3-madmedian 2.95
2D-LAII2R2-var 2.93
2D-MultiSlice-LAII2R5-madmean 2.93
2D-LAII2R5-madmedian 2.91
2D-MultiSlice-LAII2R5-robustmax 2.91
2D-MultiSlice-LAII2R8-iqr 2.89
2D-LAII2R8-madmean 2.88
2D-MultiSlice-LAII2R3-madmean 2.86
2D-LAII2R2-madmean 2.86
2D-RDS-range 2.86
2D-MultiSlice-LAII2R2-madmedian 2.83
2D-RDS-var 2.83
2D-MultiSlice-LAII2R8-madmedian 2.80
2D-MultiSlice-LAII2R8-madmean 2.78
2D-MultiSlice-LAII2R2-iqr 2.77
2D-MultiSlice-LAII2R10-madmedian 2.77
2D-MultiSlice-LAII2R5-var 2.75
2D-LAII2R3-range 2.74
2D-MultiSlice-RDS-madmean 2.74
2D-LAII2R3-var 2.74
2D-RDS-madmean 2.73
2D-LAII2R5-var 2.69
2D-MultiSlice-RDS-iqr 2.68
2D-LAII2R10-madmean 2.68
2D-LAII2R2-madmedian 2.67
2D-LAII2R8-var 2.66
2D-MultiSlice-RDS-var 2.66
2D-LAII2R3-robustmax 2.66
2D-LAII2R5-robustmax 2.65
2D-MultiSlice-RDS-madmedian 2.65
2D-LAII2R8-robustmax 2.65
2D-MultiSlice-LAII2R3-var 2.63
2D-LAII2R2-iqr 2.63
2D-MultiSlice-LAII2R10-robustmax 2.62
2D-MultiSlice-LAII2R10-madmean 2.62
2D-LAII2R10-robustmax 2.60
2D-LAII2R2-range 2.60
2D-LAII2R5-range 2.59
2D-MultiSlice-LAII2R10-iqr 2.58
2D-RDS-iqr 2.56
2D-MultiSlice-LAII2R2-madmean 2.55
2D-LAII2R10-var 2.54
2D-MultiSlice-LAII2R8-var 2.53
2D-LAII2R8-range 2.50
2D-LAII2R8-madmedian 2.49
2D-LAII2R8-iqr 2.49
2D-RDS-madmedian 2.46
2D-LAII2R10-range 2.41
2D-MultiSlice-LAII2R10-var 2.37
2D-roughness2dmean 2.35
2D-LAII2R3-max 2.32
2D-MultiSlice-roughness2dmean 2.27
2D-MultiSlice-LAII2R2-var 2.27
2D-LAII2R10-iqr 2.27
2D-LAII2R5-max 2.15
2D-MultiSlice-LAII2R10-entropy 2.15
2D-MultiSlice-LAII2R2-entropy 2.11
2D-LAII2R8-max 2.11
2D-MultiSlice-LAII2R2-robustmax 2.10
2D-LAII2R10-max 2.09
2D-LAII2R10-madmedian 2.09
2D-MultiSlice-LAII2R8-entropy 2.08
2D-MultiSlice-LAII2R5-entropy 2.04
2D-MultiSlice-LAII2R3-entropy 1.91
2D-MultiSlice-roughness2dvar 1.91
2D-MultiSlice-RDS-entropy 1.90
2D-MultiSlice-compactness2dvar 1.90
2D-MultiSlice-LAII2R5-range 1.84
2D-MultiSlice-LAII2R3-robustskewness 1.84
2D-MultiSlice-LAII2R3-range 1.76
2D-MultiSlice-HistogramRaw-robustkurtosis 1.70
2D-LAII2R2-robustmax 1.66
2D-MultiSlice-RDS-skewness 1.65
2D-MultiSlice-LAII2R2-robustskewness 1.65
2D-MultiSlice-LAII2R8-range 1.64
2D-MultiSlice-LAII2R10-range 1.63
2D-MultiSlice-RDS-range 1.60
2D-MultiSlice-RDS-robustskewness 1.58
2D-MultiSlice-LAII2R5-max 1.55
2D-LAII2R2-entropy 1.52
2D-LAII2R2-max 1.49
2D-MultiSlice-HistogramRaw-kurtosis 1.48
2D-EdgeSharpnessWindow-robustskewness 1.48
2D-MultiSlice-LAII2R3-max 1.47
2D-MultiSlice-EdgeSharpnessWindow-robustskewness 1.47
2D-LAII2R3-robustskewness 1.47
2D-MultiSlice-EdgeSharpnessBlurryness-
robustskewness
1.45
2D-compactness2dmean 0.33
2D-MultiSlice-RDS-mean 0.34
2D-MultiSlice-RDS-trimmedmean25perc 0.35
2D-RDS-robustmin 0.35
2D-RDS-min 0.35
2D-RDS-harmmean 0.36
2D-MultiSlice-RDS-harmmean 0.36
2D-MultiSlice-RDS-median 0.36
2D-RDS-mean 0.37
2D-MultiSlice-LAII2R2-median 0.38
2D-MultiSlice-compactness2dmean 0.38
2D-MultiSlice-LAII2R2-trimmedmean25perc 0.38
2D-LAII2R2-median 0.38
2D-LAII2R2-robustmin 0.38
2D-RDS-trimmedmean25perc 0.38
2D-LAII2R2-min 0.39
2D-LAII2R2-harmmean 0.39
2D-LAII2R5-robustmin 0.39
2D-LAII2R3-robustmin 0.39
2D-LAII2R2-trimmedmean25perc 0.40
2D-MultiSlice-LAII2R2-mean 0.40
2D-LAII2R5-harmmean 0.40
2D-LAII2R5-min 0.40
2D-RDS-median 0.40
2D-LAII2R3-median 0.40
2D-LAII2R3-min 0.40
2D-LAII2R3-harmmean 0.40
2D-LAII2R8-robustmin 0.41
2D-MultiSlice-LAII2R3-median 0.41
2D-MultiSlice-LAII2R3-trimmedmean25perc 0.41
2D-LAII2R8-min 0.41
2D-MultiSlice-LAII2R5-robustmin 0.43
2D-LAII2R2-mean 0.43
2D-LAII2R10-robustmin 0.43
2D-MultiSlice-LAII2R3-harmmean 0.43
2D-LAII2R10-min 0.43
2D-spherecity 0.43
2D-MultiSlice-LAII2R2-harmmean 0.43
2D-LAII2R3-trimmedmean25perc 0.45
2D-LAII2R8-harmmean 0.45
2D-MultiSlice-LAII2R8-robustmin 0.46
2D-MultiSlice-LAII2R3-mean 0.47
2D-MultiSlice-LAII2R3-robustmin 0.47
2D-MultiSlice-spherecity 0.47
2D-MultiSlice-LAII2R10-robustmin 0.48
2D-MultiSlice-RDS-robustmin 0.48
2D-MultiSlice-LAII2R2-robustkurtosis 0.50
2D-MultiSlice-LAII2R3-robustkurtosis 0.51
2D-LAII2R5-median 0.51
2D-MultiSlice-LAII2R5-trimmedmean25perc 0.52
2D-LAII2R10-harmmean 0.52
2D-MultiSlice-LAII2R5-median 0.52
2D-MultiSlice-LAII2R2-robustmin 0.53
2D-MultiSlice-RDS-robustkurtosis 0.54
2D-MultiSlice-LAII2R3-min 0.54
2D-MultiSlice-LAII2R2-kurtosis 0.54
2D-MultiSlice-LAII2R5-min 0.56
2D-MultiSlice-LAII2R2-mode 0.56
2D-MultiSlice-RDS-kurtosis 0.57
2D-LAII2R3-mode 0.58
2D-LAII2R2-mode 0.59
2D-MultiSlice-LAII2R5-harmmean 0.59
2D-MultiSlice-LAII2R2-min 0.60
2D-LAII2R3-mean 0.60
2D-MultiSlice-LAII2R3-kurtosis 0.60
2D-MultiSlice-LAII2R5-kurtosis 0.60
2D-LAII2R5-trimmedmean25perc 0.60
2D-HistogramRaw-robustskewness 0.61
2D-MultiSlice-HistogramRaw-robustskewness 0.61
2D-MultiSlice-LAII2R5-mean 0.62
2D-MultiSlice-LAII2R3-mode 0.62
2D-MultiSlice-RDS-min 0.63
2D-MultiSlice-HistogramRaw-skewness 0.63
2D-HistogramRaw-skewness 0.63
2D-MultiSlice-LAII2R8-min 0.67
Cluster 2 Image feature Fold
change
2D-MultiSlice-compactness2dmean 2.32
2D-MultiSlice-RDS-min 2.18
2D-MultiSlice-RDS-robustmin 2.17
2D-MultiSlice-LAII2R3-min 2.17
2D-MultiSlice-RDS-harmmean 2.16
2D-compactness2dmean 2.16
2D-MultiSlice-LAII2R2-robustmin 2.14
2D-MultiSlice-LAII2R3-robustmin 2.14
2D-MultiSlice-LAII2R2-min 2.10
2D-MultiSlice-RDS-mean 2.05
2D-RDS-min 2.04
2D-RDS-robustmin 2.03
2D-LAII2R5-min 1.98
2D-LAII2R8-min 1.98
2D-LAII2R3-min 1.98
2D-LAII2R5-robustmin 1.98
2D-LAII2R8-robustmin 1.98
2D-LAII2R3-robustmin 1.96
2D-MultiSlice-RDS-trimmedmean25perc 1.94
2D-LAII2R2-min 1.93
2D-LAII2R2-robustmin 1.92
2D-MultiSlice-LAII2R5-robustmin 1.92
2D-RDS-harmmean 1.92
2D-RDS-mean 1.91
2D-RDS-trimmedmean25perc 1.87
2D-MultiSlice-RDS-median 1.86
2D-RDS-median 1.84
2D-LAII2R10-robustmin 1.83
2D-MultiSlice-LAII2R2-harmmean 1.82
2D-LAII2R10-min 1.82
2D-MultiSlice-LAII2R2-trimmedmean25perc 1.80
2D-MultiSlice-LAII2R2-median 1.79
2D-MultiSlice-LAII2R2-mean 1.79
2D-MultiSlice-LAII2R5-min 1.79
2D-MultiSlice-LAII2R3-harmmean 1.77
2D-MultiSlice-LAII2R8-robustmin 1.76
2D-LAII2R2-harmmean 1.74
2D-MultiSlice-EdgeSharpnessBlurryness-entropy 1.74
2D-LAII2R2-trimmedmean25perc 1.70
2D-LAII2R3-harmmean 1.68
2D-LAII2R2-median 1.67
2D-LAII2R3-median 1.65
2D-MultiSlice-EdgeSharpnessWindow-min 1.65
2D-MultiSlice-EdgeSharpnessWindow-mode 1.65
2D-MultiSlice-EdgeSharpnessWindow-robustmin 1.65
2D-LAII2R2-mean 1.63
2D-MultiSlice-EdgeSharpnessScale-robustmin 1.63
2D-LAII2R5-harmmean 1.61
2D-MultiSlice-EdgeSharpnessScale-min 1.61
2D-MultiSlice-EdgeSharpnessScale-mode 1.61
2D-MultiSlice-LAII2R3-trimmedmean25perc 1.60
2D-MultiSlice-LAII2R3-median 1.58
2D-MultiSlice-EdgeSharpnessBlurryness-robustmin 1.58
2D-MultiSlice-spherecity 1.57
2D-MultiSlice-LAII2R10-robustmin 1.55
2D-EdgeSharpnessWindow-min 1.55
2D-EdgeSharpnessWindow-mode 1.55
2D-EdgeSharpnessWindow-robustmin 1.55
2D-LAII2R3-trimmedmean25perc 1.54
2D-MultiSlice-LAII2R3-mean 1.47
2D-LAII2R8-range 0.43
2D-LAII2R5-range 0.44
2D-MultiSlice-LAII2R3-var 0.45
2D-MultiSlice-LAII2R3-madmean 0.45
2D-MultiSlice-LAII2R3-range 0.45
2D-LAII2R10-range 0.45
2D-LAII2R8-max 0.46
2D-MultiSlice-LAII2R5-range 0.46
2D-MultiSlice-LAII2R8-robustmax 0.46
2D-MultiSlice-RDS-range 0.46
2D-LAII2R3-range 0.46
2D-MultiSlice-RDS-var 0.46
2D-MultiSlice-LAII2R5-madmean 0.46
2D-LAII2R10-max 0.46
2D-MultiSlice-LAII2R5-var 0.47
2D-MultiSlice-RDS-madmean 0.47
2D-MultiSlice-roughness2dmean 0.47
2D-LAII2R5-max 0.47
2D-MultiSlice-LAII2R2-madmean 0.47
2D-MultiSlice-LAII2R2-range 0.47
2D-LAII2R5-madmean 0.48
2D-MultiSlice-LAII2R5-robustmax 0.48
2D-MultiSlice-LAII2R2-var 0.49
2D-MultiSlice-LAII2R3-robustmax 0.49
2D-RDS-range 0.49
2D-MultiSlice-LAII2R8-max 0.49
2D-LAII2R2-range 0.49
2D-MultiSlice-LAII2R3-iqr 0.49
2D-MultiSlice-LAII2R3-madmedian 0.49
2D-MultiSlice-compactness2dvar 0.49
2D-LAII2R3-madmean 0.50
2D-MultiSlice-LAII2R5-max 0.51
2D-MultiSlice-LAII2R5-iqr 0.51
2D-MultiSlice-LAII2R2-madmedian 0.51
2D-MultiSlice-LAII2R5-madmedian 0.51
2D-MultiSlice-LAII2R8-range 0.51
2D-LAII2R2-var 0.51
2D-LAII2R8-madmean 0.52
2D-MultiSlice-RDS-iqr 0.52
2D-LAII2R5-var 0.52
2D-MultiSlice-LAII2R10-robustmax 0.52
2D-LAII2R3-max 0.52
2D-MultiSlice-LAII2R2-iqr 0.52
2D-LAII2R2-madmean 0.52
2D-MultiSlice-LAII2R10-max 0.52
2D-MultiSlice-RDS-madmedian 0.53
2D-LAII2R8-var 0.53
2D-RDS-madmean 0.53
2D-RDS-var 0.53
2D-surfaceArea 0.53
2D-LAII2R3-var 0.53
2D-MultiSlice-LAII2R10-range 0.54
2D-MultiSlice-LAII2R8-iqr 0.54
2D-MultiSlice-LAII2R8-madmean 0.54
2D-MultiSlice-LAII2R2-robustmax 0.54
2D-MultiSlice-LAII2R3-max 0.55
2D-LAII2R3-madmedian 0.55
2D-LAII2R10-kurtosis 0.55
2D-LAII2R3-iqr 0.55
2D-LAII2R8-kurtosis 0.56
2D-MultiSlice-LAII2R8-madmedian 0.56
2D-LAII2R10-madmean 0.56
2D-LAII2R10-var 0.56
2D-MultiSlice-LAII2R8-var 0.56
2D-MultiSlice-roughness2dvar 0.57
2D-LAII2R3-robustmax 0.57
2D-LAII2R5-madmedian 0.57
2D-roughness2dmean 0.57
2D-LAII2R10-robustmax 0.57
2D-LAII2R5-iqr 0.57
2D-RDS-iqr 0.57
2D-MultiSlice-surfaceArea 0.58
2D-RDS-madmedian 0.58
2D-LAII2R8-robustmax 0.58
2D-LAII2R2-iqr 0.58
2D-LAII2R5-robustmax 0.58
2D-LAII2R2-madmedian 0.58
2D-EdgeSharpnessScale-madmedian 0.59
2D-LAII2R10-robustkurtosis 0.59
2D-MultiSlice-LAII2R10-madmedian 0.59
2D-LAII2R8-robustkurtosis 0.60
2D-volume 0.60
2D-MultiSlice-EdgeSharpnessScale-range 0.60
2D-EdgeSharpnessScale-range 0.60
2D-MultiSlice-LAII2R10-madmean 0.61
2D-EdgeSharpnessScale-iqr 0.61
2D-EdgeSharpnessScale-madmean 0.61
2D-MultiSlice-EdgeSharpnessScale-madmean 0.61
2D-LAII2R5-kurtosis 0.62
2D-MultiSlice-volume 0.62
2D-MultiSlice-EdgeSharpnessScale-iqr 0.62
2D-MultiSlice-EdgeSharpnessScale-madmedian 0.62
2D-MultiSlice-EdgeSharpnessScale-var 0.62
2D-EdgeSharpnessScale-var 0.62
2D-LAII2R8-iqr 0.63
2D-MultiSlice-LAII2R10-iqr 0.63
2D-MultiSlice-LAII2R10-var 0.63
2D-LAII2R8-madmedian 0.64
2D-MultiSlice-EdgeSharpnessBlurryness-madmean 0.65
2D-MultiSlice-HistogramRaw-range 0.66
2D-LAII2R10-iqr 0.66
2D-LAII2R5-robustkurtosis 0.66
2D-LAII2R10-madmedian 0.67
2D-HistogramRaw-range 0.68
2D-MultiSlice-EdgeSharpnessBlurryness-range 0.69
2D-MultiSlice-EdgeSharpnessBlurryness-robustkurtosis 0.70
2D-MultiSlice-LAII2R2-max 0.70
2D-LAII2R2-max 0.70
2D-LAII2R2-robustmax 0.71
2D-MultiSlice-EdgeSharpnessBlurryness-iqr 0.71
2D-LAII2R3-kurtosis 0.71
2D-MultiSlice-EdgeSharpnessWindow-range 0.72
2D-MultiSlice-HistogramRaw-max 0.72
2D-MultiSlice-EdgeSharpnessScale-robustmax 0.72
2D-MultiSlice-EdgeSharpnessBlurryness-max 0.72
2D-EdgeSharpnessWindow-range 0.72
2D-MultiSlice-EdgeSharpnessBlurryness-kurtosis 0.73
2D-HistogramRaw-max 0.73
2D-MultiSlice-EdgeSharpnessBlurryness-madmedian 0.73
2D-LAII2R10-mean 0.73
2D-MultiSlice-EdgeSharpnessScale-max 0.73
2D-EdgeSharpnessScale-max 0.74
Cluster 3 Image feature Fold
change
2D-EdgeSharpnessScale-madmedian 2.58
2D-EdgeSharpnessScale-iqr 2.44
2D-EdgeSharpnessScale-range 2.42
2D-EdgeSharpnessScale-madmean 2.40
2D-EdgeSharpnessScale-var 2.27
2D-MultiSlice-EdgeSharpnessScale-madmean 2.22
2D-MultiSlice-HistogramRaw-robustskewness 2.17
2D-MultiSlice-EdgeSharpnessScale-madmedian 2.17
2D-MultiSlice-EdgeSharpnessScale-range 2.16
2D-MultiSlice-EdgeSharpnessScale-var 2.15
2D-MultiSlice-EdgeSharpnessScale-iqr 2.14
2D-spherecity 2.14
2D-HistogramRaw-robustskewness 2.09
2D-MultiSlice-HistogramRaw-skewness 2.06
2D-HistogramRaw-skewness 2.05
2D-volume 1.98
2D-MultiSlice-volume 1.95
2D-MultiSlice-EdgeSharpnessBlurryness-madmean 1.93
2D-LAII2R8-kurtosis 1.92
2D-MultiSlice-HistogramRaw-madmean 1.90
2D-LAII2R5-kurtosis 1.90
2D-HistogramRaw-range 1.89
2D-MultiSlice-LowIntensityProportion 1.89
2D-MultiSlice-EdgeSharpnessBlurryness-robustkurtosis 1.88
2D-MultiSlice-HistogramRaw-iqr 1.87
2D-MultiSlice-HistogramRaw-range 1.86
2D-LowIntensityProportion 1.85
2D-HistogramRaw-madmean 1.83
2D-MultiSlice-RDS-robustkurtosis 1.83
2D-MultiSlice-LAII2R2-robustkurtosis 1.82
2D-MultiSlice-EdgeSharpnessBlurryness-range 1.81
2D-LAII2R10-kurtosis 1.80
2D-MultiSlice-LAII2R2-range 1.80
2D-MultiSlice-surfaceArea 1.80
2D-MultiSlice-HistogramRaw-var 1.80
2D-MultiSlice-LAII2R3-robustkurtosis 1.79
2D-MultiSlice-LAII2R10-trimmedmean25perc 1.78
2D-HistogramRaw-var 1.77
2D-MultiSlice-LAII2R10-median 1.77
2D-MultiSlice-LAII2R10-mean 1.75
2D-MultiSlice-LAII2R3-kurtosis 1.75
2D-MultiSlice-LAII2R8-trimmedmean25perc 1.75
2D-HistogramRaw-max 1.75
2D-MultiSlice-HistogramRaw-max 1.74
2D-MultiSlice-LAII2R2-kurtosis 1.72
2D-MultiSlice-EdgeSharpnessWindow-range 1.71
2D-MultiSlice-LAII2R8-mean 1.70
2D-MultiSlice-LAII2R8-median 1.70
2D-HistogramRaw-iqr 1.69
2D-MultiSlice-RDS-kurtosis 1.69
2D-MultiSlice-EdgeSharpnessBlurryness-max 1.67
2D-MultiSlice-HistogramRaw-madmedian 1.66
2D-MultiSlice-LAII2R5-kurtosis 1.65
2D-MultiSlice-HistogramRaw-robustmax 1.65
2D-MultiSlice-EdgeSharpnessWindow-robustkurtosis 1.64
2D-LAII2R3-kurtosis 1.64
2D-MultiSlice-LAII2R2-max 1.64
2D-MultiSlice-EdgeSharpnessBlurryness-madmedian 1.64
2D-MultiSlice-EdgeSharpnessBlurryness-iqr 1.64
2D-surfaceArea 1.64
2D-MultiSlice-LAII2R5-median 1.63
2D-MultiSlice-LAII2R5-trimmedmean25perc 1.62
2D-MultiSlice-EdgeSharpnessBlurryness-var 1.62
2D-HistogramRaw-robustmax 1.61
2D-LAII2R10-harmmean 1.61
2D-MultiSlice-EdgeSharpnessScale-robustmax 1.61
2D-MultiSlice-LAII2R8-max 1.60
2D-MultiSlice-EdgeSharpnessScale-harmmean 1.60
2D-EdgeSharpnessScale-robustmax 1.58
2D-MultiSlice-EdgeSharpnessBlurryness-kurtosis 1.57
2D-MultiSlice-RDS-range 1.57
2D-MultiSlice-LAII2R5-mean 1.56
2D-LAII2R8-harmmean 1.56
2D-EdgeSharpnessBlurryness-robustkurtosis 1.55
2D-EdgeSharpnessBlurryness-kurtosis 1.54
2D-LAII2R8-robustkurtosis 1.53
2D-EdgeSharpnessWindow-robustkurtosis 1.53
2D-EdgeSharpnessScale-max 1.53
2D-MultiSlice-EdgeSharpnessBlurryness-robustmax 1.51
2D-MultiSlice-EdgeSharpnessScale-max 1.51
2D-LAII2R3-robustkurtosis 1.50
2D-LAII2R5-median 1.49
2D-MultiSlice-LAII2R10-max 1.49
2D-LAII2R2-kurtosis 1.48
2D-LAII2R10-median 1.47
2D-LAII2R2-median 1.45
2D-LAII2R10-mean 1.45
2D-LAII2R5-robustkurtosis 1.45
2D-MultiSlice-LAII2R3-range 1.45
2D-MultiSlice-LAII2R5-max 1.44
2D-MultiSlice-EdgeSharpnessWindow-min 0.41
2D-MultiSlice-EdgeSharpnessWindow-mode 0.41
2D-MultiSlice-EdgeSharpnessWindow-robustmin 0.41
2D-EdgeSharpnessWindow-min 0.42
2D-EdgeSharpnessWindow-mode 0.42
2D-EdgeSharpnessWindow-robustmin 0.42
2D-MultiSlice-EdgeSharpnessScale-robustmin 0.43
2D-MultiSlice-EdgeSharpnessScale-min 0.44
2D-MultiSlice-EdgeSharpnessScale-mode 0.44
2D-EdgeSharpnessScale-robustmin 0.48
2D-MultiSlice-EdgeSharpnessBlurryness-robustmin 0.48
2D-MultiSlice-EdgeSharpnessWindow-robustskewness 0.48
2D-EdgeSharpnessScale-min 0.48
2D-EdgeSharpnessScale-mode 0.48
2D-MultiSlice-LAII2R10-entropy 0.49
2D-LAII2R8-entropy 0.50
2D-EdgeSharpnessBlurryness-entropy 0.51
2D-MultiSlice-LAII2R8-entropy 0.52
2D-LAII2R10-entropy 0.52
2D-MultiSlice-EdgeSharpnessBlurryness-entropy 0.53
2D-MultiSlice-LAII2R2-entropy 0.53
2D-MultiSlice-RDS-entropy 0.53
2D-LAII2R5-entropy 0.54
2D-MultiSlice-LAII2R3-entropy 0.55
2D-MultiSlice-LAII2R5-entropy 0.55
2D-MultiSlice-EdgeSharpnessBlurryness-min 0.56
2D-MultiSlice-EdgeSharpnessBlurryness-mode 0.56
2D-MultiSlice-RDS-skewness 0.56
2D-MultiSlice-RDS-robustskewness 0.56
2D-MultiSlice-EdgeSharpnessBlurryness-
robustskewness
0.57
2D-EdgeSharpnessWindow-entropy 0.58
2D-MultiSlice-EdgeSharpnessWindow-skewness 0.60
2D-MultiSlice-LAII2R2-robustskewness 0.62
2D-LAII2R3-entropy 0.62
2D-MultiSlice-RDS-min 0.64
2D-LAII2R5-iqr 0.64
Table S5. Cluster assignment by subjects in the development cohort with and without
midline-crossing lesions. With midline-crossing, n = 140; without midline crossing, n =
121.
With midline-
crossing
lesions Cluster
Without midline-
crossing lesions Cluster
Patient_033 1 Patient_033 1
Patient_047 3 Patient_047 1
Patient_054 2 Patient_054 2
Patient_056 2 Patient_056 2
Patient_066 2 Patient_066 2
Patient_080 1 Patient_080 1
Patient_083 3 Patient_083 3
Patient_084 2 Patient_084 2
Patient_085 3 Patient_085 3
Patient_086 2 Patient_086 2
Patient_088 2 Patient_088 2
Patient_091 2 Patient_091 2
Patient_092 2 Patient_092 2
Patient_094 2 Patient_094 2
Patient_097 3 Patient_097 3
Patient_098 3 Patient_098 3
Patient_099 3 Patient_099 3
Patient_104 2 Patient_104 2
Patient_105 3 Patient_105 2
Patient_106 1 Patient_106 1
Patient_109 1 Patient_109 1
Patient_110 1 Patient_110 1
Patient_114 1 Patient_114 1
Patient_116 3 Patient_116 1
Patient_117 2 Patient_117 2
Patient_121 1 Patient_121 1
Patient_124 1 Patient_124 1
Patient_125 1 Patient_125 1
Patient_129 3 Patient_129 3
Patient_133 2 Patient_133 2
Patient_135 1 Patient_135 1
Patient_136 2 Patient_136 2
Patient_137 3 Patient_137 3
Patient_142 1 Patient_142 1
Patient_144 1 Patient_144 1
Patient_145 3 Patient_145 3
Patient_146 2 Patient_146 2
Patient_147 2 Patient_147 2
Patient_149 3 Patient_149 3
Patient_150 2 Patient_150 2
Patient_151 2 Patient_151 2
Patient_154 1 Patient_154 1
Patient_155 1 Patient_155 1
Patient_156 3 Patient_156 3
Patient_157 3 Patient_157 3
Patient_158 3 Patient_158 3
Patient_159 2 Patient_159 2
Patient_160 2 Patient_160 2
Patient_161 2 Patient_161 2
Patient_164 3 Patient_164 3
Patient_166 3 Patient_166 3
Patient_167 2 Patient_167 2
Patient_168 3 Patient_168 3
Patient_169 1 Patient_169 1
Patient_170 1 Patient_170 1
Patient_175 2 Patient_175 2
Patient_178 3 Patient_178 3
Patient_182 2 Patient_182 1
Patient_189 1 Patient_189 1
Patient_190 3 Patient_190 3
Patient_201 2 Patient_201 2
Patient_203 1 Patient_203 1
Patient_204 2 Patient_204 2
Patient_206 2 Patient_206 2
Patient_218 2 Patient_218 2
Patient_220 2 Patient_220 2
Patient_222 3 Patient_222 3
Patient_223 1 Patient_223 1
Patient_224 3 Patient_224 3
Patient_225 3 Patient_225 3
Patient_235 2 Patient_235 2
Patient_236 1 Patient_236 1
Patient_238 2 Patient_238 2
Patient_240 2 Patient_240 2
Patient_242 2 Patient_242 2
Patient_243 2 Patient_243 2
Patient_248 1 Patient_248 1
Patient_251 3 Patient_251 3
Patient_252 1 Patient_252 1
Patient_267 1 Patient_267 1
Patient_268 3 Patient_268 3
Patient_272 1 Patient_272 1
Patient_273 1 Patient_273 1
Patient_274 2 Patient_274 2
Patient_275 3 Patient_275 3
Patient_277 2 Patient_277 2
Patient_279 2 Patient_279 2
Patient_283 3 Patient_283 3
Patient_287 2 Patient_287 2
Patient_289 3 Patient_289 3
Patient_290 3 Patient_290 3
Patient_297 2 Patient_297 2
Patient_300 3 Patient_300 3
Patient_305 3 Patient_305 3
Patient_307 1 Patient_307 1
Patient_309 2 Patient_309 2
Patient_315 2 Patient_315 2
Patient_317 2 Patient_317 2
Patient_323 2 Patient_323 2
Patient_324 1 Patient_324 1
Patient_327 1 Patient_327 1
Patient_333 2 Patient_333 2
Patient_335 1 Patient_335 1
Patient_338 3 Patient_338 3
Patient_345 2 Patient_345 2
Patient_356 2 Patient_356 2
Patient_357 3 Patient_357 3
Patient_358 2 Patient_358 2
Patient_362 1 Patient_362 1
Patient_364 1 Patient_364 1
Patient_367 3 Patient_367 3
Patient_375 1 Patient_375 1
Patient_385 2 Patient_385 2
Patient_386 2 Patient_386 2
Patient_387 3 Patient_387 3
Patient_388 2 Patient_388 2
Patient_395 2 Patient_395 2
Patient_400 1 Patient_400 1
Patient_403 1 Patient_403 1
Patient_409 3 Patient_409 1
Patient_413 1 Patient_413 1
Patient_128 2
Patient_130 3
Patient_152 3
Patient_165 3
Patient_231 1
Patient_234 3
Patient_241 3
Patient_257 2
Patient_270 2
Patient_271 2
Patient_285 3
Patient_291 1
Patient_293 3
Patient_302 2
Patient_311 1
Patient_312 3
Patient_342 2
Patient_343 2
Patient_379 2
Table S6. Regulatory signaling pathways significantly associated with each cluster.
Each cluster is associated with up-regulated (≥ 1.0 fold change) or down-regulated (< 1.0
fold change) signaling pathways as determined by individual gene expression and copy
number variation data (CNV) integrated using the Pathway Recognition Algorithm Using
Data Integration on Genomic Models (PARADIGM). Only signaling pathways with a false
discovery rate (FDR or q-value) <5% are included. Signaling pathways are ranked in
descending order of fold changes.
Signaling pathway Fold
change
q-value
(%)
Cluster 1 Signaling events mediated by stem cell factor receptor (c-Kit) 1.033 0
Cluster 2 Insulin-mediated glucose transport 1.005 3.4
Signaling events mediated by prolactin (PRL) 0.997 4.5
Platelet-derived growth factor receptor-alpha (PDGFR-α)
signaling pathway
0.997 0
Reelin signaling pathway 0.997 4.5
Vascular endothelial growth factor receptor 1 (VEGFR1)–
specific signals
0.996 4.5
Polo-like kinase 1 (PLK1) signaling events 0.996 4.5
Regulation of nuclear mothers against decapentaplegic homolog
2/3 (SMAD2/3) signaling
0.995 4.5
Signaling events mediated by protein-tyrosine phosphatase 1B
(PTP1B)
0.995 4.5
Osteopontin-mediated events 0.995 4.5
Signaling events activated by hepatocyte growth factor receptor
(c-Met)
0.994 4.5
Alpha-M beta-2 (αMβ2) Integrin signaling 0.994 4.5
Syndecan-1–mediated signaling events 0.993 4.5
Erythropoietin (EPO) signaling pathway 0.993 4.5
Endothelins 0.991 0
Forkhead box protein A2 (FOXA2) and FOXA3 transcription
factor networks
0.991 0
Signaling events mediated by vascular endothelial growth factor
receptor 1 (VEGFR1) and VEGFR2
0.991 0
Interleukin 6 (IL6)–mediated signaling events 0.989 0
Angiopoietin receptor Tie2-mediated signaling 0.988 0
IL23-mediated signaling events 0.981 0
Signaling events mediated by c-Kit 0.976 0
Forkhead box protein M1 (FOXM1) transcription factor
network
0.965 0
Cluster 3 FOXA2 and FOXA3 transcription factor networks 1.013 0
PDGFR-β signaling pathway 1.013 0
Endothelins 1.012 0
Thromboxane A2 receptor signaling 1.012 0
Syndecan-4–mediated signaling events 1.012 3.62
Syndecan-1–mediated signaling events 1.011 0
IL6–mediated signaling events 1.010 3.62
Osteopontin-mediated events 1.010 0
Fc-ε receptor I signaling in mast cells 1.009 0
αMβ2 Integrin signaling 1.009 0
Angiopoietin receptor Tie2-mediated signaling 1.009 3.62
PTP1B 1.008 0
B cell receptor (BCR) signaling pathway 1.007 3.62
Retinoic acid receptor and retinoid X receptor (RXR and RAR)
heterodimerization with other nuclear receptor
1.006 0
Atypical nuclear factor-κ B pathway 1.005 0
PLK1 signaling events 1.005 0
Ceramide signaling pathway 1.005 0
Noncanonical Wnt signaling pathway 1.005 3.62
SMAD2/3 signaling 1.005 3.62
T cell receptor (TCR) signaling in naïve CD8+ T cells 1.005 3.62
IL1–mediated signaling events 1.005 0
Calcium signaling in the CD4+ TCR pathway 1.005 0
Ras signaling in the CD4+ TCR pathway 1.005 3.62
Nongenotropic androgen signaling 1.004 0
Regulation of p38-α and p38-β 1.004 3.62
VEGFR1–specific signals 1.004 0
E-cadherin signaling in the nascent adherens junction 1.004 3.62
PRL 1.004 0
PDGFR-α signaling pathway 1.004 0
IL27–mediated signaling events 1.003 3.62
Canonical Wnt signaling pathway 1.003 3.62