splice variants as novel targets in pancreac ductal ...€¦ · splice variants as novel targets in...
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Splicevariantsasnoveltargetsinpancrea0cductaladenocarcinoma
JunWang1,LaurentDumar0n1,AndreaMafficini2,PinarUlug1,AjanthahSangaralingam1,NamaaAudiAlamiry1,TomaszPRadon1,RobertoSalvia2,RitaTLawlor2,NicholasRLemoine1,AldoScarpa2,ClaudeChelala1,#andTatjanaCrnogorac-Jurcevic1,#
1CentreforMolecularOncology,BartsCancerIns0tute,QueenMaryUniversityofLondon,London,UK;2ARC-NetResearchCentreandDepartmentofDiagnos0csandPublichHealth,Sec0onofPathology,UniversityandHospitalTrustofVerona,Verona,Italy#TheseauthorsjointlysupervisedthisworkCorrespondenceandrequestsformaterialsshouldbeaddressedtoJ.W.(email:[email protected])orT.C.J.(email:[email protected])
Figure S1. Unsupervised hierarchical clustering based on probeset (A) and transcript (B) expression level
A B
Figure S2. Gene expression and sample clustering of Collisson signature (62 genes) in BCI and Zhang merged dataset
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log2 (Probeset expression) mean
log2 (FIRMA score) mean
log2 (FIRMA FC)
p_37
6220
0p_
3762
201
p_37
6220
2p_
3762
203
p_37
6220
4p_
3762
206
p_37
6220
7p_
3762
208
p_37
6221
0p_
3762
211
p_37
6221
2p_
3762
213
p_37
6221
5p_
3762
217
p_37
6221
8p_
3762
221
p_37
6222
2p_
3762
227
p_37
6222
8p_
3762
234
p_37
6223
6p_
3762
238
p_37
6223
9p_
3762
241
p_37
6224
2p_
3762
244
p_37
6224
5p_
3762
250
p_37
6225
7p_
3762
258
p_37
6226
0p_
3762
262
p_37
6226
3p_
3762
267
p_37
6226
8p_
3762
269
p_37
6227
0
−10
−5
0
5
10
15
−10
−5
0
5
10
15
−10
−5
0
5
10
15
● Normal PDAC log2FC(PDAC/normal)
Transcription direction
Figure S3A. alternative splicing in COL1A1
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log2 (Probeset expression) mean
log2 (FIRMA score) mean
log2 (FIRMA FC)
p_32
8419
1
p_32
8419
8
p_32
8419
9
p_32
8420
4
p_32
8420
5
p_32
8420
6
p_32
8420
7
p_32
8420
8
p_32
8421
0
p_32
8421
1
p_32
8421
3
p_32
8421
4
p_32
8421
5
p_32
8421
7
p_32
8421
8
p_32
8422
1
p_32
8423
0
p_32
8423
2
−5
0
5
10
−5
0
5
10
−5
0
5
10
● Normal PDAC log2FC(PDAC/normal)
Transcription direction
Figure S3B. alternative splicing in ITGB1
0 1 2 3 4 5 6
Expr
essi
on ra
tio
(PD
AC
ove
r nor
mal
)
0 1 2 3 4 5 6
Expr
essi
on ra
tio
(PD
AC
ove
r nor
mal
)
A B
Figure S4. The expression ratio (PDAC over normal) of AS probesets and gene for ROBO1 and LRP8
A B
Figure S5A/B. Expression fold changes for TGFBR1, CALD1 and MACF1 in gene and probeset/exon levels
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log2 (FIRMA FC)
log2 (FIRMA score) mean
log2 (Probeset expression) mean
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0
5
10
−5
0
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−5
0
5
10
p_31
8173
0
p_31
8174
7
p_31
8174
8
p_31
8175
2
p_31
8175
4
p_31
8175
6
p_31
8175
8
p_31
8176
0
p_31
8176
2
p_31
8176
3
p_31
8176
4
p_31
8176
5
p_31
8176
6
p_31
8176
7
● Normal PDAC log2FC(PDAC/normal)
Transcription direction
Figure S5C. Alternative splicing in TGFBR1
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log2 (FIRMA FC)
log2 (FIRMA score) mean
log2 (Probeset expression) mean
−5
0
5
10
−5
0
5
10
−5
0
5
10
p_30
2555
3p_
3025
554
p_30
2558
1p_
3025
587
p_30
2558
8p_
3025
612
p_30
2562
6p_
3025
628
p_30
2562
9p_
3025
630
p_30
2563
1p_
3025
632
p_30
2563
5p_
3025
644
p_30
2565
0p_
3025
653
p_30
2565
4p_
3025
655
p_30
2565
8p_
3025
659
p_30
2566
0p_
3025
661
p_30
2566
2p_
3025
663
p_30
2566
8p_
3025
673
p_30
2567
4p_
3025
675
p_30
2567
6p_
3025
677
● Normal PDAC log2FC(PDAC/normal)
Transcription direction
Figure S5D. Alternative splicing in CALD1
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log2 (FIRMA FC)
log2 (FIRMA score) mean
log2 (Probeset expression) mean
−5
0
5
10
−5
0
5
10
−5
0
5
10
p_23
3122
0p_
2331
221
p_23
3127
9p_
2331
282
p_23
3128
5p_
2331
299
p_23
3130
1p_
2331
302
p_23
3130
4p_
2331
306
p_23
3130
7p_
2331
308
p_23
3131
0p_
2331
311
p_23
3131
3p_
2331
314
p_23
3131
5p_
2331
316
p_23
3131
9p_
2331
325
p_23
3132
7p_
2331
328
p_23
3132
9p_
2331
330
p_23
3133
1p_
2331
332
p_23
3133
3p_
2331
334
p_23
3133
5p_
2331
337
p_23
3134
1p_
2331
342
p_23
3134
4p_
2331
347
p_23
3135
2p_
2331
353
p_23
3135
4p_
2331
355
p_23
3135
6p_
2331
357
p_23
3135
8p_
2331
359
p_23
3136
0p_
2331
361
p_23
3136
2p_
2331
364
p_23
3136
6p_
2331
368
p_23
3137
1p_
2331
372
p_23
3137
3p_
2331
374
p_23
3137
5p_
2331
376
p_23
3137
8p_
2331
379
p_23
3138
0p_
2331
383
p_23
3138
4p_
2331
387
p_23
3138
8p_
2331
390
p_23
3139
1p_
2331
392
p_23
3139
4p_
2331
395
p_23
3139
7p_
2331
398
p_23
3141
9p_
2331
420
p_23
3142
1p_
2331
422
p_23
3142
3p_
2331
426
p_23
3142
8p_
2331
429
p_23
3143
0p_
2331
431
p_23
3143
2p_
2331
433
p_23
3143
5p_
2331
436
p_23
3143
7p_
2331
438
p_23
3143
9p_
2331
440
p_23
3144
1p_
2331
442
p_23
3144
3p_
2331
444
p_23
3144
5p_
2331
446
p_23
3144
7p_
2331
448
p_23
3144
9p_
2331
451
p_23
3145
2p_
2331
454
p_23
3145
5p_
2331
457
p_23
3145
9p_
2331
461
p_23
3146
3p_
2331
465
p_23
3146
6p_
2331
468
p_23
3147
3p_
2331
479
p_23
3148
1p_
2331
484
p_23
3148
5p_
2331
486
p_23
3148
7p_
2331
488
p_23
3148
9
● Normal PDAC log2FC(PDAC/normal)
Transcription direction
Figure S5E. Alternative splicing in MACF1
Down Adj. p < 0.05 Up
Adj. p < 0.05
Figure S6. The DE signatures for previously reported spliceosomal genes