Splice variants as novel targets in pancreac ductal ... Splice variants as novel targets in pancreac

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  • Splice variants as novel targets in pancrea0c ductal adenocarcinoma

    Jun Wang1, Laurent Dumar0n1, Andrea Mafficini2, Pinar Ulug1, Ajanthah Sangaralingam1, Namaa Audi Alamiry1, Tomasz P Radon1, Roberto Salvia2, Rita T Lawlor2, Nicholas R Lemoine1, Aldo Scarpa2, Claude Chelala1,# and Tatjana Crnogorac-Jurcevic1,#

    1 Centre for Molecular Oncology, Barts Cancer Ins0tute, Queen Mary University of London, London, UK; 2 ARC-Net Research Centre and Department of Diagnos0cs and Publich Health, Sec0on of Pathology, University and Hospital Trust of Verona, Verona, Italy #These authors jointly supervised this work Correspondence and requests for materials should be addressed to J.W. (email: j.a.wang@qmul.ac.uk) or T.C.J. (email: t.c.jurcevic@qmul.ac.uk)

  • 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

    62 20

    0 p_

    37 62

    20 1

    p_ 37

    62 20

    2 p_

    37 62

    20 3

    p_ 37

    62 20

    4 p_

    37 62

    20 6

    p_ 37

    62 20

    7 p_

    37 62

    20 8

    p_ 37

    62 21

    0 p_

    37 62

    21 1

    p_ 37

    62 21

    2 p_

    37 62

    21 3

    p_ 37

    62 21

    5 p_

    37 62

    21 7

    p_ 37

    62 21

    8 p_

    37 62

    22 1

    p_ 37

    62 22

    2 p_

    37 62

    22 7

    p_ 37

    62 22

    8 p_

    37 62

    23 4

    p_ 37

    62 23

    6 p_

    37 62

    23 8

    p_ 37

    62 23

    9 p_

    37 62

    24 1

    p_ 37

    62 24

    2 p_

    37 62

    24 4

    p_ 37

    62 24

    5 p_

    37 62

    25 0

    p_ 37

    62 25

    7 p_

    37 62

    25 8

    p_ 37

    62 26

    0 p_

    37 62

    26 2

    p_ 37

    62 26

    3 p_

    37 62

    26 7

    p_ 37

    62 26

    8 p_

    37 62

    26 9

    p_ 37

    62 27

    0

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    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

    84 19

    1

    p_ 32

    84 19

    8

    p_ 32

    84 19

    9

    p_ 32

    84 20

    4

    p_ 32

    84 20

    5

    p_ 32

    84 20

    6

    p_ 32

    84 20

    7

    p_ 32

    84 20

    8

    p_ 32

    84 21

    0

    p_ 32

    84 21

    1

    p_ 32

    84 21

    3

    p_ 32

    84 21

    4

    p_ 32

    84 21

    5

    p_ 32

    84 21

    7

    p_ 32

    84 21

    8

    p_ 32

    84 22

    1

    p_ 32

    84 23

    0

    p_ 32

    84 23

    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

    Ex pr

    es si

    on ra

    tio

    (P D

    A C

    o ve

    r n or

    m al

    )

    0 1 2 3 4 5 6

    Ex pr

    es si

    on ra

    tio

    (P D

    A C

    o ve

    r n or

    m al

    )

    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

    −5

    0

    5

    10

    −5

    0

    5

    10

    −5

    0

    5

    10

    p_ 31

    81 73

    0

    p_ 31

    81 74

    7

    p_ 31

    81 74

    8

    p_ 31

    81 75

    2

    p_ 31

    81 75

    4

    p_ 31

    81 75

    6

    p_ 31

    81 75

    8

    p_ 31

    81 76

    0

    p_ 31

    81 76

    2

    p_ 31

    81 76

    3

    p_ 31

    81 76

    4

    p_ 31

    81 76

    5

    p_ 31

    81 76

    6

    p_ 31

    81 76

    7

    ● Normal PDAC log2FC(PDAC/normal)

    Transcription direction

    Figure S5C. Alternative splicing in TGFBR1

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    log2 (FIRMA score) mean

    log2 (Probeset expression) mean

    −5

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    p_ 30

    25 55

    3 p_

    30 25

    55 4

    p_ 30

    25 58

    1 p_

    30 25

    58 7

    p_ 30

    25 58

    8 p_

    30 25

    61 2

    p_ 30

    25 62

    6 p_

    30 25

    62 8

    p_ 30

    25 62

    9 p_

    30 25

    63 0

    p_ 30

    25 63

    1 p_

    30 25

    63 2

    p_ 30

    25 63

    5 p_

    30 25

    64 4

    p_ 30

    25 65

    0 p_

    30 25

    65 3

    p_ 30

    25 65

    4 p_

    30 25

    65 5

    p_ 30

    25 65

    8 p_

    30 25

    65 9

    p_ 30

    25 66

    0 p_

    30 25

    66 1

    p_ 30

    25 66

    2 p_

    30 25

    66 3

    p_ 30

    25 66

    8 p_

    30 25

    67 3

    p_ 30

    25 67

    4 p_

    30 25

    67 5

    p_ 30

    25 67

    6 p_

    30 25

    67 7

    ● Normal PDAC log2FC(PDAC/normal)

    Transcription direction

    Figure S5D. Alternative splicing in CALD1

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