a multitask multiple kernel learning algorithm for survival ...12-11-00)-12...2000/12/11  · a...

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A Multitask Multiple Kernel Learning Algorithm for Survival Analysis with Application to Cancer Biology Onur Dereli, Ceyda O˘ guz, Mehmet Gönen Koç University, ˙ Istanbul, Turkey [email protected] [email protected] [email protected] June 12, 2019 / Long Beach Dereli, O., O˘ guz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 1/9

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  • A Multitask Multiple Kernel Learning Algorithm forSurvival Analysis

    with Application to Cancer Biology

    Onur Dereli, Ceyda Oğuz, Mehmet Gönen

    Koç University, İstanbul, [email protected] [email protected] [email protected]

    June 12, 2019 / Long Beach

    Dereli, O., Oğuz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 1 / 9

  • Proposed Approach

    Gene set1G1

    G3

    G6

    G17

    G19

    G28

    G42

    ···

    Gene setP

    G8

    G12

    G19

    G25

    G42

    G47

    ···

    ···

    X1

    XT

    Genes

    Patie

    nts

    Genes

    Patie

    nts

    Genes

    Patients

    Genes

    Patients

    X1,1

    X1,P

    ···

    Genes

    Patients

    Genes

    Patients

    XT,1

    XT,P

    ···

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    K1,1

    K1,P

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    KT,1

    KT,P

    η1

    ηP

    ···

    η1

    ηP

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    K1,η

    KT,η

    Multitaskmultiple kernel learning

    f1

    Survivalanalysis Vital Days to Days to last

    status death follow-upAlive NA 678Dead 364 NA...

    ......

    Alive NA 2555Dead 520 NA

    Y1

    ···

    ···

    fT

    Survivalanalysis Vital Days to Days to last

    status death follow-upDead 456 NADead 3200 NA...

    ......

    Alive NA 2208Dead 1891 NA

    YT

    Dereli, O., Oğuz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 2 / 9

  • Proposed Approach

    Gene set1G1

    G3

    G6

    G17

    G19

    G28

    G42

    ···

    Gene setP

    G8

    G12

    G19

    G25

    G42

    G47

    ···

    ···

    X1

    XT

    Genes

    Patie

    nts

    Genes

    Patie

    nts

    Genes

    Patients

    Genes

    Patients

    X1,1

    X1,P

    ···

    Genes

    Patients

    Genes

    Patients

    XT,1

    XT,P

    ···

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    K1,1

    K1,P

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    KT,1

    KT,P

    η1

    ηP

    ···

    η1

    ηP

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    K1,η

    KT,η

    Multitaskmultiple kernel learning

    f1

    Survivalanalysis Vital Days to Days to last

    status death follow-upAlive NA 678Dead 364 NA...

    ......

    Alive NA 2555Dead 520 NA

    Y1

    ···

    ···

    fT

    Survivalanalysis Vital Days to Days to last

    status death follow-upDead 456 NADead 3200 NA...

    ......

    Alive NA 2208Dead 1891 NA

    YT

    Dereli, O., Oğuz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 2 / 9

  • Proposed Approach

    Gene set1G1

    G3

    G6

    G17

    G19

    G28

    G42

    ···

    Gene setP

    G8

    G12

    G19

    G25

    G42

    G47

    ···

    ···

    X1

    XT

    Genes

    Patie

    nts

    Genes

    Patie

    nts

    Genes

    Patients

    Genes

    Patients

    X1,1

    X1,P

    ···

    Genes

    Patients

    Genes

    Patients

    XT,1

    XT,P

    ···

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    K1,1

    K1,P

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    KT,1

    KT,P

    η1

    ηP

    ···

    η1

    ηP

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    K1,η

    KT,η

    Multitaskmultiple kernel learning

    f1

    Survivalanalysis Vital Days to Days to last

    status death follow-upAlive NA 678Dead 364 NA...

    ......

    Alive NA 2555Dead 520 NA

    Y1

    ···

    ···

    fT

    Survivalanalysis Vital Days to Days to last

    status death follow-upDead 456 NADead 3200 NA...

    ......

    Alive NA 2208Dead 1891 NA

    YT

    Dereli, O., Oğuz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 2 / 9

  • Proposed Approach

    Gene set1G1

    G3

    G6

    G17

    G19

    G28

    G42

    ···

    Gene setP

    G8

    G12

    G19

    G25

    G42

    G47

    ···

    ···

    X1

    XT

    Genes

    Patie

    nts

    Genes

    Patie

    nts

    Genes

    Patients

    Genes

    Patients

    X1,1

    X1,P

    ···

    Genes

    Patients

    Genes

    Patients

    XT,1

    XT,P

    ···

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    K1,1

    K1,P

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    KT,1

    KT,P

    η1

    ηP

    ···

    η1

    ηP

    ···

    Patients

    Patients

    ···

    Patients

    Patients

    K1,η

    KT,η

    Multitaskmultiple kernel learning

    f1

    Survivalanalysis Vital Days to Days to last

    status death follow-upAlive NA 678Dead 364 NA...

    ......

    Alive NA 2555Dead 520 NA

    Y1

    ···

    ···

    fT

    Survivalanalysis Vital Days to Days to last

    status death follow-upDead 456 NADead 3200 NA...

    ......

    Alive NA 2208Dead 1891 NA

    YT

    Dereli, O., Oğuz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 2 / 9

  • Multitask Survival MKL Formulation

    minimizeT∑

    t=1

    [12

    w>t w t + CNt∑

    i=1

    (ξ+ti + (1− δti)ξ−ti )

    ]with respect to w t ∈ RDt , ξ+t ∈ R

    Nt , ξ−t ∈ RNt , bt ∈ R

    subject to �+ ξ+ti ≥ yti −w>t x ti − bt ∀(t , i)

    �+ ξ−ti ≥ w>t x ti + bt − yti ∀(t , i)

    ξ+ti ≥ 0 ∀(t , i)ξ−ti ≥ 0 ∀(t , i)

    Dereli, O., Oğuz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 3 / 9

  • Multitask Survival MKL Formulation

    minimize −T∑

    t=1

    Nt∑i=1

    yti(α+ti − α−ti ) + �

    T∑t=1

    Nt∑i=1

    (α+ti + α−ti )

    +12

    T∑t=1

    Nt∑i=1

    Nt∑j=1

    (α+ti − α−ti )(α

    +tj − α

    −tj )

    P∑m=1

    ηmkm(x ti ,x tj)

    with respect to α+t ∈ RNt , α−t ∈ R

    Nt , η ∈ RP

    subject toNt∑

    i=1

    (α+ti − α−ti ) = 0 ∀t

    C ≥ α+ti ≥ 0 ∀(t , i)C(1− δti) ≥ α−ti ≥ 0 ∀(t , i)

    P∑m=1

    ηm = 1

    ηm ≥ 0 ∀m

    Dereli, O., Oğuz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 3 / 9

  • Multitask Survival MKL Formulation

    η(s+1)m =

    T∑t=1

    η(s)m

    √Nt∑

    i=1

    Nt∑j=1

    α(s)ti α

    (s)tj km(x ti ,x tj)

    T∑t=1

    P∑o=1

    η(s)o

    √Nt∑

    i=1

    Nt∑j=1

    α(s)ti α

    (s)tj ko(x ti ,x tj)

    ∀m

    Dereli, O., Oğuz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 3 / 9

  • Data Sets

    ●BLCA(402)

    BRCA(1067)

    CESC(291)

    COAD(433)

    ESCA(160)

    GBM(152)

    HNSC(498)

    KIRC(526)

    KIRP(285)

    LAML(130)

    LGG(506)

    LIHC(365)

    LUAD(500)

    LUSC(493)

    OV(372)

    PAAD(176)

    READ(156)

    SARC(256)

    STAD(348)

    UCEC(539)

    • 20 cancer data sets from TCGA databaseGene expression profiles and survival characteristics

    • Hallmark Gene Set [1] & PID Pathway [2] Collections

    Dereli, O., Oğuz, C., Gönen, M. (KU) ICML 2019 June 12, 2019 / Long Beach 4 / 9

  • BLCA

    p < 1e−3p = 0.640

    p < 1e−3p = 0.016

    p < 1e−3

    p < 1e−3 p < 1e−3

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    BRCA

    p < 1e−3p < 1e−3

    p < 1e−3p < 1e−3

    p < 1e−3

    p < 1e−3 p = 0.023

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    CESC

    p < 1e−3p < 1e−3

    p < 1e−3p < 1e−3

    p < 1e−3

    p < 1e−3 p < 1e−3

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    COAD

    p < 1e−3p < 1e−3

    p < 1e−3p < 1e−3

    p = 0.086

    p = 0.012 p < 1e−3

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    ESCA

    p = 0.009p = 0.360

    p = 0.074p = 0.834

    p = 0.656

    p = 0.313 p = 0.740

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    0.3

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    0.9

    GBM

    p < 1e−3p < 1e−3

    p < 1e−3p < 1e−3

    p < 1e−3

    p < 1e−3 p = 0.681

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    HNSC

    p < 1e−3p < 1e−3

    p < 1e−3p < 1e−3

    p < 1e−3

    p < 1e−3 p < 1e−3

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    KIRC

    p = 0.030p < 1e−3

    p = 0.778p = 0.083

    p = 0.331

    p < 1e−3 p < 1e−3

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    KIRP

    p = 0.230p = 0.833

    p = 0.888p = 0.096

    p = 0.592

    p = 0.866 p = 0.006●

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    1.0

    LAML

    p < 1e−3p = 0.001

    p = 0.325p < 1e−3

    p = 0.931

    p < 1e−3 p < 1e−3

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    LGG

    p < 1e−3p = 0.026

    p = 0.803p = 0.541

    p = 0.483

    p < 1e−3 p = 0.922

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    LIHC

    p = 0.349p = 0.505

    p = 0.003p = 0.620

    p = 0.008

    p = 0.004 p < 1e−3

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    LUAD

    p < 1e−3p < 1e−3

    p < 1e−3p < 1e−3

    p < 1e−3

    p < 1e−3 p < 1e−3

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    LUSC

    p < 1e−3p < 1e−3

    p < 1e−3p < 1e−3

    p < 1e−3

    p < 1e−3 p < 1e−3

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    OV

    p < 1e−3p < 1e−3

    p < 1e−3p = 0.001

    p < 1e−3

    p < 1e−3 p < 1e−3

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    PAAD

    p < 1e−3p < 1e−3

    p < 1e−3p < 1e−3

    p < 1e−3

    p < 1e−3 p = 0.001

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