Dong X. et. al. "Modeling gene expression using chromatin features in various cellular contexts"

2012/09/29 ENCODE 勉強会

Transcript

1. Dong X et. al. Modeling gene
   expression using chromatin features in
   various cellular contexts
   2012/09/29 ENCODE ษڧձ
   ೋ֊ಊѪ / @dritoshi #encodejp-28
   ཧԽֶݚڀॴ ൃੜɾ࠶ੜՊֶ૯߹ݚڀηϯλʔ
   

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2. ͜ͷࢿྉͷ࠷৽൛ͷҎԼʹ͋Γ·͢
   http://cat.hackingisbelieving.org/lecture/
   ͜ͷϑΝΠϧ͸ ΫϦΤΠςΟϒɾίϞϯζ දࣔ 2.0 Ұൠ ϥΠηϯεͷԼʹఏڙ͞Ε͍ͯ·͢ɻ
   http://genomebiology.com/content/13/9/R53
   “catway dritoshi” Ͱݕࡧ
   

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3. Chromatin features ͔ΒҨ఻ࢠൃݱ͕༧ଌͰ͖Δ͔?
   4ͭͷ໰͍
   1. Can we reproduce the quantitative relationship between
   gene expression levels and histone modifications?
   2. Does the relationship hold across different human cell lines
   and between different groups of genes?
   3. Do the most predictive chromatin features differ depending
   on the expression quantification technique used?
   4. How well can the chromatin features predict expression
   levels of RNA from different cell compartments and/or RNA
   extracted by different
   

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4. Chromatin features ͕సࣸΛ੍ޚ͢Δ
   Ҩ఻ࢠपลͷώετϯम০, ΫϩϚνϯߏ଄ʹΑΔస੍ࣸޚ
   7 histone modifications
   1 histone variant
   DNase I hypersensitivity in 7 cell
   Cause = Chromatin feature
   RNA-seq
   RNA-PET
   deepCAGE
   Effect = transcription
   Cause = Chromatin feature
   Effect = transcription
   

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5. Chromatin featuresͷσʔλΛදݱ
   Ҩ఻ࢠपลͷώετϯम০, ΫϩϚνϯߏ଄ͷϕΫτϧΛ࡞Δ
   

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6. RNAసࣸྔσʔλͷදݱ
   స͕ࣸON/OFFͷҨ఻ࢠʹ෼͚ͯ͠·͏
   Random forests ͰON/OFFͷ2܈ʹ෼ྨ͢Δ
   

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7. ϞσϧԽ͢Δ
   ճؼϞσϧ
   1. Linear regression
   2. multivariate adaptive regression splines (MARS)
   3. Random forests
   

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8. ϞσϧΛ౷߹͢Δ
   ෼ྨ*ճؼϞσϧ
   

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9. ϞσϧΛධՁ͢Δ
   ༧ଌͱ࣮ଌΛൺֱ͢Δ
   

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10. ༧ଌੑೳ1
    ༧ଌͱ࣮ଌΛൺֱ͢Δ
    

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11. ༧ଌੑೳ2
    ༧ଌͱ࣮ଌΛൺֱ͢Δ
    

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12. ·ͱΊ1
    chromatin features ͔Βసࣸྔ͕ྑ͘༧ଌͰ͖Δ
    0. chromatin features ͷసࣸ΁ͷӨڹΛఆྔతʹධՁͰ͖ͨ
    ൃݱON/OFF: H3K9ac > H3K4me3 > DNase I > H3K4me2 ...
    సࣸྔ: H3K79me2 > H3K36me3 > DNase I > H3K9ac ...
    1. 2ஈ֊ͷ༧ଌํ๏ΛఏҊ
    ON/OFFͷ෼ྨͱճؼϞσϧ
    

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13. ·ͱΊ2
    ΄͔ʹٞ࿦͞Ε͍ͯΔ͜ͱ
    1. Nucleus, Cytosol, Whole Cell ༝དྷͷRNAྔΛ༧ଌͰ͖Δ͔?
    Ͱ͖ΔɻCytosol > Whole Cell >> Nucleus
    2. RNA-seq, CAGE, RNA-PETͷͲΕ͕chromatin featuresͱͷ૬
    ͕ؔߴ͍͔?
    CAGE > RNA-PET = RNA-seq
    3. ΄͔ͷࡉ๔ͷసࣸྔΛઆ໌Ͱ͖Δ͔?
    R = 0.8 ఔ౓Ͱ
    4. CpGͱͷؔ࿈͸?
    High CpG ͷ΄͏͕༧ଌ͕Α͍
    

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14. ͜͏ߟ͑Δ
    Α͔ͬͨ͜ͱͱ࢒͞Εͨ՝୊
    Α͔ͬͨ͜ͱ
    1. ༧ଌͰ͖ͨͷ͸Α͔ͬͨͶ
    2. chromatin features ͷͦΕͧΕͷॏཁੑ͕Θ͔ͬͨͷ͸Α͔
    ͬͨ
    ՝୊
    1. bestbin Λ૬ؔͰऔ͍ͬͯΔͷ͸͍͍ͷ͔ͳ?
    2. ౷ܭϞσϧͰ͍͍ͷ͔ͳ? Ϟϊͷಈ͖͕Θ͔Βͳ͍
    3. CAGE, RNA-seq, RNA-PET͕ൺֱͰ͖Δ΄ͲϑΣΞ?
    4. Ҩ఻ࢠʹண໨ͨٞ͠࿦΋ཉ͍͠ΑͶ
    5. ༧ଌ݁Ռ͔ΒసࣸΛσβΠϯͰ͖Δͷ͔?
    

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15. Software
    ෼ྨ΍ճؼͳͲ
    Calculation of the mean density of chromatin features
    bigWigSummary: BigWig and BigBed: enabling browsing of large
    distributed datasets
    Variable importance
    relaimpo: Relative importance of regressors in linear models
    Regression/classification
    randomForest: Breiman and Cutler's random forests for
    classification and regression
    Regression
    earth: Multivariate Adaptive Regression Spline Models
    

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16. ͜ͷࢿྉͷ࠷৽൛ͷҎԼʹ͋Γ·͢
    http://cat.hackingisbelieving.org/lecture/
    ͜ͷϑΝΠϧ͸ ΫϦΤΠςΟϒɾίϞϯζ දࣔ 2.0 Ұൠ ϥΠηϯεͷԼʹఏڙ͞Ε͍ͯ·͢ɻ
    http://genomebiology.com/content/13/9/R53
    “catway dritoshi” Ͱݕࡧ
    

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