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Supported by




Prominent international speakers from




             h"p://workshop.eisbm.eu1
EISBM 2012

                                      WikiBioPath
                        new perspectives in biological data analysis
                                     laurent Buffat, MD, PhD
                                    Simon de Bernard, X, PhD

mercredi 13 juin 2012                                                  1
Core expertise
                                                            Analysis & high level
                                                            interpretation of
                                                            bio-molecular data :
                                                               •   Transcriptomics
                                                               •   Proteomics
                                                               •   Genomics




                                                                            Pharmaco-genomics
                                                                            Functional Genomics

    Samples          Data       Bio-statistical   Interpretation
                   generation      analysis          Reports
                                                                                For research & industry in
                                        WikiBioPath                             the Life Sciences
                                   Integrative data analysis


mercredi 13 juin 2012                                                                                        2
Core expertise : application fields


                            Analysis & interpretation
                             & Data mIning of bio-
                                molecular data




                           Molecules
                            repositionning - new
                                                                              Biomarker discovery
                            market applications



                                                Pharmaco-genomics

     Pathway studies,                                     Functional Genomics
      Toxicity studies                                                                  Patient class
                                                                                         Identification /
                                                                                         support to
                                                                                         personalized
                                                                                         medecine
                                         Drug compound
                                          Optimization



mercredi 13 juin 2012                                                                                       3
Challenge
                                                Bio-statistical
                                                                  Interpretation
         Experimental Data                         analysis




                                                                                   Discovery
                        Data Warehouses


                                                           ?
                        Scientific litterature



                 Private / Public
mercredi 13 juin 2012                                                                      4
Knowledge integration
                                          Bio-statistical
                                                            Interpretation
           Data generation                   analysis




                                                                             Discovery
    Data Warehouses



                            Knowledge integration
    Scientific litterature
                            WikiBioPath

Private / Public
mercredi 13 juin 2012                                                                5
expression Experimental
           Data Analysis

             Experimental data
           •    MicroArray (Illumina, RNG/MRC, Agilent, Affymetrix, etc.)
           •    High Throughput Sequencing
           •    SNPs
           •    Copy Number
           •    GenoTyping




mercredi 13 juin 2012                                                       6
expression Experimental
           Data Analysis

        • PreProcessing & Quality Control
           •    Hybridization issues solving
           •    Background corrections
           •    Probeset summarization
           •    RNA degradation correction
           •    identification of annotations errors
           •    Correction of systematic bias
           •    etc.



mercredi 13 juin 2012                                 7
expression Experimental
           Data Analysis

    Statistical Analysis

 • Gene level:
   • expression level modelization                                                                                                                                                                                                                                                                                                                                                                                                   − KRT75
                                                                                                                                                                                                                                                                                                                                                                                                                                     − RNASE7
                                                                                                                                                                                                                                                                                                                                                                                                                                     − UPP1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − LCN2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − C4orf19
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SPRR2G
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SPRR2A
                                                                                                                                                                                                                                                                                                                                                                                                                                     − KRT17
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ODC1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − RPTN
                                                                                                                                                                                                                                                                                                                                                                                                                                     − HMGCS2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − DHRS9




     & visualization (linear models,
                                                                                                                                                                                                                                                                                                                                                                                                                                     − C14orf34
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SPRR3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TCHH
                                                                                                                                                                                                                                                                                                                                                                                                                                     − MMP3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − MMP10
                                                                                                                                                                                                                                                                                                                                                                                                                                     − S100A12
                                                                                                                                                                                                                                                                                                                                                                                                                                     − S100A7
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CCAR1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TAF1D
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TSPAN5
                                                                                                                                                                                                                                                                                                                                                                                                                                     − LEPROT
                                                                                                                                                                                                                                                                                                                                                                                                                                     − DNAJC1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SECISBP2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ANKRD11
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SFRS18
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PVRL4
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SMC3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − MALAT1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TAOK1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − HIST1H4C
                                                                                                                                                                                                                                                                                                                                                                                                                                     − USO1




           contrasts, multitesting correction)
                                                                                                                                                                                                                                                                                                                                                                                                                                     − M6PR
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TOP1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − LOC100131261
                                                                                                                                                                                                                                                                                                                                                                                                                                     − EPRS
                                                                                                                                                                                                                                                                                                                                                                                                                                     − FABP4
                                                                                                                                                                                                                                                                                                                                                                                                                                     − KRT9
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CHST2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SYNM
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SPRR4
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PI3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SPINK6
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IGFL1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IFIT3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IFIT1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IFIH1




     • statistical expression level
                                                                                                                                                                                                                                                                                                                                                                                                                                     − MX1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − XAF1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IFI44
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IFITM1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − DDX60
                                                                                                                                                                                                                                                                                                                                                                                                                                     − HLA−B
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ISG15
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IFITM3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IFI27
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IFI6
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PRSS23
                                                                                                                                                                                                                                                                                                                                                                                                                                     − YARS
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PCK2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ASNS
                                                                                                                                                                                                                                                                                                                                                                                                                                     − AARS
                                                                                                                                                                                                                                                                                                                                                                                                                                     − XBP1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TARS
                                                                                                                                                                                                                                                                                                                                                                                                                                     − MARS
                                                                                                                                                                                                                                                                                                                                                                                                                                     − HERPUD1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CHAC1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TUBE1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PSPH




       comparison
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SLC7A11
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SERPINE2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − BCHE
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CADM1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CBS
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SHMT2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − MOCOS
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PSAT1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − RCN1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ASS1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − NUPR1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − EIF4EBP1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PHGDH
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ECM2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − STC2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − S100P
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CH25H
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PHLDA1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SLC7A5
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ANKRD30BL
                                                                                                                                                                                                                                                                                                                                                                                                                                     − S100A7A
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TCN1




     • etc.
                                                                                                                                                                                                                                                                                                                                                                                                                                     − KCTD11
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ADM
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PPP1R3C
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ANGPTL4
                                                                                                                                                                                                                                                                                                                                                                                                                                     − C7orf68
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PFKFB3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ANKRD37
                                                                                                                                                                                                                                                                                                                                                                                                                                     − NDRG1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − FUT11
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SERPINE1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − MT1X
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PFKFB4
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PPFIA4
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PGF
                                                                                                                                                                                                                                                                                                                                                                                                                                     − LRMP
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IER3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − P4HA1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CA9
                                                                                                                                                                                                                                                                                                                                                                                                                                     − EGLN3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − DDIT4
                                                                                                                                                                                                                                                                                                                                                                                                                                     − FOS
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ALDOC
                                                                                                                                                                                                                                                                                                                                                                                                                                     − IGFBP3
                                                                                                                                                                                                                                                                                                                                                                                                                                     − NDUFA4L2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PFKP
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PTTG1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CLCA4
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SLC6A8
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ZNF395
                                                                                                                                                                                                                                                                                                                                                                                                                                     − MKNK2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − HOXC6
                                                                                                                                                                                                                                                                                                                                                                                                                                     − HMGB2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − NUAK1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TYRP1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − C15orf59
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SLC46A2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SLC1A6
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ALOX12
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SLC16A10
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TMEM99
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SLC45A4
                                                                                                                                                                                                                                                                                                                                                                                                                                     − GAN
                                                                                                                                                                                                                                                                                                                                                                                                                                     − ACPP
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CA6
                                                                                                                                                                                                                                                                                                                                                                                                                                     − RARRES1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − FAM83D
                                                                                                                                                                                                                                                                                                                                                                                                                                     − C1orf105
                                                                                                                                                                                                                                                                                                                                                                                                                                     − HSD11B1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SERPINB12
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TNNC1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − PTGS1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − TPX2
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SLC40A1
                                                                                                                                                                                                                                                                                                                                                                                                                                     − INHBB
                                                                                                                                                                                                                                                                                                                                                                                                                                     − KRT77
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CRNN
                                                                                                                                                                                                                                                                                                                                                                                                                                     − CASP14
                                                                                                                                                                                                                                                                                                                                                                                                                                     − SERPINB4




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mercredi 13 juin 2012                                                                                                                                                                                                                                                                                                                                                                                                                                 8
expression Experimental
           Data Analysis
       Statistical Analysis, Knowledge integration
    • Geneset level:
      • geneset based analyses / correlation identification
      • parametric analysis of geneset enrichment
                                             p−values

                                   < 1e−04              Broad:NAGASHIMA_EGF_SIGNALING
                                   < 1e−04              Broad:JIANG_HYPOXIA_NORMAL
                                   < 1e−04              Broad:MENSE_HYPOXIA
                                   < 1e−04              Broad:ZHOU_INFLAMMATORY_RESPONSE_LIVE
                                   < 1e−04              Broad:ZHOU_INFLAMMATORY_RESPONSE_LPS
                                   < 1e−04              ...
                                   0.00022              Broad:LEONARD_HYPOXIA
                                   0.00025              CTD:Carbaryl
                                   0.00032              CTD:Amiloride
                                   0.00038              CTD:Kainic Acid
                                   0.00050              positive regulation of response to stimulus (GO:0048584)
                                   0.00082              CTD:Buthionine Sulfoximine
                                   0.00085              Broad:BIOCARTA_TOLL_PATHWAY
                                   0.00085              serine family amino acid metabolic process (GO:0009069)
                                   0.00088              Broad:GOLDRATH_IMMUNE_MEMORY
                                   0.00097              Broad:SCIAN_INVERSED_TARGETS_OF_TP53_AND_TP73
                                   0.00112              neutral amino acid transport (GO:0015804)
                                   0.00133              CTD:allylpyrocatechol
                                   0.00160              CTD:temozolomide
                                   0.00178              CTD:2,4−dinitrotoluene
                                   0.00183              L2L:hypoxia_reg
                                   0.00198              Broad:GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_RED
                                   0.00252              CTD:Paraquat
                                   0.00258              One carbon pool by folate (KEGG:00670)
                                   0.00265              L2L:calres_mouse
                                   0.00267              Broad:SABATES_COLORECTAL_ADENOMA_SIZE
                                   0.00275              Broad:BREDEMEYER_RAG_SIGNALING_VIA_ATM_NOT_VIA_NFKB
                                   0.00300              CTD:butylbenzyl phthalate
                                   0.00300              CTD:Cocaine
                                   0.00300              Broad:ST_GAQ_PATHWAY
                                   0.00308              Broad:SCHLOSSER_MYC_TARGETS_AND_SERUM_RESPONSE
                                   0.00323              CTD:Diclofenac
                                   0.00340              secretion (GO:0046903)
                                   0.00352              positive regulation of endothelial cell migration (GO:0010595)
                                   0.00358              ...
                                   0.00385              Broad:GENTILE_UV_RESPONSE_CLUSTER_D6
                                   0.00390              nucleoside catabolic process (GO:0009164)
                                   0.00395              L2L:hdaci_colon_cursul
                                   0.00405              CTD:2−nitrotoluene
                                   0.00405              CTD:Platelet Activating Factor
                                   0.00417              CTD:Allopurinol
                                   0.00455              CTD:2,4−diaminotoluene
                                   0.00477              CTD:Pam(3)CSK(4) peptide
                                   0.00480              secretion by cell (GO:0032940)
                                   0.00505              protein amino acid O−linked glycosylation (GO:0006493)
                                   0.00513              CTD:bis(maltolato)oxovanadium(IV)
                                   0.00522              CTD:Apigenin
                                   0.00565              L2L:stress_genotoxic_specific
                                   0.00568              CTD:4−(4−fluorophenyl)−2−(4−hydroxyphenyl)−5−(4−pyridyl)imidazole
                                   0.00568              Broad:ST_GA13_PATHWAY
                                              PBS A
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mercredi 13 juin 2012                                                                                                       9
expression Experimental
           Data Analysis
       Population structuration
    • Structuring genes (hidden state models)




                         Distance from closest class
                                                                              New classes




                                                                              Known




                                                       Discriminative power
mercredi 13 juin 2012                                                                       10
expression Experimental
           Data Analysis
       Population structuration
    • Structuring genesets, knowledge integration
      • geneset based analyses / correlation identification
      • parametric analysis of geneset enrichment
                                      Pvalues               Concepts




              Genes       GeneSets                Samples
mercredi 13 juin 2012                                                  11
Interpretation of Data
             Analysis Results
             Why interpretation:
           • Data analysis: Crucial step
           • but need to contextualize results within the context
             of biological knowledge to turn data into really
             actionable results

            Interpretation challenges: Integrative Data Analysis
           • Gathering heterogeneous Knowledge and Data
             resources
           • Present Knowledge & Data in a manageable way

mercredi 13 juin 2012                                               12
Interpretation of Data
             Analysis Results
        WikiBioPath (in short):
        Web App with online specific tools for
        • storing/managing Knowledge & Data (K&D)
        • enriching/curating K&D
        • querying/exploring/visualizing / mining K&D

        Allows heterogeneous K&D integration into the
        interpretation process

        Will be available as Free & Open Source
        We are currently looking for collaborations / beta testers
mercredi 13 juin 2012                                                13
Web Portals/Apps, Applications                                                             Wikis
public/external + private/internal                                                        public/external + private/internal
                                       External AND/OR              External & WikiBioPath’s
                                       private Web Portals/         dedicated specialized
                                       Apps, Applications           Wikis (Genes, Proteins,
                                       (NCBI, Kegg, ... )           Diseases, ... )




                  WBP’s linking & “bridging”                       WBP’s specialized functionalities for
                              functionalities                      knowledge storing/querying/managing/...



                                         WikiBioPath Core
                                      Web based interface & online Tools for
                                  Data & Knowledge storing, managing, querying,
                                         visualizing, mining and more...

                         Text Mining based Search                    WBP’s specialized functionalities for
                         Engine & Explorer                            data storing/querying/managing/...



Textual Data (Unstructured data repositories)                                                  Data Warehouses
public/external + private/internal                                                          public/external + private/internal

                                       Bibliographical Databases    Experimental Data &
                                       with low structured          Experimental Data Analyses
                                       textual data                 Data Warehouses
                                       (Medline, own text           (Micro Array Exp. Data, Micro
                                       collection ...)              Array Analyses Results ...)


mercredi 13 juin 2012                                                                                                      14

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International speakers biological data analysis

  • 1. Supported by Prominent international speakers from h"p://workshop.eisbm.eu1
  • 2. EISBM 2012 WikiBioPath new perspectives in biological data analysis laurent Buffat, MD, PhD Simon de Bernard, X, PhD mercredi 13 juin 2012 1
  • 3. Core expertise Analysis & high level interpretation of bio-molecular data : • Transcriptomics • Proteomics • Genomics  Pharmaco-genomics  Functional Genomics Samples Data Bio-statistical Interpretation generation analysis Reports For research & industry in WikiBioPath the Life Sciences Integrative data analysis mercredi 13 juin 2012 2
  • 4. Core expertise : application fields Analysis & interpretation & Data mIning of bio- molecular data  Molecules repositionning - new  Biomarker discovery market applications  Pharmaco-genomics  Pathway studies,  Functional Genomics Toxicity studies  Patient class Identification / support to personalized medecine  Drug compound Optimization mercredi 13 juin 2012 3
  • 5. Challenge Bio-statistical Interpretation Experimental Data analysis Discovery Data Warehouses ? Scientific litterature Private / Public mercredi 13 juin 2012 4
  • 6. Knowledge integration Bio-statistical Interpretation Data generation analysis Discovery Data Warehouses Knowledge integration Scientific litterature WikiBioPath Private / Public mercredi 13 juin 2012 5
  • 7. expression Experimental Data Analysis Experimental data • MicroArray (Illumina, RNG/MRC, Agilent, Affymetrix, etc.) • High Throughput Sequencing • SNPs • Copy Number • GenoTyping mercredi 13 juin 2012 6
  • 8. expression Experimental Data Analysis • PreProcessing & Quality Control • Hybridization issues solving • Background corrections • Probeset summarization • RNA degradation correction • identification of annotations errors • Correction of systematic bias • etc. mercredi 13 juin 2012 7
  • 9. expression Experimental Data Analysis Statistical Analysis • Gene level: • expression level modelization − KRT75 − RNASE7 − UPP1 − LCN2 − C4orf19 − SPRR2G − SPRR2A − KRT17 − ODC1 − RPTN − HMGCS2 − DHRS9 & visualization (linear models, − C14orf34 − SPRR3 − TCHH − MMP3 − MMP10 − S100A12 − S100A7 − CCAR1 − TAF1D − TSPAN5 − LEPROT − DNAJC1 − SECISBP2 − ANKRD11 − SFRS18 − PVRL4 − SMC3 − MALAT1 − TAOK1 − HIST1H4C − USO1 contrasts, multitesting correction) − M6PR − TOP1 − LOC100131261 − EPRS − FABP4 − KRT9 − CHST2 − SYNM − SPRR4 − PI3 − SPINK6 − IGFL1 − IFIT3 − IFIT1 − IFIH1 • statistical expression level − MX1 − XAF1 − IFI44 − IFITM1 − DDX60 − HLA−B − ISG15 − IFITM3 − IFI27 − IFI6 − PRSS23 − YARS − PCK2 − ASNS − AARS − XBP1 − TARS − MARS − HERPUD1 − CHAC1 − TUBE1 − PSPH comparison − SLC7A11 − SERPINE2 − BCHE − CADM1 − CBS − SHMT2 − MOCOS − PSAT1 − RCN1 − ASS1 − NUPR1 − EIF4EBP1 − PHGDH − ECM2 − STC2 − S100P − CH25H − PHLDA1 − SLC7A5 − ANKRD30BL − S100A7A − TCN1 • etc. − KCTD11 − ADM − PPP1R3C − ANGPTL4 − C7orf68 − PFKFB3 − ANKRD37 − NDRG1 − FUT11 − SERPINE1 − MT1X − PFKFB4 − PPFIA4 − PGF − LRMP − IER3 − P4HA1 − CA9 − EGLN3 − DDIT4 − FOS − ALDOC − IGFBP3 − NDUFA4L2 − PFKP − PTTG1 − CLCA4 − SLC6A8 − ZNF395 − MKNK2 − HOXC6 − HMGB2 − NUAK1 − TYRP1 − C15orf59 − SLC46A2 − SLC1A6 − ALOX12 − SLC16A10 − TMEM99 − SLC45A4 − GAN − ACPP − CA6 − RARRES1 − FAM83D − C1orf105 − HSD11B1 − SERPINB12 − TNNC1 − PTGS1 − TPX2 − SLC40A1 − INHBB − KRT77 − CRNN − CASP14 − SERPINB4 PBS A PBS A PBS A PBS A PBS A PBS B PBS B PBS B PBS B PBS B None B None B None B None B None B None B T1 A T1 A T1 A T1 A T1 A T1 A T1 B T1 B T1 B T1 B T1 B T1 B T2 A T2 A T2 A T2 A T2 A T2 B T2 B T2 B T2 B T2 B T2 B T3 A T3 A T3 A T3 A T3 A T3 B T3 B T3 B T3 B T3 B T3 B mercredi 13 juin 2012 8
  • 10. expression Experimental Data Analysis Statistical Analysis, Knowledge integration • Geneset level: • geneset based analyses / correlation identification • parametric analysis of geneset enrichment p−values < 1e−04 Broad:NAGASHIMA_EGF_SIGNALING < 1e−04 Broad:JIANG_HYPOXIA_NORMAL < 1e−04 Broad:MENSE_HYPOXIA < 1e−04 Broad:ZHOU_INFLAMMATORY_RESPONSE_LIVE < 1e−04 Broad:ZHOU_INFLAMMATORY_RESPONSE_LPS < 1e−04 ... 0.00022 Broad:LEONARD_HYPOXIA 0.00025 CTD:Carbaryl 0.00032 CTD:Amiloride 0.00038 CTD:Kainic Acid 0.00050 positive regulation of response to stimulus (GO:0048584) 0.00082 CTD:Buthionine Sulfoximine 0.00085 Broad:BIOCARTA_TOLL_PATHWAY 0.00085 serine family amino acid metabolic process (GO:0009069) 0.00088 Broad:GOLDRATH_IMMUNE_MEMORY 0.00097 Broad:SCIAN_INVERSED_TARGETS_OF_TP53_AND_TP73 0.00112 neutral amino acid transport (GO:0015804) 0.00133 CTD:allylpyrocatechol 0.00160 CTD:temozolomide 0.00178 CTD:2,4−dinitrotoluene 0.00183 L2L:hypoxia_reg 0.00198 Broad:GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_RED 0.00252 CTD:Paraquat 0.00258 One carbon pool by folate (KEGG:00670) 0.00265 L2L:calres_mouse 0.00267 Broad:SABATES_COLORECTAL_ADENOMA_SIZE 0.00275 Broad:BREDEMEYER_RAG_SIGNALING_VIA_ATM_NOT_VIA_NFKB 0.00300 CTD:butylbenzyl phthalate 0.00300 CTD:Cocaine 0.00300 Broad:ST_GAQ_PATHWAY 0.00308 Broad:SCHLOSSER_MYC_TARGETS_AND_SERUM_RESPONSE 0.00323 CTD:Diclofenac 0.00340 secretion (GO:0046903) 0.00352 positive regulation of endothelial cell migration (GO:0010595) 0.00358 ... 0.00385 Broad:GENTILE_UV_RESPONSE_CLUSTER_D6 0.00390 nucleoside catabolic process (GO:0009164) 0.00395 L2L:hdaci_colon_cursul 0.00405 CTD:2−nitrotoluene 0.00405 CTD:Platelet Activating Factor 0.00417 CTD:Allopurinol 0.00455 CTD:2,4−diaminotoluene 0.00477 CTD:Pam(3)CSK(4) peptide 0.00480 secretion by cell (GO:0032940) 0.00505 protein amino acid O−linked glycosylation (GO:0006493) 0.00513 CTD:bis(maltolato)oxovanadium(IV) 0.00522 CTD:Apigenin 0.00565 L2L:stress_genotoxic_specific 0.00568 CTD:4−(4−fluorophenyl)−2−(4−hydroxyphenyl)−5−(4−pyridyl)imidazole 0.00568 Broad:ST_GA13_PATHWAY PBS A PBS A PBS A PBS A PBS A PBS B PBS B PBS B PBS B PBS B None B None B None B None B None B None B T1 A T1 A T1 A T1 A T1 A T1 A T1 B T1 B T1 B T1 B T1 B T1 B T2 A T2 A T2 A T2 A T2 A T2 B T2 B T2 B T2 B T2 B T2 B T3 A T3 A T3 A T3 A T3 A T3 B T3 B T3 B T3 B T3 B T3 B mercredi 13 juin 2012 9
  • 11. expression Experimental Data Analysis Population structuration • Structuring genes (hidden state models) Distance from closest class New classes Known Discriminative power mercredi 13 juin 2012 10
  • 12. expression Experimental Data Analysis Population structuration • Structuring genesets, knowledge integration • geneset based analyses / correlation identification • parametric analysis of geneset enrichment Pvalues Concepts Genes GeneSets Samples mercredi 13 juin 2012 11
  • 13. Interpretation of Data Analysis Results Why interpretation: • Data analysis: Crucial step • but need to contextualize results within the context of biological knowledge to turn data into really actionable results Interpretation challenges: Integrative Data Analysis • Gathering heterogeneous Knowledge and Data resources • Present Knowledge & Data in a manageable way mercredi 13 juin 2012 12
  • 14. Interpretation of Data Analysis Results WikiBioPath (in short): Web App with online specific tools for • storing/managing Knowledge & Data (K&D) • enriching/curating K&D • querying/exploring/visualizing / mining K&D Allows heterogeneous K&D integration into the interpretation process Will be available as Free & Open Source We are currently looking for collaborations / beta testers mercredi 13 juin 2012 13
  • 15. Web Portals/Apps, Applications Wikis public/external + private/internal public/external + private/internal External AND/OR External & WikiBioPath’s private Web Portals/ dedicated specialized Apps, Applications Wikis (Genes, Proteins, (NCBI, Kegg, ... ) Diseases, ... ) WBP’s linking & “bridging” WBP’s specialized functionalities for functionalities knowledge storing/querying/managing/... WikiBioPath Core Web based interface & online Tools for Data & Knowledge storing, managing, querying, visualizing, mining and more... Text Mining based Search WBP’s specialized functionalities for Engine & Explorer data storing/querying/managing/... Textual Data (Unstructured data repositories) Data Warehouses public/external + private/internal public/external + private/internal Bibliographical Databases Experimental Data & with low structured Experimental Data Analyses textual data Data Warehouses (Medline, own text (Micro Array Exp. Data, Micro collection ...) Array Analyses Results ...) mercredi 13 juin 2012 14