From personal genomics to personal diagnos1cs. The data management and interpreta.on challenge

Transcription

1 From personal genomics to personal diagnos1cs The data management and interpreta.on challenge

2 Program 11:30 11:50 Terry Vrijenhoek Personal genomics - diagnos1c DNA sequencing 11:50 12:10 Peter Walgemoed The Dutch Health Hub 12:10 12:30 Maud Radstake Responsible Data Management for Personalised Diagnos1cs

3 Personal genomics Diagnos.c DNA sequencing

4 DNA developments

5 Utrecht DNA sequencing facility Hubrecht Institute WKZ Children s Hospital UMC Utrecht Stratenum

6

7 It is 'me to develop guidelines to harmonise further implementa'on [of NGS into diagnos'cs] Work program Health Council The primary goal of this program is to develop infrastructure, procedures and guidelines for NGS- based personalized diagnos'cs for na'on- wide implementa'on. Grant applica1on CGD

8 CARDIO pilot project 10 (9) pa.ents with cardiomyopathy DNA and medical reports Iden.fy need for policy

9 Four phases; five topics 1. Intake samples and medical reports 2. Sequencing library prepara.on, enrichment and sequencing procedures 3. Data analysis tools and pipelines 4. Diagnosis interpreta.on and counseling 5. Ethical and legal framework consent, pa.ent rights, data protec.on, liability

10 GENOME EXOME CARDIO GENE SET

11 Detected variants!"#" $%&' ()*+",# -"#*.,$/$**) &' $:113;!<= >:')-3778"? 1@1561;5AA BC(D3 $:2737E1!<' F>G,$" 11@ ;: BC(D3 $:2374H2375,#FD >:=)>7I2J")KF 11@4735I27IH4735I2A; BC(D3 $:23730?> >:=)>7I2KF/L/>:=)>7I2MNGKFO17 11@4735I2A; BC(D3 $:I27P2'<! F>G,$" 11@47367I BQ7 $:26;I!<' >:')-A7;Q,F 14@23AI4;4A =&&R3 $:4I7D<= >:J")166(S" 1I@ ; (8& $:4;H420"G'!' >:')-140"G 6@11AAA;124H11AAA; ==&=2 $:662=<D >:RG"221=S) 1@2;1331;6A =&&=2 $:6A3=<D >:RG"22A=S) 1@2;1331;6A 'D=&2 $:AI3!<' >:')-2IAQ,F 1@236I;261A ;: TBT2 $:6555E17D<= >:RG"37ARG" 1@2377I4A5A 1 1 &' 1 1 TBT2 $:A162=<D >:RG"2721=S) 1@237A &' B(& $:1134D<= 1;@6II;A113 ;: %C3 $:1;A3'<D >:U 1;@AA452311V &' 'CDDI $:366I!<' >:=S)1223=S) 12@21IA1AI2 &' BQ7 $:4172'<D >:8WF13I1=S) 14@23AA6AI BQ7 $:2I45=<D >:9"+IA2=S) 14@23AI2I1; XY( $:I;IE6D<= 17@3II &' &' %JD2 $:A;2'<! >:=S)26A'GN 1A@2A66667I 1 1 &' ;:5 1 ==& $:74571!<D >:!G#24A57Q,F 2@17I3II576 &' &' &' ==& $:71;47D<= >:')-236A3DWF 2@17I4;455; &' &' &' ==& $:6I;57'<! >:U 2@17I4;A61I &' &' &' ==& $:6I;3ID<= 2@17I4;A637 &' &' &' ==& $:64;6;!<' >:'GN21354=S) 2@17I &' &' &' ==& $:2I767!<' >:MNGII23RG" 2@17I463475V &' &' &' ==& $:253I7=<D >:MNGA466'GN 2@17I473;1A &' &' &' ==& $:2;A;3!<D >:'F>6I35Q,F 2@17I4A161A &' &' &' ==& $:I442D<= >:')-314ADWF 2@17I631231V &' &' &' ==& $:I3;4D<= >:')-31;2DWF 2@17I &' &' &' ==& $:I221!<' >:')-3;74!G# 2@17I6325IA &' &' &' ==& $:7;2A=<! >:9"+2343')- 2@17I63A72I &' &' &' ==& $:776D<= >:()*25I8"? 2@17I &' &' &' ==& $:2I6P14=<D 2@17I &' &' &' X(Q2 $:64A!<' >:8WF2168WF 2;@427AA77I &' &' &' &' &' &' 1 9B83 $:476D<= >:=S)15I9"+ 3@46I;;I7; !8' $:427!<' >:'GN143=S) O@1;;65674; ='Z $:5I4D<= >:U O@15364A3A %9% $:5723'<= >:'F>1I;AMNG O@ &' 1 &' &'

12 General observa1on The diagnos.c outcomes for the CARDIO pa.ents are generally similar despite the differences in sequencing approach, plaqorm and data analysis So, do we need guidelines?

13 Numbers 3,154,971,228 56,217,673,809 2,885,536,685 2,208,479,859 2,155, ,938 5, ? Bases in human genome assembly Bases in SOLiD run (2 slides paired- end) 18x Bases covered at least once (93.6%) Bases covered at least 10 x (~70%) SNPs Indels Non- synonymous coding variants Splice sites affected Essen.al splice site affected Stop codon introduced

14 Post- CARDIO RESEARCH PROPOSALS FROM COMMUNITY

15 P- o- C CENTRAL DATA INFRASTRUCTURE Ini.a.ve from EMC and LUMC in collabora.on with SURF/ DHH Exploring opportuni.es for central data infrastructure Features to test: Data transport Access to central storage Virtualisa.on Authen.ca.on Legal aspects

16 TOWARDS RESPONSIBLE DATA MANAGEMENT IN PERSONALISED DIAGNOSTICS Collabora.on with Centre for Society and Genomics Mee.ng of minds: technology, clinic, ethics, society, legal To facilitate a proposal for a (European) program on societal responsible diagnos.c use of large- scale biomedical data Kick- off October 1

17 Thank you Marcel Mannens Ronald Lekanne Dit Deprez Raoul Hennekam Elcke Kranendonk Correne Ploem Wilbert van Workum Kees van der Berg Derek Butler Adalberto Costessi Bas Reichert Marjolein Kriek Johan den Dunnen Ken Kraaijeveld Gijs Santen Claudia Ruivenkamp Nienke van der Stoep Erik Sistermans Bauke Ylstra Remond Fijneman Jannek Weiss Quinten Waisfisz Frans Hogervorst Hans Kris.an Ploos van Amstel Jasper Saris Marjon van Slegtenhorst Wilfred van Ijcken Ingrid van der Laar Marja Wessels Maarten van den Berg Richard Sinke Morris Swertz Peter van Tintelen Jan Jongbloed Birgit Sikkema Marian Verkerk Nine Knoers Wim Dorlijn Winfried van Eijndhoven Rogier Drenth Gijs van Haaoen Edwin Cuppen Maartje Vogel Bert van der Zwaag Ellen van Binsbergen Mariëlle Swinkels Patrick van Zon Marcel Nelen Chris.an Gilissen Joep de Ligt Joris Veltman Helger Ijntema Ilse Feenstra Steven van Hove Ewout Ouwerkerk Bart de Koning Ingrid Kapels Bert Smeets Arthur van der Wijngaard Rick Kamps Suzanne Frints Marco Rijnen Jan Ghyssaert Simone Guenther Maud Radstake Wybo Dondorp Guido de Wert Tonnie Rijkers Colja Laane Graciela Mar.nez