bioshare - umcg close out meeting 20160118

UMCG Close Out meeting January 18th, 2016

Het Schimmelpenninck Huys, Groningen

Agenda

AGENDA

16:15 Welcome - Ronald

16:20 BioSHaRE project and results overview - Lisette

16:40 Summary of WP1 - Coordination and management - Lisette

Summary of WP2 - Data repository and epidemiological/ clinical harmonization - Morris

Summary of WP3 - Epidemiology and Biostatistics for Biobank Harmonization/ Core Project statistics - Lisette

Summary of WP4 - Bioinformatics standardization/ harmonization for optimised information management - Morris Summary of WP5 - Biospecimen harmonization/standardization / Healthy Obese Project - Bruce

Summary of WP7 - Societal and environmental risk factors for complex diseases / Environmental Core Project - Wilma

17:15 Beyond BioSHaRE - Ronald

Any other business

BioSHaRE project and results overview - Lisette

MissionOrganisationResults

Our share in BioSHaRE

Mission

Development of harmonized measures and standardized computing infrastructures enabling the effective pooling of data to investigate common complex diseases

Work Packages1. Coordination and management Ronald Stolk

2. Data repository and epidemiological/ clinical harmonization (Hans Hillege)Morris Swertz

3. Epidemiology and Biostatistics for Biobank Harmonization Paul Burton

4. Bioinformatics standardization/ harmonization for optimised information management

Anthony Brookes

5. Biospecimen harmonization/standardization (Thomas Illig)Melanie Waldenberger

6. Metabolomic and genetic risk factors for clustering of complex diseases Markus Perola

7. Societal and environmental risk factors for complex diseases Kristian Hveem

8. Strategic integration and coordination with major biobanking initiatives, partnerships and dissemination

Jennifer Harris

9. Implementation & Roll-out Samuli Ripatti

Ethical, legal and social issues Bartha Knoppers

Core Projects

Statistical Methods for Longitudinal Harmonization

Data harmonisation and federated analysis

Work Packages and Core Projects1. Coordination and management Ronald Stolk

2. Data repository and epidemiological/ clinical harmonization (Hans Hillege)Morris Swertz

3. Epidemiology and Biostatistics for Biobank Harmonization Paul Burton

4. Bioinformatics standardization/ harmonization for optimised information management

Anthony Brookes

5. Biospecimen harmonization/standardization (Thomas Illig)Melanie Waldenberger

6. Metabolomic and genetic risk factors for clustering of complex diseases Markus Perola

7. Societal and environmental risk factors for complex diseases Kristian Hveem

8. Strategic integration and coordination with major biobanking initiatives, partnerships and dissemination

Jennifer Harris

9. Implementation & Roll-out Samuli Ripatti

Ethical, legal and social issues Bartha Knoppers

1

LifeLines

Prevention of REnal and Vascular

ENd-stage Disease (PREVEND)

Estonian Genome Center

Cooperative Health Research in the Region

of Augsburg, Southern Germany (KORA)

Study of Health in Pomerania (SHIP)

Microisolates in South Tyrol Study (MICROS)

Collaborative Health Research in South Tyrol

Study (CHRIS)

EPIC-Turin

Cork and Kerry Diabetes and

Heart disease study

National Child Development Study (NCDS)

UK Biobank

The European Prospective Investigation

into Cancer and Nutrition (EPIC) Oxford

Salford cohort

The National FINRISK Study 2007 (FINRISK)

Health 2000

Nord-Trøndelag Health Study (HUNT)

Participating Biobanks

Overview of the studies participating in HOP and ECP

Study name Country HOP ECPCartagene Canada X

Cooperative Health Research in South Tyrol Study (CHRIS) Italy X

EPIC-Oxford United Kingdom X

Estonian Genome Project of University of Tartu (EGCUT) Biobank

Estonia X

FINRISK2007 (DILGOM and Health-2000) Finland X

Cooperative health research in the Region of Augsburg (KORA) Germany X

LifeLines Cohort Study & Biobank Netherlands X X

Microisolates in South Tyrol Study (MICROS) Italy XMitchelstown/ Cork and Kerry Diabetes and Heart Disease Study Phase II

Ireland X

National Child Development Study (1958 Birth Cohort) United Kingdom X

Nord-Trøndelag Health Study (HUNT) Norway X X

Prevention of REnal and Vascular ENd-stage Disease(PREVEND)

Netherlands X

Study of Health in Pomerania (SHIP) Germany X

UK Biobank (UKB) United Kingdom X

BioSHaRE Results

DeliverablesForeground

Tools and methodsDataKnowledge

Publications

Deliverables

A total of 53 deliverables, most of which are available from our website

BioSHaRE Foreground

Tools and methods

BioSHaRE offers tools and methods for database owners and researchers:

1. data description and presentation (database owner) and data search (researcher);

2. data harmonisation across databases (researcher); 3. data analysis across databases (researcher); 4. contributor recognition(database owner and researcher); 5. standardisation of sample handling (database owner); 6. guidance and standards on ethical, legal and social implications (ELSI)

(database owner and researcher).

Data

The harmonisation process carried out in BioSHaRE generated new data and data tools including:

1. A catalogue with metadata of the participating biobanks2. Data schemas with the target variables (HOP, ECP)3. Harmonisation algorithms (HOP)4. Harmonised variables (stay at local servers, with respective biobanks)

Knowledge

The scientific knowledge, as well as the recommendations, best practices and standards resulting from the project are reported in deliverables and peer-reviewed publications. BioSHaRE partners published nearly 100 scientific papers describing the foreground produced in BioSHaRE.The publications are listed and searchable by topic, author, year of publication at our website (period 5 publications will be added before end of Jan 2016)

Publications

Our share in BioSHaRE

Overall UMCG % realization %

Budget €11.998.152 €3.011.795 25 € 3.248.994 108

Person Months 1580 360 23 352 98

Deliverables 53 25 47

Publications 91 12 13

Workforce 178 31 17

female 87 15

male 91 16

SUMMARY OF WP1 - COORDINATION AND MANAGEMENT

Overview of work/ deliverables

WP n°Deliverable N° Title

UMCG involved

1 1 Copies of currently used ethical approvals and informed consent forms x

1 2 BioSHaRE website x

1 3 Periodic EC reports #1 x




1 7 Final EC report x

1 8 Catalogue of standardized data within European biobanks x


8 5 Final plan for the use and dissemination of foreground x

8 6 Report on Awareness and Wider Societal Implications x

Successes

Amendment #1 and #2 to the Grant Agreement Midterm review Conference “LATEST TOOLS and SERVICES for DATA

SHARING”, July 28th, 2015 in Milan, Italy Catalogue of tools and services for data sharing BioSHaRE Youtube channel, short intro movie,

instruction movies LinkedIn group Beyond BioSHaRE

SUMMARY WP2 - DATA REPOSITORY AND EPIDEMIOLOGICAL/ CLINICAL HARMONIZATION

Chao Pang + (Joel Kuiper, Hans Hillege) + MOLGENIS team



UMCG involved

2 1 Definition of a minimal datasets x

2 2 Validated phenotype systems x

2 3DataSHaPER harmonization rules defined and integrated into phenotype system

2 4 Data sharing protocols

2 5 Carry out a review of the requirements for the sharing of data

Goal: data harmonization for pooled analysis

1. Defining the variables of the target DataSchema

2. Matching biobank data elements to the target DataSchema

3. Generate algorithms to convert data values to the target DataSchema

Successes – Harmonization for HOP

10 studies, 7240 variables (Fortier, Doiron et al)

Successes - SORTA

System for Ontology-based Re-coding and Technical Annotation of biomedical phenotype data

Pang et al, Database (Oxford), 2015, bav089

Successes - BiobankConnect

to rapidly connect data elements for pooled analysis across biobanks using ontological and lexical indexing

Search for‘History of hypertension’

Searching by system

Manual mapping:‘CM ever had high

blood pressure’

Searching by expert

Rank is one in 57% and 10 in 96%!

Pang et al, 2014, JAMIA

Successes – BiobankConnect 2.0

for the automatic generation data integration algorithms

Pang et al, Submitted

Successes – BiobankConnect 2.0

Remaining challenges

• Sustainability of the development• Ease of deployment• Prospective harmonization• Adoption beyond bioshare

• Training!• to get the world to also adopt rigorous harmonization methods• Reduce duplicated efforts accross networks

• Bridge EU with other continents (and overcome politics)

Beyond BioSHaRE

The DataSchema harmonization protocol is taken forward in Maelstrom organisation with applications including BBMRI-LPC•see https://www.maelstrom-research.org/

The BiobankConnect/SORTA technology is being adopted in RD-Connect, CORBEL/EXCELERATE, BBMRI-NL/ERIC as permanent application within the MOLGENIS suite.•See https://molgenis.org and http://molgenis.github.io•See https://molgenis.org/sorta •See https://biobankconnect.org•See https://molgenis.org/connect

In particular: BioSHaRE tools flow into BBMRI projects

SUMMARY OF WP3 - EPIDEMIOLOGY AND BIOSTATISTICS FOR BIOBANK HARMONIZATION/ CORE PROJECT STATISTICS



UMCG involved

3 1 ESPRESSO-forte Study Simulation Platform completed

3 2 Working version of DataSHIELD completed

3 3Complete analysis and report results of two case studies in collaboration with WP9

3 4 Ethico-legal code of conduct for research

3 5 Implementation of model(s) in DataSHIELD for use in BioSHaRE x

3 6 Manuscript on model(s) for harmonizing longitudinal data x

3 7Report on the social and epistemic implications of the DataSHIELD methodology

3 8Report on Social and epistemic implications of biobank standardisation and harmonisation

Successes

D3.6 Implementation of model(s) in DataSHIELD for use in BioSHaRED3.7 Manuscript on model(s) for harmonizing longitudinal data

Major challenges

Change in staff, Edwin leaving to Eindhoven No longitudinal data in BioSHaRE cohorts that are suitable to develop and test

statistics model and analyse across multiple cohorts

SUMMARY WP4 - BIOINFORMATICS STANDARDIZATION/ HARMONIZATION FOR OPTIMISED INFORMATION MANAGEMENT

(Joeri van der Velde), Fleur Kelpin + MOLGENIS team



UMCG involved

4 1 Full scope data exchange format x

4 2 Final version modular database system x

4 3Validated researcher digital IDs for control of data access, including ELSI

4 4 Object models for experiment and molecular data x

Overview

Successes – Model & Exchange format

Observ-OM and Observ-TAB: Universal syntax solutions for the integration, search, and exchange of phenotype and genotype information

Adamusiak, et al, Swertz, 2012, Human Mutation

Successes – Model & Exchange format 2.0

Entity Model extensible (EMX)

Successes – Refactoring of MOLGENIS

Success – Refactoring of MOLGENIS

Successes – Upload in Excel

Participant Height Weight BMI ..LL_123041 176 68 25 ..LL_123042 163 62 23 ..LL_123043 188 75 25 ..LL_123044 180 60 23 ..LL_123045 165 106 32 .... .. .. .. ..

Attributes

name description unit dataTypeParticipant Indivdual observed ref PatientHeight Height standing up by nurse cm decimalWeight Weight on digital floor scale by nurse kg decimalBMI Body Mass Index kg/cm^2 decimal.. .. .. ..

(d)

(b)Entities

name description ..Study 1 Lifelines base

collection

(a)

Successes – Data explorer

47

Successes – Integrate R

48

http://molgenis.org/ase

Importer

49

Challenge 4

Insight / action?

DNA / phenotyp

e

50

Challenge 4DNA /

phenotype

Population

genomic variants

Insight / action?

Clinical symptom

s & diseases

Biochem-ical

pathways

Imputation

Patho-genicity

predictions

Model organism knockouts

Actionable genes

Known pathogeni

c & benign variants

Allele specific

expression

Tissue specific

expression

Pedigree analysis

Protein conser-vation

Age, onset,

heritability modes

GWAS and QTL studies

Conseq-uence

51

Upload VCF file

Successes – OMX (‘omics’) for loading, browsing and annotating genomics data

=Open source at http://github.com/molgenis/molgenis

Success – Federated analysis using Opal, DataShield and Mica (Ferretti et al)

Success – Federated genomics in OmicsConnect and CafeVariome (with Brookes et al)

Successes – OmicsConnect visual data integration (Brookes et al)

Major challenges

• Scale of genomic data• Deployment / maintenance cost• Too many projects now

• Data warehouse/research portal• Data integration / biobankconnect• Biobank catalogues for NL, ERIC, RD• Genomics data interpretation for UMCG, VKGL, etc

Beyond BioSHaRE

BioSHaRE has given a major boost to Opal, DataSHield, MOLGENIS, Café Variome, GWAS central, ea

Part of many projects, e.g. MOLGENIS is in RD-connect, CORBEL, BBMRI + 25 other installations.

In particular: BioSHaRE tools flow into BBMRI projects

SUMMARY OF WP5 - BIOSPECIMEN HARMONIZATION/STANDARDIZATION / HEALTHY OBESE

PROJECT



UMCG involved

5 1Evidence-based minimal standards for important samples types and measurement techniques

5 2SOPs for standardisation of sample collection, sample pre-treatment and sample analysis

5 3Temperature effects of preparing and thawing samples on different analyses techniques

5 4SOPs for shipment of samples and laboratory analyses of inflammatory markers from different biobanks x

5 5 ELSI standards for the use of biospecimen from multiple biobanks

5 6Scientific report on harmonization and standardization of prospective phenotypes for future research x

5 7Scientific paper on GWA / GWI studies on obesity, healthy obesity and associated comorbidity x

5 8Scientific paper on health outcome (cardiovascular diabetes domain) for Healthy Obese phenotypes x

5 9Scientific paper on the use and utility of inflammatory markers in Healthy Obese individuals x

Successes

New collaboration and friendshipsWe are still alive after these 5 yearsThere are some publications

HOP DataSchema update:

Now at 98 variables (Phases 1 – prevalence of HO, and phase 2 - risk factors of HO)10 studies have their data on Opal servers:

NCDS (n= 7,210)Prevend (n=8,592)LifeLines (n=90,920)Mitchelstown (n=2,047)Finrisk (n=5,024)

45 harmonized variables validated and available for analyses on DataSHIELD for 10 studies:

Healthy Obese, MetS (strict and moderate criteria)8 Physical measures: blood pressure, height/weight, BMI, hip/waist size10 lab/biochem measures: gluc, HDL, trig, TSC, creatinin, hsCRP, mALb, LDL, Renal Function (Cockcroft Gault Glomerular filtration rate)Medication intake and disease history (cardio-vascular, diabetes)Gender, age, marital status, employment status, tobacco

Data harmonization work

Kora (n=3,080) MICROS (1,060) CHRIS (n=1,583) HUNT (n=78,968) SHIP (n=4,308)

No publications other than baseline paper

Present list of accepted phase 1-2-3 studies comprises:Total/LDL-chol and statin use E ReischlMethodology & harmonization phase 1 variables D Doiron published by Emerging Themes EpidemiologyInterrelation of smoking and MS S SlagterIndividual components metabolic syndrome B WolffenbuttelType 2 diabetes across Europe M WendkerGenetics of HOP M.L. NuotioAdditional genetic analysis 'Manchester'BP, hypertension & use of medication noneGender differences in obesity noneHOP phenotype extension B Wolffenbuttel

HOP Additional phase 1 papers

No preliminary manuscripts yet

HR-QOL harmonization difficult

Physical activity less difficult ??

The WP5 inflammatory project timeline

Nov 13, 2014: results presented

Dec 2011: protocol submissionJan 2012: protocol approval

April 2014: additional samples sent

May 2013: samples sentJune 2013: samples analyzed

May 2014: samples analyzed

2012

2013

2014

Sept 9, 2014: final phenotypes available

Overall conclusion of the WP5 inflammatory project

This project showed every flaw that can ever occur in scientific research:delay in delivery of sampleshuman factor in picking wrong samples, loosing valid assay and overall validity of resultsone specific TNFa ELISA kit which has very low quality

It also showed:excellent sample stability when inflammatory marker hsCRP is measured after 4 years of storage at -80Cno major differences in reproducibility when 'complexity' of sample is taken into account

Server down, researcher depressed

Major challenges

Updating the DATA-Shield / Data-SHIELD software until it really becomes a mature environment

Beyond BioSHaRE

indicate if and how the work is being used and continued in other projects

WE DO HOPE SO …The imposed LifeLines 'policy' of max. two papers per project makes this however a very expensive issue, for some of my projects this turns out 100.000 Euro per paper !

SUMMARY OF WP7 - SOCIETAL AND ENVIRONMENTAL RISK FACTORS FOR COMPLEX DISEASES / ENVIRONMENTAL CORE

PROJECT



UMCG involved

7 1 ELSI guidance on the specific issues

7 2 Georeferencing of individual cohort data

7 3 Integrated EU GIS toolkit

7 4 Working version of EnviroSHaPER completed

7 5 Complex lifestyle and risk factor variables harmonized x

7 6Scientific paper on the relation between the harmonized complex variables and risk factors and specific health outcomes x

7 7Scientific report on harmonization of life habits/behaviors, physical and social environment, and socio-economic status variables x

Successes

European noise model and user friendly interface to facilitate the application of this model across other cohorts.Assigned harmonised air pollution and noise exposure variables to four key European cohorts, across 3 countries, for use in the BioSHaRE ECP analyses, and in subsequent analyses by other researchers in the community.

Cohorts

UK Biobank

UK Biobank - 500,000 participants, recruited 2006-2010 from across UKEPIC-Oxford - 57,000 participants, recruited 1993-1999 from across UKHUNT - 50,000 participants, recruited 1984-1986 from the Nord-Trøndelag County, NorwayLifelines - 95,000 participants, recruited 2007-2013 from the Groningen, Friesland, Drenthe regions of the Netherlands

Successes

European noise model and user friendly interface to facilitate the application of this model across other cohorts.Assigned harmonised air pollution and noise exposure variables to four key European cohorts, across 3 countries, for use in the BioSHaRE ECP analyses, and in subsequent analyses by other researchers in the community.Retrospective harmonisation of the key variables required to undertake the main analyses.Made recommendations to support the prospective harmonization of common somatic symptoms.Published papers (6) and disseminated output at National and International conferences (14); 2 finalised PhD projects.

My PhD thesisMain findings-Differential health impact of urbanity according to disease-Road traffic noise and increased heart rate-Noise annoyance and common somatic symptoms-No evidence for relations between noise and increased blood pressure; noise and somatic symptoms; air pollution and depression

Major challenges

Obtaining cohort dataData access time consuming, complex, non standardised

HarmonisationAssigning ‘harmonised’ environmental exposures (e.g. no ESCAPE data for HUNT)Harmonisation not possible for a number of target variablesLoss of detailed data

Analysis (e.g. via DataSHIELD)Heterogeneous and clustered data

Beyond BioSHaRE

Some BioSHaRE projects are still ongoing:Samuel Cai: Associations between road traffic noise, air pollution and cardiorespiratory health Kirsti Kvaloy: Effects of road traffic noise and air pollution on diabetes in European cohorts: a harmonized approach in the BioSHaRE project

New projects with BioSHaRE data/tools:Dany Doiron: Associations between air pollution and respiratory heath in large European cohorts UMCG: Genome-wide interaction study of gene-by-air pollution exposure interactions in relation to lung function levels in LifeLines

bioshare - umcg close out meeting 20160118

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