April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATRO
BioSHaRE - UMCG Close out meeting 20160118
1. UMCG Close Out meeting
January 18th
, 2016
Het Schimmelpenninck Huys, Groningen
2. 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
5. Work Packages
1. 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
7. Work Packages and Core Projects
1. 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
8. Work Packages and Core Projects
1. 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
9. Work Packages and Core Projects
1. 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
10. Work Packages and Core Projects
1. 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
11. 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
12. Overview of the studies participating in HOP
and ECP
Study name Country HOP ECP
Cartagene 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 X
Mitchelstown/ 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
16. 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).
18. 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)
22. Overview of work/ deliverables
WP n°
Delivera
ble 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 4 Periodic EC reports #2 x
1 5 Periodic EC reports #3 x
1 6 Periodic EC reports #4 x
1 7 Final EC report x
1 8 Catalogue of standardized data within European biobanks x
23. Overview of work/ deliverables
8 5 Final plan for the use and dissemination of foreground x
8 6 Report on Awareness and Wider Societal Implications x
24. 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
25. SUMMARY WP2 - DATA REPOSITORY AND
EPIDEMIOLOGICAL/ CLINICAL HARMONIZATION
Chao Pang + (Joel Kuiper, Hans Hillege) + MOLGENIS team
26. Overview of work/ deliverables
WP n°
Deliver
able N° Title
UMCG
involved
2 1 Definition of a minimal datasets x
2 2 Validated phenotype systems x
2 3
DataSHaPER 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
27. Goal: data harmonization for pooled analysis
PREVEND
Harmoniza on process
Which individual will develop
cardiovascular disease?
Example of research ques on
Pooled data
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
29. Successes - SORTA
System for Ontology-based Re-coding and Technical
Annotation of biomedical phenotype data
Pang et al, Database (Oxford), 2015, bav089
30. 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
31. Successes – BiobankConnect 2.0
for the automatic generation data integration
algorithms
Pang et al, Submitted
32. Successes – BiobankConnect 2.0
P r e v ie w
A lg o r it h m fo r ‘M e a s u r e d S t a n d in g H e ig h t ’
P re v ie w
A lg o r it h m f o r ‘H is t o r y o f H y p e r t e n s io n ’
a b
33. 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)
34. 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
35. SUMMARY OF WP3 - EPIDEMIOLOGY AND BIOSTATISTICS
FOR BIOBANK HARMONIZATION/ CORE PROJECT STATISTICS
36. Overview of work/ deliverables
WP n°
Deliver
able N° Title
UMCG
involved
3 1 ESPRESSO-forte Study Simulation Platform completed
3 2 Working version of DataSHIELD completed
3 3
Complete 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 7
Report on the social and epistemic implications of the DataSHIELD
methodology
3 8
Report on Social and epistemic implications of biobank standardisation
and harmonisation
37. Successes
D3.6 Implementation of model(s) in DataSHIELD for use in BioSHaRE
D3.7 Manuscript on model(s) for harmonizing longitudinal data
38. 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
39. SUMMARY WP4 - BIOINFORMATICS STANDARDIZATION/
HARMONIZATION FOR OPTIMISED INFORMATION MANAGEMENT
(Joeri van der Velde), Fleur Kelpin + MOLGENIS team
40. Overview of work/ deliverables
WP n°
Deliver
able N° Title
UMCG
involved
4 1 Full scope data exchange format x
4 2 Final version modular database system x
4 3
Validated researcher digital IDs for control of data access, including
ELSI
4 4 Object models for experiment and molecular data x
42. 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
43. Successes – Model & Exchange format 2.0
Entity Model extensible (EMX)
g e n d e r s
e n t y n a m e la b e l d a t a T y p e re fEn t y d e scrip o n
p a e n t Id _ 1 id s t r in g Id e n fi e r o f t h e p a e n t
p a e n t S e x _ 1 g e n d e r c a t e g o r ic a l g e n d e r s P a e n t g e n d e r
p a e n t L e n g t h _ 1 h e ig h t d e c im a l H e ig h t w h ile s t a n d in g in m
p a e n t D is e a s e _ 1 d is e a s e x r e f d is e a s e s S e lf-r e p o r t e d d is e a s e
a r ib u t e s
Id h e ig h t ge n d e r d ise a se
1 1 8 5 .3 m a le T y p e 2 D ia b e t e s
2 1 7 9 .4 fe m a le C a r c in o m a
3 1 7 0 .0 fe m a le S t r o k e
4 1 9 2 .0 m a le H y p e r t e n s io n
p a e n t s
Co d e La b e l
1 m a le
2 fe m a le
N a m e Cla ssifica o n
T y p e 2 D ia b e t e s D is e a s e o n t o lo g y
T y p e 1 D ia b e t e s D is e a s e o n t o lo g y
C a r c in o m a D is e a s e o n t o lo g y
S t r o k e D is e a s e o n t o lo g y
H y p e r t e n s io n D is e a s e o n t o lo g y
P r o s t a t e c a n c e r D is e a s e o n t o lo g y
B r e a s t c a n c e r D is e a s e o n t o lo g y
… … … …
d is e a s e s
x re f
ca t e go rica l
57. 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
58. 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
60. Overview of work/ deliverables
WP n°
Deliver
able N° Title
UMCG
involved
5 1
Evidence-based minimal standards for important samples types and
measurement techniques
5 2
SOPs for standardisation of sample collection, sample pre-treatment and
sample analysis
5 3
Temperature effects of preparing and thawing samples on different
analyses techniques
5 4
SOPs 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 6
Scientific report on harmonization and standardization of prospective
phenotypes for future research x
5 7
Scientific paper on GWA / GWI studies on obesity, healthy obesity and
associated comorbidity x
5 8
Scientific paper on health outcome (cardiovascular diabetes domain) for
Healthy Obese phenotypes x
5 9
Scientific paper on the use and utility of inflammatory markers in Healthy
Obese individuals x
62. 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 size
10 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)
Data harmonization work
Kora (n=3,080)
MICROS (1,060)
CHRIS (n=1,583)
HUNT (n=78,968)
SHIP (n=4,308)
64. Present list of accepted phase 1-2-3 studies comprises:
Total/LDL-chol and statin use E Reischl
Methodology & harmonization phase 1 variables D Doiron
published by Emerging Themes Epidemiology
Interrelation of smoking and MS S Slagter
Individual components metabolic syndrome B Wolffenbuttel
Type 2 diabetes across Europe M
Wendker
Genetics of HOP M.L. Nuotio
Additional genetic analysis 'Manchester'
BP, hypertension & use of medication none
Gender differences in obesity none
HOP phenotype extension B Wolffenbuttel
HOP Additional phase 1 papers
No preliminary manuscripts yet
67. The WP5 inflammatory project timeline
Nov 13, 2014: results presented
Dec 2011: protocol submission
Jan 2012: protocol approval
April 2014: additional samples sent
May 2013: samples sent
June 2013: samples analyzed
May 2014: samples analyzed
2012
2013
2014
Sept 9, 2014: final phenotypes available
68. Overall conclusion of the WP5 inflammatory
project
This project showed every flaw that can ever occur in scientific research:
delay in delivery of samples
human factor in picking wrong samples, loosing valid assay and overall
validity of results
one 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 -80C
no major differences in reproducibility when 'complexity' of sample is
taken into account
71. 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 !
72. SUMMARY OF WP7 - SOCIETAL AND ENVIRONMENTAL RISK
FACTORS FOR COMPLEX DISEASES / ENVIRONMENTAL CORE
PROJECT
73. Overview of work/ deliverables
WP n°
Deliver
able N° Title
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 6
Scientific paper on the relation between the harmonized complex
variables and risk factors and specific health outcomes x
7 7
Scientific report on harmonization of life habits/behaviors, physical and
social environment, and socio-economic status variables x
74. 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.
75. Cohorts
UK
Biobank
UK Biobank - 500,000
participants, recruited 2006-
2010 from across UK
EPIC-Oxford - 57,000
participants, recruited 1993-
1999 from across UK
HUNT - 50,000 participants,
recruited 1984-1986 from the
Nord-Trøndelag County,
Norway
Lifelines - 95,000 participants,
recruited 2007-2013 from the
Groningen, Friesland, Drenthe
regions of the Netherlands
76. 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.
77. My PhD thesis
Main 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
78. Major challenges
Obtaining cohort data
Data access time consuming, complex, non standardised
Harmonisation
Assigning ‘harmonised’ environmental exposures (e.g. no
ESCAPE data for HUNT)
Harmonisation not possible for a number of target
variables
Loss of detailed data
Analysis (e.g. via DataSHIELD)
Heterogeneous and clustered data
79. 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