#20 IN THIS ISSUE. #20 December 2015

#20 IN THIS ISSUE Editorial 2 Biobank Open Online Courses 3 Prostate cancer test saves healthcare resources 4 Large-scale Open Access is now a realit...
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Editorial 2 Biobank Open Online Courses 3 Prostate cancer test saves healthcare resources 4 Large-scale Open Access is now a reality 6 BBMRI.se National Repository 7 Big Data Handling in Biobanking 8 News In Brief 9 Towards an Open Science Commons 10 Dried blood spots 11 System for Cervical Cytology Biobanking 12 Interview with Mats G. Hansson 13 National hearing in laboratory medicine 14 News In Brief 15 Towards Evidence-Based Practices 16

#20 December 2015

Photo: Stefan Zimmerman, KI

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Major breakthroughs enabled by the infrastructure When BBMRI.se was started in 2009, the Swedish Research Council gave us a set of Key Performance Indicators (KPI). These were reviewed at our first working meeting and there was one of the KPIs that caused some smiles: “Major breakthroughs enabled by the infrastructure”. How realistic was it that providing infrastructural services would enable major medical breakthroughs? Six years later, we are proud to have provided the sample management services for the large-scale prostate cancer screening study by professor Henrik Grönberg. The new prostate cancer screening algorithm he has developed can not only be classified as a major medical breakthrough, it had a very short implementation time-frame and will be offered as a part of the clinical routine already in March 2016. We have always said that development of a largescale biobanking infrastructure will not only increase the efficiency of medical research, the fact that large-scale, reliable data from real patients are obtained will also shorten the time from discovery until implementation in clinical practice and realized patient benefits. Our work plan for the first quarter of 2016, although spanning only a limited amount of time, describes several important new steps in the development of BBMRI.se. For example:

• BBMRI.se will continue to support the development of the pan-European biobanking infrastructure BBMRI-ERIC by participating in providing IT Services for biobanking on the European level, within the framework of the BBMRI-ERIC European Common Service on IT Services for Biobanking that is led by BBMRI.de.

• The National Service Center for Sample Management, which is now a self-sustainable service facility, will expand with additional services such as: -RNA extraction -DNA extraction from dried blood spots -DNA extraction from cytology samples -Data Warehouse service to link and visu- alize data sets • The National Service Center for Analysis Technologies and Reagents will finalize validation of an inexpensive means of collecting plasma/blood samples on filter papers for protein analysis also after long term storage. • The BBMRI.se IT Services will offer support in implementation and custom-development of Open Source softwares, starting with open source LIMS (Laboratory Information Management Systems). • Our very popular services to support healthcare-integrated biobanking will be further expanded across the country and be expanded to include support to additional clinical specialities, e.g. clinical microbiology and clinical chemistry. During 2015 BBMRI.se has developed extraordinarily fast and it is clear that there will also be very exciting developments during the beginning of next year. With that I would like to wish all employees and all customers a Merry Christmas and a Happy New Year. Joakim Dillner Director of BBMRI.se

Education & International Networking

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Biobank Open Online Courses: A road from the auditorium to the internet There is an increasing international demand fortrained interdisciplinary expertise in biobank-based research. A recent post-graduate course, arranged by BBMRI.se, in collaboration with Lund University and University of Copenhagen, “Biobanking and Big Data: possibilities and challenges” was given not only as a classroom course but also as a Biobanking Open Online Course (BOOC).

The presentations were streamed live using Adobe Connect and displayed at the on-line platform BOOC. The students who passed the online course were entitled to 3 ECTs. Student from all over the world registered and logged in to the course (graph 1), slides were browsed 215 times (graph 2) and video recordings 76 times (graph 3). Documents such as course syllabus, reading materials and online course instruction were read 137 times. The BOOC format enabled reaching and teaching a larger numbers of students from many countries, opening doors to broad global education, in-

teraction and debate within the field of biobanking and education on how to optimally exploit the global biobank infrastructure.

The internet educational platform BOOC is one of the 2015 strategic projects launched by the Board of BBMRI.se. Students interested in the Biobanking and Big Data course can browse it at booc.bbmri.se. For questions, please contact BBMRI.se communications director Ulla Rudsander, [email protected]


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Sweden   Denmark   Europé   Global  

The distribution of students that logged into the site booc.bbmri.se (Graph 1), viewed the slides (Graph 2) or viewed the videos (Graph 3). Colour coding Blue: Sweden, Red: Denmark, Green: Europe, Violet: Global.

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BBMRI.se National Sample Management Services

Novel prostate cancer test saves healthcare resources and spares unnecessary treatments The new “STHLM3 test” developed by professor Henrik Grönberg and his team can be said to constitute a major breakthrough in research on prostate cancer screening. Efficient logistical services of the BBMRI.se Biobank Facility was crucial for the handling of the samples from >60 000 participants in the STHLM3 study and the analysis services were also essential for the development of the test. Another success factor was collaboration with industrial partners who manufactured the screening chips. Henrik Grönberg became a professor in cancer research at Umeå University in 2001. He had his post-doc period at John Hopkins in Baltimore and has also worked as practicing oncologist at Norrland University Hospital in Umeå. In 2005 he became professor at Karolinska Institute, studying risk factors and genetic b i o m a r ke r s of prostate cancer. During the last five years, his research has focused on improving prostate cancer testing by identification Henrik Grönberg/Photo: Stefan Zimmerman and validation of new screening tests. - PSA testing has been around for 25 years, but PSA-tests result in overdiagnosis, with painful biopsies taken unnecessarily, Henrik Grönberg says. In the STHLM3 study, we established a significantly improved screening test. The test uses ordinary blood samples and is fast and easy to use in a clinical setting. The STHLM3 test includes more biomarkers than any other test and the model is also validated in a large prospective study, which no other tests have been. The Karolinska University Laboratory at Karolin-

ska Hospital will have the STHLM3 test available already in March 2016. The price will be quite affordable, well below the limit based on a health economic assessment. The STHLM3 model is a prediction algorithm where in total six protein biomarkers (two are previously unknown), over two hundred genetic polymorphisms, and clinical variables such as age and family history are taken into account to generate an individual risk score. The model was optimized for maximum detection of high-grade prostate cancers (high Gleason score), while taking as few prostate biopsies as possible. The model was first trained with a STHLM3 training cohort comprising 11000 men. The trained model was then evaluated in a validation cohort of nearly 50 000 prospectively followed men. - The STHLM3 study would not have been possible without the excellent services of the BBMRI. se Biobank facility. One challenge we were facing, Henrik Grönberg explains, had to do with handling large numbers of samples from patients. During the most intense period blood samples from 300-400 participants (that had to be extracted for DNA) arrived every day at the BBMRI.

“During the most intense period blood samples from 300-400 participants (that had to be extracted for DNA) arrived every day at the BBMRI.se Biobank facility.”

se Biobank facility. Several platforms were evaluated for the genotyping. The Real-Time PCR System that James Thompson and Mark Divers of the BBMRI.se Biobank facility offered in collaboration with


LifeTechnologies was found to be the optimal solution. In March 2016, when the STHLM3 test will be available for clinical use by the Karolinska University Hospital (KUL), the BBMRI.se Biobank facility will run the genotyping chip and KUL will run the protein chip. - I hope that the STHLM3 study will inspire other researchers to embark on the large-scale biobank journey. The STHLM3 cohort is established under the open access principle and can be used for investigations of other diseases (For example,

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retrieval of samples from heavy smokers for research on lung cancer screening).

What will happen next? - It will be exciting to evaluate the STHLM3 test in new countries such as Norway, Denmark, England and the USA. We will also run a smaller study where we will combine the STHLM3 test with imaging of the prostate gland (MRI), which will probably improve the test characteristics further.

Prostate Cancer and the STHLM3 test: • • • • • • • • • •

10000 new cases of prostate cancer every year in Sweden 2500 annual deaths, just in Sweden 80000 prevalent cancers (men living with prostate cancer in Sweden). 300 MEuro in healthcare costs in Sweden The STHLM3 test is a combination of 6 plasma protein biomarkers, 232 genotypes and clinical information. All components were significantly and independently associated with prostate cancer (multivariate analysis). The main aim is to reduce the number of unnecessary procedures, saving patient harm and reducing use of healthcare resources. While maintaining the same sensitivity to detect high-grade prostate cancer, the total number of prostate biopsies required is reduced by 32%. Lancet Oncology. 2015 Nov 9. pii: S1470-2045(15)00361-7

The BBMRI.se National Large-Scale Biobanking Facility • Development started in January 2010 and has closely followed the original BBMRI.se application to the Swedish Research Council in 2009. • Operational service was launched on 9th November 2010. • A wide range of services for handling of samples and data are offered (see www.bbmri.se). • The pilot phase of the National Large-Scale Facility was supported by the Swedish Research Council and was evaluated by the BBMRI.se Board in 2014. • Samples from about 500,000 individuals are deposited, from >150 studies. Major customers featured in this issue of Biobank Sweden include Sthlm3 and LifeGene. • Customers served should be of national significance, for example by enrolling participants in several areas of Sweden and/or being particularly large-scale studies. • All customers agree to the principle of Open Access, with well-defined procedures for applying for access from other scientists globally. • All customers use the same procedures for collecting samples and data. • All customers agree to display aggregated data on available research materials in the BBMRI.se biobank registry (www.bbmri.se).

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BBMRI.se National Sample Management Services

Large-scale Open Access is now a reality: Providing DNA from 20000 subjects for a Social Science study The population-based cohort and research infrastructure Life Gene has collected blood samples and medical data since 2009. LifeGene has used the BBMRI.se biobanking services and all materials are available on an Open Access basis. That the era of large-scale open access is here is proven by the large withdrawal requested from Markus Heilig and coworkers of Linköping University: Extracted DNA from all 20000 adult participants will be retrieved by the efficient retrieval services of BBMRI.se. The samples will be used in a social science project of genotypes coupled to decision making from online games. During the six years that LifeGene has been in operation more than 40 000 participants have answered

Figure of the growing number of samples and data

the LifeGene questionnaire and almost half of them took a health test, including donation of blood and urine samples. The questionnaire covers as many medical areas as possible. It has between 400 to 1200 questions (depending on the answers) and takes about an hour to complete. The blood is collected in seven different tubes with special additives (such as anticoagulant) to enable a variety of future analyses. When LifeGene started, participants were enrolled in test centers in 3 parts of Sweden (in Stockholm, Umeå and Alingsås). The currently open test center in Stockholm is operated in collaboration with the

Stockholm County Healthcare Provider. - This is a cost-effective way of enrolling and testing study participants, and we hope to extend operations in collaboration with additional Healthcare Providers across Sweden, says Kicki Kjaergaard, CEO of LifeGene. In 2019, the first LifeGene participants will have a follow-up health test, which will increase the val-

“- The analysis data that researchers produce will be returned to the biobank […]. In this way the resource will be refined and expanded every time it´s being used.” ue of LifeGene as a resource for longitudinal studies. Researchers interested in using the LifeGene resource can apply anytime from the web and receive all necessary information. A “showroom” of the LifeGene resources with a search function has been set up together with the BBMRI.se Biobank Facility. The questionnaire items are displayed and how many participants answered a certain question is displayed at an aggregated level (see figure of the growing number of samples and data). - The analysis data that researchers produce will be returned to the biobank, Kicki Kjaergaard explains. In this way the resource will be refined and expanded every time it´s being used. Currently, ten withdrawals from LifeGene have been made. The big withdrawal comprising DNA from all 20 000 participants aged 20-55 years has been started with a pilot, where the first batch of DNA samples has been delivered to the Mutation Analy-


sis Core Facility (MAF) at Karolinska Institute in Huddinge. A panel of 30 genetic markers associated with pain and reward will be analysed, namely within the gene encoding the μ-opiodreceptors. The LifeGene participants will be invited to play online games to test various aspects of decision making, and the influence of social factors.

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scouted to Linköping University as a VR excellency researcher. - I have only been in Sweden a couple of months now, but we have plans for a broad portfolio of psychiatric research, from clinical studies in complex behaviours to mechanistic studies of disease, Markus Heilig says.

The present study could in the long The study is performed in collaborun have implications for treatment Kicki Kjaergaard, ration between Gustav Tinghög, a of depression. The strength of the study CEO of LifeGene group leader in the NeuroEconomics lies in the large-scale, prospective and program at Linköping Univ, and Markus Heilig, real-world setup. recruited from National Institute of Health in the -LifeGene offers a fantastic opportunity to move outUSA. Markus Heilig worked as director of clinical side of the walls of the laboratory, even for complex research at the National Institute on Alcohol Abuse brain functions such as decision making, Markus and Alcoholism for over a decade. In 2015 he was Heilig concludes.

BBMRI.se National Repository

Catalogue of Services issued for the BBMRI.se National Repository BBMRI.se operates a national service for longterm, flexible and quality-assured storage of specimens, the BBMRI.se National Repository. We take national responsibility for saving of important existing sample collections that otherwise would be destroyed (legacy collections). Services provided include sample storage, traceability, withdrawal of samples and sample handling as well as help with administration and agreements. Furthermore, services with how to add data for research projects by linkages of specimens to registries and assistance with associated administration are offered. Customers that need services that include collection of new samples are referred to the BBMRI.se National Large-Scale Sample Management Facility (BBMRI.se Nationella Biobanksfacilitet) that also offers help with planning, administration, IT support, processing and aliquoting of new sam-

ples, freezing, withdrawal, DNA extraction and genotyping. For more information, see: http:// bbmri.se/Global/Publicerade%20dokument/ tj%C3%A4nstekatalog%20biobank.pdf

Both the National Repository and the National Large-Scale Sample Management Facility are parts of the range of services offered by BBMRI. se and are located at the Karolinska Institutet in Stockholm.

Read the National Repository Service Catalogue here: http://bbmri.se/Global/Publicerade%20 dokument/Service%20Catalogue%20National%20Repository_02Dec2015.pdf For inquiries about the services offered by the BBMRI.se National Repository please contact project manager Lars I. Andersson, [email protected] ki.se or 076-209 96 87.

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BBMRI.se IT Services & International Networking

Nordic Workshop on Best Practices for Big Data Handling in Biobanking Modern biomedical research includes storage, analysis and sharing of huge and complex health-related data (Big Data). NIASC (Nordicehealth.se) and NeIC (neic.nordforsk.org) organized a three-day Nordic workshop on Big Data handling in Biobanking in November 2015. The workshop brought together four Nordic national biobanks & infrastructures (BBMRI.se, BBMRI.fi, BBMRI.no/Biobank Norway and Biobank Denmark) and Nordic large-scale e-infrastructure service providers (altogether 23 participants). We exchanged experiences how to build and use efficient and sustainable einfrastructures, maintaining associated workflows, pipelines and bioinformatics softwares for storing, analyzing and sharing large amounts of health-related data. Biobanks are increasingly becoming “Big Data banks” and the shift results in new computational needs. The BBMRI.se director emphasized that the unique advantage of Nordic biobanks is the ability to link different databases through the unique personal identification numbers resulting in prominent epidemiological research based on linking biobanks and registries. However, there are surprisingly few examples of joint Nordic biobank-based research studies and we need to overcome the logistic bottlenecks that prevent the exploitation of this advantage. The directors of the Danish National Biobank and BBMRI.no/Biobank Norway (Mads Melbye and Kristian Hveem) showed how national biobanks are moving from freezers to computers with large-scale digitalization. Genomics for whole populations and linkage to medical registries will enable mapping of gene knockout effects in humans by screening for knock-out-associated phenotypes (reverse data mining). Turning big data into actionable infor-

mation requires a variety of of softwares and bioinformatics pipelines. The challenge is not only to store the large amounts of data but also to analyze it in a reasonable time. The bottleneck is not only the CPU capabilities but also scalable bioinformatics softwares that can effectively utilize new parallel computing hardware. Einar Ryeng, from the NTNU ( w w w. n t n u . no) Genomics Core Facility described strategical system designs for bioinformatics analysis. National e-infrastructure service providers, from Nordic countries and from Poland, presented their services and experiences in building big data infrastructures. TSD (http://www.uio.no/tjenester/it/forskning/sensitiv/) in Norway and Mosler (https:// bils.se/resources/mosler.html) in Sweden described their platform as a service (PaaS) that enables processing and storing of large amounts of medical data. BiobankCloud (www.biobankcloud.com) is also a PaaS that supports secure storage analysis and sharing of large amounts of data. Rewriting/development of bioinformatics methods that will be suitable to the MapReduce framework is essential. The Swedish National Infrastructure for Computing (SNIC) (www.snic.vr.se) provides a set of resources and user support for large-scale computation and data storage. In Finland, similar services are provided by CSC – IT Center for Science (https://research.csc.fi). CSC is providing the cloud-computing infrastructure as a service


(IaaS) ePouta (https://research.csc.fi/epouta), which combines virtual computational resources with the customers’ own resources using a dedicated point-to-point network connection (light path). The ePouta environment meets the elevated information security level regulations and is suitable for research organizations with IT expertise and users that can freely administer their own virtual machines and software on it. ePouta services are not restricted to Finnish research organizations. In Poland, both IaaS and PaaS services are provided by the Polish National Grid Infrastructure (PL GRID) (www.plgrid.pl/). PL GRID has an agreement with Karolinska Institutet to enable joint development of PL GRID computational and bioinformatics resources. The workshop highlighted the wide range of Nordic e-infrastructure services. When a national biobank requires scalable computational infrastructure, but has all the IT expertise in place and would like to freely administer their own systems, the ePouta services in CSC Finland can be provided to national biobanks also in other countries. PaaS(s), such as Mosler and TSD are suitable if the customer does not need to have a need to have a full control over the entire system administration. Mosler and TSD have many data analysis softwares already available and/or possible to install by the user. In Sweden, advice and

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support is provided by SNIC and the Bioinformatics Infrastructure for Life Science (BILS) (https:// bils.se/). The Nordic Tryggve project provides a secure computing environment for analysis of medical data, by “Building blocks” from different Nordic countries, such as TSD (Norway), Mosler (Sweden) and ePouta (Finland).

In summary, the Nordic national biobanks & infrastructures and the Nordic e-infrastructure service providers have many common interests and much to gain from collaboration. Three working groups were formed that will i) formulate a joint use case on IT needs for the Nordic National Biobanks & infrastructures. Ii) develop and optimize useful bioinformatics softwares/algorithms that are scalable and able to efficiently utilize parallel computing and iii) Develop IT solutions that will enable mapping of multiple outcomes from registries with different biomedical data sources.

News In Brief Save the date for European Biobanking week, September 13-16, 2016 On 30 September 2015, BBMRI-ERIC and ESBB (European, Middle Eastern and African Society for Biopreservation & Biobanking) have formed a strategic alliance for the benefit of European biobanking efforts. Starting in 2016, the two organisations will jointly organise the most important annual biobanking conference in Europe and facilitate collaboration on activities related to biobanking and biopreservation of samples for research and development. This agreement emphasises that biobanks are a European strength. The Europe Biobank Week 2016 will be held from September 13-16 in Vienna, Austria. It is organized in association with the International Biobank Summit and the BBMRI-LPC Forum Meeting 2016 and hosted by BBMRI.at the Austrian National Node of BBMRI-ERIC. Read more here: http://europebiobankweek.eu/

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BBMRI.se IT Services & International Networking

Engaging the Research Community towards an Open Science Commons During the past decades biobanking has been transformed from being local bio-specimen repositories to an international research infrastructure that promises great potential development of better predictive, preventive, personalized and participatory healthcare. Today, large national and international biobanking facilities provide services that require large storage capability and parallel data analysis. Therefore, a high level of collaboration is being developed in the biobank community to provide the necessary IT infrastructure that supports global interoperability, big data storage, analysis and sharing.

The European Grid Infrastructure (EGI) through the project EGI-Engage (Engaging the Research Community towards an Open Science Commons) has created a Competence Centre (CC) for largescale international biobanking IT. The CC will: • increase biobank interoperability and data discovery by providing a secure and standard way to share large-scale biobank data, • provide a federated infrastructure for big data storage and intensive data analysis,

EGI-Engage builds on a series of large international infrastructural projects, notably the EGI Federated Infrastructure as a Service (EGI IaaS), EUDAT’s services and technologies, the ELIXIR Cloud working group, and the BBMRI-ERIC IT Common Services, where BBMRI.se is a participant. In EGI-Engage, BBMRI.se is a use case (example) of a large-scale infrastructure that needs highthroughput processing of biobank-derived data.

By simplifying the technologies for sharing largescale data and resources, we expect that EGI-Engage will accelerate the embracing of the open science spirit, which is an important goal of BBMRI.se.


Support by

Nordic Information for Action eScience Center of Excellence




Multinational implementation of OpenSource software for biobank registries

B3Africa - Bridging Biomolecular resources and Biobanks across Europe and Africa




Multinational development and implementation of Open Source softwares for operation of biobanks

Login  (tot  34)   EGI-ENGAGE: Engaging the Research Community towards an Open Science Commons


https://www.egi.eu/about/ #20 egi-engage/

Promoting Open Science. Building relations with the European Grid Infrastructure, beneficial for the BBMRI.se IT services



BBMRI.se programmers are programming the Open Source softwares to be used by BC-Net.

http://www.bbmri-lpc. org/


http://www.ntnu.no/ biobanknorge/nordicbiobank-


Network of national large-scale biobanking facilities share experiences towards joint development & improvement of services. Network of national biobanks & infrastructures share experiences towards joint development

BC-Net: Low & Middle Income WHO/IARC Countries Biobank & Cohort building Network BBMRI-Large Prospective EU Cohorts Nordic Biobank Network



• facilitate efficient use of bio-resources by supporting visibility and sharing, while ensuring personal data protection, • facilitate efficient use of economic resources by providing a common IT infrastructure for storage and processing of big data.

Presented Role for and advantage for BBMRI.se in

Sweden   Denmark   Europé   Global  

Internationalization of services is an important part of the BBMRI.se strategy for sustainability. BBMRI.se currently has 7 international grants, providing a sustainable diversification of our support and ensuring optimally internationally recognized services. A major basic idea of BBMRI.se is that building of high quality infrastructural services will promote competiveness in international evaluations. The international projects are presented in Biobank Sweden, as exemplified above.

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BBMRI.se Service Center for Analysis Technologies & Reagents

Dried blood spots enable advanced protein affinity analyses and versatile diagnostics Dried blood spots (DBS) on filter paper is a classical tool for biobanking. Ulf Landegren and co-workers are investigating how protein biomarkers can be accurately measured from DBS by the highly sensitive Proseek/ PEA method. The BBMRI.se Board has funded a 2015 strategic project to develop the use of DBS for analysis of plasma proteins derived from whole blood collected on DBS. All newborns in Sweden participate in screening for metabolic diseases such as phenylketonuria (PKU), which are analyzed using dried blood spots (DBS). DNA from stored DBS is also an important resource for medical research. Use of DBS enables minimal invasiveness for the patient, low cost, minimal need for trained personnel in the sampling routines, simple transportation using regular mail, and no need for low-temperature storage.

Protein biomarkers may dynamically reflect disease processes and may also allow disease to be detected in an early, treatable phase. Evaluation of such biomarkers will need longitudinal studies nested in biobanks, and if protein biomarkers could be reliably quantified from DBS, their validation and development for clinical use would be greatly simplified. - Analyses of proteins from DBS has so far been achieved by mass spectrometry in combination with trypsin digestion, Ulf Landegren explains, but we used affinity reagents. Target recognition by pairs of DNA-conjugated antibodies, coupled to PCR amplification, increases the specificity and sensitivity so that we are able to sensitively detect sets of proteins in small sample aliquots, using the proximity extension assay (PEA). PEA has been commercialized by the company Olink under the name Proseek. Johan Björkesten started in 2013 as a diploma worker at Olink to investigate procedures and reagents for extraction of proteins from DBS. - My diploma work showed that it is best to probe the molecules directly in a small sample excised from a DBS, Johan Björkesten says. A separate

elution step does not improve the performance of the assay but only dilutes the sample. After incubation and DNA extension the probed sample is transferred to a microfluidic real-time PCR machine, capable of analysing 96 samples with respect to 96 proteins, including controls.

Photo: Johan Björkesten

In the present strategic BBMRI.se project, procedures and reagents for separating blood cells from plasma directly while collecting DBS are investigated, a process usually done by laboratory-based centrifugation. Nowadays almost all hospital diagnostics is performed on plasma samples, due to large variability of blood cells among healthy individuals. Existing commercial solutions for the separation of plasma and blood cells from finger pricks are expensive and not suitable for large-scale biobanking. Johan Björkesten has tried out a membrane with decreasing pore sizes in a sandwich construction. - We have compared plasma samples prepared in different ways, and we see a nice correlation of results between wet and dried centrifuged plasma and plasma filtered from finger pricks, Johan Björkesten says. The next step is stability measurements of a large number of plasma proteins using the Olink Proseek panels. Each panel consists of 92 proteins, focused on cardiovascular disease, cancer, in-


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flammation and an upcoming panel for neurology. Small discs punched out of DBS samples from children born 1975, 1985, 2005 and 2015 will be retrieved from the Swedish National PKU Biobank and analyzed by PEA. If all goes well the new separation method will allow building of extensive paper-based biobanks for research and/ or diagnostic purposes. The technology is also

attractive for building of biobanks in developing countries. - In future work, we would like to look also at cell-free DNA, exosomes and microRNAs, which are often present at low levels in the blood and seem to be promising as biomarkers, Ulf Landegren adds, and see if we can detect some of these markers from DBS as well.

BBMRI.se Healthcare Biobanking Support Services

Efficient Retrieval System for Cervical Cytology Biobanking Currently, >400000 women have had cervical cell samples stored using the standardised BBMRI. se biobanking solution. Now that the optimized system for receipt, handling and storage is implemented for most of Sweden, the next phase is to optimize the output processing for distribution of samples to the users. As the size and quality of the cytology biobank continues to evolve, an increasing number of innovative projects from both academia, from healthcare and from the life sciences industry are requesting samples. The future of the services offered by BBMRI.se is dependent on the quality and efficiency of the offered services. In August 2015, the Board of BBMRI.se decided on a strategic project for development of an automated high throughput robotic

system for retrieval of cervical cytology samples. The system is being developed as a national pilot project at the Cervical Cytology Biobank at the Karolinska Hospital in Huddinge, Stockholm. The retrieval system is now operational and consists of i) A “cherry picking” robot that can locate and retrieve the specific samples requested ii) Software for the instrument iii) Software for the samples (LIMS) iv) worktable-materials such as racks, holders et cetera. The efficient retrieval system is the key to future medical discoveries and the successful implementation represents a major advancement of the BBMRI.se services. If you are interested in obtaining cervical cell samples for research, please contact [email protected]

Combined retrieval and aliquoting system in operation.

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BBMRI.se Services on Ethical Legal & Societal Issues (ELSI)

Interview with Mats G. Hansson, director of BBMRI.se ELSI Service Center What service does the ELSI service center offer? I have prepared some bullet points to describe our services: • Advice on specific ethical issues for researchers, for example advice on how to interpret the Swedish data protection law or how to interpret the ethical review act in association with certain projects, either before applying for ethical approval or after applying when researchers have received comments from the review board • Investigations of ethical and legal issues associated with biobank and registry-based research. Results of the investigations are published in reports and peer-reviewed publications. • Dissemination of research in bioethics and law to the research comMats G. Hansson munity through newsletters, reports and in conferences • Training and contribution in courses on ELSI issues and research ethics • Participation in research projects. We can assume responsibility for ELSI work packages or be part of an integrated approach. • Preparatory material to help and guide universities, research consortia, research funders in their dialogue with governmental agencies on referrals or policy documents regarding new legislation which is relevant to biobanks and registry-based research, for example new guidelines issued by the Helsinki declaration. • Exchange of information and discussion with policy makers and the general public on a wider scale. For example the ethics blog, which is available both in Swedish and in English, have a lot of followers and last year we published a book with excerpts from the blog. The book was recently requested in several hundred copies by the Dutch genetics research community.

Why do you offer this service to the research community? The service is very much appreciated by the research community. If you conduct biobank and registry-based research in Sweden and Europe there are constant changes in legal and ethical issues that you have to relate to and keep yourself updated about. Research ethics, opportunities and challenges coupled to modern genetics, have become very complex and researchers need guidance. What resources are available for the BBMRI.se ELSI service center? We are part of a large network of people with expertise in all sorts of legal and ethical aspects, and we can forward requests to the right person. Recently we had a question related to patenting in life science and we contacted our network of IPR experts to solve the issue.

How to proceed if you want to get access to the BBMRI.se ELSI service? Big projects involving international partners usually require help from European nodes, where national laws are covered by national experts. Within BBMRI-ERIC ELSI common service we are building such as network of experts, a so called “help desk for ethics check”. Many Swedish projects can be handled within BBMRI.se. Then you should be clear about what the research is about, of course, and the best for us is to take responsibility of a separate ELSI work package. In smaller projects, an integrated approach can be better and then we prefer to get involved early on to be able to predict the ethical and legal issues that could arise. Just send an e-mail, to [email protected]!

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National & International Networking

National hearing on highly specialized laboratory medicine A national hearing on highly specialized laboratory medicine was organized at the Karolinska University Hospital in Huddinge on the 30th of October 2015. The initiators were Nasrin Perskvist, director and national coordinator of biobanking in clinical cytology, and Joakim Dillner, director of BBMRI.se. Some 60 participants showed up including representatives from county councils, universities and industry. The purpose and objective of the meeting was in particular to seek answers on how priorities should be implemented by universities and county councils for national competitive healthcare and research, and how universities and healthcare can collaborate for the development of highly specialized laboratory medicine.

Poul Erik Hansen from Sundhedsdatastyrelsen in Denmark presented the Danish National Register of Medical Laboratory Data. A national register of Laboratory Medicine provides an overview of the laboratory diagnostics performed and the data can be made available for both healthcare providers and researchers for quality assurance, development and medical research. Questions about the quality of laboratory diagnostics as well as how Sweden will take the next step towards improving human health through research and education were discussed in a panel discussion. It was pointed out that a National Quality Register of Laboratory Medicine in Sweden, similar to what already exists in Denmark, can be an attractive alternative for the reinforcement of Swedish healthcare and clinical research.

Figure: Total number of samples analysed in Denmark for Hemoglobin (left) or Creatinine (right), by the analysis results (Histograms show the number of samples that had different concentrations of hemoglobin and creatinine). Data from the National Laboratory Medicine Registry of Denmark. Courtesy of Dr. P.E. Hansen, Danish National Board of Health Data.

News In Brief

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New issue Biobank perspective: current issues in biobank ethics and law In the latest version of Current issues in biobank ethics and law, Moa Kindström Dahlin gives her perspective on the ELSI common service BBMRI-ERIC provides and how legal frameworks are interconnected with ethical and social issues. Anna-Sara Lind gives an update about what happens now that the European Court of Justice ruled that the Safe Harbour Clause is not a legally valid ground for sharing data between EU and the USA. You can also read about projects looking at how participants in the Swedish SCAPIS study perceive risk information and what and how they would like to know about their potential individual risks for disease and disorders. Read more here: http://bbmri.se/Global/Nyhetsarkiv/2015/Biobank-Perspectives-4-2015.pdf

Biobanks Europe, the newsletter from BBMRI-ERIC - Issue No. 3 / 2015 Introduction of the BBMRI-ERIC node on Malta, the BBMRI-ERIC´s position paper on the General Data Protection Regulations, and the impact of the ´Safe Harbour´ invalidation on European medical research. Read the newsletter here: http://bbmri-eric.eu/news-letter

The Kingdom of Norway joins BBMRI-ERIC The Assembly of Members of BBMRI-ERIC, has at the request from the Research Council of Norway, admitted the the Kingdom of Norway as a full member of BBMRI-ERIC. Karianne Solaas will be the head of the Norwegian delegation to the BBMRI-ERIC Assembly of Members. Norway will be full member as of 1 January 2016.

BBMRI-LPC: third scientific call for access BBMRI-LPC (Large Prospective Cohorts) supports innovative research projects conducted jointly in large prospective cohorts (LPC) across Europe. This is done by offering free access (waiving of pick-up fees) to samples for specific research projects selected through open scientific calls. Building on the success of the first call in 2014 and the second call in spring 2015, a third BBMRI-LPC Scientific Call for Access is now being launched. This is an outstanding opportunity for European scientists to gain access to the unique collections of data and biosamples from the BBMRI-LPC network of high quality cohort studies and carry out ground-breaking research projects.

Report from the first BCNet international training course for biobanking in low and middle income countries. The WHO/IARC (International Agency for Research on Cancer) recently organised and hosted the first BCNet training Workshop on biobank building in low and middle income countries, in Lyon from 3 – 5 November 2015. Read the article here: http://bbmri-eric.eu/documents/10181/125935/BC_Net_MM.pdf/3d0791ad-52c5-4fd88438-b1e2ad7786a1

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National & International Networking

Towards Evidence-Based Practices for Biobank Quality Harmonization! Standardization! Common SOPs! These are keys to being able to utilize and share biospecimens with some assurance that different tissues collected from different facilities used similar procedures. How do I know whether the ‘‘best’’ way is really best? What evidence is there for doing things one way versus another? Can the facility purchase and utilize the reagents needed for the ‘‘best’’ way? What will really happen in the field when a new standard operating procedure (SOP) is implemented? There is a growing number of harmonizing practices, in- cluding SOPs posted for public use. To understand the evidence base for using one SOP over another, and annotating biospecimens with information about how they were collected, processed, and stored, the NCI has a Biospecimen Research Database, a well-utilized, online literature database for biospecimen science, including a structured approach to annotating biospecimen procedures (SPREC1) and an NCIrecommended organized approach to including such information in publications (BRISQ2). The NCI BRN program3 (Biospecimen Research Network) and the SPIDIA program4 (standardisation and improvement of generic pre- analytical tools and procedures for in-vitro diagnostics) in the European Union have both addressed the need for basic and applied research to build the knowledge base in biospecimen science. NCI is building evidence-based procedures from idealized practices supported by literature references5. Under-

standing the evidence underlying a procedure, including what may be compromised if the procedure is not followed, will help us to craft practical SOPs that will be fit for the purpose of the biospecimen and the capabilities of the facility. International harmonization on biospecimen collection, processing, and storage procedures, as well as proper annotation, would have immeasurable positive effects for research and development. Development and validation of clinical assays performed on stored biospecimens, collected under international SOPs, would provide patient benefits from more robust research and development.

References 1. Betsou F et al Standard preanalytical coding for biospecimens Cancer Epidemiol Biomarkers Prev 2010;19:1004– 1011. 2. Moore HM et al Biospecimen reporting for improved study quality (BRISQ). J Proteome Res 2011;10:3429–3438. 3. http://biospecimens.cancer.gov/researchnetwork/default.asp. 4. http://www.spidia.eu/. 5. Engel K, Vaught J, Moore H. NCI biospecimen evidencebased practices Biopreserv Biobank. 2014;12:148–150.

This is an excerpt from an Editorial provided to Biobank Sweden by Dr. Helen M. Moore Director Biorepositories and Biospecimen Research Branch National Cancer Institute USA

We wish you all a Merry Christmas and a Happy New Year, from BBMRI.se!

biobank SWEDEN is the newsletter of the BioBanking and Molecular Resource Infrastructure of Sweden (BBMRI.se).

BBMRI.se is part of the European biobanking infrastructure BBMRI ERIC and is funded by the Swedish Research Council and by partner universities.

To stay informed subscribe to [email protected] Also visit www.bbmri.se to find the newsletter as a pdf. Publisher: Joakim Dillner