An external quality assurance scheme. Workshop and report

Throughout the first and second period of BBMRI-LPC, WP 9 has gradually built an extensive network of more than 20 large-scale biobanks from at least 8 BBMRI-LPC partners, the main contributors being NTNU, KI, UU, FIMM, SSI, UMCG, UTARTU, IARC and NIPH. Based on a total of 5 consecutive workshops in collaboration with the Nordic biobank forum, an external quality assurance scheme was agreed upon based on four clearly defined interest groups,   i) Nucleic acids a. Methods for automated and manual extraction b. Protocols for evaluation of DNA and RNA quality c. Appropriate sample size and requested DNA/RNA quality for genomics platforms ii) Samples quality and integrity (pre-analytic evaluation) a. Implementing protocols for evaluation of sample quality related to both legacy collection and de novo collections b. Evaluation of serum/plasma sample quality/integrity based on proteomic, metabolomic screening and biochemical analysis c. Long term sample stability at different storage modalities and temperatures iii) Biospecimen processing (BRISQ) a. Methods,  b. Protocols,  c. SOP´s for processing and storage of liquid based samples, e.g.  serum, plasma, whole blood and urine.  iv) Tubes/labware. a. Tube format,  b. capping/sealing, devises for capping/sealing c. suitability for downstream applications d. security issues, hydration issues e. Share experiences and define the need for further development on tubes and accompanying devises  
 
On average, approximately 10 biobank laboratory engineers and managers have signed up for each group (40 in total) and have started to execute their separate work plan as indicated above. All interest groups have contributed to the web-based BRISQ-report and will maintain and further develop their entries, procedures and SOPs on regular bases.   Protocols from all quality studies will be published and shared on the MolMeth database (www.molmeth.org) with the entire biobank community. This external quality assurance scheme will 
Deliverable no 9.3 Deliverable Title An external quality assurance scheme. Workshop and report Responsible Partner Norwegian University of Science and Technology (NTNU) 
provide an excellent infrastructure for communicating sample quality issues or issues related to existing or new technologies, tender-processes and other industry-related topics 
When required, validation of the recommended standard protocols will be conducted as scientifically designed studies, both from a process perspective and in terms of quality and robustness of the results obtained in the new high throughput analyses. Quality assurance will be coordinated with and through WP2.2. 
The optimized and integrated high throughput analyses will be applied to large biobanked series of DNA and plasma samples from the diversity of large population cohorts participating in BBMRI-LPC with emphasis on consecutive samples, in order to demonstrate the robustness of these methodologies when applied in joint transnational studies. The aim is to provide a uniquely large database on inter-cohort, intersubject and inter‐assay consistency, providing a solid platform for efficient biomarker validation. 
KI has completed a study on protein profiling using a multiplex antibody array with a panel of cardiovascular and inflammatory proteins including the effect of repeated freezing and thawing cycles using the panel of inflammatory markers. Furthermore, they have completed the study comparing EDTA blood tubes with and without a gel separation plug. Based on the performed analyses, it appears quite clear that separating plasma from cells soon after phlebotomy will strongly reduce the cell leakage. This also explains why it has not been seen any effect on protein levels of freezing and thawing once the plasma has been separated.  
A previously reported non-target metabolomics screening at KI using Gas-Chromatography/time-of-flight mass spectrometry (GC-TOF-MS) has now been completed and a manuscript has been submitted. This study confirms earlier published reports that the metabolomic profile is highly time and temperature depended. Samples processed within 3 hours and at + 4 C will minimize the impact on metabolites. The study also demonstrates the concentration ratio of glucose and lactate can serve as a quality marker for samples processed within 8 hours. The usefulness for this must be further validated. 
Sample quality studies are also ongoing at several of the other biobanks involved (i.e. HUNT, SSI, NIPH-Oslo, Cancer registry of Norway (Janus biobank) and Uppsala) and the results will subsequently be published either as reports on www.molmeth.org or as manuscripts in peer-reviewed journals. 
In Jan 2015, a workshop arranged at KI with representatives from several high-through put technology platforms, discussed their strategies for how to define sample quality and to ensure that the samples received are fit for purpose for the specific markers.   
A PhD course “Biobanks as a resource for biomedical research” was successfully conducted at KI in week 7, 2015, with 40 participants from Sweden, Finland, Norway, Denmark, Estonia, Ireland, UK and Germany.  In period 2, partners in WP9 have met at three larger workshops; in Copenhagen October 27-28 2014, Helsinki April 20-21, 2015 and in Stockholm November 24-25, 2015. 
At the Helsinki-workshop in April 2015, the focus was on defining sample quality, differentiation between effects of pre-analytical sample handling and storage as well as long term storage and sample quality. Other topics were DNA quality requirements in epigenetic studies and new NGS methods with very long reads and Quality requirements for RNA sequencing and long term stability of extracted RNA.