1. IntroductionThe human genome project has completed mapping the human genome, and the next-generation sequencing technique expands the availability of personal DNA sequencing, which increases the possibility of customized medical treatment. This means that the bottleneck of customized medical treatment is transited from the technical field to the fields of biological samples and data/knowledge management. The role of biobanks as an infrastructure of human biospecimen supply is important for the development of customized medical treatment, development of new drugs, and prevention of diseases [1,2]. A biobank stores human biospecimens from volunteer participants with various clinical conditions, conducts quality checks, creates a database to handle related information (e.g., clinical/epidemiological data), and distributes biospecimens for researches . Well-documented, up-to-date epidemiological data, along with extensive human biospecimen information connected with clinical and biological information, are necessary to draw statistically significant, effective results in retrospective researches . Furthermore, it is also the role of the biobank to ensure the participants’ rights and to provide the ethical and legal framework for the use of biospecimen in biobanks .The UK biobank, one of the major population-based biobanks, has secured biospecimens of 500,000 volunteers aged 45–69 years with related information and distributed these biospecimen to researchers in 2012 . The Kadoorie Study collects Chinese human biospecimens; the baseline survey on 0.5 million participants was completed in 2008, and follow-up resurvey was subsequently performed . In addition, many countries including the United States, EU, Mexico, and India, have constructed and run large-scale biobanks with more than 200,000 participants . There are various biobank networks to draw collaboration among biobanks and standard operating procedures (SOPs).www.p3g.org) and BBMRI (Biobanking and Biomolecular Resources Research Infrastructure; www. bbmri.eu) discuss challenges and critical issues for development, success, and business continuity for biobanks, and look for harmonization among biobanks [8-10].The Korea National Institute of Health (KNIH) organized a task force to plan the construction of a biobank in 2007 and started the Korea Biobank Project (KBP) in 2008 to set up biobanks and a biobank network. To systematically manage the biospecimens of population-based cohorts, which was already carried out and run in the KNIH, and collect biospecimens for chronic diseases and rare diseases such as cancers, diabetes, and hypertension, the Korea Biobank Network was established including the National Biobank of Korea (NBK) and 17 regional biobanks within 17 university hospitals (Figure 1).This report discusses the details of the 2008e2012 biobank construction in Korea (the first term of the KBP) and major achievements (e.g., biospecimen collection and creation of database) along with a description of the facilities and instruments used in the NBK, and to share the experience in running a largescale human biospecimen network.
2. Overview of the Korea Biobank ProjectThe KBP’s (first term, 2008–2012) aim was to secure a total of 500,000 Korean human biospecimens (consisting of 300,000 specimens from the general population and 200,000 from diseased participants). The NBK secured the general population’s biospecimens from various cohorts organized by the KNIH since 2001. Regional biobanks secured disease-based biospecimens in 17 university hospitals, representing diseases such as cancers, chronic diseases, and rare diseases. As of December 2011, a total of 525,416 specimens (325,952 from the general population and 199,464 from diseased populations) have been secured, reaching the first term’s goal 1 year early (Figure 2).When KBP began in 2008, eight regional biobanks were established; four, one, and four additional regional biobanks were constructed in 2009, 2010, and 2011, respectively. Each regional bank can perform an independent biobank function to secure, store, and distribute by input of standardized human biospecimen information and clinical information under Biospecimen Information Management System (BIMS), run by NBK. The second term (2013–2015) plans to provide the userfriendly, one-stop distribution service of KBN in a coordination center.NBK’s functions include securing and distributing population-based cohort biospecimens, planning of the KBP project, providing education for regional biobank staffs, handling public relations, and construction and running of BIMS and the KBP portal site (http://kbn.cdc.go.kr).
3. Status of Population-based Human BiospecimensThe population-based human biospecimens come from population-based cohorts, separately run by the KNIH (Division of Epidemiology and Health Index, Division of Health and Nutrition Examination Survey),Table 1).KoGES is a large-scale Korean genome epidemiology cohort with 220,000 participants as of 2012. The cohort started from the AnsungeAnsan Community-based Cohort in 2001. The communitybased cohort is composed of 10,038 participants aged 40–69 years (5,020 in Ansan, 5,018 in Ansung); it distributes questionnaires and performs biospecimen collection and physical examination every 2 years. About 2,000 items for each person are collected including lifestyle, medical history, physical activity, food consumption, disease-related blood test results and body measurement. The information and biospecimens from the rural Ansung community and urban Ansan community cohort are utilized in analytical studies on interaction of risk factors of chronic diseases and genomic characteristics and observational studies on environmental risk factors. The fifth follow-up examination was completed in 2011, and now the sixth follow-up examination is under progress (http://biomi.cdc.go.kr).The production of human biospecimens is conducted by a company contracted with NBK. Blood samples from the nationwide collection sites using preconfirmed standard protocol are transported by vehicles equipped with refrigerators (set at 4 ℃) and thermal monitoring systems, and are turned into biospecimens of blood plasma, serum, and DNA and temporarily stored at –80 ℃. Next, the biospecimens in refrigerators are transported to NBK and undergo examination and quality check, then classified and stored according to SOPs into three classes: for distribution, backup, or permanent reference.
4. Status of Disease-related Human BiospecimensKBP’s disease-related human biospecimens are secured through 17 regional biobanks located in 17 university hospitals. Figure 4 shows the number and type of biospecimens obtained from the first-term KBP in 17 regional biobanks. The proportion of neoplastic diseases is 45%, whereas that of non-neoplastic diseases is 55%. The characteristic of a regional biobank determines the kinds of biospecimens that are collected. For example, Kyungsang University Hospital specializes in childhoodFigure 3).
5. Status and Results of the Distribution in the First Term KBPThe first term KBP (2008–2012) focuses on securing Korean human biospecimens and constructing and running the network. Since 2001, when biospecimen distribution of KNIH started, until the end of 2011 (when the first term of KBP ended), collected biospecimen and information have been distributed for a total of 454 research projects: 117 projects from NBKs and 347 projects from regional biobanks.DNA biospecimen distribution takes the lion’s share (163,939, or 87%) of the total number of distributions (188,380). It is followed by distribution of serum (14,971, 8%), plasma (6,515, 3%), and other specimens including cells (2,958, 1.6%) (Figure 5). Most studies have been conducted by using poplubation-based human biospecimens of the Ansan and Ansung Cohort . A large-scale genomic study, the Korean Association Resource (KARE) project, analyzed GWAS (genomewide association study) utilizing 8,842 Korean genomic DNA samples secured through KoGES and KBP, and reported the identified genomes related to hypertension, the waist/hip ratio, and bone mineral density . In 2011, Cho found and reported the common loci for metabolic diseases in East Asians after a large-scale GWAS analysis such as repetitive comparison analysis of 30,395 participants’ DNA using Korean Association Resource and the Health Examinee cohorts with Bio- Bank Japan genome-wide association study and Health2 and Shanghai Jiao Tong University Diabetes Cohort in China . The information and biospecimens, which were distributed to cohort researchers and general researchers, made it possible to identify the diet patterns causing certain diseases , index of sleeping pattern, and genome relating to the height of Koreans .As the KBP continues to operate, requests for distribution increase. The automated biospecimen storage and distribution system was introduced for quick distribution of preserved biospecimens. The system has distributed 33,331 biospecimens since its launching in June 2010.A total of 89 papers have been produced through the studies using distributed human biospecimens from NBK: 11 intramural research studies from the KNIH, 18 extramural research, and 60 collaboration researches (Figure 6).
6. Quality Check of Biospecimens in KBNThe standardization of management on human biospecimen, the manual, regulations, guidelines for biospecimen distribution, and working-level guidelines are documented in “Workabout Collection, Storage, Distribution of Biospecimens,” which obtained ISO 9001:2008 quality management system accreditation from the Korea Standard Association in November 2005 and has maintained this accreditation status with periodic post-evaluations.Quality assurance on human biospecimens consists of DNA stability test by electrophoresis, DNA purity test by spectrophotometer, microorganism contamination test by polymerase chain reaction, cross-contamination test by analysis of homogeneity. All biospecimens collected in KoGES undergo DNA degradation test and
7. Opening of Newly Constructed NBK Building and FacilitiesConstruction of the NBK was finally completed (area = 12,301 m2), and the opening ceremony was held on April 26, 2012 at the Osong Health Technology and Administration Complex, Chungcheongbuk-do, Korea (Figure 7). The three-story building including a basement houses storage rooms that can contain 26 million vials of biospecimens; this volume is expected to increase as soon as the automated large archive and related facilities will be installed. The structure also houses laboratories (for quality assurance of biospecimen and pathogens), an auditorium with 150 seats, a main video conference room, nine conference rooms, and staff offices. The budget for the project was secured from the Korean central government in 2008, and it took 24 months to complete the construction (starting from April 2010), shortly followed by a preliminary operation period.As of 2012, NBK has used two different types of freezer to store the biospecimens steadily for a long
8. ConclusionA biobank is an indispensible infrastructure of the post-genome era and continues to evolve in a sophisticated manner. To facilitate the next generation of genome studies for customized medicine and development of biomarkers, the support of an advanced biobank is necessary. To enhance the quality and availability of specimens, a biobank network system is run, and the networking will be even more enhanced. In the future, the SOPs and guidelines suggested by this network will dominate the biobank management and research on biobank specimens. To keep up with this trend, the NBK has obtained accreditation of biobank management system (ISO 9001: 2008) and the establishment of human biospecimen management standard protocol, so that it can enhance the stability and quality of specimens by constructing NBK with 17 regional biobanks and ensuring good quality specimen and information. With the introduction of an automated biospecimen storage and distribution system, the NBK enhances the precision and efficiency of the distribution of human biospecimens, and continues to develop quality assurance techniques and research on the utilization of biospecimens. In the future, the NBK will not only participate in domestic and international biobank networks, but will also seek to encourage the standardization of biospecimen quality and harmonization of biobanks. By doing so, it seeks to promote biomedical researches for the genome protein study to treat and prevent diseases, as well as the development of new medicines, that will eventually lead to realizing customized medical treatment.