Building Research Support Capacity across Human Health Biobanks during the COVID-19 Pandemic.

Human health biobanks are forms of research infrastructure that supply biospecimens and associated data to researchers, and therefore juxtapose the activities of clinical care and biomedical research. The discipline of biobanking has existed for over 20 years and is supported by several international professional societies and dedicated academic journals. However, despite both rising research demand for human biospecimens, and the growth of biobanking as an academic discipline, many individual biobanks continue to experience sustainability challenges. This commentary will summarize how the COVID-19 pandemic is creating new challenges and opportunities for both the health biobanking sector and the supporting discipline of biobanking. While the challenges for biobanks may be numerous and acute, there are opportunities for both individual biobanks and the discipline of biobanking to embrace change such that biobanks can continue to support and drive biomedical research. We will therefore describe numerous practical steps that individual biobanks and/or the discipline of biobanking can take to survive and possibly thrive in response to the COVID-19 pandemic.

Toward a Synergistic Operating Model for Westmead Research Hub Biobanks: A Questionnaire Study.

Standardization and sustainability are ideals within the biobanking world, and the demand for high-quality well-annotated specimens is growing just as rapidly as the ever-increasing precision and throughput of today's high-tech scientific methods. In the state of New South Wales (NSW) in Australia, the state government has allocated significant funding toward this requirement in recent years, with the launch of the NSW Health Statewide Biobank in central Sydney in 2017, and the introduction of the voluntary NSW Biobank Certification Program, and Consent Toolkit. For new and established biobanks, the influence of these new resources has been twofold: first they have provided valuable guidance for moving toward standardized practices and raising the bar for biobanking quality standards; second, they have brought to the forefront the challenges of sustainability and transitioning to a certification standard of biobanking. In Westmead, ∼20 km from Sydney's central business district, the Westmead Research Hub has responded to these challenges with a collaborative biobanking project initiated in 2015. As the site of almost 30 individual biobanks, and to inform a pilot project of central biobank services, a questionnaire was developed and administered to all of the biobanks. This article reports on the results from the questionnaire and the rationale for subsequent initiation of a core biobanking facility.

Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer.

Triple-negative breast cancers (TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles of TNBCs are similar to those of breast tumours in women with BRCA1 mutations. Reports to date indicate that up to 20 % of TNBC patients harbour germline BRCA mutations; however, the prevalence of BRCA mutations in TNBC patients varies widely between countries and from study to study. We studied 774 women with triple-negative breast cancer, diagnosed on average at age 58.0 years. Samples of genomic DNA were provided by the Australian Breast Cancer Tissue Bank (ABCTB) (439 patients) and by the Department of Genetics and Pathology of the Pomeranian Medical University (335 patients). The entire coding regions and the exon-intron boundaries of BRCA1 and BRCA2 were amplified and sequenced by next-generation sequencing. We identified a BRCA1 or BRCA2 mutation in 74 of 774 (9.6 %) triple-negative patients. The mutation prevalence was 9.3 % in Australia and was 9.9 % in Poland. In both countries, the mean age of diagnoses of BRCA1 mutation carriers was significantly lower than that of non-carriers, while the age of onset of BRCA2 mutation carriers was similar to that of non-carriers. In the Australian cohort, 59 % of the mutation-positive patients did not have a family history of breast or ovarian cancer, and would not have qualified for genetic testing. The triple-negative phenotype should be added as a criterion to genetic screening guidelines.

Biobanking sustainability--experiences of the Australian Breast Cancer Tissue Bank (ABCTB).

Sustainability of biorepositories is a key issue globally. This article is a description of the different strategies and mechanisms used by the Australian Breast Cancer Tissue Bank (ABCTB) in developing and operating the resource since its inception in 2005. ABCTB operates according to a hub and spoke model, with a central management hub that is responsible for overall management of the resource including financial, ethical, and legal processes, researcher applications for material, clinical follow-up, information/database activities, and security. A centralized processing laboratory also operates from the hub site where DNA and RNA extractions are performed, digital imaging of stained tumor sections occurs, and specimens are assembled for dispatch for research projects. ABCTB collection sites where donors are identified, consent obtained, and specimens collected and processed for initial storage are located across Australia. Each of the activities of the resource requires financial support and different sources of revenue, some of which are allocated to a specific function of the ABCTB. Different models are in use at different collection centers where local variations may exist and local financial support may sometimes be obtained. There is also significant in-kind support by clinics and diagnostic and research facilities that house the various activities of the resource. However, long-term financial commitment to ensure the survival of the resource is not in place, and forward planning of operations remains challenging under these circumstances.

Open source tools for management and archiving of digital microscopy data to allow integration with patient pathology and treatment information.

BACKGROUND: Virtual microscopy includes digitisation of histology slides and the use of computer technologies for complex investigation of diseases such as cancer. However, automated image analysis, or website publishing of such digital images, is hampered by their large file sizes. RESULTS: We have developed two Java based open source tools: Snapshot Creator and NDPI-Splitter. Snapshot Creator converts a portion of a large digital slide into a desired quality JPEG image. The image is linked to the patient's clinical and treatment information in a customised open source cancer data management software (Caisis) in use at the Australian Breast Cancer Tissue Bank (ABCTB) and then published on the ABCTB website (http://www.abctb.org.au) using Deep Zoom open source technology. Using the ABCTB online search engine, digital images can be searched by defining various criteria such as cancer type, or biomarkers expressed. NDPI-Splitter splits a large image file into smaller sections of TIFF images so that they can be easily analysed by image analysis software such as Metamorph or Matlab. NDPI-Splitter also has the capacity to filter out empty images. CONCLUSIONS: Snapshot Creator and NDPI-Splitter are novel open source Java tools. They convert digital slides into files of smaller size for further processing. In conjunction with other open source tools such as Deep Zoom and Caisis, this suite of tools is used for the management and archiving of digital microscopy images, enabling digitised images to be explored and zoomed online. Our online image repository also has the capacity to be used as a teaching resource. These tools also enable large files to be sectioned for image analysis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5330903258483934.

A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11.

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

Development of a data entry auditing protocol and quality assurance for a tissue bank database.

Human transcription error is an acknowledged risk when extracting information from paper records for entry into a database. For a tissue bank, it is critical that accurate data are provided to researchers with approved access to tissue bank material. The challenges of tissue bank data collection include manual extraction of data from complex medical reports that are accessed from a number of sources and that differ in style and layout. As a quality assurance measure, the Breast Cancer Tissue Bank (http:\\www.abctb.org.au) has implemented an auditing protocol and in order to efficiently execute the process, has developed an open source database plug-in tool (eAuditor) to assist in auditing of data held in our tissue bank database. Using eAuditor, we have identified that human entry errors range from 0.01% when entering donor's clinical follow-up details, to 0.53% when entering pathological details, highlighting the importance of an audit protocol tool such as eAuditor in a tissue bank database. eAuditor was developed and tested on the Caisis open source clinical-research database; however, it can be integrated in other databases where similar functionality is required.

Electronic biorepository application system: web-based software to manage receipt, peer review, and approval of researcher applications to a biobank.

The importance of suitably characterized and preserved biospecimens for research is acknowledged, yet providing information about the availability of biospecimens and associated data, responding to enquiries from researchers, processing applications for material, and seeking independent scientific review of proposed projects are complex and time-consuming processes. Most biorepositories operate as not-for-profit entities; therefore, cost containment is a major consideration. We identified that online systematizing and automation of all of the tasks associated with application management could reduce the administrative workload and therefore reduce costs and improve the efficiency of a biobank. Accordingly, we have developed a Web-based electronic Biorepository Application System (eBAS) that allows researchers to search for suitable material from the biobank database, submit an online expression of interest, and complete all the information required for a full application. Peer review is also managed through eBAS. Implementation of eBAS has streamlined application management and external peer review of researcher applications, and has facilitated automated record storage and management. This approach has potential to reduce the costs and complexities of administering researcher applications. We have also linked eBAS to an open-source clinical research and specimen management database, Caisis.

A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer.

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.

Common breast cancer susceptibility loci are associated with triple-negative breast cancer.

Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six single-nucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer.