Human Biobank Research Articles

Current status of Human tissue Biobank —Biobanks in Europe and Japan—

Current status of Human tissue Biobank —Biobanks in Europe and Japan—

Genomic landscape of ovarian clear cell carcinoma via whole exome sequencing

ObjectiveTo analyze whole exome sequencing (WES) data on ovarian clear cell carcinoma (OCCC) in Korean patients via the technique of next generation sequencing (NGS). Genomic profiles were compared between endometriosis-associated OCCC (EMS-OCCC) and Non-EMS-OCCC. MethodsWe used serum samples and cancer tissues, stored at the Seoul National University Hospital Human Biobank, that were initially collected from women diagnosed with OCCC between 2012 and 2016. In total, 15 patients were enrolled: 5 with pathologically confirmed EMS-OCCC and 10 with Non-EMS-OCCC. We performed NGS WES on 15 fresh frozen OCCC tissues and matched serum samples, enabling comprehensive genomic characterization of OCCC. ResultsOCCC was characterized by complex genomic alterations, with a median of 178 exonic mutations (range, 111-25,798) and a median of 343 somatic copy number variations (range, 43-1,820) per tumor sample. In all, 54 somatic mutations were discovered across 14 genes, including PIK3CA (40%), ARID1A (40%), and KRAS (20%) in the 15 Korean OCCCs. Copy number gains in NTRK1 (33%), MYC (40%), and GNAS (47%) and copy number losses in TET2 (73%), TSC1 (67%), BRCA2 (60%), and SMAD4 (47%) were frequent. The significantly altered pathways were associated with proliferation and survival (including the PI3K/AKT, TP53, and ERBB2 pathways) in 87% of OCCCs and with chromatin remodeling in 47% of OCCCs. No significant differences in frequencies of genetic alterations were detected between EMS-OCCC and Non-EMS-OCCC groups. ConclusionWe successfully characterized the genomic landscape of 15 Korean patients with OCCC. We identified potential therapeutic targets for the treatment of this malignancy.

Abstract 23: Identification of NCF4 as a Novel Regulator in Arterial Remodeling and Advanced Atherosclerosis

Arterial wall remodeling is a central multifactorial process in the development and progression of cardiovascular diseases. We employed an approach aimed at observing genetic variants associated with the progression of carotid intima-media thickness (cIMT) in order to identify novel pathways effecting vessel remodeling. This was achieved by conducting gene-centric analysis of 400,000 variants in 3,042 subjects with repeated cIMT measurements. Rs16997464 on chr22 intergenic between neutrophil cytosolic factor-4 ( NCF4) and colony stimulating factor 2 receptor beta ( CSF2RB ) was associated with cIMT progression at array-wide significance (p <4.5x10 -7 ). The potential causative genes within this locus were investigated using a human vascular and non-vascular tissue biobank. Expression of 9 genes near rs16997464, were analyzed with the most significant association being with NCF4 in aortic adventitia. The effect of the variant on the function of the NCF4 gene product was further analyzed by comparing the oxidative burst capacity of neutrophils from subjects with different rs16997464 genotypes. We observed that neutrophils homozygous for the minor T allele, associated with slower cIMT progression, produced more extracellular ROS than neutrophils homozygous for the G allele, indicating a functional effect of rs16997464 on the NCF4 gene product p40 phox , a component of the NADPH oxidase 2 complex (NOX2). In parallel, we investigated if the chr22 locus also influenced the cellular composition of the atherosclerotic plaque, by utilizing data from the Athero-Express Biobank. Here we found that the minor T allele associated with a higher smooth muscle cell (SMC) content in the plaque. Finally, using a partial ligation model in mice where ncf4 is mutated, resulting in a reduced but not absent NOX2-associated ROS formation, we observed a reduced neointima formation in the ncf4 -mutated strain compared with wild-type littermates. Thus, this study identified rs16997464 in the NCF4-CSF2RB locus as a novel genetic determinant of cIMT progression, and provides evidence suggesting that NCF4 is involved in SMC proliferation and alteration of vessel wall pathophysiology.

Label-free Raman spectroscopic imaging to extract morphological and chemical information from a formalin-fixed, paraffin-embedded rat colon tissue section.

SummaryAnimal models and archived human biobank tissues are useful resources for research in disease development, diagnostics and therapeutics. For the preservation of microscopic anatomical features and to facilitate long‐term storage, a majority of tissue samples are denatured by the chemical treatments required for fixation, paraffin embedding and subsequent deparaffinization. These aggressive chemical processes are thought to modify the biochemical composition of the sample and potentially compromise reliable spectroscopic examination useful for the diagnosis or biomarking. As a result, spectroscopy is often conducted on fresh/frozen samples. In this study, we provide an extensive characterization of the biochemical signals remaining in processed samples (formalin fixation and paraffin embedding, FFPE) and especially those originating from the anatomical layers of a healthy rat colon. The application of chemometric analytical methods (unsupervised and supervised) was shown to eliminate the need for tissue staining and easily revealed microscopic features consistent with goblet cells and the dense populations of cells within the mucosa, principally via strong nucleic acid signals. We were also able to identify the collagenous submucosa‐ and serosa‐ as well as the muscle‐associated signals from the muscular regions and blood vessels. Applying linear regression analysis to the data, we were able to corroborate this initial assignment of cell and tissue types by confirming the biological origin of each layer by reference to a subset of authentic biomolecular standards. Our results demonstrate the potential of using label‐free Raman microspectroscopy to obtain superior imaging contrast in FFPE sections when compared directly to conventional haematoxylin and eosin (H&E) staining.

Status Quo Analysis of Human Clinical Biobank in China and Countermeasure Study

Biobank is an important resource for biomedical research, which plays a tremendous role in basic research of clinical diagnosis and treatment of human diseases. In China, the biobank for major diseases was built mainly by large general hospitals which have capacity to access and store large amount of human samples. Such model of repository building is relatively independent, and flexible in operation, but it also has several defects, such as insufficient resources, duplication even in the same hospital, dispersion, and lack of effective and standardized management. This article focuses on the strategy of the standardization of the repository building in large general hospitals, aiming to promote the clinical research platform building in hospital and invigorate medical development. Key words: human clinical biobank; precision medicine; large hospital; standardization

Patient-derived xenograft platform of OSCC: a renewable human bio-bank for preclinical cancer research and a new co-clinical model for treatment optimization.

Advances in next-generation sequencing and bioinformatics have begun to reveal the complex genetic landscape in human cancer genomes, including oral squamous cell carcinoma (OSCC). Sophisticated preclinical models that fully represent intra- and inter-tumoral heterogeneity are required to understand the molecular diversity of cancer and achieve the goal of personalized therapies. Over the last decade, patient-derived xenograft (PDX) models generated from human tumor samples that can retain the histological and genetic features of their donor tumors have been shown to be the preferred preclinical tool in translational cancer research compared with other conventional preclinical models. Specifically, genetically well-defined PDX models can be applied to accelerate targeted antitumor drug development and biomarker discovery. Recently, we have successfully established and characterized an OSCC PDX panel as part of our tumor bio-bank for translational cancer research. In this paper, we discuss the establishment, characterization, and preclinical applications of the PDX models. In particular, we focus on the classification and applications of the PDX models based on validated annotations, including clinicopathological features, genomic profiles, and pharmacological testing information. We also explore the translational value of this well-annotated PDX panel in the development of co-clinical trials for patient stratification and treatment optimization in the near future. Although various limitations still exist, this preclinical approach should be further tested and improved.

Emphasis on the application of precision medicine in ophthalmology

Accompany with dramatically growth of large-scale biological databases (such as human genome sequence), improvement of life science and development of international clinical trials, science offers great potential for improving health care through precision medicine. As a hot topic recently, precision medicine might launch a revolution of the methodology in medical research. How to achieve precision medicine in clinical ophthalmology by means of biological data mining is a challenge for ophthalmologist-scientists. The best approach for advanced individual medicine is to buildup the digital ophthalmology, which includes human eye biobank, national biological databases network, clinical department, basic research lab, and international clinical trial center. The system of digital ophthalmology could explore the methods for ophthalmology research, integrate the source of eye biologic databases, promote international cooperation, and thus eventually supply the opportunity for translational medicine.

Decreased adiponectin links elevated adipose tissue autophagy with adipocyte endocrine dysfunction in obesity.

Adipose tissue (AT) autophagy gene expression is elevated in human obesity, correlating with increased metabolic risk, but mechanistic links between the two remain unclear. Thus, the objective of this study was to assess whether elevated autophagy may cause AT endocrine dysfunction, emphasizing the putative role of adiponectin in fat-liver endocrine communication. We utilized a large (N=186) human AT biobank to assess clinical associations between human visceral AT autophagy genes, adiponectin and leptin, by multivariate models. A broader view of adipocytokines association with elevated autophagy was assessed using adipocytokine array. Finally, to establish causality, ex vivo studies utilizing a murine AT-hepatocyte cell line co-culture system was used. Circulating high-molecular-weight adiponectin and leptin levels were associated with human omental-AT expression of ATG5 mRNA, associations that remained significant (β=-0.197, P=0.011; β=0.267, P<0.001, respectively) in a multivariate model adjusted for age, sex, body mass index and interleukin-6 (IL-6). A similar association was observed with omental-AT LC3A mRNA levels. Bafilomycin-A1 (Baf A) pretreatment of AT explants from high-fat-fed (HFF) mice had no effect on the secretion of some AT-derived endocrine factors, but partially or fully reversed obesity-related changes in secretion of a subset of adipocytokines by >30%, including the obesity-associated upregulation of IL-6, vascular endothelial growth factor, tumor necrosis factor alpha (TNFα) and certain insulin-like growth factor-binding proteins, and the HFF-induced downregulated secretion of IL-10 and adiponectin. Similarly, decreased adiponectin and increased leptin secretion from cultured adipocytes stimulated with TNFα+IL-1β was partially reversed by small interfering RNA-mediated knockdown of ATG7. AT explants from HFF mice co-cultured with Hepa1c hepatoma cells impaired insulin-induced Akt and GSK3 phosphorylation. This effect was significantly reversed by pretreating explants with Baf A, but not if adiponectin was immunodepleted from the conditioned media. Reduced secretion of adiponectin may link obesity-associated elevated AT autophagy/lysosomal activity with adipose endocrine dysfunction.

Establishing and operating a human biobank. Ethical aspects

Particularly in the past decade which has been marked by efforts to foster individualized/personalized medicine the need for well-characterized high-quality collections of human biological material has significantly increased. When establishing and operating a human biobank the interests and the "freedom" of biomedical research must always be weighed against the interests and rights of patients and/or donors; in this process ethical aspects should be considered systematically. In addition, the importance of quality control and quality assurance has largely increased in human biobanking, both from a scientific and even more from an ethical point of view, because donated biological materials are potentially stored for decades and (on request) might serve for currently not foreseeable biomedical research purposes. In addition, the compatibility of national human biobanks with international biobank networks becomes increasingly important.

Human tissue biobank -current and future trends-

Human tissue biobank -current and future trends-

Promising waste: biobanking, embryo research, and infrastructures of ethical efficiency.

Biobanks are custodial institutions that enhance the utility and value of biological materials by collecting and curating them. Their custodial functions tend to include ethical oversight and governance. This paper explores how biobanks increase the value of biological materials by standardizing routines of governance in order to engender "ethical efficiency." Focusing in particular upon banking of human embryos for research, the article offers an historical account of how human embryos came to be "waste" available for use by researchersin the US. It offers a case study of a human embryo biobank and the practices of ethical governance that the biobank employs to capture this waste and convert it into a valuable resource for research use. The article draws attention to the ways biobanks' emphasis on efficiency and resolving problems of ethical governance up front codifiesotherwise contested normative relationships and authorizes uses of human biological materials that some see as ethically problematic,even as it eliminates institutionalized mechanisms of reflection in which such problems would otherwise be acknowledged and confronted.

Closure of a human tissue biobank: individual, institutional, and field expectations during cycles of promise and disappointment

Biobanks are increasingly being established to act as mediators between patient-donors and researchers. In practice, some of these will close. This paper details the experiences of one such bank. We report interviews with the bank's staff and oversight group during the period when the bank ceased biobanking activity, reconfigured as a disseminator of best practice, before then closing altogether. The paper makes three distinct contributions: (i) to provide a detailed account of the establishment, operational challenges, and eventual closure of the bank, which makes clear the rapid turnover in a cycle of promise and disappointment; (ii) to explore this in terms of a novel analytical focus upon field, institutional, and individual expectations; and (iii) to use this typology to demonstrate how, even after the bank's closure, aspects of its work were reconfigured and reused in new contexts. This provides a unique empirical analysis of the under-reported issue of biobank closure.

The International Society of Biological and Environmental Repositories presents Abstracts from their Annual MeetingBridging the Canyon – Connecting Biobank Communities through Innovations in Global Health, Research and Environmental PreservationMay 5–9, 2015Phoenix, Arizona

The International Society of Biological and Environmental Repositories presents Abstracts from their Annual MeetingBridging the Canyon – Connecting Biobank Communities through Innovations in Global Health, Research and Environmental PreservationMay 5–9, 2015Phoenix, Arizona

Analysis of Heterogeneous Concepts during Projection of Facilities of Good Manufacturing Practice and Human Biobank

The aim of this thesis is to analyse and to present heterogeneous concepts during projection of facilities of good manufacturing practice and human biobank.Feasibility study for bio banks of stem cells is prepared for one current health institution in Republic of Macedonia. The space covers 105 square meters for biobank for stem cells, as well as additional space. With this projects program are defined requested needs of the investor during preparation of the basic project for the biobank for stem cells. The prepared architectural – constructive solution allow smooth flow of the technology defined by the investor. The solution is optimal related to the function, construction and economics. It was established that in the Republic of Macedonia there is not present any kind of bank for stem cells, but there are present several liaison offices for collection and deposition of stem cells from several foreign countries. It is necessary to project, construct and to put in function several banks for stem cells in the Republic of Macedonia in order to fulfil the needs of patients with malignant diseases.

Analysis of heterogeneous concepts during projection of facilities of good manufacturing practice and human biobank

Analysis of heterogeneous concepts during projection of facilities of good manufacturing practice and human biobank

Elimination of heparin interference during microarray processing of fresh and biobank-archived blood samples.

In the context of environmental health research, biobank blood samples have recently been identified as suitable for high-throughput omics analyses enabling the identification of new biomarkers of exposure and disease. However, blood samples containing the anti-coagulant heparin could complicate transcriptomic analysis because heparin may inhibit RNA polymerase causing inefficient cRNA synthesis and fluorophore labelling. We investigated the inhibitory effect of heparin and the influence of storage conditions (0 or 3 hr bench times, storage at room temperature or -80°C) on fluorophore labelling in heparinized fresh human buffy coat and whole blood biobank samples during the mRNA work-up protocol for microarray analysis. Subsequently, we removed heparin by lithium chloride (LiCl) treatment and performed a quality control analysis of LiCl-treated biobank sample microarrays to prove their suitability for downstream data analysis. Both fresh and biobank samples experienced varying degrees of heparin-induced inhibition of fluorophore labelling, making most samples unusable for microarray analysis. RNA derived from EDTA and citrate blood was not inhibited. No effect of bench time was observed but room temperature storage gave slightly better results. Strong correlations were observed between original blood sample RNA yield and the amount of synthesized cRNA. LiCl treatment restored sample quality to normal standards in both fresh and biobank samples and the previously identified correlations disappeared. Microarrays hybridized with LiCl-treated biobank samples were of excellent quality with no identifiable influence of heparin. We conclude that, to obtain high quality results, in most cases heparin removal is essential in blood-derived RNA samples intended for microarray analysis.

Re: Biopreserv Biobank 11:77–82

Biopreservation and BiobankingVol. 11, No. 3 CorrectionFree AccessRe: Biopreserv Biobank 11:77–82Published Online:25 Apr 2013https://doi.org/10.1089/bio.2013.1139AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Mucci NR, Moore HM, Brigham LE, Goldthwaite CA, Little AR, Lockhart NC, Scott MP, Struewing JP, Vincent SL, Compton CC, for the cancer Human Biobank (caHUB)Acquisition of Normal Tissue Subgroup, National Cancer Institute. Meeting research needs with postmortem biospecimen donation: Summary of recommendations for postmortem recovery of normal human biospecimens for research. Biopreserv Biobank 11:77–82.On page 78, column one, line two and page 81, column one, Conclusion section, line 11, there is a typographic error in the Web site address. The correct address is http://biospecimens.cancer.gov/resources/oelpr.asp.The publisher regrets the error.FiguresReferencesRelatedDetailsCited byLow Pass Genomes of 141,431 Chinese Reveal Patterns of Viral Infection, Novel Phenotypic Associations, and the Genetic History of ChinaSSRN Electronic Journal Volume 11Issue 3Jun 2013 InformationCopyright 2013, Mary Ann Liebert, Inc.To cite this article:Re: Biopreserv Biobank 11:77–82.Biopreservation and Biobanking.Jun 2013.191-191.http://doi.org/10.1089/bio.2013.1139Published in Volume: 11 Issue 3: April 25, 2013Online Ahead of Print:April 16, 2013PDF download

Abstract 5297: The caHUB biospecimen pre-analytical variables program.

Abstract The Cancer Human Biobank is an infrastructure that the Biorepositories and Biospecimen Research Branch of the Cancer Diagnosis Program at NCI uses to carry out highly specialized tissue collections to support biospecimen research programs. Specifically, the caHUB Biospecimen Pre-analytical Variables Program collects data on how variables in tissue collection, handling, storing and shipping standard operating procedures affect downstream analysis. Phase one of this program will assess variations in formalin fixation procedures. This will include examining the effects of (i) time delay to the start of tissue fixation after resection and (ii) overall tissue formalin fixation time on the signal of key proteomic markers used for diagnostic treatment that will be assessed by immunohistochemistry. Future phases of this study will address a variety of pre-analytical variables and alternate analysis platforms. The results of this project will be used to determine best practices for molecular preservation and lead to the development of evidence-based protocols for optimal collection, processing, and storage of biospecimens. Citation Format: Latarsha Carithers, Jim Vaught. The caHUB biospecimen pre-analytical variables program. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5297. doi:10.1158/1538-7445.AM2013-5297

Observ-OM and Observ-TAB: Universal syntax solutions for the integration, search, and exchange of phenotype and genotype information

Genetic and epidemiological research increasingly employs large collections of phenotypic and molecular observation data from high quality human and model organism samples. Standardization efforts have produced a few simple formats for exchange of these various data, but a lightweight and convenient data representation scheme for all data modalities does not exist, hindering successful data integration, such as assignment of mouse models to orphan diseases and phenotypic clustering for pathways. We report a unified system to integrate and compare observation data across experimental projects, disease databases, and clinical biobanks. The core object model (Observ-OM) comprises only four basic concepts to represent any kind of observation: Targets, Features, Protocols (and their Applications), and Values. An easy-to-use file format (Observ-TAB) employs Excel to represent individual and aggregate data in straightforward spreadsheets. The systems have been tested successfully on human biobank, genome-wide association studies, quantitative trait loci, model organism, and patient registry data using the MOLGENIS platform to quickly setup custom data portals. Our system will dramatically lower the barrier for future data sharing and facilitate integrated search across panels and species. All models, formats, documentation, and software are available for free and open source (LGPLv3) at http://www.observ-om.org.

An NCI Perspective on Creating Sustainable Biospecimen Resources

High-quality biospecimens with appropriate clinical annotation are critical in the era of personalized medicine. It is now widely recognized that biospecimen resources need to be developed and operated under established scientific, technical, business, and ethical/legal standards. To date, such standards have not been widely practiced, resulting in variable biospecimen quality that may compromise research efforts. The National Cancer Institute (NCI) Office of Biorepositories and Biospecimen Research (OBBR) was established in 2005 to coordinate NCI's biospecimen resource activities and address those issues that affect access to the high-quality specimens and data necessary for its research enterprises as well as the broader translational research field. OBBR and the NCI Biorepository Coordinating Committee developed NCI's "Best Practices for Biospecimen Resources" after consultation with a broad array of experts. A Biospecimen Research Network was established to fund research to develop additional evidence-based practices. Although these initiatives will improve the overall availability of high-quality specimens and data for cancer research, OBBR has been authorized to implement a national biobanking effort, cancer HUman Biobank (caHUB). caHUB will address systematically the gaps in knowledge needed to improve the state-of-the-science and strengthen the standards for human biobanking. This commentary outlines the progressive efforts by NCI in technical, governance, and economic considerations that will be important as the new caHUB enterprise is undertaken.