Medical Biobanks Research Articles

Biobanks: Archives or Resources? Their Secondary Use for Forensic Purposes—A Systematic Review

Since the biobanks’ inception in 1980, millions of human biological samples have been stored worldwide for medical research or treatment purposes. Today the secondary use of biobanks plays an increasingly important role in research projects because it allows large-scale research starting from professional collections of biospecimens and related clinical data. It would be limiting, in the “-omics” era, to not consider the enormous potential value to law enforcement of these biospecimens, where the availability of high-performance techniques makes it possible to obtain a large amount of data, even within a single session. Therefore, the quality of the sample, in addition to the associated clinical information, becomes of crucial importance to derive scientifically valid information, including for forensic research purposes. Proposing the introduction of the concept of “solidarity”, traditionally applied only to medical and research biobanks, led to public commitment to forensic medicine. Granting the forensic researcher this possibility certainly raises some questions regarding regulatory and ethical aspects of consent, privacy, confidentiality, transparency, and participant/donor trust. Since the debate has not stopped since the origin of biobanks, this review aims to explore the state of the art relating to the use of human biological material in medical biobanks for biomedical and forensic research.

Abstract 1332: Extracted mRNA from frozen buffy coat samples shows promise for use in downstream sequencing analyses

Abstract Frozen blood samples are routinely collected and stored in medical biobanks across the world, often for periods of several decades, and later used for medical research such as biomarker studies. Some common biomarker targets have included DNA alterations, protein or antibody levels or metabolomics. However, despite the potential importance of gene-expression alterations in circulating immune cells, transcriptional studies on blood samples from biobanks have been limited due to preanalytical technical difficulties of extracting high-quality RNA. In the absence of an RNA preservative, RNA degrades rapidly during the thawing process. Our aim was, therefore, to investigate the possibility of using biobanked blood samples for transcriptomics analyses. First, we used a CryoXtract CXT 350 to establish a protocol capable of isolating high-quality RNA from frozen core aliquots of buffy coat without thawing the entire sample tube. Then, we performed RNA sequencing on RNA extracted from 20 pre-diagnostic buffy coat samples from colorectal cancer patients and matched controls included in the population-based, prospective Northern Sweden Health and Disease Study (NSHDS). For all samples, two different library preparation methods were used (Illumina TruSeq Stranded mRNA poly-A selection and Illumina Stranded Total RNA with Ribo-Zero Globin). We obtained RNA yields of more than 1 µg from a majority of the NSHDS samples (mean=2.57 µg), and more than 92% of samples had RIN values of 6 or higher, indicating suitability for downstream analyses. Preliminary random forest analyses showed expected discriminatory ability between men and women based on data generated from each of the two library preparation methods. In conclusion, our newly established RNA extraction method enables extraction of RNA from frozen, biobanked buffy coat samples, collected in standard tubes, that is of sufficient quantity and quality for use in downstream whole-genome transcriptomic analyses, such as RNA sequencing. Citation Format: Erik Bovinder Ylitalo, Linda Vidman, Sophia Harlid, Bethany Van Guelpen. Extracted mRNA from frozen buffy coat samples shows promise for use in downstream sequencing analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1332.

Exome-wide association analysis of CT imaging-derived hepatic fat in a medical biobank

Nonalcoholic fatty liver disease is common and highly heritable. Genetic studies of hepatic fat have not sufficiently addressed non-European and rare variants. In a medical biobank, we quantitate hepatic fat from clinical computed tomography (CT) scans via deep learning in 10,283 participants with whole-exome sequences available. We conduct exome-wide associations of single variants and rare predicted loss-of-function (pLOF) variants with CT-based hepatic fat and perform cross-modality replication in the UK Biobank (UKB) by linking whole-exome sequences to MRI-based hepatic fat. We confirm single variants previously associated with hepatic fat and identify several additional variants, including two (FGD5 H600Y and CITED2 S198_G199del) that replicated in UKB. A burden of rare pLOF variants in LMF2 is associated with increased hepatic fat and replicates in UKB. Quantitative phenotypes generated from clinical imaging studies and intersected with genomic data in medical biobanks have the potential to identify molecular pathways associated with human traits and disease.

The Penn Medicine BioBank: Towards a Genomics-Enabled Learning Healthcare System to Accelerate Precision Medicine in a Diverse Population.

The Penn Medicine BioBank (PMBB) is an electronic health record (EHR)-linked biobank at the University of Pennsylvania (Penn Medicine). A large variety of health-related information, ranging from diagnosis codes to laboratory measurements, imaging data and lifestyle information, is integrated with genomic and biomarker data in the PMBB to facilitate discoveries and translational science. To date, 174,712 participants have been enrolled into the PMBB, including approximately 30% of participants of non-European ancestry, making it one of the most diverse medical biobanks. There is a median of seven years of longitudinal data in the EHR available on participants, who also consent to permission to recontact. Herein, we describe the operations and infrastructure of the PMBB, summarize the phenotypic architecture of the enrolled participants, and use body mass index (BMI) as a proof-of-concept quantitative phenotype for PheWAS, LabWAS, and GWAS. The major representation of African-American participants in the PMBB addresses the essential need to expand the diversity in genetic and translational research. There is a critical need for a "medical biobank consortium" to facilitate replication, increase power for rare phenotypes and variants, and promote harmonized collaboration to optimize the potential for biological discovery and precision medicine.

GENOMIC POLITICS AND EQUALITY

GENOMIC POLITICS AND EQUALITY

Public law regulation of the system of medical biobanks: problem statement

Public law regulation of the system of medical biobanks: problem statement

Artificial intelligence in cardiology: the debate continues.

In 1955, when John McCarthy and his colleagues proposed their first study of artificial intelligence, they suggested that 'every aspect of learning or any other feature of intelligence can in principle be so precisely described that a machine can be made to simulate it'. Whether that might ever be possible would depend on how we define intelligence, but what is indisputable is that new methods are needed to analyse and interpret the copious information provided by digital medical images, genomic databases, and biobanks. Technological advances have enabled applications of artificial intelligence (AI) including machine learning (ML) to be implemented into clinical practice, and their related scientific literature is exploding. Advocates argue enthusiastically that AI will transform many aspects of clinical cardiovascular medicine, while sceptics stress the importance of caution and the need for more evidence. This report summarizes the main opposing arguments that were presented in a debate at the 2021 Congress of the European Society of Cardiology. Artificial intelligence is an advanced analytical technique that should be considered when conventional statistical methods are insufficient, but testing a hypothesis or solving a clinical problem-not finding another application for AI-remains the most important objective. Artificial intelligence and ML methods should be transparent and interpretable, if they are to be approved by regulators and trusted to provide support for clinical decisions. Physicians need to understand AI methods and collaborate with engineers. Few applications have yet been shown to have a positive impact on clinical outcomes, so investment in research is essential.

Exome-wide evaluation of rare coding variants using electronic health records identifies new gene-phenotype associations.

The clinical impact of rare loss-of-function variants has yet to be determined for most genes. Integration of DNA sequencing data with electronic health records (EHRs) could enhance our understanding of the contribution of rare genetic variation to human disease1. By leveraging 10,900 whole-exome sequences linked to EHR data in the Penn Medicine Biobank, we addressed the association of the cumulative effects of rare predicted loss-of-function variants for each individual gene on human disease on an exome-wide scale, as assessed using a set of diverse EHR phenotypes. After discovering 97 genes with exome-by-phenome-wide significant phenotype associations (P < 10-6), we replicated 26 of these in the Penn Medicine Biobank, as well as in three other medical biobanks and the population-based UK Biobank. Of these 26 genes, five had associations that have been previously reported and represented positive controls, whereas 21 had phenotype associations not previously reported, among which were genes implicated in glaucoma, aortic ectasia, diabetes mellitus, muscular dystrophy and hearing loss. These findings show the value of aggregating rare predicted loss-of-function variants into 'gene burdens' for identifying new gene-disease associations using EHR phenotypes in a medical biobank. We suggest that application of this approach to even larger numbers of individuals will provide the statistical power required to uncover unexplored relationships between rare genetic variation and disease phenotypes.

Radiología y COVID-19: Un Repaso a una Actuación

The role of Radiology in SARS-CoV-2 infection has been relevant but marginal. Even though it offers important information on pulmonary and vascular involvement in these patients, its contributions should not be considered diagnostic for COVID-19. Although there are characteristic patterns of involvement, these same radiological findings can be observed in other entities. Mainly it should be considered that Radiology contributes to the disease severity gradation, extension, complications, follow-up and in the prognostic evaluation of these patients. In this review, these contributions will be discussed together with the role of imaging in clinical trials and in the evaluation of new epidemic situations through the creation of Medical Imaging Biobanks capable of using the estimating potential of Artificial Intelligence.

Association of the V122I Hereditary Transthyretin Amyloidosis Genetic Variant With Heart Failure Among Individuals of African or Hispanic/Latino Ancestry

Hereditary transthyretin (TTR) amyloid cardiomyopathy (hATTR-CM) due to the TTR V122I variant is an autosomal-dominant disorder that causes heart failure in elderly individuals of African ancestry. The clinical associations of carrying the variant, its effect in other African ancestry populations including Hispanic/Latino individuals, and the rates of achieving a clinical diagnosis in carriers are unknown. To assess the association between the TTR V122I variant and heart failure and identify rates of hATTR-CM diagnosis among carriers with heart failure. Cross-sectional analysis of carriers and noncarriers of TTR V122I of African ancestry aged 50 years or older enrolled in the Penn Medicine Biobank between 2008 and 2017 using electronic health record data from 1996 to 2017. Case-control study in participants of African and Hispanic/Latino ancestry with and without heart failure in the Mount Sinai BioMe Biobank enrolled between 2007 and 2015 using electronic health record data from 2007 to 2018. TTR V122I carrier status. The primary outcome was prevalent heart failure. The rate of diagnosis with hATTR-CM among TTR V122I carriers with heart failure was measured. The cross-sectional cohort included 3724 individuals of African ancestry with a median age of 64 years (interquartile range, 57-71); 1755 (47%) were male, 2896 (78%) had a diagnosis of hypertension, and 753 (20%) had a history of myocardial infarction or coronary revascularization. There were 116 TTR V122I carriers (3.1%); 1121 participants (30%) had heart failure. The case-control study consisted of 2307 individuals of African ancestry and 3663 Hispanic/Latino individuals; the median age was 73 years (interquartile range, 68-80), 2271 (38%) were male, 4709 (79%) had a diagnosis of hypertension, and 1008 (17%) had a history of myocardial infarction or coronary revascularization. There were 1376 cases of heart failure. TTR V122I was associated with higher rates of heart failure (cross-sectional cohort: n = 51/116 TTR V122I carriers [44%], n = 1070/3608 noncarriers [30%], adjusted odds ratio, 1.7 [95% CI, 1.2-2.4], P = .006; case-control study: n = 36/1376 heart failure cases [2.6%], n = 82/4594 controls [1.8%], adjusted odds ratio, 1.8 [95% CI, 1.2-2.7], P = .008). Ten of 92 TTR V122I carriers with heart failure (11%) were diagnosed as having hATTR-CM; the median time from onset of symptoms to clinical diagnosis was 3 years. Among individuals of African or Hispanic/Latino ancestry enrolled in 2 academic medical center-based biobanks, the TTR V122I genetic variant was significantly associated with heart failure.

Encouraging Participation And Transparency In Biobank Research.

Medical biobanks often struggle to obtain sustainable funding. Commercialization of specimens is one solution, but disclosure of commercial interests to potential contributors can be dissuasive. Recent revisions to the federal human subjects research regulations will soon mandate such commercialization disclosure in some circumstances, which raises questions about implications for practice. In this nationally representative, probability-based survey sample of the US adult population, we found that 67percent of participants agreed that clear notification of potential commercialization of biospecimens is warranted, but only 23percent were comfortable with such use. Sixty-two percent believed that profits should be used only to support future research, and 41percent supported sharing profits with the public. We also considered other factors related to disclosure in our analysis and argue for a "disclosure plus" standard: informing potential contributors that their biospecimens might be accessed by commercial organizations and explaining how profits would be used to both enhance transparency and facilitate contributors' altruistic motivations.

Development of imaging biomarkers and generation of big data.

Several image processing algorithms have emerged to cover unmet clinical needs but their application to radiological routine with a clear clinical impact is still not straightforward. Moving from local to big infrastructures, such as Medical Imaging Biobanks (millions of studies), or even more, Federations of Medical Imaging Biobanks (in some cases totaling to hundreds of millions of studies) require the integration of automated pipelines for fast analysis of pooled data to extract clinically relevant conclusions, not uniquely linked to medical imaging, but in combination to other information such as genetic profiling. A general strategy for the development of imaging biomarkers and their integration in the cloud for the quantitative management and exploitation in large databases is herein presented. The proposed platform has been successfully launched and is being validated nowadays among the early adopters' community of radiologists, clinicians, and medical imaging researchers.

Community Perceptions of Biobanking Participation: A Qualitative Study among Mexican-Americans in Three Texas Cities

Background: Most biospecimens in the US are collected from non-Hispanic Whites, limiting the generalizability of findings. There is a need to increase participation in biobanking among ethnic and racial minorities. The purpose of this study was to use qualitative methods to identify factors that may influence Mexican-American individuals' willingness to participate in biobanking. Methods: We conducted 15 focus groups in three Texas cities with Mexican-American individuals, in both Spanish and English. Results: Lack of knowledge about medical research and biobanks, lack of information about the specifics of biobanking participation, lack of communication of the results, fear of pain or harm, and distrust of the healthcare system or health research were identified as barriers to biobanking participation. Facilitators to participation were altruism, safety, understanding biobanking procedures and purposes, perceived benefits to participation, and culturally appropriate recruitment strategies. Although Mexican-Americans living in Texas are willing to donate biospecimens for altruistic reasons, such as helping society or advancing science, they want more information about what biobanking entails. They want to be assured that participation will not cause them harm and that the research is conducted with good intentions. Conclusion: Results from this study can inform educational materials or interventions to increase Hispanic participation in biobanking.

A Unique Source for Innovative Longitudinal Research: The POPLINK Database

&#x0D; &#x0D; &#x0D; This paper presents the longitudinal database POPLINK, which has been developed at the Demographic Data Base at Umeå University, Sweden. Based on digitized Swedish population registers between c. 1700-1950, the database contains micro-data that covers the agrarian society through industrialization and further on to the Swedish welfare state and contemporary society. It is now possible to study the profound processes of the second demographic transition using individual level data with a proper size population. POPLINK allows for a large array of longitudinal studies, such as social mobility, migration, fertility, mortality, civil status, kinship relations, diseases, disability and causes of death. International standards of occupations (HISCO) and diseases (ICD-10) have been applied, facilitating comparability. POPLINK covers two large regions in Northern Sweden and is built on complete registrations. It is one of the world’s most information-dense historical population databases, covering up to 15 generations and 350,000 individuals described by 300 variables, allowing the ability to monitor populations over time. POPLINK has been built to allow linkage to modern registries, clinical data and medical biobanks, which enables the study of transgenerational effects, heredity and genetic transfers in disease incidence of the population today. DDB serves as an infrastructure for research and is open to researchers of any nationality.&#x0D; &#x0D; &#x0D;

'Get Your Swabs Out of My Face!': Americanss Optimism and Pessimism About Scientific Innovation

This paper examines when and why Americans are optimistic or pessimistic about societal uses of scientific innovation. Public opinion is not, of course, dispositive in shaping policy choices about innovations in science, but neither is it immaterial. Constituents’ views may be especially important to elected officials in the case of issues about which they have no prior record, views, or expertise; in such a case, politicians may follow the lead of their voters. Our vehicle for examining optimism about science or technology is genomics, in particular, Americans’ views of medical and forensic biobanks. The theoretical framework is the interaction between ideology and the institutionalization, or lack thereof, of the innovation. The evidence comes from a new national survey of about 4000 Americans , with parallel items on medical and forensic biobanks and almost 4000 open ended comments explaining the respondents’ stances on biobanking.We find that Americans tend toward optimism about medical biobanks, which are not institutionalized, and even greater optimism about forensic biobanks, which have much broader and deeper roots in the policy arena. Despite the fact that Americans know nothing about medical biobanks, Republicans are less enthusiastic about them than are Democrats, extreme conservatives are more pessimistic than are other conservatives, and Blacks are less enthusiastic than are Whites or Asians. Supported by insights emerging from the open-ended responses, we interpret these results as further evidence of the importance of institutionalization on attitudes -- through partisanship in the case of Republicans and Democrats, rejection of all institutions in the case of extreme conservatives, and experience-based mistrust of institutions in the case of African Americans.We conclude that comparison across of types of biobanks offers a fairly precise way to measure the impact of institutionalization on public opinion, and the relative importance of the scientific innovation itself compared with respondents’ prior histories, stereotypes, or commitments. We open the possibility of comparing views on genomics across countries as a way to further explore the interaction of ideology and institutionalization.

Public participation in genetic databases: crossing the boundaries between biobanks and forensic DNA databases through the principle of solidarity

The ethical aspects of biobanks and forensic DNA databases are often treated as separate issues. As a reflection of this, public participation, or the involvement of citizens in genetic databases,...

Where should we draw the line between quality of care and other ethical concerns related to medical registries and biobanks?

Together with large biobanks of human samples, medical registries with aggregated data from many clinical centers are vital parts of an infrastructure for maintaining high standards of quality with regard to medical diagnosis and treatment. The rapid development in personalized medicine and pharmaco-genomics only underscores the future need for these infrastructures. However, registries and biobanks have been criticized as constituting great risks to individual privacy. In this article, I suggest that quality with regard to diagnosis and treatment is an inherent, morally normative requirement of health care, and argue that quality concerns in this sense may be balanced with privacy concerns.

Will forensic use of medical biobanks decrease public trust in healthcare services? Some empirical observations

The authors tested the prevalent hypothesis that forensic use of medical biobanks has a negative impact on public trust in healthcare services. A questionnaire was sent to 1,184 inhabitant in the age group 20-80 years in Stockholm County, Sweden, in November 2005. With a response rate of 68.4%, the results showed that a majority (88.1%) of the respondents thought that it would be acceptable for the police to gain access to genetic samples stored in relation to healthcare; 5.6% said no and 6.3% were uncertain. In the case of police access to medical biobanks, a minority (6.3%) indicated that this would have a negative impact on their trust, a larger proportion (37.8%) that it would influence their trust in the healthcare services positively, and 56% stated that it would not affect their trust at all. The hypothesis tested appears to be unfounded. This should cause us to reconsider prevalent assumptions and current policies on the interface of medical and forensic genetics.