The Implementation of an Integrated Management System at Qatar Biobank

Qatar Biobank (QBB) is a platform that will make vital health research possible through its collection of samples and information on health and lifestyle from the local population of Qatar. The goal of QBB is to collect, process, store, and finally share high-quality biological samples and associated data for research purposes with the research community. To do this, a series of standardized procedures following evidence-based practices are required, and QBB is achieving this by implementing an integrated management system (IMS) that incorporates ISO 9001: 2015 and ISO 27001: 2013 standards. ISO 9001 is one of the most commonly implemented quality management systems as it is applicable to any size of organization. ISO 27001: 2013 is increasingly popular as organizations look to manage their data and information security, especially in the light of the recent General Data Protection Regulation legislation and an ever-changing digital landscape. QBB has achieved certification in both ISO 9001: 2015 (originally 2008 standard) and ISO 27001: 2013 since 2014. In 2016, during preparations for recertification of both standards in 2017, QBB chose to integrate both of the management systems in preference to running them in parallel, without compromising the goals and objectives of QBB. The IMS has ensured that rigorous processes and controls are implemented to not only manage the quality of internal and external processes and services provided, but the privacy and confidentiality of data collected during a participant visit are consistently protected as well as a proactive approach to identifying and managing risk within the organization. This article will explore the impact of implementing an IMS on the continuous improvement of services within QBB

Impact of Different Cooling Methods on the Stability of Peripheral Blood Mononuclear Cells (PBMCs)

During cryopreservation of peripheral blood mononuclear cells (PBMCs), there are several recognized cooling methods, which include different cooling rates that might influence the stability of the PBMCs. This chapter will focus on three cooling methods trialled and will describe the different principles they are based on and the outcomes. One cooling method is based on repeatable −1°C/min cooling rate that requires only isopropyl alcohol (method A). The second cooling method is based on the cooling rate of −1° C/min solely (method B). The third cooling method is based on a user-predefined programmable controlled rate of freezing (method C). The first method was discontinued for safety reasons. A small comparative study was performed using 12 cell preparation tubes (CPT) using methods B and C. Cell Viability was measured based on the difference between pre-thaw and post-thaw viability percentages that were obtained from the flow cytometry. From our data, we conclude that although there were no significant differences in the outcomes of the comparative study of cooling methods, the use of either method B or C are the most suitable for long-term storage that will preserve the quality of the sample suitable for future research and clinical applications

Qatar Biobank: COVID-19 biorepository project

Background: The rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its resulting disease (COVID-19) is one of the greatest global public health crisis of the recent decades 1 . The COVID-19 Biorepository is a national project aimed to support the high demand of biomedical research by multiple groups and the need to have access to high quality, curated clinical data, and specimens contributing to the understanding of, and response to, the COVID-19 pandemic and its impacts in Qatar 2, 3 . Methods/Case presentation: Patients with a laboratory diagnosis of COVID-19, who were Qatar residents that could communicate in Arabic, English, Hindi, and Urdu were eligible to participate in the study. COVID-19 diagnosed patients were recruited at the time of their disease period from the main three public hospitals (Communicable Disease Center, Cuban, and Hazm Mebaireek Hospitals) serving as isolation facilities of symptomatic patients in Qatar, during a 7-month period from March 2020 until September 2020. Consented participants were followed up on a weekly basis until recovery, and then monthly for a year. Sociodemographic and clinical data were collected in electronic questionnaires via a face-to-face interview by trained Qatar Biobank (QBB) staff. Results: A total of 2097 consented participants were recruited up to September 2020, males (N = 1050) and females (N = 1047), with a mean age of 41 years (SD: 15.5). 61.0% of the participants had at least one follow up while 27% adhered to monthly follow up visits. Data was collected for 99.7% of the participants, while the follow up process is still ongoing. In total there are 107,171 high quality specimens in the biorepository including plasma, erythrocytes, buffy coat, serum, PAXgene whole blood, nasopharyngeal secretions, and DNA. Conclusion: The COVID-19 Biorepository is a national asset to illuminate the pathophysiological and identify markers of disease prognosis as well as to describe the clinical features and epidemiology of COVID-19 in Qatar and worldwide.qscienc

Glioma extracellular vesicles for precision medicine: prognostic and theragnostic application

EV produced by tumour cells carry a diverse population of proteins, lipids, DNA, and RNA molecules throughout the body and appear to play an important role in the overall development of the disease state, according to growing data. Gliomas account for a sizable fraction of all primary brain tumours and the vast majority of brain malignancies. Glioblastoma multiforme (GBM) is a kind of grade IV glioma that has a very dismal prognosis despite advancements in diagnostic methods and therapeutic options. The authors discuss advances in understanding the function of extracellular vesicles (EVs), in overall glioma growth, as well as how recent research is uncovering the utility of EVs in glioma diagnostics, prognostic and therapeutics approaches

Willingness to participate in genome testing: a survey of public attitudes from Qatar

Genomics has the potential to revolutionize medical approaches to disease prevention, diagnosis, and treatment, but it does not come without challenges. The success of a national population-based genome program, like the Qatar Genome Program (QGP), depends on the willingness of citizens to donate samples and take up genomic testing services. This study explores public attitudes of the Qatari population toward genetic testing and toward participating in the QGP. A representative sample of 837 adult Qataris was surveyed in May 2016. Approximately 71% of respondents surveyed reported that they were willing to participate in the activities of the QGP. Willingness to participate was significantly associated with basic literacy in genetics, a family history of genetic diseases, and previous experience with genetic testing through premarital screening. Respondents cited the desire to know more about their health status as the principle motivation for participating, while lack of time and information were reported as the most important barriers. With QGP plans to ramp up the scale of its national operation toward more integration into clinical care settings, it is critical to understand public attitudes and their determinants. The results demonstrate public support but also identify the need for more education and individual counseling that not only provide information on the process, challenges, and benefits of genomic testing, but that also address concerns about information security

Assessment of Broadly Reactive Responses in Patients With MERS-CoV Infection and SARS-CoV-2 Vaccination

Importance: In the ongoing COVID-19 pandemic, there remain unanswered questions regarding the nature and importance of the humoral immune response against other coronaviruses. Although coinfection of the Middle East respiratory syndrome coronavirus (MERS-CoV) with the SARS-CoV-2 has not been documented yet, several patients previously infected with MERS-CoV received the COVID-19 vaccine; data describing how preexisting MERS-CoV immunity may shape the response to SARS-CoV-2 following infection or vaccination are lacking. Objective: To characterize the cross-reactive and protective humoral responses in patients exposed to both MERS-CoV infection and SARS-CoV-2 vaccination. Design, Setting, and Participants: This cohort study involved a total of 18 sera samples collected from 14 patients with MERS-CoV infection before (n = 12) and after (n = 6) vaccination with 2 doses of COVID-19 mRNA vaccine (BNT162b2 or mRNA-1273). Of those patients, 4 had prevaccination and postvaccination samples. Antibody responses to SARS-CoV-2 and MERS-CoV were assessed as well as cross-reactive responses to other human coronaviruses. Main Outcomes and Measures: The main outcomes measured were binding antibody responses, neutralizing antibodies, and antibody-dependent cellular cytotoxicity (ADCC) activity. Binding antibodies targeting SARS-CoV-2 main antigens (spike [S], nucleocapsid, and receptor-binding domain) were detected using automated immunoassays. Cross-reactive antibodies with the S1 protein of SARS-CoV, MERS-CoV, and common human coronaviruses were analyzed using a bead-based assay. Neutralizing antibodies (NAbs) against MERS-CoV and SARS-CoV-2 as well as ADCC activity against SARS-CoV-2 were assessed. Results: A total of 18 samples were collected from 14 male patients with MERS-CoV infection (mean [SD] age, 43.8 [14.6] years). Median (IQR) duration between primary COVID-19 vaccination and sample collection was 146 (47-189) days. Prevaccination samples had high levels of anti-MERS S1 immunoglobin M (IgM) and IgG (reactivity index ranging from 0.80 to 54.7 for IgM and from 0.85 to 176.3 for IgG). Cross-reactive antibodies with SARS-CoV and SARS-CoV-2 were also detected in these samples. However, cross-reactivity against other coronaviruses was not detected by the microarray assay. Postvaccination samples showed significantly higher levels of total antibodies, IgG, and IgA targeting SARS-CoV-2 S protein compared with prevaccination samples (eg, mean total antibodies: 8955.0 AU/mL; 95% CI, -5025.0 to 22936.0 arbitrary units/mL; P =.002). In addition, significantly higher anti-SARS S1 IgG levels were detected following vaccination (mean reactivity index, 55.4; 95% CI, -9.1 to 120.0; P =.001), suggesting potential cross-reactivity with these coronaviruses. Also, anti-S NAbs were significantly boosted against SARS-CoV-2 (50.5% neutralization; 95% CI, 17.6% to 83.2% neutralization; P <.001) after vaccination. Furthermore, there was no significant increase in antibody-dependent cellular cytotoxicity against SARS-CoV-2 S protein postvaccination. Conclusions and Relevance: This cohort study found a significant boost in cross-reactive NAbs in some patients exposed to MERS-CoV and SARS-CoV-2 antigens. These findings suggest that isolation of broadly reactive antibodies from these patients may help guide the development of a pancoronavirus vaccine by targeting cross-reactive epitopes between distinct strains of human coronaviruses..This work was supported by internal funds from the Biomedical Research Center of Qatar University. Dr Nasrallah received funding from The WHO Eastern Mediterranean Regional Office (WHO-EMRO) Special Grant for COVID-19 Research

Gene Expression Profiling of Embryonic Human Neural Stem Cells and Dopaminergic Neurons from Adult Human Substantia Nigra

Neural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN) which are rich in dopaminergic (DA) neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6%) genes were up-regulated in the hENSC, 4116 (30.4%) genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93%) were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA) differentiation, and to identify the crucial signaling pathways that direct the process of differentiation. The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies