Biobanks and biomarkers:Their current and future role in biomedical research

The importance and utility of biobanks has increased exponentially since their inception and creation.Initially used as part of translational research,they now contribute over 40%of data for all cancer research papers in the United States of America and play a crucial role in all aspects of healthcare.Multiple classification systems exist but a simplified approach is to either classify as population-based or disease-oriented entities.Whilst historically publicly funded institutions,there has been a significant increase in industry funded entities across the world which has changed the dynamic of biobanks offering new possibilities but also new challenges.Biobanks face legal questions over data sharing and intellectual property as well as ethical and sustainability questions particularly as the world attempts to move to a low-carbon economy.International collaboration is required to address some of these challenges but this in itself is fraught with complexity and difficulty.This review will examine the current utility of biobanks in the modern healthcare setting as well as the current and future challenges these vital institutions face.

Clinical Biobanks, from the World to China

The 2009 annual special issue of Time Magazine on March 23rd summarized the ＇10 Ideas Changing the World Right Now＇, in which ＇Biobank＇ had been listed as the eighth. Biobank or biorepository has been developed since last century. Tissue banks represented the early type of clinical biobanks and mainly concentrated on clinical usage such as transplantation at the beginning. The first tissue bank in the United States started in 1949 is the United States Navy Tissue Bank. In 1976, the foundation of American Association of Tissue Banks （AATB） claimed the official show of biobanks on social stage （www.aatb.org）. From the end of 20th Century to the beginning of 21st Century, diverse biobanks of clinical samples, seed banks, gene banks, germplasm banks of non-human species and other various types have sprung up.

Assessment of Knowledge, Attitudes and Support of Health Professionals towards Biobanks in Eastern Morocco

Background: Health professionals play a key role in increasing the rate of biobanking participation. Here, we assessed the knowledge and attitude of health professionals in Eastern Morocco towards biobanks and their willingness to recruit patients into biobanks. Methods: A cross-sectional study carried out among health professionals working in various public and private health centers in Eastern Morocco. The data were obtained using a self-administered anonymous questionnaire. Results: 600 health professionals were included in the study. Only 37.5% of them had knowledge of biobanks. Associations analysis showed that among health professionals, physicians had more knowledge of biobanks (OR = 2.50, p = 0.000), and health professionals working at the University Hospital had more knowledge of biobanks compared to those working in the other participating health centers (p Conclusions: This study indicates that health professionals in Eastern Morocco showed a notable lack of knowledge about biobanks. However, the majority were willing to donate their own biospecimens and supported the recruitment of patients into biobanks. This study was a good opportunity to raise awareness among health professionals about the interest of biobanks in the development of biomedical research in Eastern Morocco.

长期饮酒人群发生急性胰腺炎的风险因素分析:一项基于UK Biobank的自然人群研究

目的探讨有长期饮酒习惯人群急性胰腺炎(acute pancreatitis,AP)发生的风险因素。方法将由UK Biobank数据库中筛选的初次参与调查(2006年—2010年)和第二次随访(2014+)均为“目前饮酒状态”的志愿者作为目标人群(观察至2022年11月30日,期间新诊断AP 176人,未患AP 59512人)。收集目标人群入组时的手术史、饮食习惯等,并通过多因素Cox比例风险模型探讨其是否为AP发生的风险因素。同时以目标人群中有“饮酒类型”记录的人群为亚组,通过多因素Cox比例风险模型探讨不同酒类摄入量及增长量是否为AP发生的风险因素。结果多因素分析结果显示,每天摄入熟菜1~4汤匙,患AP风险分别为不摄入熟菜的44%(HR=0.44,95%CI:0.20~0.95)、39%(HR=0.39,95%CI:0.19~0.82)、42%(HR=0.42,95%CI:0.20~0.89)和41%(HR=0.41,95%CI:0.19~0.88);每天摄入2和3杯咖啡患AP风险为不摄入咖啡人群的45%(HR=0.45,95%CI:0.27~0.75)和39%(HR=0.39,95%CI:0.21~0.72);有胆源性疾病(BD)但未行胆囊切除术(CHO)患AP风险为无BD且未行CHO的7.82倍(HR=7.82,95%CI:5.30~11.54),有BD且行CHO患AP的风险仅为无BD且未行CHO的2.15倍(HR=2.15,95%CI:1.15~4.01)。亚组分析结果显示,不同酒类的摄入量均不影响AP的发生,但在此基础上纳入不同酒类摄入增长量后的结果表明,烈酒摄入增长量每升高1瓶/周、患AP的风险增长1.05倍(HR=1.05,95%CI:1.02~1.09,P<0.05)。结论在有长期饮酒习惯的人群中,熟菜和适量的咖啡摄入是AP发生的保护因素;患BD且不切除胆囊为AP发生的危险因素,而患BD且进行CHO人群的AP发生显著降低;烈酒摄入增长量上升也是AP发生的危险因素。

Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

Harmonizing the COVID-19 sample biobanks: Barriers and opportunities for standards, best practices and networks

The coronavirus disease 2019(COVID-19)pandemic has highlighted the practice of infectious diseases biobanking,as well as existing challenges and opportunities.Thus,the future of infectious diseases biobanking in the post-pandemic era,shall not be an“entry-level version”of its counterpart in non-communicable diseases and large population cohorts,but incorporate the lessons learned.Biobanks constitute a critical research infrastructure supported by harmonized practices through the implementation of international standards,and perceived within the broader scope of healthcare's intersection with research.This perspective paper considers the barriers in biobanking and standardization of practices,as well as the emerging opportunities in the field.

Integrating research infrastructures into infectious diseases surveillance operations:Focus on biobanks

Technological advances in the first two decades of the 21^(st)century have profoundly impacted medical research in many ways,with large population cohorts,biological sample collections and datasets through biobanks becoming valued global resources to guide biomedical research,drug development,and medical practice.However,in order for biobanks to maximize their impact and scientific reach of their resources,they would need to act within a complex network of infrastructures and activities.Therefore,different ways have emerged in which biobanks,including those for infectious diseases,can emerge as(part of)infrastructures,integrate within existing ones,or become an independent,yet an interoperable component of the existing infrastructural landscape.However,there has been a limited understanding and study of such mechanisms to date.This perspective aims to address this knowledge gap and illustrates these three high-level ways in which such infrastructures could integrate their activities and identifies the necessary key pre-conditions for doing so,while drawing from specific examples.

Heart rate response and recovery during exercise predict future delirium risk——A prospective cohort study in middle-to older-aged adults

Background:Delirium is a neurocognitive disorder characterized by an abrupt decline in attention,awareness,and cognition after surgical/illness-induced stressors on the brain.There is now an increasing focus on how cardiovascular health interacts with neurocognitive disorders given their overlapping risk factors and links to subsequent dementia and mortality.One common indicator for cardiovascular health is the heart rate response/recovery(HRR)to exercise,but how this relates to future delirium is unknown.Methods:Electrocardiogram data were examined in 38,740 middle-to older-aged UK Biobank participants(mean age=58.1 years,range:40-72 years;47.3%males)who completed a standardized submaximal exercise stress test(15-s baseline,6-min exercise,and 1-min recovery)and required hospitalization during follow-up.An HRR index was derived as the product of the heart rate(HR)responses during exercise(peak/resting HRs)and recovery(peak/recovery HRs)and categorized into low/average/high groups as the bottom quartile/middle 2 quartiles/top quartile,respectively.Associations between 3 HRR groups and new-onset delirium were investigated using Cox proportional hazards models and a2-year landmark analysis to minimize reverse causation.Sociodemographic factors,lifestyle factors/physical activity,cardiovascular risk,comorbidities,cognition,and maximal workload achieved were included as covariates.Results:During a median follow-up period of 11 years,348 participants(9/1000)newly developed delirium.Compared with the high HRR group(16/1000),the risk for delirium was almost doubled in those with low HRR(hazard ratio=1.90,95%)confidence interval(95%CI):1.30-2.79,p=0.001)and average HRR(hazard ratio=1.54,95%CI:1.07-2.22,p=0.020)).Low HRR was equivalent to being 6 years older,a current smoker,or>3 additional cardiovascular disease risks.Results were robust in sensitivity analysis,but the risk appeared larger in those with better cognition and when only postoperative delirium was considered(n=147;hazard ratio=2.66,95%CI:1.46-4.85,p=0.001).Conclusion:HRR during submaximal exercise is associated with future risk for delirium.Given that HRR is potentially modifiable,it may prove useful for neurological risk stratification alongside traditional cardiovascular risk factors.

Stair climbing,genetic predisposition,and the risk of incident type 2 diabetes:A large population-based prospective cohort study

Background:Cross-sectional evidence and small-scale trials suggest positive effects of stair climbing on cardiometabolic disease and glucose regulation.However,few studies have examined the long-term association between stair climbing and the incidence of type 2 diabetes(T2D).We aimed to prospectively evaluate the association of stair climbing with T2D and assess modifications by genetic predisposition to T2D.Methods:We included 451,699 adults(mean age=56.3±8.1 years,mean±SD;55.2%females)without T2D at baseline in the UK Biobank and followed up to March 31,2021.Stair climbing information was collected through the touchscreen questionnaire.Genetic risk score for T2D consisted of 424 single nucleotide polymorphisms.Results:During a median follow up of 12.1 years,14,896 T2D cases were documented.Compared with participants who reported no stair climbing,those who climbed stairs regularly had a lower risk of incident T2D(10-50 steps/day:hazard ratio(HR)=0.95,95%confidence interval(95%CI):0.89-1.00;60-100 steps/day:HR=0.92,95%CI:0.87-0.98;110-150 steps/day:HR=0.86,95%CI:0.80-0.91;>150 steps/day:HR=0.93,95%CI:0.87-0.99,p for trend=0.0007).We observed a significant interaction between stair climbing and genetic risk score on the subsequent T2D risk(p for interaction=0.0004),where the risk of T2D showed a downward trend in subjects with low genetic risk and those who reported stair climbing activity of 110-150 steps/day appeared to have the lowest overall T2D risk among those with intermediate to high genetic risk.Conclusion:A higher number of stairs climbed at home was associated with lower T2D incidence risk,especially among individuals with a low genetic predisposition to T2D.These findings highlight that stair climbing,as incidental physical activity,offers a simple and low-cost complement to public health interventions for T2D prevention.

Clinical Analysis of the Colorectal Cohort within the Wales Cancer Biobank: A Study of Outcomes and Genetic Screening

Over the last 12 years, the Wales Cancer Biobank (WCB) has consented to more than 2000 patients with colorectal cancer (CRC). From these patients, clinical data has been collected and patients have been followed through their cancer journey. Clinical data from these patients have been analyzed to identify any correlation between disease grade and outcome. In a small cohort, consisting of 407 patients, WCB has performed genetic analysis on patient primary tumor samples, identifying and characterizing mutations in the KRAS, NRAS, BRAF, PIK3CA and TP53 genes. The majority of patients with CRC who were consented to WCB were male with a mean age of 69 years and received surgery as the primary treatment for their disease. Pathology and disease-free survival data confirmed worse prognoses associated with more advanced disease. Heterogeneity within the primary tumor was explored in a subgroup of patients. Analysis of the KRAS and TP53 genes confirmed that more than 40% of CRC patients who were tested, harbored a genetic mutation within these genes in their primary tumor. Due to the limited sample size tested, most mutations did not show significant differences in disease-free survival, however, mutation of the BRAF gene did show a decrease in the disease specific survival, in keeping with the published data. Analysis of the patients diagnosed with CRC within the Biobank has provided us with valuable information on the status of CRC disease and treatment within the Welsh population. Over 12 years of consenting, we have witnessed significant changes in the information that researchers are interested in when sourcing samples for translational research. The development of new drugs that are tailored to the genetics of a cancer is emerging and at WCB we are focusing our collections on samples and data that meet the needs of this ever-evolving field.

生物样本库建设管理现状与建议

系统梳理国外生物样本库建设模式、国内生物样本库管理建设情况,探讨疾病预防控制系统内建立公共卫生生物样本库的机遇、优势和挑战,为今后指导疾病预防控制系统生物样本库建设管理的实际工作提出政策建议和解决途径。

Living biobank-based cancer organoids: prospects and challenges in cancer research

Biobanks bridge the gap between basic and translational research.Traditional cancer biobanks typically contain normal and tumor tissues,and matched blood.However,biospecimens in traditional biobanks are usually nonrenewable.In recent years,increased interest has focused on establishing living biobanks,including organoid biobanks,for the collection and storage of viable and functional tissues for long periods of time.The organoid model is based on a 3D in vitro cell culture system,is highly similar to primary tissues and organs in vivo,and can recapitulate the phenotypic and genetic characteristics of target organs.Publications on cancer organoids have recently increased,and many types of cancer organoids have been used for modeling cancer processes,as well as for drug discovery and screening.On the basis of the current research status,more exploration of cancer organoids through technical advancements is required to improve reproducibility and scalability.Moreover,given the natural characteristics of organoids,greater attention must be paid to ethical considerations.Here,we summarize recent advances in cancer organoid biobanking research,encompassing rectal,gastric,pancreatic,breast,and glioblastoma cancers.Living cancer biobanks that contain cancerous tissues and matched organoids with different genetic backgrounds,subtypes,and individualized characteristics will eventually contribute to the understanding of cancer and ultimately facilitate the development of innovative treatments.

Use of Residual Material in Biobanking： Solidarity, Common Good, and Informed Consent

Biological residual materials can be obtained from surgical activities or from pathological waste material collected for analysis and stored in formalin. This material can be stored in biobanks with the purpose of future research. Formalin-fixed tissue and also formalin-fixed paraffin embedded tissues are not suitable for all kinds of genetic studies on DNA or RNA, as formalin solution is well known for damaging nucleic acids. Therefore, for the purpose of conducting genetic studies, samples should be frozen in order to maintain a good quality of DNA/RNA over time Biobanks, in which waste samples are frozen, are undoubtedly expensive to maintain; however, it could be useful and important to consider their possible implication in particular research, regarding for example the tumor cells growth process, or when the procurement of samples is difficult. Regarding the relationship between informed consent and tissue collection, storage and research, two choices are possible： irreversible or reversible sample anonymization. These procedures involve different approaches and possible solutions that we will seek to define. Also, an important ethical aspect in regard to the role of biobanks is encouraging sample donation. For donors, seeing human sample being kept rather than discarded and seeing them become useful for research highlight the importance of the human body and improve the attitude towards donation. This process might also facilitate the giving of informed consent more trustfully and willingly.

Regional Differences of the Urinary Proteomes in Healthy Chinese Individuals

Objective Urine is a promising biomarker source for clinical proteomics studies.Regional physiological differences are common in multi-center clinical studies.In this study,we investigate whether significant differences are present in the urinary proteomes of individuals from different regions in China.Methods In this study,morning urine samples were collected from healthy urban residents in three regions of China(Haikou,Xi’an and Xining)and urinary proteins were preserved using a membrane-based method(Urimem).The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among three regions.Functional annotation of the differential proteins among the three areas was analyzed using the DAVID online database,and pathway enrichment of the differential urinary proteins was analyzed using KEGG.Results We identified 1898 proteins from Urimem samples using label-free proteome quantification,of which 56 urine proteins were differentially expressed among the three regions(P<0.05).Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than intersex differences.After gender stratification,16 differential proteins were identified in male samples and 84 differential proteins were identified in female samples.Among these differential proteins,several proteins have been previously reported as urinary disease biomarkers.Conclusions Urimem will facilitate urinary protein storage for large-scale urine sample collection.Regional differences are a confounding factor influencing the urine proteome and should be considered in future multicenter biomarker studies.

如何利用UK Biobank申请研究数据和生物样本

UK Biobank是一项庞大和详细的前瞻性研究工程,由维康信托基金、英国医学研究委员会、英国卫生部、苏格兰政府和西北地区发展局发起成立。其储存着海量疾病与健康相关的研究数据和生物样本,全球的科研人员均可通过在线申请获得这些研究数据和生物样本并将其用于已批准的研究项目中。本文详细介绍了如何通过UK Biobank检索及申请研究数据和生物样本。

我国母婴出生队列特色生物样本库的建设和管理

阐述我国母婴出生队列特色生物样本库的建设意义和现状,基于母婴出生队列“样本类型多样、样本来源关联、研究范围广泛”特点及法律规范,从管理体系、设施设备与人员、过程控制、样本利用等角度,结合自动化和信息化手段,探讨我国母婴出生队列特色生物样本库规范化建设及管理方法,助力妊娠期高血压、糖尿病、流产、早产、出生缺陷等发病机制研究,推动母婴特色资源合作与共享。

Risk factors for cardiovascular disease in the Chinese population:recent progress and implications

Cardiovascular disease(CVD)is the leading cause of death in both urban and rural areas of China.The current evidence regarding CVD risk factors was primarily established in Western countries,with limited generalizability to the Chinese population.In China,a growing number of population-based prospective cohort studies have emerged that have yielded substantial research data on CVD risk factors in the past five years.The research studies have covered biological risk factors(e.g.,blood lipids,blood pressure,blood glucose,adiposity),lifestyle risk factors(e.g.,smoking,alcohol,diet,physical activity),environmental risk factors(e.g.,ambient and indoor air pollution),and risk prediction.This study aimed to systematically review the research progress on CVD risk factors in the Chinese population in the past five years.Prospective studies in China have identified biological,lifestyle,and environmental risk factors for CVD and its main subtypes,along with some protective factors unique to the Chinese(e.g.,spicy food and green tea).This review aimed to provide high-quality evidence for achieving the Outline of Healthy China 2030,developing disease prevention guidelines and measures,and deepening efforts for popularization of health knowledge.

The dark side of technological advances in analysis of microbial ecosystems

Recent technological advances mean that samples from animal experiments may be analysed more cheaply,more easily and with a much greater return of data than previously.Research groups are frequently faced with a choice of continuing to use established technology in which they may have made a significant investment of time and resources,and have significant amounts of reference data,or switching to new technology where reference data may be limited.Apart from cost,the choice needs to be based on a comparison between the increase in data available from future experiments by switching and the value of comparison with reference data from historical experiments analysed with earlier technology.One approach to this problem is to ensure that sufficient quantity and variety of samples are taken from each experiment and appropriately stored to allow re-establishment of a sufficiently large reference set and to avoid the need to repeat animal experiments.The establishment of ‘biobanks' of experimental material will require funding for infrastructure,consistent storage of metadata and,importantly,horizon-scanning to ensure that samples are taken appropriately for techniques which will become accessible in future.Such biobanks are a recognised resource in human medicine,where the value of samples increases as more analysis is carried out and added to the metadata.

Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity

AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers.METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80&#x02005;&#x000b0;C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria.RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 &#x003bc;g/g in 2 participants, and above 50 &#x003bc;g/g in a further 5 participants.CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.