Biobanking: sample acquisition and quality assurance for ‘omics’ research

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New Biotechnology �Volume 00, Number 00 �December 2012 RESEARCH PAPER

Biobanking: sample acquisition andquality assurance for ‘omics’ researchAyse Yu zbasıoglu and Meral Ozgu c

Hacettepe University Faculty of Medicine, Department of Medical Biology & DNA/Cell Bank for Rare Diseases, Sıhhiye, Ankara, Turkey

After the human genome sequence has been solved using random individuals through the Human

Genome Project (HGP), rapid advances in whole genome sequencing technologies with effective use at a

reasonable cost, is moving the genomics research field to an era of ‘personal genomes’.

Biobanks in this context have played an important role by providing high quality biological samples

for genomics and functional genomics research. Here we are describing biobanking and the importance

of governance in biobanking activity for reliable and reproducible high throughput ‘omics’ data.

IntroductionAn important expectation from HGP was to be able to use the

genome variation datasets in prediction of disease.

In this context, investigation of associations of SNPs, which are

the most common form of genome variation, with susceptibility to

disease in common disorders become a very important step in

bringing the results of research to clinical applications. These

genome wide association studies (GWAS) need large number of

individuals involved so that proper statistical inferences can be

made.

In parallel, functional genomics technologies to annotate the

function of genes and define cellular circuits such as signal signal-

ing and metabolic pathways, is making it possible to identify

targets in disease progression [1].

Use of genomic variation data for the development of new

diagnostic tests, designing new and more effective drugs that

can be used for personalized and targeted therapies (pharmaco-

genomics) are goals that can be realized as results from genomics

and functional genomics research are being translated to patient

care and prediction and prevention of disease [2].

Moving to the paradigm of personalized medicine, new projects

are being initiated. Personal Genome Project (PGP) is an example

of such a new project that aims at collection of genome data

supplemented with tissues from the participants and environmen-

tal data so that when analyzed from a large (100,000) cohort of

Please cite this article in press as: Yuzbasıoglu, A., and Ozguc, M., Biobanking: sample acquisi10.1016/j.nbt.2012.11.016

Corresponding author: Ozguc, M. ([email protected])

1871-6784/$ - see front matter � 2012 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.nbt.2012.11.016

individuals will be able to give information about the emergence

of phenotypes [3].

Samples from well-characterised cohorts or tissues and cells

from patients especially in cancer is a prerequisite for studies such

as GWAS [4] or tumor genome profiling [5].

Biobanks, that carry biological samples such as DNA, RNA, tissue

and cells and associated data, have high impact in genomics and

personalized medicine era [6].

The genomics era with increasing high resolution technologies

and decreasing cost for genome analysis is moving into the per-

sonalized medicine field. Thus biobanks are also accommodating

to sample collections for future research using next generation

technologies.

The 3 P paradigm for personalized, predictive and preventive

medicine depends on the personal genome information to reveal

the risk for disease and preventive routes before the onset of full

blown pathology. For personalized medicine approach to become

a mainstream activity in clinical settings, well characterized large

data sets are needed from individual genome analyses and bio-

banks are the major tools for this mission [7,8].

Types of biobanksThere are different types of biobanks as to the size, types of

registries, research design and collection procedures. Large scale

biobanks are population based and are active in long term long-

itudinal prospective studies. Smaller scale biobanks are set up

mostly for specific research projects. Despite their smaller scale,

tion and quality assurance for ‘omics’ research, New Biotechnol. (2012), http://dx.doi.org/

www.elsevier.com/locate/nbt 1

http://dx.doi.org/10.1016/j.nbt.2012.11.016


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these types of biobanks are an important resource for clinical

research [9]. Besides research only purpose, biobanks can be based

on routine hospital collections, including pathology samples

[10,11].

Further to the unraveling of disease genes and mutations in

monogenic diseases, multifactorial diseases are gaining more atten-

tion since they affect large number of individuals in a population.

They are a part of public health issues and need health care policies

for preventive measures. Thus genetic components may yield early

markers that may be used for early detection and prevention.

Research is being tailored to understand the interplay between the

environment, life styles and multiple genes that play a role in the

development of multifactorial diseases such as diabetes, cancer and

cardiovascular diseases. For this purpose biological samples and

related data sets are required from a very large number of individuals.

In this context population biobanks are biological samples linked

to personal and medical records from randomly selected healthy

individuals from a specific population. Such biobanks play a role in

identification of biomarkers for prediction of disease and give clues

to occurrence of common diseases in that population [12]. Very

well known examples for population biobanks can be given: the

UK Biobank [13], the Estonian Genome Project [14] and the

CARTaGENE project in Canada [15].

By contrast, disease specific biobanks collect biological samples

such as tissues, cells, blood and other body fluids from rare or

common diseases. The strength of such biobanks is the high

number of disease specific registries and sample archives that will

be instrumental in medical research aimed at diagnosis and treat-

ment of that particular disease [16,17].

Collection of tissues for clinical and diagnostic purposes kept in

long term storage serve as a tissue biobank that is an indispensable

resource for research. Tissue samples as fresh frozen or formalin

fixed paraffin embedded tissues (FFPE) from routine pathology labs

are a good source as long as the integrity of biomolecules such as

RNA, DNA and proteins can be preserved for genomics/proteomics

studies [18].

Besides tissues, other samples such as newborn screening cards,

umbilical cord blood samples and body fluids are also candidates

for biobank registries. Newborns screening programs from neo-

nates provide a vast amount of samples. As an example, ‘Guthrie

Cards’ make up the national Swedish PKU Biobank [19]. With new

approaches to stem cell research and for new modes of therapies

such as cell and regenerative therapies, stem cell repositories

become an important tool. UK Stem Cell Bank is a repository of

embryonic, fetal and adult stem cells with a further potential for

regenerative medicine [20].

GovernanceGovernance for biobanking can be described as:

‘‘Governance consists of formally constituted regulatorybodies, statute and other legal instruments as well asinformal mechanisms such as advisory boards, profes-sional guidance, biobank policies, and professional valuesand culture that help to guide decision making’’ [9].

The crucial input of a biobank for genomics/functional geno-

mics research is the availability of high quality-well annotated


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biological samples. High throughput technologies such as tran-

scriptomics or proteomics employ systems for parallel processing

of samples [21]. Here the crucial denominator is the quality of the

biological sample.

What a biobank provides to ensure this requisite is the govern-

ance systems that provide quality assurance for the physical

infrastructure such as cryopreservation and data management

facility and also ethical and legal guidelines that a biobank adheres

to. This yields research results of high academic standard comply-

ing with ethical norms. This is a systems approach that covers the

phases of sample collection, processing of the sample, mainte-

nance of the archive and access to the registries for research.

Protection of the privacy of the individuals and the security of

the samples is the cardinal responsibility of a biobank governance

system. With written protocols and policy statements, a balanced

system should be established between the long term storage and

the organization and rules of agreement for distribution of samples

for research purposes. To ensure the privacy and confidentiality of

the registries, samples can be coded as identified, de-identified and

re-identifiable. In identifiable samples personal data includes

items such as name, birth date and a residence address and for

re-identifiable samples, personal identifiers can be separated from

the biological sample through a coding system with access only to

the data managers of the biobank. In de-identified samples, per-

sonal identifiers are permanently destroyed [22].

Quality assuranceReaching sufficient number of samples of high quality is a reported

problem and stored samples may actually lack the expected quality

for use in research [23,24]. For biobanking activities, quality

assurance (QA) and quality control (QC) programs are a prerequi-

site to ensure the high quality of samples required for research

purposes. Adhering to QA minimizes the preanalytical variations

that affect the stability of the biomarkers that are investigated.

Furthermore, QC programs must be established to check the

compliance with the standard operating procedures in specimen

handling and analyses [25,26].

Stability of biological samples depends on the handling from

the time of acquisition to the time of processing and storage. Use

of anticoagulants, stabilizing agents, time from collection to sto-

rage and temperature of handling the samples must be controlled.

For example live cells can be kept at room temperature for about 48

hours but then must be kept in liquid nitrogen or its vapor for long

term storage.

A biobank archive will have a complete cryostorage capacity at

�808C, and �208C and also at �1968C [27].

Quality control in the freezing and fixation of the tissues, time

from the resection of the tissue to the preservation medium need

to be considered. The quantity and length of the isolated DNA or

RNA, integrity of RNA upon thawing circles, preservation of

biological activity of proteins, morphological records of the tissues

used are some parameters included in the quality control process

[28–31].

Genome wide expression analyses requires that mRNA should

remain intact which sometimes cannot be possible with fragmen-

tation caused by formalin in fixed tissues. Fresh frozen samples are

more suitable, however FFPE are also being investigated to obtain

RNA of higher quality [32–34].




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BioethicsIn the management of a biobank there is also an ethical dimension

[35,36].

Biobanks that are archives of biological samples and health data

from individual donors require drawing up of guidelines related to

privacy issues and consent in obtaining the samples [37]. Informed

consent of the donor is a major ethical standard that must be

employed to ensure the individual’s autonomy in participation for

sample donation. For the consent, written information should be

given before sampling such as type of samples to be donated,

duration of storage, type of research, access to the samples, right to

withdraw from participation and possible intellectual property

rights that may result from research results [38].

The procedure of informed consent is being opened to discus-

sions with the use of genomics technologies for stored samples.

There is an inherent risk that DNA technologies hold the possi-

bility to render the identity of the individual donors making well

recognized points in consent such as protection of confidentiality

and anonymity questionable. For further arguments, concepts

such as ‘general permission’ or’ broad consent’ for future research

is being employed for sample collection instead of individual

consent for each ensuing project covering the donated samples

[39].


One other major ethical debate is the issue of return of

research results to the individual donors when ‘incidental find-

ings’ arise from genomics technologies used such as parallel

sequencing. One result of a study recommends that If the finding

has proved analytical validity and is a potential risk factor for

health, then the results should be shared with the re-identifiable

donors [40].

In biobanks from children importance of informed consent

becomes more evident since in practice parents or guardians are

in a position to give consent for their involvement in research [41].

Nowadays biobanks for research purposes form networks, share

samples and data so harmonization and governance at transna-

tional level is required [42].

ConclusionIn conclusion, biobanks have evolved in parallel to genomics

technologies and are playing a major role moving into the post

genomics era. With emerging technologies such as next genera-

tion sequencing and its applications for personal genomics, bio-

banks will be an essential cornerstone as crucial stakeholders in

personalized medicine applications in the near future. Already

biobanks have been cited as ‘top ten ideas changing the world right

now’ [43].

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Biobanking: sample acquisition and quality assurance for ‘omics’ research