Biobank literature update week 45 (2015)
[1] Ensuring Sample Quality for Biomarker Discovery Studies - Use of ICT Tools to Trace Biosample Life-cycle. Riondino
S, Ferroni P, Spila A et al. Cancer genomics & proteomics 2015; 12:291-299. The growing demand of personalized
medicine marked the transition from an empirical medicine to a molecular one, aimed at predicting safer and more
effective medical treatment for every patient, while minimizing adverse effects. This passage has emphasized the
importance of biomarker discovery studies, and has led sample availability to assume a crucial role in biomedical
research. Accordingly, a great interest in Biological Bank science has grown concomitantly. In biobanks, biological
material and its accompanying data are collected, handled and stored in accordance with standard operating procedures
(SOPs) and existing legislation. Sample quality is ensured by adherence to SOPs and sample whole life-cycle can be
recorded by innovative tracking systems employing information technology (IT) tools for monitoring storage conditions
and characterization of vast amount of data. All the above will ensure proper sample exchangeability among research
facilities and will represent the starting point of all future personalized medicine-based clinical trials.
[2] Biobanking of fresh-frozen endoscopic biopsy specimens from esophageal adenocarcinoma. Stiekema J, Cats A,
Boot H et al. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus /
I.S.D.E 2015. The process of preparing endoscopic esophageal adenocarcinoma samples for next-generation DNA/RNA
sequencing is poorly described. Therefore, we assessed the feasibility and pitfalls of preparing esophageal
adenocarcinoma endoscopic biopsies toward DNA/RNA samples suitable for next-generation sequencing. In this
prospective study, four tumor biopsy samples were collected from consecutive esophageal cancer patients during
esophagogastroduodenoscopy and fresh-frozen in liquid nitrogen. DNA and RNA were isolated from samples with a
tumor percentage of at least 50%. For next-generation sequencing, double-stranded DNA (dsDNA) is required and highquality RNA preferred. The quantity dsDNA and RNA quantity and quality were assessed with the Nanodrop 2000
spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA) and Agilent 2100 Bioanalyzer (Agilent, Santa Clara,
CA, USA). Biopsy samples of 69 consecutive patients with esophageal adenocarcinoma were included. In five patients
(7%), the tumor percentage was less than 50% in all four biopsies. Using a protocol allowing simultaneous DNA and RNA
isolation, the median dsDNA yield was 2.4 mug (range 0.1-12.0 mug) and the median RNA yield was 0.5 mug (range 0.012.05 mug). The median RNA integrity number of samples that were fresh-frozen within 30 minutes after sampling was
6.7 (range 4.2-8.9) compared with 2.5 (1.8-4.5) for samples that were fresh-frozen after 2 hours. The results from this
study show that obtaining dsDNA and RNA for next-generation sequencing from endoscopic esophageal
adenocarcinoma samples is feasible. Tumor percentage and dsDNA/RNA yield and quality emphasize the need for
sampling multiple biopsies and minimizing the delay before fresh-freezing.
[3] The Central Biobank and Virtual Biobank of BIOMARKAPD: A Resource for Studies on Neurodegenerative Diseases.
Reijs BL, Teunissen CE, Goncharenko N et al. Frontiers in neurology 2015; 6:216. Biobanks are important resources for
biomarker discovery and assay development. Biomarkers for Alzheimer's and Parkinson's disease (BIOMARKAPD) is a
European multicenter study, funded by the EU Joint Programme-Neurodegenerative Disease Research, which aims to
improve the clinical use of body fluid markers for the diagnosis and prognosis of Alzheimer's disease (AD) and
Parkinson's disease (PD). The objective was to standardize the assessment of existing assays and to validate novel fluid
biomarkers for AD and PD. To support the validation of novel biomarkers and assays, a central and a virtual biobank for
body fluids and associated data from subjects with neurodegenerative diseases have been established. In the central
biobank, cerebrospinal fluid (CSF) and blood samples were collected according to the BIOMARKAPD standardized preanalytical procedures and stored at Integrated BioBank of Luxembourg. The virtual biobank provides an overview of
available CSF, plasma, serum, and DNA samples at each site. Currently, at the central biobank of BIOMARKAPD samples
are available from over 400 subjects with normal cognition, mild cognitive impairment (MCI), AD, frontotemporal
dementia (FTD), vascular dementia, multiple system atrophy, progressive supranuclear palsy, PD, PD with dementia, and
dementia with Lewy bodies. The virtual biobank contains information on over 8,600 subjects with varying diagnoses
from 21 local biobanks. A website has been launched to enable sample requests from the central biobank and virtual
biobank.
Biobank literature update week 45 (2015)
[4] Integrated Data Repository Toolkit (IDRT). A Suite of Programs to Facilitate Health Analytics on Heterogeneous
Medical Data. Bauer CR, Ganslandt T, Baum B et al. Methods of information in medicine 2015; 54. BACKGROUND: In
recent years, research data warehouses moved increasingly into the focus of interest of medical research. Nevertheless,
there are only a few center-independent infrastructure solutions available. They aim to provide a consolidated view on
medical data from various sources such as clinical trials, electronic health records, epidemiological registries or
longitudinal cohorts. The i2b2 framework is a well-established solution for such repositories, but it lacks support for
importing and integrating clinical data and metadata. OBJECTIVES: The goal of this project was to develop a platform for
easy integration and administration of data from heterogeneous sources, to provide capabilities for linking them to
medical terminologies and to allow for transforming and mapping of data streams for user-specific views. METHODS: A
suite of three tools has been developed: the i2b2 Wizard for simplifying administration of i2b2, the IDRT Import and
Mapping Tool for loading clinical data from various formats like CSV, SQL, CDISC ODM or biobanks and the IDRT i2b2
Web Client Plugin for advanced export options. The Import and Mapping Tool also includes an ontology editor for
rearranging and mapping patient data and structures as well as annotating clinical data with medical terminologies,
primarily those used in Germany (ICD-10-GM, OPS, ICD-O, etc.). RESULTS: With the three tools functional, new i2b2based research projects can be created, populated and customized to researcher's needs in a few hours. Amalgamating
data and metadata from different databases can be managed easily. With regards to data privacy a pseudonymization
service can be plugged in. Using common ontologies and reference terminologies rather than project-specific ones leads
to a consistent understanding of the data semantics. CONCLUSIONS: i2b2's promise is to enable clinical researchers to
devise and test new hypothesis even without a deep knowledge in statistical programing. The approach presented here
has been tested in a number of scenarios with millions of observations and tens of thousands of patients. Initially mostly
observant, trained researchers were able to construct new analyses on their own. Early feedback indicates that timely
and extensive access to their "own" data is appreciated most, but it is also lowering the barrier for other tasks, for
instance checking data quality and completeness (missing data, wrong coding).
[5] [Physicochemical Environmental Change during Bio-Preservation in Cellular and Biomolecular Suspension Samples
and Its Effects on the Sample Quality]. Shirakashi R. Rinsho byori. The Japanese journal of clinical pathology 2015;
63:102-110. The quality of biospecimens is an important issue for clinical assays. These specimens contain various
biomarkers, e.g., cells, proteins, nucleic acids, and phospholipids, most of which start to degrade just after sampling
from patients. Because this degradation proceeds in a water-rich condition, under which water, as a solvent, dominates
the degradation rate, the samples are often preserved at a low temperature in a frozen, lyophilized, or desiccated state
to inhibit the motion of water molecules. However, frozen and/or desiccated water solutions surrounding the
biomarkers markedly change the physicochemical environment, and can sometimes accelerate the degradation process.
This physicochemical variation in water solutions includes dehydration by freezing or desiccation, osmotic stress by
frozen-induced condensation, intra-/extracellular ice formation, and vitrification. This article provides an outline of such
physicochemical variation in water solutions and its effects, especially on a fluid specimen, like a blood sample. The
outline is composed of three parts after the introduction chapter: 1) general physicochemical changes in the water
solution during freezing, frozen storage, and thawing, 2) damage of cells and proteins during freezing, frozen storage,
and thawing, and 3) physicochemical changes of the water solution during desiccation and lyophilization and their
effects on cells and proteins. As the mechanism of cellular damage is different from that of protein damage, they are
discussed separately.