Biospecimen Science Background
Biospecimens consist of living cells or suspensions of molecules extracted from living organisms. They are used to help researchers and physicians better understand and diagnose disease. Biospecimens may be affected by environmental changes, surgical procedures, or stresses during handling, storage, and transport. Even factors such as medications or medical procedures can alter a biospecimen and affect the data collected from it for use in assays such as clinical diagnostics. These changes caused by non-natural conditions represent a type of variation known in medical research as "pre-analytical factors." Such pre-analytical factors can contribute to variation in research results and can make it difficult for researchers and medical professionals to reproduce their findings. Findings may be misinterpreted as disease-related or even disease-specific, when they are actually caused by pre-analytical factors.
There is a considerable lack of scientific understanding of the effects of pre-analytical variables on human tissues and how these affect clinical and research results. BBRB is an international leader in the scientific field of biospecimen science, which includes the study of pre-analytical factors, to better understand how to best collect, process and store biospecimens, and how to best use existing biospecimen resources. Our research helps to discover important relationships between biospecimen handling and quality and reproducibility of clinical and research findings.
BPV Analytical Platforms
Highly annotated biospecimens were collected for the Biospecimen Pre-analytical Variables (BPV) program through an organized and well-controlled infrastructure of Biospecimen Source Sites (BSS). Various analytical platforms were used by BSS to determine pre-analytical variable effects on a wide range of studies including DNA methylation, copy number variation, genotyping, mRNA expression, miRNA expression, and protein expression.
BSS received in-person training on the proper use of standard operating procedures developed by NCI to ensure that uniform collection and handling procedures were used across all sites. All BPV biospecimens were collected using kits provided by the Comprehensive Biospecimen Resource (CBR), a centralized site that assembled collection and shipping kits. The CBR received most biospecimens from the BSSs for processing and storage and shipped biospecimens from the BSSs to the processing and analysis facilities.
BSS used a web-based interface (the Comprehensive Data Resource (CDR)) to enter data regarding collection, processing, and handling of donor biospecimens and clinical information as well as pathological evaluation of the tumor. Over 300 common data elements were collected in CDR for each case, which were reviewed by data quality managers. BPV specimens were tracked via specimen IDs and unique barcodes using the Laboratory Information Management System (LIMS).
Analysis, cancer type, and platforms used in the BPV program
| Study | Cancer Type | Platform and Analysis |
|---|---|---|
| DNA Methylation | Kidney | MethyLight- methylation-specific PCR amplification of methylation markers |
| Copy Number Variation | Kidney | Genome e-wide CNV evaluation by array-based genomic hybridization (aCGH) |
| Genotyping | Kidney, Colon, Ovary | Whole exome sequencing by NGS |
| RNA Expression | Kidney, Colon, Ovary | Transcriptome profiling by NGS |
| miRNA Expression | Kidney, Ovary | Human miRNA profiling by WaferGen SmartChip (Human miRNA Panel) |
| miRNA Expression | Kidney | Oncopanel evaluation by TaqMan Open Array |
| miRNA Expression | Kidney | Cold-ischemic biomarker expression by TaqMan |
| miRNA Expression | Kidney, Colon, Ovary | Expression biomarkers by RNA in-situ hybridization (RNAscope) |
| Protein Expression (Tissue) | Kidney, Colon, Ovary | Cancer specific biomarker expression by Immunohistochemistry (IHC) assay |
| Protein Expression (Tissue) | Kidney, Colon, Ovary | Total protein and phosphoprotein expression by MassSpec |
| Protein Expression (Plasma) | Kidney, Colon, Ovary, Lung | Targeted protein expression by multiplexed Multiple Reaction Monitoring (MRM) assay |
| Protein Expression (Plasma) | Kidney, Colon, Ovary, Lung | Cancer specific protein expression by Luminex assay (HumanMap) |
| Metabolite Profile (Plasma) | Kidney, Colon, Ovary, Lung | Global metabolite profiling by MassSpec |
BPV Publications
- Formalin Fixation, Delay to Fixation, and Time in Fixative Adversely Impact Copy Number Variation Analysis by aCGH. Li J, Greytak SR, Guan P, Engel KB, Goerlitz DS, Islam M, Varghese RS, Moore HM, Ressom HW. Biopreserv Biobank. 2022 Sept 27. Epub ahead of print.
- Organocatalyst treatment improves variant calling and mutant detection in archival clinical samples. Wehmas LC, Wood CE, Guan P, M Gosink, SD Hester. Sci Rep. 2022 Apr 20;12(1):6509.
- Impact of preanalytical factors on the measurement of tumor tissue biomarkers using immunohistochemistry. Bagchi A, Madaj Z, Engel KB, Guan P, Rohrer DC, Valley DR, Wolfrum E, Feenstra K, Roche N, Hostetter G, Moore HM, Jewell SD. J Histochem Cytochem. 2021 May;69(5):297-320.
- Deleterious effects of formalin-fixation and delays to fixation on RNA and miRNA-Seq profiles. Jones W, Greytak S, Odeh H, Guan P, Powers J, Bavarva J, Moore HM. Sci Rep. 2019 May 6;9(1):6980.
Find the full list of BPV publications here
BPV biospecimens are available for research use
The remaining specimens are currently managed through a collaboration between Van Andel Research Institute and NCI. Specimens may be accessed for biospecimen research or clinical assay development upon request. Researchers may also enter into a collaborative research agreement with NCI to extend the BPV studies; please contact us at ncibbrb@nih.gov for more information.