Mapping the inputs, analyses, and outputs of biobank research systems to identify sources of incidental findings and individual research results for potential return to participants

Abstract

Progress in the debate over returning incidental findings (IFs) and individual research results (IRRs) to research participants who provide specimens and data to biobanks in genetic and genomic research requires a new tool to allow comparison across heterogeneous biobank research systems and in-depth analysis of the sources and types of findings generated for potential return. This article presents a new visual mapping tool to allow systematic and standardized depiction of (i) the specimens initially collected, (ii) the materials and data sets then created, (iii) the analyses then performed, and finally (iv) the genetic and genomic results generated, including potential IFs and IRRs. For any individual biobank research system, this sequence of four maps can be created to anticipate the sources and types of IFs and IRRs to be generated, to plan how to handle them, and then to manage them responsibly over time. We discuss how this four-map tool was created and describe its application to four national biobank systems, thereby demonstrating that this tool can provide a common platform to visualize biobank content, anticipate how IFs and IRRs will arise in a biobank research context, and inform policy development.

Fig. 1

The first map: Human biological samples collected for genetic and genomic biobanking research. When investigating whether IFs and IRRs are possible, one must first consider the types of samples collected and their derivatives. The trapezoid is used to symbolize the samples that are initially collected for biobanking research. The pentagon is used to represent derived materials.

Fig. 2

The second map: Biological datasets stored in genetic and genomic biobanking research. The second consideration necessary to management of potential IFs and IRRs is the datasets created and stored. The hexagon is used represent biological datasets. Derived biological materials are symbolized by the pentagon. Abbreviations: CGH, Comparative Genomic Hybridization. FISH, Florescence In Situ Hybridization. SNPs, Single Nucleotide Polymorphisms. DNA, Deoxyribonucleic Acid. mtDNA, Mitochondrial DNA. RNA, Ribonucleic Acid. mRNA, Messenger RNA. miRNA, Micro RNA. cDNA, Complementary DNA.

Fig. 3

The third map: Genetic and genomic analyses. The third consideration necessary to management of potential IFs and IRRs is the types of analyses performed on the biological samples, materials, and datasets. The analyses are represented by circles. Where datasets and derived materials can result in multiple analyses, the hexagons and pentagons are reproduced, respectively. Abbreviations: CGH, Comparative Genomic Hybridization. FISH, Florescence In Situ Hybridization. SNPs, Single Nucleotide Polymorphisms. DNA, Deoxyribonucleic Acid. mtDNA, Mitochondrial DNA. RNA, Ribonucleic Acid. mRNA, Messenger RNA. miRNA, Micro RNA. cDNA, Complementary DNA.

Fig. 4

The fourth map: Results of genetic and genomic analyses and associated meanings. The results are coded with symbols to represent the following categories: (1) information such as ancestry or traits that is not generally thought of as related to health (X), (2) results typically considered “normal” (i.e., no detected variations or changes such as polymorphisms or CNVs that are generally considered benign or normal variation) (circle), (3) inherited and acquired variants that are typically considered abnormal and have associated health or reproductive consequences (solid hexagon), and (4) variants for which the clinical significance is unknown (upper left corner shaded). Abbreviation: LOD, Log of the Odds, VUS, Variant of Unknown Significance.