Multi-omics analysis from archival neonatal dried blood spots: limitations and opportunities
Investigate the feasibility of multi-omics analyses of DBS samples.
Newborn screening programmes (NBS) are implemented in various countries worldwide and involve the analysis of millions of dry blood cards / dried blood spots (DBS) samples per year. The main objective of NBS is to detect adverse health outcomes in newborns at an early stage. In addition to this, DBS samples can also serve as an important resource for population-based research in child and adolescent health. Despite their potential, the feasibility of using archived DBS samples for emerging targeted and untargeted multi-omics analyses has not been explored in the literature. Therefore, this review aims to assess recent developments to identify the opportunities and challenges of applying omics analyses to NBS cards in a research setting.
Search for publications that use DBS for omics analysis
To locate studies using DBS for genomic, proteomic and metabolomic assays, the authors conducted a search of the Medline, Embase and PubMed databases and initially identified 800 records, which were narrowed down to 23 for this review. These studies included one combined genomic/metabolomic, four genomic, three epigenomic, four proteomic and 11 metabolomic studies.
Advantages of using DBS samples for omics analyses
The advantages of using DBS samples include the stability of many biomolecules once plotted on a card, allowing for easy transport and storage. However, for specific measures, factors such as short-term vs. long-term stability, storage temperature and different analyte compositions need to be considered.
Assessment of the stability of biomolecules in DBS samples during sample travel
The sample journey from collection to processing can vary depending on the clinical setting and patient circumstances, but often occurs at room temperature (RT). It is therefore critical to assess the stability of specific biomolecules in DBS samples at room temperature over time. Some studies have shown that certain biomolecules such as carbohydrates, nucleotides and vitamins in DBS cards are sensitive to storage at RT and 37 °C, while others have found no significant differences in metabolite concentration at RT for most clinically relevant compounds.
Recommendations for storage of DBS samples for reliable multi-omics analyses
Current recommendations suggest storing DBS samples at -20 °C or -80 °C for long-term storage of at least two years. However, analyses performed within 28 days of sample collection at room temperature (RT) are also possible, albeit with a gradual decline in metabolite concentration. Different analytes may degrade at different rates at different temperatures, so this should be considered when selecting targets for biobank access.
Challenges in using DBS samples for multi-omics analyses
Despite these challenges, DBS sampling offers several advantages for population-based research, including simplicity, minimal volume requirements and economical transport and storage. The use of omics technology to assess the molecular profiles of neonatal blood samples is very achievable and valuable to the scientific community. Although the technology is likely to evolve, there is already sufficient evidence to validate the current use of high-throughput omics assays, followed by targeted analyses to identify core biomarkers of neonatal disease.
Verwendung von NBS-Proben für große Kohortenstudien mit kontrollierter Lagerung von DBS-Proben.
Use of NBS samples for large cohort studies with controlled storage of DBS samples.
Filter paper / dried blood spots used in the publications
Whatman 903 Protein-Saver-Karten, Dänische DBS-Karten, Guthrie-Karten, Dänische Neugeborenen-DBS-Karten, Whatman FTA-Karte, Ahlstrom Grad 226 Filterpapier, Centocard, HemaSpot-HF Blutentnahmegerät, Karte ImmunoHealth, Glasfaserstreifen ImmunoHealth, schleicher & schuell 2.992, schleicher & schuell 903, Ahlströmer 226