A systematic review of the barcoding strategy that contributes to COVID-19 diagnostics at a population level

Abstract

The outbreak of SARS-CoV-2 has made us more alert to the importance of viral diagnostics at a population level to rapidly control the spread of the disease. The critical question would be how to scale up testing capacity and perform a diagnostic test in a high-throughput manner with robust results and affordable costs. Here, the latest 26 articles using barcoding technology for COVID-19 diagnostics and biologically-relevant studies are reviewed. Barcodes are molecular tags, that allow proceeding an array of samples at once. To date, barcoding technology followed by high-throughput sequencing has been made for molecular diagnostics for SARS-CoV-2 infections because it can synchronously analyze up to tens of thousands of clinical samples within a short diagnostic time. Essentially, this technology can also be used together with different biotechnologies, allowing for investigation with resolution of single molecules. In this Mini-Review, I first explain the general principle of the barcoding strategy and then put forward recent studies using this technology to accomplish COVID-19 diagnostics and basic research. In the meantime, I provide the viewpoint to improve the current COVID-19 diagnostic strategy with potential solutions. Finally, and importantly, two practical ideas about how barcodes can be further applied in studying SARS-CoV-2 to accelerate our understanding of this virus are proposed.

Keywords: COVID-19; COVID-19 diagnostics; SARS-CoV-2; barcoding technology; population diagnostics.

FIGURE 1

Schematic representation of mechanistic strategies of barcoding. (A–C) Barcodes can be introduced to a template using adaptors through direct ligation (A), using RT- or PCR primers at the reverse transcription or PCR amplification step (B), and using hybridizing molecular inversion probes (C). (D) Schematic representation of the difference between “barcodes” and “sample indexes”. Barcodes aim to correct sequencing errors. For example, a misreading nucleotide, guanosine (G) can be corrected in final consensus sequences for a pool of Sample 1 (top panel). Sample indexes are used to multiplex different sequencing amplicons generated from different pools of samples (Sample 1, 2, and 3) (bottom panel). Panel (A) is modified based on Figure 1 in (Schmitt et al., 2012) and panel (C) is modified based on Figure 1 in (Hiatt et al., 2013).