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Development of a program for in silico optimized selection of oligonucleotide-based molecular barcodes

Authors
 In Seok Yang  ;  Sang Won Bae  ;  BeumJin Park  ;  Sangwoo Kim 
Citation
 PLOS ONE, Vol.16(2) : e0246354, 2021-02 
Journal Title
PLOS ONE
Issue Date
2021-02
MeSH
Computer Simulation ; DNA / genetics ; DNA Barcoding, Taxonomic / methods* ; Gene Expression Profiling / methods ; Models, Statistical ; Mutation / genetics ; Oligonucleotides / genetics* ; Single-Cell Analysis / methods
Abstract
Short DNA oligonucleotides (~4 mer) have been used to index samples from different sources, such as in multiplex sequencing. Presently, longer oligonucleotides (8-12 mer) are being used as molecular barcodes with which to distinguish among raw DNA molecules in many high-tech sequence analyses, including low-frequent mutation detection, quantitative transcriptome analysis, and single-cell sequencing. Despite some advantages of using molecular barcodes with random sequences, such an approach, however, makes it impossible to know the exact sequences used in an experiment and can lead to inaccurate interpretation due to misclustering of barcodes arising from the occurrence of unexpected mutations in the barcodes. The present study introduces a tool developed for selecting an optimal barcode subset during molecular barcoding. The program considers five barcode factors: GC content, homopolymers, simple sequence repeats with repeated units of dinucleotides, Hamming distance, and complementarity between barcodes. To evaluate a selected barcode set, penalty scores for the factors are defined based on their distributions observed in random barcodes. The algorithm employed in the program comprises two steps: i) random generation of an initial set and ii) optimal barcode selection via iterative replacement. Users can execute the program by inputting barcode length and the number of barcodes to be generated. Furthermore, the program accepts a user's own values for other parameters, including penalty scores, for advanced use, allowing it to be applied in various conditions. In many test runs to obtain 100000 barcodes with lengths of 12 nucleotides, the program showed fast performance, efficient enough to generate optimal barcode sequences with merely the use of a desktop PC. We also showed that VFOS has comparable performance, flexibility in program running, consideration of simple sequence repeats, and fast computation time in comparison with other two tools (DNABarcodes and FreeBarcodes). Owing to the versatility and fast performance of the program, we expect that many researchers will opt to apply it for selecting optimal barcode sets during their experiments, including next-generation sequencing.
Files in This Item:
T202105069.pdf Download
DOI
10.1371/journal.pone.0246354
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sangwoo(김상우) ORCID logo https://orcid.org/0000-0001-5356-0827
Yang, In Seok(양인석) ORCID logo https://orcid.org/0000-0001-5224-2587
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187125
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