Chimerism monitoring using biallelic single nucleotide or insertion/deletion polymorphisms: How many markers to screen?
Biallelic
Chimerism
Indel
Informativity
Next-generation sequencing
Snp
Journal
Clinica chimica acta; international journal of clinical chemistry
ISSN: 1873-3492
Titre abrégé: Clin Chim Acta
Pays: Netherlands
ID NLM: 1302422
Informations de publication
Date de publication:
01 Jul 2022
01 Jul 2022
Historique:
received:
15
04
2022
revised:
30
05
2022
accepted:
30
05
2022
pubmed:
7
6
2022
medline:
22
6
2022
entrez:
6
6
2022
Statut:
ppublish
Résumé
Chimerism monitoring by means of high-throughput sequencing or quantitative PCR of biallelic single nucleotide and insertion/deletion polymorphisms has shown potential for improved patient care when compared to the gold standard capillary electrophoresis assays. When designing chimerism assays the number of markers to screen needs consideration: it determines the informativity rate and accuracy of the assay, but screening too many markers increases the assay's cost and complexity. The minimal number of biallelic markers to screen is currently unstudied. A simulation framework accounting for marker minor allele frequencies, the number of markers screened, marker allelic constellations and donor-recipient relatedness was constructed. The framework was validated through analysis of 324 clinical samples. Empirical clinical data confirm the validity of the simulation framework. With guidelines suggesting to monitor at least three informative markers, we demonstrate that, for optimized assays, at least 40 biallelic markers need to be screened to achieve enough informative markers in over 99% of cases. We propose and discuss several assay optimization strategies. Currently used chimerism assays often screen too little or too many markers, leaving room for optimization. Through support of the simulation framework here introduced and validated, more informative, cost-effective chimerism assays can be designed.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
Chimerism monitoring by means of high-throughput sequencing or quantitative PCR of biallelic single nucleotide and insertion/deletion polymorphisms has shown potential for improved patient care when compared to the gold standard capillary electrophoresis assays. When designing chimerism assays the number of markers to screen needs consideration: it determines the informativity rate and accuracy of the assay, but screening too many markers increases the assay's cost and complexity. The minimal number of biallelic markers to screen is currently unstudied.
MATERIALS/METHODS
METHODS
A simulation framework accounting for marker minor allele frequencies, the number of markers screened, marker allelic constellations and donor-recipient relatedness was constructed. The framework was validated through analysis of 324 clinical samples.
RESULTS
RESULTS
Empirical clinical data confirm the validity of the simulation framework. With guidelines suggesting to monitor at least three informative markers, we demonstrate that, for optimized assays, at least 40 biallelic markers need to be screened to achieve enough informative markers in over 99% of cases. We propose and discuss several assay optimization strategies.
CONCLUSION
CONCLUSIONS
Currently used chimerism assays often screen too little or too many markers, leaving room for optimization. Through support of the simulation framework here introduced and validated, more informative, cost-effective chimerism assays can be designed.
Identifiants
pubmed: 35667475
pii: S0009-8981(22)01179-2
doi: 10.1016/j.cca.2022.05.026
pii:
doi:
Substances chimiques
Nucleotides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
123-129Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.