{"title":"使用FABCASE实现敏感和具有成本效益的嵌合分析：一种快速估计分析信息的方法。","authors":"Matthijs Vynck","doi":"10.1111/ijlh.14460","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Chimerism monitoring is part of the standard of care for patients following an allogeneic hematopoietic stem cell transplantation. There has recently been a move towards sensitive, high-throughput (next-generation) sequencing analysis of biallelic markers for this purpose. Determining the number and properties of the markers to include in an assay to achieve reliable yet cost-effective chimerism quantification is an underexposed but critical part of chimerism assay development, optimization, and validation.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We develop <i>FABCASE</i> (Fast and Accurate Biallelic Chimerism Assay Size Estimation), an approach to estimate the required number of markers to screen to obtain a given informativity rate. We explore several practical examples that illustrate the diverse applications of <i>FABCASE</i> beyond calculating the required number of markers to screen.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p><i>FABCASE</i> offers a more than four orders of magnitude speed improvement compared to a previously introduced Monte Carlo simulation approach, unlocking extensive <i>in silico</i> scenario analyses. We find that minor allele frequency (MAF) and informative rate estimation based on small sample series (tens) are reasonably accurate. MAFs may vary drastically between populations, and the number of required markers to attain a preset informativity rate is inflated (here, +28%) when not optimized. Marker subset selection from a pool of candidate markers is little impacted by small-to-medium MAF differences (0%–20% MAF). Prioritizing markers with uniform amplification efficiency reduces sequencing depth requirements and improves cost-effectiveness. A web graphical user interface facilitating marker set informativity evaluation is available at https://mvynck.shinyapps.io/FABCASE.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>FABCASE facilitates the design, refinement, and implementation of sensitive and cost-effective chimerism assays. Due attention should be given to an assay's marker MAFs, sensitivities, and amplification efficiencies.</p>\n </section>\n </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":"47 4","pages":"690-697"},"PeriodicalIF":2.3000,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Towards Sensitive and Cost-Effective Chimerism Assays Using FABCASE: A Fast Approach for Estimating Assay Informativity\",\"authors\":\"Matthijs Vynck\",\"doi\":\"10.1111/ijlh.14460\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Chimerism monitoring is part of the standard of care for patients following an allogeneic hematopoietic stem cell transplantation. There has recently been a move towards sensitive, high-throughput (next-generation) sequencing analysis of biallelic markers for this purpose. Determining the number and properties of the markers to include in an assay to achieve reliable yet cost-effective chimerism quantification is an underexposed but critical part of chimerism assay development, optimization, and validation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We develop <i>FABCASE</i> (Fast and Accurate Biallelic Chimerism Assay Size Estimation), an approach to estimate the required number of markers to screen to obtain a given informativity rate. We explore several practical examples that illustrate the diverse applications of <i>FABCASE</i> beyond calculating the required number of markers to screen.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p><i>FABCASE</i> offers a more than four orders of magnitude speed improvement compared to a previously introduced Monte Carlo simulation approach, unlocking extensive <i>in silico</i> scenario analyses. We find that minor allele frequency (MAF) and informative rate estimation based on small sample series (tens) are reasonably accurate. MAFs may vary drastically between populations, and the number of required markers to attain a preset informativity rate is inflated (here, +28%) when not optimized. Marker subset selection from a pool of candidate markers is little impacted by small-to-medium MAF differences (0%–20% MAF). Prioritizing markers with uniform amplification efficiency reduces sequencing depth requirements and improves cost-effectiveness. A web graphical user interface facilitating marker set informativity evaluation is available at https://mvynck.shinyapps.io/FABCASE.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>FABCASE facilitates the design, refinement, and implementation of sensitive and cost-effective chimerism assays. Due attention should be given to an assay's marker MAFs, sensitivities, and amplification efficiencies.</p>\\n </section>\\n </div>\",\"PeriodicalId\":14120,\"journal\":{\"name\":\"International Journal of Laboratory Hematology\",\"volume\":\"47 4\",\"pages\":\"690-697\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-03-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Laboratory Hematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/ijlh.14460\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Laboratory Hematology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/ijlh.14460","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Towards Sensitive and Cost-Effective Chimerism Assays Using FABCASE: A Fast Approach for Estimating Assay Informativity
Background
Chimerism monitoring is part of the standard of care for patients following an allogeneic hematopoietic stem cell transplantation. There has recently been a move towards sensitive, high-throughput (next-generation) sequencing analysis of biallelic markers for this purpose. Determining the number and properties of the markers to include in an assay to achieve reliable yet cost-effective chimerism quantification is an underexposed but critical part of chimerism assay development, optimization, and validation.
Methods
We develop FABCASE (Fast and Accurate Biallelic Chimerism Assay Size Estimation), an approach to estimate the required number of markers to screen to obtain a given informativity rate. We explore several practical examples that illustrate the diverse applications of FABCASE beyond calculating the required number of markers to screen.
Results
FABCASE offers a more than four orders of magnitude speed improvement compared to a previously introduced Monte Carlo simulation approach, unlocking extensive in silico scenario analyses. We find that minor allele frequency (MAF) and informative rate estimation based on small sample series (tens) are reasonably accurate. MAFs may vary drastically between populations, and the number of required markers to attain a preset informativity rate is inflated (here, +28%) when not optimized. Marker subset selection from a pool of candidate markers is little impacted by small-to-medium MAF differences (0%–20% MAF). Prioritizing markers with uniform amplification efficiency reduces sequencing depth requirements and improves cost-effectiveness. A web graphical user interface facilitating marker set informativity evaluation is available at https://mvynck.shinyapps.io/FABCASE.
Conclusion
FABCASE facilitates the design, refinement, and implementation of sensitive and cost-effective chimerism assays. Due attention should be given to an assay's marker MAFs, sensitivities, and amplification efficiencies.
期刊介绍：
The International Journal of Laboratory Hematology provides a forum for the communication of new developments, research topics and the practice of laboratory haematology.
The journal publishes invited reviews, full length original articles, and correspondence.
The International Journal of Laboratory Hematology is the official journal of the International Society for Laboratory Hematology, which addresses the following sub-disciplines: cellular analysis, flow cytometry, haemostasis and thrombosis, molecular diagnostics, haematology informatics, haemoglobinopathies, point of care testing, standards and guidelines.
The journal was launched in 2006 as the successor to Clinical and Laboratory Hematology, which was first published in 1979. An active and positive editorial policy ensures that work of a high scientific standard is reported, in order to bridge the gap between practical and academic aspects of laboratory haematology.
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