Rebecca N Palmer, Sam Abujudeh, Magdalena Stolarek-Januszkiewicz, Ana-Luisa Silva, Justyna M Mordaka, Kristine von Bargen, Alejandra Collazos, Simonetta Andreazza, Nicola D Potts, Chau Ha Ho, Iyelola Turner, Jinsy Jose, Dilyara Nugent, Prarthna Barot, Christina Xyrafaki, Alessandro Tomassini, Ryan T Evans, Katherine E Knudsen, Elizabeth Gillon-Zhang, Julia N Brown, Candace King, Cory Kiser, Mary Beth Rossi, Eleanor R Gray, Robert J Osborne, Barnaby W Balmforth
{"title":"Aspyre肺血机器学习模型的开发：一种快速检测非小细胞肺癌患者血浆中可操作变异的新方法。","authors":"Rebecca N Palmer, Sam Abujudeh, Magdalena Stolarek-Januszkiewicz, Ana-Luisa Silva, Justyna M Mordaka, Kristine von Bargen, Alejandra Collazos, Simonetta Andreazza, Nicola D Potts, Chau Ha Ho, Iyelola Turner, Jinsy Jose, Dilyara Nugent, Prarthna Barot, Christina Xyrafaki, Alessandro Tomassini, Ryan T Evans, Katherine E Knudsen, Elizabeth Gillon-Zhang, Julia N Brown, Candace King, Cory Kiser, Mary Beth Rossi, Eleanor R Gray, Robert J Osborne, Barnaby W Balmforth","doi":"10.1200/CCI-25-00050","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Aspyre Lung is a targeted biomarker panel of 114 genomic variants across 11 guideline-recommended genes with simultaneous DNA and RNA for non-small cell lung cancer (NSCLC). In this study, we developed a machine learning algorithm to interpret fluorescence data outputs from Aspyre Lung, enabling the assay to be applied to both plasma and tissue samples.</p><p><strong>Materials and methods: </strong>Data for model training and testing were generated from over 13,500 DNA and RNA contrived samples, with variants spiked in at a variant allele frequency (VAF) of 0.1%-82% for DNA and 6-5,000 copies for RNA. The training and testing data sets used 67 reagent batches and 23 operators using nine quantitative polymerase chain reaction machines at two sites. Variant calling machine learning models were assessed in terms of median assay-wide 95% limit of detection (LoD95), observed sensitivity, false-positive rate per sample, per-variant LoD95, and per-variant observed sensitivity. The model was optimized by varying the training data subsets, features used, and model hyperparameters. Models were assessed against target specifications.</p><p><strong>Results: </strong>Verification with reference samples established experimental performance characteristics: a LoD95 of 0.19% VAF for SNV/indels, one amplifiable copy for gene fusions, 69 copies for <i>MET</i> exon 14 skipping events, and 100% specificity for all targets.</p><p><strong>Conclusion: </strong>Implementation of the model for liquid biopsy sample analysis enables running of these samples alongside tissue in a single workflow with high sensitivity, specificity, and accuracy. These results demonstrate that the Aspyre Lung assay, powered by a robust machine learning algorithm, offers a reliable and scalable solution for molecular testing in NSCLC, enabling a diverse range of laboratories to confidently perform high-sensitivity, high-specificity testing on both tissue and liquid biopsy samples.</p>","PeriodicalId":51626,"journal":{"name":"JCO Clinical Cancer Informatics","volume":"9 ","pages":"e2500050"},"PeriodicalIF":2.8000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366736/pdf/","citationCount":"0","resultStr":"{\"title\":\"Development of a Machine Learning Model for Aspyre Lung Blood: A New Assay for Rapid Detection of Actionable Variants From Plasma in Patients With Non-Small Cell Lung Cancer.\",\"authors\":\"Rebecca N Palmer, Sam Abujudeh, Magdalena Stolarek-Januszkiewicz, Ana-Luisa Silva, Justyna M Mordaka, Kristine von Bargen, Alejandra Collazos, Simonetta Andreazza, Nicola D Potts, Chau Ha Ho, Iyelola Turner, Jinsy Jose, Dilyara Nugent, Prarthna Barot, Christina Xyrafaki, Alessandro Tomassini, Ryan T Evans, Katherine E Knudsen, Elizabeth Gillon-Zhang, Julia N Brown, Candace King, Cory Kiser, Mary Beth Rossi, Eleanor R Gray, Robert J Osborne, Barnaby W Balmforth\",\"doi\":\"10.1200/CCI-25-00050\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Aspyre Lung is a targeted biomarker panel of 114 genomic variants across 11 guideline-recommended genes with simultaneous DNA and RNA for non-small cell lung cancer (NSCLC). In this study, we developed a machine learning algorithm to interpret fluorescence data outputs from Aspyre Lung, enabling the assay to be applied to both plasma and tissue samples.</p><p><strong>Materials and methods: </strong>Data for model training and testing were generated from over 13,500 DNA and RNA contrived samples, with variants spiked in at a variant allele frequency (VAF) of 0.1%-82% for DNA and 6-5,000 copies for RNA. The training and testing data sets used 67 reagent batches and 23 operators using nine quantitative polymerase chain reaction machines at two sites. Variant calling machine learning models were assessed in terms of median assay-wide 95% limit of detection (LoD95), observed sensitivity, false-positive rate per sample, per-variant LoD95, and per-variant observed sensitivity. The model was optimized by varying the training data subsets, features used, and model hyperparameters. Models were assessed against target specifications.</p><p><strong>Results: </strong>Verification with reference samples established experimental performance characteristics: a LoD95 of 0.19% VAF for SNV/indels, one amplifiable copy for gene fusions, 69 copies for <i>MET</i> exon 14 skipping events, and 100% specificity for all targets.</p><p><strong>Conclusion: </strong>Implementation of the model for liquid biopsy sample analysis enables running of these samples alongside tissue in a single workflow with high sensitivity, specificity, and accuracy. These results demonstrate that the Aspyre Lung assay, powered by a robust machine learning algorithm, offers a reliable and scalable solution for molecular testing in NSCLC, enabling a diverse range of laboratories to confidently perform high-sensitivity, high-specificity testing on both tissue and liquid biopsy samples.</p>\",\"PeriodicalId\":51626,\"journal\":{\"name\":\"JCO Clinical Cancer Informatics\",\"volume\":\"9 \",\"pages\":\"e2500050\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12366736/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCO Clinical Cancer Informatics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1200/CCI-25-00050\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO Clinical Cancer Informatics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1200/CCI-25-00050","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/15 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Development of a Machine Learning Model for Aspyre Lung Blood: A New Assay for Rapid Detection of Actionable Variants From Plasma in Patients With Non-Small Cell Lung Cancer.
Purpose: Aspyre Lung is a targeted biomarker panel of 114 genomic variants across 11 guideline-recommended genes with simultaneous DNA and RNA for non-small cell lung cancer (NSCLC). In this study, we developed a machine learning algorithm to interpret fluorescence data outputs from Aspyre Lung, enabling the assay to be applied to both plasma and tissue samples.
Materials and methods: Data for model training and testing were generated from over 13,500 DNA and RNA contrived samples, with variants spiked in at a variant allele frequency (VAF) of 0.1%-82% for DNA and 6-5,000 copies for RNA. The training and testing data sets used 67 reagent batches and 23 operators using nine quantitative polymerase chain reaction machines at two sites. Variant calling machine learning models were assessed in terms of median assay-wide 95% limit of detection (LoD95), observed sensitivity, false-positive rate per sample, per-variant LoD95, and per-variant observed sensitivity. The model was optimized by varying the training data subsets, features used, and model hyperparameters. Models were assessed against target specifications.
Results: Verification with reference samples established experimental performance characteristics: a LoD95 of 0.19% VAF for SNV/indels, one amplifiable copy for gene fusions, 69 copies for MET exon 14 skipping events, and 100% specificity for all targets.
Conclusion: Implementation of the model for liquid biopsy sample analysis enables running of these samples alongside tissue in a single workflow with high sensitivity, specificity, and accuracy. These results demonstrate that the Aspyre Lung assay, powered by a robust machine learning algorithm, offers a reliable and scalable solution for molecular testing in NSCLC, enabling a diverse range of laboratories to confidently perform high-sensitivity, high-specificity testing on both tissue and liquid biopsy samples.
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