Validation of an AI-enabled exome/transcriptome liquid biopsy platform for early detection, MRD, disease monitoring, and therapy selection for solid tumors
Abstract Effective clinical management of patients with cancer requires highly accurate diagnosis, precise therapy selection, and highly sensitive monitoring of disease burden. Caris Assure is a multifunctional blood-based assay that couples whole exome and whole transcriptome sequencing on plasma a...
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Nature Portfolio
2025-07-01
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| author | J. Abraham V. Domenyuk N. Perdigones S. Klimov S. Antani T. Yoshino E. I. Heath E. Lou S. V. Liu J. L. Marshall W. S. El-Deiry A. F. Shields M. F. Dietrich Y. Nakamura T. Fujisawa G. D. Demetri A. Barker J. Xiu D. A. Sacchetti S. Stahl R. Hahn-Lowry A. Stark J. Swensen G. Poste D. D. Halbert M. Oberley M. Radovich G. W. Sledge David B. Spetzler |
| author_facet | J. Abraham V. Domenyuk N. Perdigones S. Klimov S. Antani T. Yoshino E. I. Heath E. Lou S. V. Liu J. L. Marshall W. S. El-Deiry A. F. Shields M. F. Dietrich Y. Nakamura T. Fujisawa G. D. Demetri A. Barker J. Xiu D. A. Sacchetti S. Stahl R. Hahn-Lowry A. Stark J. Swensen G. Poste D. D. Halbert M. Oberley M. Radovich G. W. Sledge David B. Spetzler |
| author_sort | J. Abraham |
| collection | DOAJ |
| description | Abstract Effective clinical management of patients with cancer requires highly accurate diagnosis, precise therapy selection, and highly sensitive monitoring of disease burden. Caris Assure is a multifunctional blood-based assay that couples whole exome and whole transcriptome sequencing on plasma and leukocytes with advanced machine learning techniques to satisfy all three clinical testing needs on one platform. Caris Assure for therapy selection was CLIA validated using 1,910 samples. 376,197 tissue profiles along with 7,061 paired blood and tissue profiles were used to engineer features for three machine learning models. The MCED model was trained on 1,013 patients and validated on an independent set of 2,675 patients. The tissue of origin for MCED model was trained on 1,166 samples and validated using 5-fold cross validation. The MRD & Monitoring model was trained on 3,439 patients and validated on two independent sets of 86 patients for MRD and 101 patients for monitoring. For early detection, sensitivities for stages I-IV cancers (n = 284, 129, 90, 23 respectively) were 83.1%, 86.0%, 84.4%, and 95.7%, all at 99.6% specificity (n = 2149). The diagnostic first-line procedure for tissue of origin was determined for 8 categories with a top-3 accuracy of 85% for stage I and II cancers. Detection of driver mutations for therapy selection from blood collected within 30 days of matched tumor tissue, demonstrated high concordance (PPA of 93.8%, PPV of 96.8%) using CHIP subtraction. For MRD and recurrence monitoring, the disease-free survival of patients whose cancers were predicted to have an event was significantly shorter than those predicted not to have an event using a tumor naïve approach (HR = 33.4, p < 0.005, HR = 4.39, p = 0.008, respectively). The data presented here demonstrate a unified liquid biopsy platform that uses blood-based whole-exome and transcriptome sequencing coupled with artificial intelligence to address the important clinical needs in multi-cancer early detection, monitoring of MRD and recurrent cancers, and precision selection of molecularly targeted therapies. |
| format | Article |
| id | doaj-art-4eca185a40c34ca4b3fb51c82c4fe1c3 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-4eca185a40c34ca4b3fb51c82c4fe1c32025-08-20T03:37:24ZengNature PortfolioScientific Reports2045-23222025-07-0115111610.1038/s41598-025-08986-0Validation of an AI-enabled exome/transcriptome liquid biopsy platform for early detection, MRD, disease monitoring, and therapy selection for solid tumorsJ. Abraham0V. Domenyuk1N. Perdigones2S. Klimov3S. Antani4T. Yoshino5E. I. Heath6E. Lou7S. V. Liu8J. L. Marshall9W. S. El-Deiry10A. F. Shields11M. F. Dietrich12Y. Nakamura13T. Fujisawa14G. D. Demetri15A. Barker16J. Xiu17D. A. Sacchetti18S. Stahl19R. Hahn-Lowry20A. Stark21J. Swensen22G. Poste23D. D. Halbert24M. Oberley25M. Radovich26G. W. Sledge27David B. Spetzler28Caris Life SciencesCaris Life SciencesCaris Life SciencesCaris Life SciencesCaris Life SciencesNational Cancer Center Hospital EastKarmanos Cancer Institute, Wayne State UniversityUniversity of MinnesotaLombardi Comprehensive Cancer CenterLombardi Comprehensive Cancer CenterBrown UniversityKarmanos Cancer Institute, Wayne State UniversityOncology NetworkNational Cancer Center Hospital EastNational Cancer Center Hospital EastDana-Farber Cancer Institute and Ludwig Center, Harvard Medical SchoolArizona State UniversityCaris Life SciencesCaris Life SciencesCaris Life SciencesCaris Life SciencesCaris Life SciencesCaris Life SciencesArizona State UniversityCaris Life SciencesCaris Life SciencesCaris Life SciencesCaris Life SciencesCaris Life SciencesAbstract Effective clinical management of patients with cancer requires highly accurate diagnosis, precise therapy selection, and highly sensitive monitoring of disease burden. Caris Assure is a multifunctional blood-based assay that couples whole exome and whole transcriptome sequencing on plasma and leukocytes with advanced machine learning techniques to satisfy all three clinical testing needs on one platform. Caris Assure for therapy selection was CLIA validated using 1,910 samples. 376,197 tissue profiles along with 7,061 paired blood and tissue profiles were used to engineer features for three machine learning models. The MCED model was trained on 1,013 patients and validated on an independent set of 2,675 patients. The tissue of origin for MCED model was trained on 1,166 samples and validated using 5-fold cross validation. The MRD & Monitoring model was trained on 3,439 patients and validated on two independent sets of 86 patients for MRD and 101 patients for monitoring. For early detection, sensitivities for stages I-IV cancers (n = 284, 129, 90, 23 respectively) were 83.1%, 86.0%, 84.4%, and 95.7%, all at 99.6% specificity (n = 2149). The diagnostic first-line procedure for tissue of origin was determined for 8 categories with a top-3 accuracy of 85% for stage I and II cancers. Detection of driver mutations for therapy selection from blood collected within 30 days of matched tumor tissue, demonstrated high concordance (PPA of 93.8%, PPV of 96.8%) using CHIP subtraction. For MRD and recurrence monitoring, the disease-free survival of patients whose cancers were predicted to have an event was significantly shorter than those predicted not to have an event using a tumor naïve approach (HR = 33.4, p < 0.005, HR = 4.39, p = 0.008, respectively). The data presented here demonstrate a unified liquid biopsy platform that uses blood-based whole-exome and transcriptome sequencing coupled with artificial intelligence to address the important clinical needs in multi-cancer early detection, monitoring of MRD and recurrent cancers, and precision selection of molecularly targeted therapies.https://doi.org/10.1038/s41598-025-08986-0MCEDLiquid biopsyWhole exomeWhole transcriptomeMRDAI |
| spellingShingle | J. Abraham V. Domenyuk N. Perdigones S. Klimov S. Antani T. Yoshino E. I. Heath E. Lou S. V. Liu J. L. Marshall W. S. El-Deiry A. F. Shields M. F. Dietrich Y. Nakamura T. Fujisawa G. D. Demetri A. Barker J. Xiu D. A. Sacchetti S. Stahl R. Hahn-Lowry A. Stark J. Swensen G. Poste D. D. Halbert M. Oberley M. Radovich G. W. Sledge David B. Spetzler Validation of an AI-enabled exome/transcriptome liquid biopsy platform for early detection, MRD, disease monitoring, and therapy selection for solid tumors Scientific Reports MCED Liquid biopsy Whole exome Whole transcriptome MRD AI |
| title | Validation of an AI-enabled exome/transcriptome liquid biopsy platform for early detection, MRD, disease monitoring, and therapy selection for solid tumors |
| title_full | Validation of an AI-enabled exome/transcriptome liquid biopsy platform for early detection, MRD, disease monitoring, and therapy selection for solid tumors |
| title_fullStr | Validation of an AI-enabled exome/transcriptome liquid biopsy platform for early detection, MRD, disease monitoring, and therapy selection for solid tumors |
| title_full_unstemmed | Validation of an AI-enabled exome/transcriptome liquid biopsy platform for early detection, MRD, disease monitoring, and therapy selection for solid tumors |
| title_short | Validation of an AI-enabled exome/transcriptome liquid biopsy platform for early detection, MRD, disease monitoring, and therapy selection for solid tumors |
| title_sort | validation of an ai enabled exome transcriptome liquid biopsy platform for early detection mrd disease monitoring and therapy selection for solid tumors |
| topic | MCED Liquid biopsy Whole exome Whole transcriptome MRD AI |
| url | https://doi.org/10.1038/s41598-025-08986-0 |
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