Abstract 6202: Liquid biopsy multi-omic TempO-Seq platform for efficacy, safety, diagnosis, and subtyping using fingerstick blood

Background and Purpose: While liquid biopsy assays are well described for plasma obtained from venipuncture, we used blood from a fingerstick, spotted onto filter paper, to profile gene expression of the whole transcriptome with the TempO-Seq® DBS assay and established a classifier for Alzheimer’s Disease (AD) [Seligmann et. al., J. Alz. Dis. 101(2024) 813-822] achieving 98% accuracy classifying patients. Fingerstick samples can be self-collected, making this method a potentially transformative diagnostic tool. We describe expanding this fingerstick liquid biopsy assay to measure DNA variants and protein biomarkers, increasing its diagnostic potential and ability to monitor therapeutic response. Methods: Blood was spotted onto 903 Proteinsaver cards and dried. Areas from each spot were then punched out into wells to measure the whole transcriptome (mRNA), alternatively spliced isoforms, the whole miRNome (miRNA), select DNA variants, and, after elution, select protein biomarkers providing a multi-omic profile of each sample. Commercial TempO-Seq assays were used, with additional attenuators added to reduce signal from highly expressed genes in blood. TempO-Seq DBS results were benchmarked against standard assays. Results: Genotyped DNA was spotted and analyzed to derive calling algorithms for AD pathogenic and polygenic risk DNA variants, including APOE4. Assays for Tau and β-amyloid were established. Then patient samples were tested, and clinical diagnosis of AD and plasma biomarker results were correlated to the liquid biopsy protein, mRNA, miRNA, mRNA isoforms, and DNA variant profiles derived from TempO-Seq DBS data. The results demonstrated that the criteria for a definitive diagnosis of Alzheimer’s Disease, suitability for immunotherapy, and prognosis via polygenic risk could all be assessed from the same fingerstick blood sample. To demonstrate its applicability monitoring drug response, samples were profiled from a subject administering weekly injections of the GLP-1 agonist (a therapeutic target for Type 2 diabetes and AD) peptide Zepbound. These results will be presented. Conclusions: The results demonstrate the utility of the TempO-Seq DBS multi-omic liquid biopsy assay of gene expression, DNA variants, and protein biomarkers from a fingerstick. We demonstrate the potential to diagnose disease using AD as an exemplar case, and to monitor drug response. Since fingerstick samples can be self-collected, or collected in any doctor’s office or clinic without a lab visit or phlebotomist, this test has the ability to address health disparities and may have the utility to; a) enable early at home diagnosis; b) provide home monitoring of therapy; c) facilitate recruitment of subjects for trials; d) serve as a companion diagnostic; and e) potentially provide a novel approach for early diagnosis of cancer and monitoring of recurrence through a convenient at-home test. Citation Format: Bruce Seligmann, Megan Opichka, Monica Hernandez, Zhoutao Chen, Joanne Yeakley, Joel McComb, Gregory Sahagian, Salvatore Camiolo. Liquid biopsy multi-omic TempO-Seq platform for efficacy, safety, diagnosis, and subtyping using fingerstick blood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6202.