The FateAI Line is designed for the early identification and histological characterization of tumors through DNA methylation markers. It is a solution based on recent discoveries, led by one of the proponents: Dr. Pier Vitale Nuzzo. Immunoprecipitation of circulating free DNA methylation (cfDNA) followed by high-throughput sequencing (cfMeDIP-seq) is an innovative and highly sensitive technique that allows non-invasive identification and classification of tumors through the identification of the tumor methylation profile in biological fluids. The identification and characterization of the cfDNA methylome through the CfMeDIP-seq assay has allowed the identification of the presence of the methylation profile of seven types of tumors (colon, pancreatic, renal, breast, lung, urothelial, and acute myeloid leukemia) in plasma with high sensitivity and specificity, using small amounts of DNA (10ng) at a lower cost than traditional methylation analysis techniques (Shu Yi Shen, Rajat Singhania, Gordon Fehringer, Ankur Chakravarthy, et al. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature 2018 volume 563:579-583).

Dr. Nuzzo’s recent publications have demonstrated how the cfMeDIP-seq technique is significantly superior to classic genetic somatic variant analysis of cfDNA in identifying metastatic renal tumors (100% vs 39%) (Lasseter K, Nassar AH, Hamieh L, Berchuck JE, Nuzzo PV, et al. Plasma cell-free DNA variant analysis compared with methylated DNA analysis in renal cell carcinoma. Genet Med. 2020 Aug;22(8):1366-1373). In the publication Nuzzo et al. “Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes” Nature Medicine 26 1041-1043(2020), it was shown that cfMeDIP-seq achieved an accuracy of over 99% for the early and non-invasive diagnosis of renal carcinoma and 97.9% for the identification of metastatic urothelial tumors. Moreover, for the first time, the cfMeDIP-seq assay was successfully performed on urine samples, which are easier to obtain, do not require nursing staff, and allow for greater amounts of cfDNA for required analyses.

The development of the cfMeDIP-seq assay has also demonstrated how the tumor methylation profile detected in plasma is able to accurately discriminate common primary intracranial tumor histologies, which are difficult to diagnose through classical instrumental investigations, consequently avoiding potential invasive surgery for histological diagnosis (Nassiri F, et al. Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes. Nat Med. 2020 Jul;26(7):1044-1047).

With the development of the cfMeDIP-seq assay, it is possible to introduce screening and early identification methods for tumors in clinical practice, especially for those tumors with high mortality rates for which there are currently no screening tests. Possible additional applications may include the early identification of minimal residual disease after surgical treatment, to select patients who may benefit from adjuvant therapy; the ability to early identify patients at risk of developing adverse events associated with immunotherapy, and the early identification of resistant phenotypes that may allow for timely therapy changes by the clinician. The ONCO-ORACLE platform will be based on the optimization and industrialization of the cfMeDIP-seq test, with the possibility of using it for all tumor types, as each tumor has a specific and stable methylation profile.