A high-throughput real-time PCR tissue-of-origin test to distinguish blood from lymphoblastoid cell line DNA for (epi)genomic studies.

Lymphoblastoid cell lines (LCLs) derive from blood infected in vitro by Epstein-Barr virus and were used in several genetic, transcriptomic and epigenomic studies. Although few changes were shown between LCL and blood genotypes (SNPs) validating their use in genetics, more were highlighted for other genomic features and/or in their transcriptome and epigenome. This could render them less appropriate for these studies, notably when blood DNA could still be available. Here we developed a simple, high-throughput and cost-effective real-time PCR approach allowing to distinguish blood from LCL DNA samples based on the presence of EBV relative load and rearranged T-cell receptors γ and β. Our approach was able to achieve 98.5% sensitivity and 100% specificity on DNA of known origin (458 blood and 316 LCL DNA). It was further applied to 1957 DNA samples from the CEPH Aging cohort comprising DNA of uncertain origin, identifying 784 blood and 1016 LCL DNA. A subset of these DNA was further analyzed with an epigenetic clock indicating that DNA extracted from blood should be preferred to LCL for DNA methylation-based age prediction analysis. Our approach could thereby be a powerful tool to ascertain the origin of DNA in old collections prior to (epi)genomic studies.