Digital transcriptome subtraction

Digital transcriptome subtraction (DTS) is a bioinformatics method to detect the presence of novel pathogen transcripts through computational removal of the host sequences. DTS is the direct in silico analogue of the wet-lab approach Representational Difference Analysis (RDA), and is made possible by unbiased high-throughput sequencing and the availability of a high-quality, annotated reference genome of the host. The method specifically examines the etiological agent of infectious diseases and is best known for discovering Merkel cell polymavirus, the suspect causative agent in Merkel cell carcinoma.

Using computational subtraction to discover novel pathogens was first proposed in 2002 by Meyerson et al. using human expressed sequence tag (EST) datasets. In a proof of principle experiment, Meyerson et al. demonstrated that it was a feasible approach using Epstein-Barr virus-infected lymphocytes in post-transplant lymphoproliferative disorder (PTLD).

In 2007, the term "Digital Transcriptome Subtraction" was coined by the Chang-Moore group, and was used to discover Merkel cell polymavirus in Merkel cell carcinoma.

Simultaneously to the MCV discovery, this approach was used to implicate a novel arenavirus as cause of fatality in a case where three patients died of similar illnesses shortly following organ transplantations from a single donor.

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