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Updated: Mar 20, 2026
Novel Sequence Discovery by Subtractive Genomics
Published on: January 25, 2019
Strategies for Human Tumor Virus Discoveries: From Microscopic Observation to Digital Transcriptome Subtraction
Ezra D Mirvish1, Masahiro Shuda2
1Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh PA, USA.
Abstract:
Over 20% of human cancers worldwide are associated with infectious agents, including viruses, bacteria, and parasites. Various methods have been used to identify human tumor viruses, including electron microscopic observations of viral particles, immunologic screening, cDNA library screening, nucleic acid hybridization, consensus PCR, viral DNA array chip, and representational difference analysis. With the Human Genome Project, a large amount of genetic information from humans and other organisms has accumulated over the last decade. Utilizing the available genetic databases, Feng et al. (2007) developed digital transcriptome subtraction (DTS), an in silico method to sequentially subtract human sequences from tissue or cellular transcriptome, and discovered Merkel cell polyomavirus (MCV) from Merkel cell carcinoma. Here, we review the background and methods underlying the human tumor virus discoveries and explain how DTS was developed and used for the discovery of MCV.
Insights
Infectious agents cause over 20% of human cancers. Digital transcriptome subtraction (DTS) is an in silico method that aided in discovering Merkel cell polyomavirus (MCV), a human tumor virus.
Area of Science:
- Oncology
- Virology
- Bioinformatics
Background:
- Infectious agents, including viruses, are linked to over 20% of global cancer cases.
- Traditional methods for identifying human tumor viruses are often labor-intensive and may miss novel pathogens.
- The Human Genome Project has generated vast genetic data, enabling new computational approaches.
Purpose of the Study:
- To review historical and current methods for discovering human tumor viruses.
- To explain the development and application of digital transcriptome subtraction (DTS) for identifying novel viruses in human cancers.
- To highlight the discovery of Merkel cell polyomavirus (MCV) using DTS.
Main Methods:
- Review of established techniques like electron microscopy, hybridization, and PCR for viral detection.
- Detailed explanation of the in silico digital transcriptome subtraction (DTS) methodology.
- Application of DTS to subtract human sequences from transcriptome data to identify non-human sequences.
Main Results:
- DTS was successfully developed as an in silico method for virus discovery.
- The DTS method was instrumental in the discovery of Merkel cell polyomavirus (MCV).
- This approach offers a powerful new avenue for identifying infectious agents associated with cancer.
Conclusions:
- Digital transcriptome subtraction (DTS) represents a significant advancement in the discovery of human tumor viruses.
- The identification of MCV underscores the importance of computational methods in virology and oncology.
- Further application of DTS may lead to the discovery of additional infectious agents implicated in human cancers.
