Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression
| Autor: | Gustavo Reyes-Terán, Aarón Lecanda-Sánchez, Lubbertus C. F. Mulder, Luis P. Iñiguez, Matthew L. Bendall, Christopher E. Ormsby, Mario A. Ostrowski, Keith A. Crandall, R.B. Jones, Miguel de Mulder, Marcos Pérez-Losada, Douglas F. Nixon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Subfamily Molecular biology Astronomy Astronomical Sciences law.invention Database and Informatics Methods Sequencing techniques 0302 clinical medicine law Mobile Genetic Elements Biology (General) 0303 health sciences Ecology Software Engineering RNA sequencing Genome project Genomics Computational Theory and Mathematics Optical Equipment Organ Specificity Modeling and Simulation 030220 oncology & carcinogenesis Physical Sciences Engineering and Technology Sequence Analysis Transcriptome Analysis Astronomical Instruments Research Article Transposable element Computer and Information Sciences Sequence analysis QH301-705.5 Bioinformatics Cytological Techniques Bayesian probability Equipment Computational biology Research and Analysis Methods ENCODE Cell Line Telescope Cellular and Molecular Neuroscience 03 medical and health sciences Genetic Elements Fragment (logic) Genetics Humans Ecology Evolution Behavior and Systematics 030304 developmental biology Sequence Analysis RNA Software Tools Gene Expression Profiling Endogenous Retroviruses Transposable Elements Computational Biology Biology and Life Sciences Statistical model Genome Analysis Expression (mathematics) 030104 developmental biology Molecular biology techniques Genetic Loci DNA Transposable Elements Transcriptome Sequence Alignment 030217 neurology & neurosurgery Software Telescopes |
| Zdroj: | PLoS Computational Biology PLoS Computational Biology, Vol 15, Iss 9, p e1006453 (2019) |
| DOI: | 10.1101/398172 |
| Popis: | Characterization of Human Endogenous Retrovirus (HERV) expression within the transcriptomic landscape using RNA-seq is complicated by uncertainty in fragment assignment because of sequence similarity. We present Telescope, a computational software tool that provides accurate estimation of transposable element expression (retrotranscriptome) resolved to specific genomic locations. Telescope directly addresses uncertainty in fragment assignment by reassigning ambiguously mapped fragments to the most probable source transcript as determined within a Bayesian statistical model. We demonstrate the utility of our approach through single locus analysis of HERV expression in 13 ENCODE cell types. When examined at this resolution, we find that the magnitude and breadth of the retrotranscriptome can be vastly different among cell types. Furthermore, our approach is robust to differences in sequencing technology and demonstrates that the retrotranscriptome has potential to be used for cell type identification. We compared our tool with other approaches for quantifying transposable element (TE) expression, and found that Telescope has the greatest resolution, as it estimates expression at specific TE insertions rather than at the TE subfamily level. Telescope performs highly accurate quantification of the retrotranscriptomic landscape in RNA-seq experiments, revealing a differential complexity in the transposable element biology of complex systems not previously observed. Telescope is available at https://github.com/mlbendall/telescope. Author summary Almost half of the human genome is composed of transposable elements (TEs), but their contribution to the transcriptome, their cell-type specific expression patterns, and their role in disease remains poorly understood. Recent studies have found many elements to be actively expressed and involved in key cellular processes. For example, human endogenous retroviruses (HERVs) are reported to be involved in human embryonic stem cell differentiation. Discovering which exact HERVs are differentially expressed in RNA-seq data would be a major advance in understanding such processes. However, because HERVs have a high level of sequence similarity it is hard to identify which exact HERV is differentially expressed. To solve this problem, we developed a computer program which addressed uncertainty in fragment assignment by reassigning ambiguously mapped fragments to the most probable source transcript as determined within a Bayesian statistical model. We call this program, “Telescope”. We then used Telescope to identify HERV expression in 13 well-studied cell types from the ENCODE consortium and found that different cell types could be characterized by enrichment for different HERV families, and for locus specific expression. We also showed that Telescope performed better than other methods currently used to determine TE expression. The use of this computational tool to examine new and existing RNA-seq data sets may lead to new understanding of the roles of TEs in health and disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|