Telescope: Characterization of the retrotranscriptome by accurate estimation of transposable element expression

Matthew L Bendall,Gustavo Reyes-Terán,R Brad Jones,Aarón Lecanda-Sánchez,Marcos Pérez-Losada,Douglas F Nixon,Christopher E Ormsby,Mario A Ostrowski,Lubbertus C F Mulder,Keith A Crandall,Miguel De Mulder,Luis Pedro Iñiguez,Rob Patro

doi:10.1371/journal.pcbi.1006453

Abstract

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.

Highlights

Transposable elements (TEs) represent the largest class of biochemically functional DNA elements in mammalian genomes[1,2] comprising nearly 50% of the human genome
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
We used Telescope to identify Human Endogenous Retrovirus (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

Summary

Introduction

Transposable elements (TEs) represent the largest class of biochemically functional DNA elements in mammalian genomes[1,2] comprising nearly 50% of the human genome. As many of these transcriptionally active elements originated as retroelements, we refer to the set of RNA molecules transcribed from these elements in a population of cells as the retrotranscriptome. Others, have shown that HIV-1 infection increases HERV transcription[11,12,13,14,15] These lines of evidence indicate that TEs have important roles in the regulation of human health and disease

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Results

Discussion

Conclusion