TEDDY: An integrative workflow for TE-chimeric isoform reconstruction and systematic characterization of TE-dependent transcriptional regulation

Transposable elements (TEs) play a significant role in expanding transcriptional regulation and complexity. Current sequencing technologies, however, do not allow for systematic interrogation of TE-dependent transcripts across various samples and platforms. To address this limitation, researchers have developed TEDDY, a computational workflow designed for large-scale reconstruction, quantification, and regulatory inference of TE-dependent isoforms.

By using TEDDY, scientists have been able to map the landscape of TE-dependent isoforms in mammalian preimplantation development. The results reveal a conserved pattern of stage-specific isoform generation, with species-specific TE exonization driving this process.

Using TEDDY, researchers were able to reconstruct a TE-dependent regulatory network underlying the pluripotent-to-totipotent transition. This network revealed that key transcription factors were driven by TE-derived promoters. The findings were experimentally validated, with a novel regulator named Arid3a identified by TEDDY. Further investigation confirmed that Arid3a is essential for totipotency establishment and early development.

The application of TEDDY to hepatocellular carcinoma provided valuable insights by identifying recurrence-associated prognostic isoforms, highlighting the clinical relevance of TE-dependent isoforms. TEDDY's unique capabilities include full-length isoform recovery, cross-sample and platform analysis, visualization, and TF-TE-gene network reconstruction. These features make TEDDY a versatile tool applicable across diverse biological contexts, establishing its accuracy and efficiency.