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

Authors

Xiao, Y., Shen, L., Jiang, C., Zhang, Y., Liang, Y., Yin, J., Wang, H., Gao, S., Le, R., Shi, J.

Abstract

Transposable elements (TEs) substantially expand transcriptional regulation and complexity. Despite advances in sequencing technologies, the systematic interrogation of TE-dependent transcripts across diverse samples and platforms remains limited. Here we introduce TEDDY, a computational workflow for large-scale reconstruction, quantification and regulatory inference of TE-dependent isoforms. Using TEDDY, we resolved the landscape of TE-dependent isoforms in mammalian preimplantation development, revealing a conserved pattern of stage-specific isoform generation via species-specific TE exonization. We reconstruct a TE-dependent regulatory network underlying pluripotent-to-totipotent transition wherein key transcription factors are driven by TE-derived promoters and validated experimentally. Within this network, Arid3a, a novel regulator nominated by TEDDY, was functionally validated as essential for totipotency establishment and early development. Further application of TEDDY to hepatocellular carcinoma identified recurrence-associated prognostic isoforms, underscoring their clinical relevance. Benchmarking establishes TEDDY's accuracy and efficiency with unique capabilities in full-length isoform recovery, cross-sample and -platform analysis, visualization, and TF-TE-gene network reconstruction, making TEDDY applicable across diverse biological contexts.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 27 Aug 2026.

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