SpliSync: Genomic language model-driven splice site correction of long RNA sequencing reads
Abstract
Long RNA sequencing reads are rapidly replacing short reads in transcriptomic analyses, enabling full-length transcript sequencing and better identification of isoforms, alternative splicing events, and other transcript variants. However, their higher sequencing error rates can cause misalignments, especially at splice junctions, reducing the accuracy of transcript reconstruction and analysis. We developed SpliSync, a genomic language model-driven method for splice site correction that integrates a pre-trained genomic sequence model (HyenaDNA), alignment data, and a U-net architecture to predict splice sites at nucleotide resolution. SpliSync substantially improved the precision of RNA long-read alignments by 27%-194% across diverse datasets and consistently outperformed competing tools. As a preprocessing step, it increased alternative splicing detection accuracy by 26%-330%. In contrast, its benefit for transcript reconstruction was limited, likely due to the tools' built-in correction mechanisms. The code, developed in Python using the PyTorch package, is freely available at https://github.com/splicebox/SpliSync.
Lifecycle
- biorxiv v1 2026-07-06 source ↗
Discussion
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Sina Majidian @sinamajidian.bsky.social · 1459 followers neutral
Wui Wang Lui presented "SpliSync—Genomic-language-model-driven splice site correction of long RNA sequencing reads" It uses sequence embeddings from HyenaDNA in addition to feed-forward NN form alignment pileup for splice detection, which is very cool!
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AI x Bio Discovery @aixbiobot.bsky.social · 787 followers neutral
SpliSync: Genomic language model-driven splice site correction of long RNA sequencing reads [new] ...integrates a genomic sequence model (HyenaDNA), alignment data, & U-net to predict splice sites at nt resolution for long RNA reads.
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bioRxivpreprint @biorxivpreprint.bsky.social · 8895 followers neutral
SpliSync: Genomic language model-driven splice site correction of long RNA sequencing reads https://www.biorxiv.org/content/10.64898/2026.07.04.736518v1
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bioRxiv Bioinfo @biorxiv-bioinfo.bsky.social · 4920 followers neutral
SpliSync: Genomic language model-driven splice site correction of long RNA sequencing reads https://www.biorxiv.org/content/10.64898/2026.07.04.736518v1