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bioRxiv · 10.1101/2025.07.31.667983

Prioritising Functional Noncoding Variants via eRNA Post-transcriptional Interaction Maps in Human Samples

Benova, N.·Kuklinkova, R.·Haigh, J. L.·Boyne, J. R.·Anene, C. A.
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Abstract

Noncoding variants and mutations outnumber their coding counterparts but remain challenging to interpret functionally. We present TranCi, a method that prioritises human genetic variations by integrating enhancer RNA (eRNA) expression with eRNA-mRNA interactome maps. By linking variant-associated changes in eRNA to downstream gene regulation, TranCi captures functional effects missed by sequence-based or chromatin-centric approaches. In esophageal squamous cell cancer, TranCi identifies noncoding mutations with roles in disease initiation and progression. A personalised mode enables analysis at single-patient resolution, uncovering potential individual-specific regulatory variants. TranCi thus provides a mechanistic framework for interpreting noncoding variations and uniquely identifies their downstream targets, where standard methods often fall short. TranCi is available as a module within the eRNAkit R package (https://github.com/AneneLab/eRNAkit), leveraging its database of eRNA expression and interactions for functional variant interpretation.

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Benova, N., Kuklinkova, R., Haigh, J. L., Boyne, J. R., Anene, C. A.. 2025-08-01. Prioritising Functional Noncoding Variants via eRNA Post-transcriptional Interaction Maps in Human Samples. https://doi.org/10.1101/2025.07.31.667983

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