miRStart 2.0: enhancing miRNA regulatory insights through deep learning-based TSS identification

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to the 3′-untranslated regions of target mRNAs, influencing various biological processes at the post-transcriptional level. Identifying miRNA transcription start sites (TSSs) and transcription factors’ (TFs) regulatory roles is crucial for elucidating miRNA function and transcriptional regulation. miRStart 2.0 integrates over 4500 high-throughput datasets across five data types, utilizing a multi-modal approach to annotate 28 828 putative TSSs for 1745 human and 1181 mouse miRNAs, supported by sequencing-based signals. Over 6 million tissue-specific TF–miRNA interactions, integrated from ChIP-seq data, are supplemented by DNase hypersensitivity and UCSC conservation data, with network visualizations. Our deep learning-based model outperforms existing tools in miRNA TSS prediction, achieving the most overlaps with both cell-specific and non-cell-specific validated TSSs. The user-friendly web interface and visualization tools make miRStart 2.0 easily accessible to researchers, enabling efficient identification of miRNA upstream regulatory elements in relation to their TSSs. This updated database provides systems-level insights into gene regulation and disease mechanisms, offering a valuable resource for translational research, facilitating the discovery of novel therapeutic targets and precision medicine strategies. miRStart 2.0 is now accessible at https://awi.cuhk.edu.cn/∼miRStart2.