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Tirabassi, A.

Publications and source records attributed to Tirabassi, A..

2 recordsLinked to original sources

PARNET: A CLIP-SEQ-BASED FOUNDATION MODEL FOR RNA SEQUENCE REPRESENTATION LEARNING

RNA-binding proteins (RBPs) orchestrate a complex combinatorial regulatory "code" that governs RNA splicing, stability, localization, and translation. Learning the relationship between RNA sequences and these processes is a central challenge in genomics. Foundation models, notably RNA language models, have emerged as the dominant approach, learning general-purpose representations from unlabeled sequence at scale. While RNA language models have demonstrated impressive performance across a broad range of downstream tasks, they generally learn from sequence reconstruction objectives alone, lacking direct connections to the regulatory principles that govern RNA function. Here we introduce Parnet, an RNA foundation model trained directly and exclusively on experimental CLIP-seq data. Parnet is a multi-task foundation model trained end-to-end on 223 eCLIP-seq experiments spanning 150 RBPs to predict base-resolution RBP binding profiles directly from RNA sequence. This CLIP-seq pretraining strategy departs fundamentally from the masked-language-modeling paradigm, anchoring learned RNA representations directly in measured protein-RNA interactions rather than sequence statistics. Parnet substantially outperforms its single-task predecessor RBPNet in binding profile and motif recovery, generalizes to unseen cell types and iCLIP data, and recapitulates position-dependent splicing regulation. Frozen Parnet embeddings, without task-specific fine-tuning, match or exceed the performance of both task-specific tools, as well as larger self-supervised RNA and genomic language models across diverse downstream tasks, including RNA biotype classification, lncRNA chromatin localization, translational efficiency, splice-site recognition, intron retention, and non-coding variant effect prediction. Importantly, Parnet remains mechanistically interpretable, tracing predictions back to the specific RBPs and motifs that drive them. These results establish the RBP interactome as a compact, functionally sufficient, and interpretable basis for foundation model pretraining in RNA biology.

bioinformatics↗

Integration of single-cell multi-omic data with graph-based topic modelling

Recent advances in single-cell biology enable the profiling of multiple molecular layers, such as the transcriptome, epigenome, and surface proteins, within a single cell. Tackling the complexity of these data from different perspectives allows researchers to get the most complete insights into the biological properties of cells. Here, we propose a graph-based topic modelling method called bionSBM. Our method leverages well-known community-detection methods for multipartite graphs and the interpretability of topic modelling to cluster and explain high-dimensional, sparse, and noisy single-cell matrices. We applied our algorithm to paired single-cell multi-omics data, such as 10X Multiome, SHARE-seq, and CITE-seq. We showed that it achieves superior performance compared to state-of-the-art methods for ground-truth label retrieval, with high specificity and distinct biological interpretability.

bioinformatics↗