bioRxiv Science⌕ Search

Biology subjects

Sammut, S.

Publications and source records attributed to Sammut, S..

3 recordsLinked to original sources

miRBind2 enables sequence-only prediction of miRNA binding and transcript repression

MotivationMicroRNAs (miRNAs) regulate gene expression by guiding Argonaute proteins to partially complementary sites on target RNAs. While classical prediction methods rely on engineered features such as seed match categories, evolutionary conservation, and site context, recent advances in deep learning offer the potential to learn targeting rules directly from sequence. We developed a sequence-based deep learning model that improves miRNA target site prediction, and further validated the learned target site representations by extending the model to gene-level functional repression prediction. ResultsWe introduce miRBind2, a deep learning method for miRNA target site prediction that incorporates a novel pairwise nucleotide representation capturing all possible miRNA-target nucleotide interactions, with a CNN-based architecture. miRBind2 outperforms previous SotA models across four independent datasets from the debiased miRBench benchmark, while using 92% fewer parameters. We show that the convolutional features and weights learned by miRBind2 can be transferred to transcript-level prediction by extending the miRBind2 architecture and fine-tuning it on miRNA perturbation experiments. This miRBind2-3UTR model predicts gene repression from sequence alone. On a dataset of 50,549 miRNA-gene pairs, miRBind2-3UTR significantly outperforms TargetScan. These results show that deep models pretrained on target site data can capture regulatory signals and predict functional repression without requiring conventional engineered biological features. AvailabilityModels and source code are freely available via GitHub (https://github.com/BioGeMT/miRBind_2.0). A publicly available web-tool for novel predictions and visualization is available at : (https://huggingface.co/spaces/dimostzim/BioGeMT-miRBind2) Contactpanagiotis.alexiou@um.edu.mt

bioinformatics↗

miRBench: A Comprehensive microRNA Binding Site Prediction Training and Benchmarking Dataset

MotivationMicroRNAs (miRNAs) are crucial regulators of gene expression, but the precise mechanisms governing their binding to target sites remain unclear. A major contributing factor to this is the lack of unbiased experimental datasets for training accurate prediction models. While recent experimental advances have provided numerous miRNA-target interactions, these are solely positive interactions. Generating negative examples in silico is challenging and prone to introducing biases, such as the miRNA frequency class bias identified in this work. Biases within datasets can compromise model generalization, leading models to learn dataset-specific artifacts rather than true biological patterns. ResultsWe introduce a novel methodology for negative sample generation that effectively mitigates the miRNA frequency class bias. Using this methodology, we curate several new, extensive datasets and benchmark several state-of-the-art methods on them. We find that a simple convolutional neural network model, retrained on some of these datasets, is able to outperform state-of-the-art methods. This highlights the potential for leveraging unbiased datasets to achieve improved performance in miRNA binding site prediction. To facilitate further research and lower the barrier to entry for machine learning researchers, we provide an easily accessible Python package, miRBench, for dataset retrieval, sequence encoding, and the execution of state-of-the-art models. AvailabilityThe miRBench Python Package is accessible at https://github.com/katarinagresova/miRBench/releases/tag/v1.0.0

bioinformatics↗

Compensation Strategies for Bioelectric Signal Changes in Chronic Selective Nerve Cuff Recordings: A Simulation Study

Peripheral nerve interfaces (PNIs) allow us to extract motor, sensory and autonomic information from the nervous system and use it as control signals in neuroprosthetic and neuromodulation applications. Recent efforts have aimed to improve the recording selectivity of PNIs, including by using spatiotemporal patterns from multi-contact nerve cuff electrodes as input to a convolutional neural network (CNN). Before such a methodology can be translated to humans, its performance in chronic implantation scenarios must be evaluated. In this simulation study, approaches were evaluated for maintaining selective recording performance in the presence of two chronic implantation challenges: the growth of encapsulation tissue and rotation of the nerve cuff electrode. Performance over time was examined in three conditions: training the CNN at baseline only, supervised re-training with explicitly labeled data at periodic intervals, and a semi-supervised self-learning approach. This study demonstrated that a selective recording algorithm trained at baseline will likely fail over time due to changes in signal characteristics resulting from the chronic challenges. Results further showed that periodically recalibrating the selective recording algorithm can maintain its performance over time, and that a self-learning approach has the potential to reduce the frequency of recalibration.

bioengineering↗