CytoLNCpred - A computational method for predicting cytoplasm associated long-coding RNAs in 15 cell-lines

ABSTRACT The function of long non-coding RNA (lncRNA) is largely determined by its specific location within a cell. Previous methods have used noisy datasets, including mRNA transcripts in tools intended for lncRNAs, and excluded lncRNAs lacking significant differential localization between the cytoplasm and nucleus. In order to overcome these shortcomings, a method has been developed for predicting cytoplasm-associated lncRNAs in 15 human cell-lines, identifying which lncRNAs are more abundant in the cytoplasm compared to the nucleus. All models in this study were trained using five-fold cross validation and tested on an independent dataset. Initially, we developed machine and deep learning based models using traditional features like composition and correlation. Using composition and correlation based features, machine learning algorithms achieved an average AUC of 0.7049 and 0.7089, respectively for 15 cell-lines. Secondly, we developed machine based models developed using embedding features obtained from the large language model DNABERT-2. The average AUC for all the cell-lines achieved by this approach was 0.6604. Subsequently, we also fine-tuned DNABERT-2 on our training dataset and evaluated the fine-tuned DNABERT-2 model on the independent dataset. The fine-tuned DNABERT-2 model achieved an average AUC of 0.6336. Correlation-based features combined with ML algorithms outperform LLM-based models, in the case of predicting differential lncRNA localization. These cell-line specific models as well as web-based service are available to the public from our web server ( https://webs.iiitd.edu.in/raghava/cytolncpred/ ) . HIGHLIGHTS Prediction of cytoplasm-associated lncRNAs in 15 human cell lines Machine learning using composition and correlation features DNABERT-2 embeddings for lncRNA localization prediction Correlation-based models outperform LLM-based models Web server and models available for public use AUTHOR’S BIOGRAPHY Shubham Choudhury is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India. Naman Kumar Mehta is currently working as Ph.D. in Computational Biology from Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India. Gajendra P. S. Raghava is currently working as Professor and Head of Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India