RPIPLM: Prediction of ncRNA-protein interaction by post-training a dual-tower pretrained biological model with supervised contrastive learning

Y Yiwei Liu (Department of Chemistry) T Ting Bao P Peng Yin (Wyss Institute of Biologically Inspired Engineering) S Shumin Wang (Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, MOE, State Key Laboratory of Advanced Optical Polymer and Manufacturing Technology, College of Chemistry and Molecular Engineering) Y Yanbin Wang (Center for Advanced Radiation Sources, The University of Chicago)

Abstract

The field of biological research has been profoundly impacted by the emergence of biological pre-trained models, which have resulted in remarkable advancements in life sciences and medicine. However, the current landscape of biological pre-trained language models suffers from a shortcoming, i.e., their inability to grasp the intricacies of molecular interactions, such as ncRNA-protein interactions. It is in this context that our paper introduces a two-tower computational framework, termed RPIPLM, which brings forth a new paradigm for the prediction of ncRNA-protein interactions. The core of RPIPLM lies in its harnessing of the pre-trained RNA language model and protein language model to process ncRNA and protein sequences, thereby enabling the transfer of the general knowledge gained from self-supervised learning of vast data to ncRNA-protein interaction tasks. Additionally, to learn the intricate interaction patterns between RNA and protein embeddings across diverse scales, we employ a fusion of scaled dot-product self-attention mechanism and Multi-scale convolution operations on the output of the dual-tower architecture, effectively capturing both global and local information. Furthermore, we introduce supervised contrastive learning into the training of RPIPLM, enabling the model to effectively capture discriminative information by distinguishing between interacting and non-interacting samples in the learned representations. Through extensive experiments and an interpretability study, we demonstrate the effectiveness of RPIPLM and its superiority over other methods, establishing new state-of-the-art performance. RPIPLM is a powerful and scalable computational framework that holds the potential to unlock enormous insights from vast biological data, thereby accelerating the discovery of molecular interactions.

Article Details

Journal PLoS ONE
Volume / Issue Vol. 20, Issue 8
Published August 14, 2025
Pages e0329174
ISSN 1932-6203
Publisher Public Library of Science

Journal Info

PLoS ONE

Public Library of Science

ISSN: 1932-6203 Open Access Health Sciences

Authors (5)

Y

Yiwei Liu

Department of Chemistry

T

Ting Bao

P

Peng Yin

Wyss Institute of Biologically Inspired Engineering

S

Shumin Wang

Key Laboratory of Optic-Electric Sensing and Analytical Chemistry for Life Science, MOE, State Key Laboratory of Advanced Optical Polymer and Manufacturing Technology, College of Chemistry and Molecular Engineering

Y

Yanbin Wang

Center for Advanced Radiation Sources, The University of Chicago