A Multi-Modal Contrastive Diffusion Model for Therapeutic Peptide Generation

Therapeutic peptides represent a unique class of pharmaceutical agents crucial for the treatment of human diseases. Recently, deep generative models have exhibited remarkable potential for generating therapeutic peptides, but they only utilize sequence or structure information alone, which hinders the performance in generation. In this study, we propose a Multi-Modal Contrastive Diffusion model (MMCD), fusing both sequence and structure modalities in a diffusion framework to co-generate novel peptide sequences and structures. Specifically, MMCD constructs the sequence-modal and structure-modal diffusion models, respectively, and devises a multi-modal contrastive learning strategy with intercontrastive and intra-contrastive in each diffusion timestep, aiming to capture the consistency between two modalities and boost model performance. The inter-contrastive aligns sequences and structures of peptides by maximizing the agreement of their embeddings, while the intra-contrastive differentiates therapeutic and non-therapeutic peptides by maximizing the disagreement of their sequence/structure embeddings simultaneously. The extensive experiments demonstrate that MMCD performs better than other state-of-theart deep generative methods in generating therapeutic peptides across various metrics, including antimicrobial/anticancer score, diversity, and peptide-docking.

Predicting microRNA-disease associations from knowledge graph using tensor decomposition with relational constraints

Motivation: MiRNAs are a kind of small non-coding RNAs that are not translated into proteins, and aberrant expression of miRNAs is associated with human diseases. Since miRNAs have different roles in diseases, the miRNA-disease associations are categorized into multiple types according to their roles. Predicting miRNA-disease associations and types is critical to understand the underlying pathogenesis of human diseases from the molecular level. Results: In this paper, we formulate the problem as a link prediction in knowledge graphs. We use biomedical knowledge bases to build a knowledge graph of entities representing miRNAs and disease and multi-relations, and we propose a tensor decomposition-based model named TDRC to predict miRNA-disease associations and their types from the knowledge graph. We have experimentally evaluated our method and compared it to several baseline methods. The results demonstrate that the proposed method has high-accuracy and high-efficiency performances.