Drug combination therapy plays a vital role in disease treatment, including cancer, as it contributes to treatment efficacy and can alleviate the effect of drug resistance. Although clinical trials and screening may provide valuable information about synergistic drug combinations, they suffer from challenging combinatorial space. Multiple methods are proposed to address those issues. However, they still fail in making full use of global and local triplet context relationships of known synergistic combinations. To this end, a deep learning model which leverages dual view hypergraph representation fusion for synergistic drug combinations identification is proposed, namely DVHSyn. It first extracts the transcriptome features of cancer cell lines and molecular structures of drugs. Subsequently, by modeling the synergistic effect on a hypergraph, DVHSyn simultaneously learns the local and global context of the sample triplets via a hypergraph view and its expanded heterogeneous graph view. Finally, the learned representations of the above two branches are fused selectively to predict synergistic drug combinations. Experiment results demonstrate that DVHSyn surpasses six other competing methods. One case study also reflects that DVHSyn has the potential to predict novel synergistic drug combinations. Overall, our method is effective in identifying synergistic drug combinations and provides new insights for novel drug development.

Cell type identification plays a vital role in single-cell RNA sequencing (scRNA-seq) data analysis. Although many deep embedded methods to cluster scRNA-seq data have been proposed, they still fail in elucidating the intrinsic properties of cells and genes. Here, we present a novel end-to-end deep graph clustering model for single-cell transcriptomics data based on unsupervised Gene-Cell Collective representation learning and Optimal Transport (scGCOT) which integrates both cell and gene correlations. Specifically, scGCOT learns the latent embedding of cells and genes simultaneously and reconstructs the cell graph, the gene graph, and the gene expression count matrix. A zero-inflated negative binomial (ZINB) model is estimated via the reconstructed count matrix to capture the essential properties of scRNA-seq data. By leveraging the optimal transport-based joint representation alignment, scGCOT learns the clustering process and the latent representations through a mutually supervised self optimization strategy. Extensive experiments with 14 competing methods on 15 real scRNA-seq datasets demonstrate the competitive edges of scGCOT.

Bioactive peptide therapeutics has been a long-standing research topic. Notably, the antimicrobial peptides (AMPs) have been extensively studied for its therapeutic potential. Meanwhile, the demand for annotating other therapeutic peptides, such as antiviral peptides (AVPs) and anticancer peptides (ACPs), also witnessed an increase in recent years. However, we conceive that the structure of peptide chains and the intrinsic information between the amino acids is not fully investigated among the existing protocols. Therefore, we develop a new graph deep learning model, namely TP-LMMSG, which offers lightweight and easy-to-deploy advantages while improving the annotation performance in a generalizable manner. The results indicate that our model can accurately predict the properties of different peptides. The model surpasses the other state-of-the-art models on AMP, AVP and ACP prediction across multiple experimental validated datasets. Moreover, TP-LMMSG also addresses the challenges of time-consuming pre-processing in graph neural network frameworks. With its flexibility in integrating heterogeneous peptide features, our model can provide substantial impacts on the screening and discovery of therapeutic peptides. The source code is available at https://github.com/NanjunChen37/TP_LMMSG.

Protein acetylation is one of the extensively studied post-translational modifications (PTMs) due to its significant roles across a myriad of biological processes. Although many computational tools for acetylation site identification have been developed, there is a lack of benchmark dataset and bespoke predictors for non-histone acetylation site prediction. To address these problems, we have contributed to both dataset creation and predictor benchmark in this study. First, we construct a non-histone acetylation site benchmark dataset, namely NHAC, which includes 11 subsets according to the sequence length ranging from 11 to 61 amino acids. There are totally 886 positive samples and 4707 negative samples for each sequence length. Secondly, we propose TransPTM, a transformer-based neural network model for non-histone acetylation site predication. During the data representation phase, per-residue contextualized embeddings are extracted using ProtT5 (an existing pre-trained protein language model). This is followed by the implementation of a graph neural network framework, which consists of three TransformerConv layers for feature extraction and a multilayer perceptron module for classification. The benchmark results reflect that TransPTM has the competitive performance for non-histone acetylation site prediction over three state-of-the-art tools. It improves our comprehension on the PTM mechanism and provides a theoretical basis for developing drug targets for diseases. Moreover, the created PTM datasets fills the gap in non-histone acetylation site datasets and is beneficial to the related communities. The related source code and data utilized by TransPTM are accessible at https://www.github.com/TransPTM/TransPTM.

MOTIVATION: Chromothripsis, associated with poor clinical outcomes, is prognostically vital in multiple myeloma. The catastrophic event is reported to be detectable prior to the progression of multiple myeloma. As a result, chromothripsis detection can contribute to risk estimation and early treatment guidelines for multiple myeloma patients. However, manual diagnosis remains the gold standard approach to detect chromothripsis events with the whole-genome sequencing technology to retrieve both copy number variation (CNV) and structural variation data. Meanwhile, CNV data are much easier to obtain than structural variation data. Hence, in order to reduce the reliance on human experts' efforts and structural variation data extraction, it is necessary to establish a reliable and accurate chromothripsis detection method based on CNV data. RESULTS: To address those issues, we propose a method to detect chromothripsis solely based on CNV data. With the help of structure learning, the intrinsic relationship-directed acyclic graph of CNV features is inferred to derive a CNV embedding graph (i.e. CNV-DAG). Subsequently, a neural network based on Graph Transformer, local feature extraction, and non-linear feature interaction, is proposed with the embedding graph as the input to distinguish whether the chromothripsis event occurs. Ablation experiments, clustering, and feature importance analysis are also conducted to enable the proposed model to be explained by capturing mechanistic insights. AVAILABILITY AND IMPLEMENTATION: The source code and data are freely available at https://github.com/luvyfdawnYu/CNV_chromothripsis.