Interdisciplinary Sciences: Computational Life Sciences最新文献

The exploration of drug combinations presents an opportunity to amplify therapeutic effectiveness while alleviating undesirable side effects. Nevertheless, the extensive array of potential combinations poses challenges in terms of cost and time constraints for experimental screening. Thus, it is crucial to narrow down the search space. Deep learning approaches have gained widespread popularity in predicting synergistic drug combinations tailored for specific cell lines in vitro settings. In the present study, we introduce a novel method termed GTextSyn, which utilizes the integration of gene expression data and chemical structure information for the prediction of synergistic effects in drug combinations. GTextSyn employs a sentence classification model within the domain of Natural Language Processing (NLP), wherein drugs and cell lines are regarded as entities possessing biochemical relevance. Meanwhile, combinations of drug pairs and cell lines are construed as sentences with biochemical relational significance. To assess the efficacy of GTextSyn, we conduct a comparative analysis with alternative deep learning approaches using a standard benchmark dataset. The results from a five-fold cross-validation demonstrate a 49.5% reduction in Mean Square Error (MSE) achieved by GTextSyn, surpassing the performance of the next best method in the regression task. Furthermore, we conduct a comprehensive literature survey on the predicted novel drug combinations and find substantial support from prior experimental studies for many of the combinations identified by GTextSyn.

In cancer treatment, adaptive therapy holds promise for delaying the onset of recurrence through regulating the competition between drug-sensitive and drug-resistant cells. Adaptive therapy has been studied in well-mixed models assuming free mixing of all cells and spatial models considering the interactions of single cells with their immediate adjacent cells. Both models do not reflect the spatial structure in glandular tumours where intra-gland cellular interaction is high, while inter-gland interaction is limited. Here, we use mathematical modelling to study the effects of adaptive therapy on glandular tumours that expand using either glandular fission or invasive growth. A two-dimensional, lattice-based model of sites containing sensitive and resistant cells within individual glands is developed to study the evolution of glandular tumour cells under continuous and adaptive therapies. We found that although both growth models benefit from adaptive therapy's ability to prevent recurrence, invasive growth benefits more from it than fission growth. This difference is due to the migration of daughter cells into neighboring glands that is absent in fission but present in invasive growth. The migration resulted in greater mixing of cells, enhancing competition induced by adaptive therapy. By varying the initial spatial spread and location of the resistant cells within the tumour, we found that modifying the conditions within the resistant cells containing glands affect both fission and invasive growth. However, modifying the conditions surrounding these glands affect invasive growth only. Our work reveals the interplay between growth mechanism and tumour topology in modulating the effectiveness of cancer therapy.

Vascular disease is one of the major causes of death worldwide. Endothelial cells are important components of the vascular structure. A better understanding of the endothelial cell changes in the development of vascular disease may provide new targets for clinical treatment strategies. Single-cell RNA sequencing can serve as a powerful tool to explore transcription patterns, as well as cell type identity. Our current study is based on comprehensive scRNA-seq data of several types of human vascular disease datasets with deep-learning-based algorithm. A gene set scoring system, created based on cell clustering, may help to identify the relative stage of the development of vascular disease. Metabolic preference patterns were estimated using a graphic neural network model. Overall, our study may provide potential treatment targets for retaining normal endothelial function under pathological situations.

Autism spectrum disorder (ASD) is a neurological and developmental disorder and its early diagnosis is a challenging task. The dynamic brain network (DBN) offers a wealth of information for the diagnosis and treatment of ASD. Mining the spatio-temporal characteristics of DBN is critical for finding dynamic communication across brain regions and, ultimately, identifying the ASD diagnostic biomarker. We proposed the dgEmbed-KNN and the Aggregation-SVM diagnostic models, which use the spatio-temporal information from DBN and interactive information among brain regions represented by dynamic graph embedding. The classification accuracies show that dgEmbed-KNN model performs slightly better than traditional machine learning and deep learning methods, while the Aggregation-SVM model has a very good capacity to diagnose ASD using aggregation brain network connections as features. We discovered over- and under-connections in ASD at the level of dynamic connections, involving brain regions of the postcentral gyrus, the insula, the cerebellum, the caudate nucleus, and the temporal pole. We also found abnormal dynamic interactions associated with ASD within/between the functional subnetworks, including default mode network, visual network, auditory network and saliency network. These can provide potential DBN biomarkers for ASD identification.

Stroke is still the World's second major factor of death, as well as the third major factor of death and disability. Ischemic stroke is a type of stroke, in which early detection and treatment are the keys to preventing ischemic strokes. However, due to the limitation of privacy protection and labeling difficulties, there are only a few studies on the intelligent automatic diagnosis of stroke or ischemic stroke, and the results are unsatisfactory. Therefore, we collect some data and propose a 3D carotid Computed Tomography Angiography (CTA) image segmentation model called CA-UNet for fully automated extraction of carotid arteries. We explore the number of down-sampling times applicable to carotid segmentation and design a multi-scale loss function to resolve the loss of detailed features during the process of down-sampling. Moreover, based on CA-Unet, we propose an ischemic stroke risk prediction model to predict the risk in patients using their 3D CTA images, electronic medical records, and medical history. We have validated the efficacy of our segmentation model and prediction model through comparison tests. Our method can provide reliable diagnoses and results that benefit patients and medical professionals.

Single-cell RNA sequencing technology is one of the most cost-effective ways to uncover transcriptomic heterogeneity. With the rapid rise of this technology, enormous amounts of scRNA-seq data have been produced. Due to the high dimensionality, noise, sparsity and missing features of the available scRNA-seq data, accurately clustering the scRNA-seq data for downstream analysis is a significant challenge. Many computational methods have been designed to address this issue; nevertheless, the efficacy of the available methods is still inadequate. In addition, most similarity-based methods require a number of clusters as input, which is difficult to achieve in real applications. In this study, we developed a novel computational method for clustering scRNA-seq data by considering both global and local information, named GCFG. This method characterizes the global properties of data by applying concept factorization, and the regularized Gaussian graphical model is utilized to evaluate the local embedding relationship of data. To learn the cell-cell similarity matrix, we integrated the two components, and an iterative optimization algorithm was developed. The categorization of single cells is obtained by applying Louvain, a modularity-based community discovery algorithm, to the similarity matrix. The behavior of the GCFG approach is assessed on 14 real scRNA-seq datasets in terms of ACC and ARI, and comparison results with 17 other competitive methods suggest that GCFG is effective and robust.

The precise identification of associations between diseases and drugs is paramount for comprehending the etiology and mechanisms underlying parasitic diseases. Computational approaches are highly effective in discovering and predicting disease-drug associations. However, the majority of these approaches primarily rely on link-based methodologies within distinct biomedical bipartite networks. In this study, we reorganized a fundamental dataset of parasitic disease-drug associations using the latest databases, and proposed a prediction model called PDDGCN, based on a multi-view graph convolutional network. To begin with, we fused similarity networks with binary networks to establish multi-view heterogeneous networks. We utilized neighborhood information aggregation layers to refine node embeddings within each view of the multi-view heterogeneous networks, leveraging inter- and intra-domain message passing to aggregate information from neighboring nodes. Subsequently, we integrated multiple embeddings from each view and fed them into the ultimate discriminator. The experimental results demonstrate that PDDGCN outperforms five state-of-the-art methods and four compared machine learning algorithms. Additionally, case studies have substantiated the effectiveness of PDDGCN in identifying associations between parasitic diseases and drugs. In summary, the PDDGCN model has the potential to facilitate the discovery of potential treatments for parasitic diseases and advance our comprehension of the etiology in this field. The source code is available at https://github.com/AhauBioinformatics/PDDGCN .

Circular RNA is a single-stranded RNA with a closed-loop structure. In recent years, academic research has revealed that circular RNAs play critical roles in biological processes and are related to human diseases. The discovery of potential circRNAs as disease biomarkers and drug targets is crucial since it can help diagnose diseases in the early stages and be used to treat people. However, in conventional experimental methods, conducting experiments to detect associations between circular RNAs and diseases is time-consuming and costly. To overcome this problem, various computational methodologies are proposed to extract essential features for both circular RNAs and diseases and predict the associations. Studies showed that computational methods successfully predicted performance and made it possible to detect possible highly related circular RNAs for diseases. This study proposes a deep learning-based circRNA-disease association predictor methodology called DCDA, which uses multiple data sources to create circRNA and disease features and reveal hidden feature codings of a circular RNA-disease pair with a deep autoencoder, then predict the relation score of the pair by a deep neural network. Fivefold cross-validation results on the benchmark dataset showed that our model outperforms state-of-the-art prediction methods in the literature with the AUC score of 0.9794.

MicroRNA (miRNA) serves as a pivotal regulator of numerous cellular processes, and the identification of miRNA-disease associations (MDAs) is crucial for comprehending complex diseases. Recently, graph neural networks (GNN) have made significant advancements in MDA prediction. However, these methods tend to learn one type of node representation from a single heterogeneous network, ignoring the importance of multiple network topologies and node attributes. Here, we propose SMDAP (Sequence hierarchical modeling-based Mirna-Disease Association Prediction framework), a novel GNN-based framework that incorporates multiple network topologies and various node attributes including miRNA seed and full-length sequences to predict potential MDAs. Specifically, SMDAP consists of two types of MDA representation: following a heterogeneous pattern, we construct a transfer learning-like synchronous mutual learning network to learn the first MDA representation in conjunction with the miRNA seed sequence. Meanwhile, following a homogeneous pattern, we design a subgraph-inspired asynchronous multi-scale embedding network to obtain the second MDA representation based on the miRNA full-length sequence. Subsequently, an adaptive fusion approach is designed to combine the two branches such that we can score the MDAs by the downstream classifier and infer novel MDAs. Comprehensive experiments demonstrate that SMDAP integrates the advantages of multiple network topologies and node attributes into two branch representations. Moreover, the area under the receiver operating characteristic curve is 0.9622 on DB1, which is a 5.06% increase from the baselines. The area under the precision–recall curve is 0.9777, which is a 7.33% increase from the baselines. In addition, case studies on three human cancers validated the predictive performance of SMDAP. Overall, SMDAP represents a powerful tool for MDA prediction.

Graphical Abstract

Abstract

Drug repositioning is critical to drug development. Previous drug repositioning methods mainly constructed drug–disease heterogeneous networks to extract drug–disease features. However, these methods faced difficulty when we are using structurally simple models to deal with complex heterogeneous networks. Therefore, in this study, the researchers introduced a drug repositioning method named DRDSA. The method utilizes a deep sparse autoencoder and integrates drug–disease similarities. First, the researchers constructed a drug–disease feature network by incorporating information from drug chemical structure, disease semantic data, and existing known drug–disease associations. Then, we learned the low-dimensional representation of the feature network using a deep sparse autoencoder. Finally, we utilized a deep neural network to make predictions on new drug–disease associations based on the feature representation. The experimental results show that our proposed method has achieved optimal results on all four benchmark datasets, especially on the CTD dataset where AUC and AUPR reached 0.9619 and 0.9676, respectively, outperforming other baseline methods. In the case study, the researchers predicted the top ten antiviral drugs for COVID-19. Remarkably, six out of these predictions were subsequently validated by other literature sources.