In the recent few years, an increasing number of studies have shown that microRNAs (miRNAs) play critical roles in many fundamental and important biological processes. As one of pathogenetic factors, the molecular mechanisms underlying human complex diseases still have not been completely understood from the perspective of miRNA. Predicting potential miRNA-disease associations makes important contributions to understanding the pathogenesis of diseases, developing new drugs, and formulating individualized diagnosis and treatment for diverse human complex diseases. Instead of only depending on expensive and time-consuming biological experiments, computational prediction models are effective by predicting potential miRNA-disease associations, prioritizing candidate miRNAs for the investigated diseases, and selecting those miRNAs with higher association probabilities for further experimental validation. In this study, Path-Based MiRNA-Disease Association (PBMDA) prediction model was proposed by integrating known human miRNA-disease associations, miRNA functional similarity, disease semantic similarity, and Gaussian interaction profile kernel similarity for miRNAs and diseases. This model constructed a heterogeneous graph consisting of three interlinked sub-graphs and further adopted depth-first search algorithm to infer potential miRNA-disease associations. As a result, PBMDA achieved reliable performance in the frameworks of both local and global LOOCV (AUCs of 0.8341 and 0.9169, respectively) and 5-fold cross validation (average AUC of 0.9172). In the cases studies of three important human diseases, 88% (Esophageal Neoplasms), 88% (Kidney Neoplasms) and 90% (Colon Neoplasms) of top-50 predicted miRNAs have been manually confirmed by previous experimental reports from literatures. Through the comparison performance between PBMDA and other previous models in case studies, the reliable performance also demonstrates that PBMDA could serve as a powerful computational tool to accelerate the identification of disease-miRNA associations. Identification of miRNA-disease associations is considered as a key way for the development of pathology, diagnose and therapy. Computational prediction models contribute to discovering the underlying disease-related miRNAs on a large scale. Based on the assumption that functionally related miRNAs tend to be involved in phenotypically similar disease and vice versa, the model of PBMDA was developed to prioritize the underlying miRNA-disease associations by adopting a special depth-first search algorithm in a heterogeneous graph, which was composed of known miRNA-disease association network, miRNA similarity network, and disease similarity network. Through leave-one-out cross validation and 5-fold cross validation, the promising results demonstrated the effectiveness of the proposed model. We further implemented the case studies of three important human complex diseases, 88%, 88% and 90% of top-50 predicted miRNA-disease associations have been manually confirmed based on recent experimental reports. It is anticipated that PBMDA could prioritize the most potential miRNA-disease associations on a large scale for advancing the progress of biological experiment validation in the future, which could further contribute to the understanding of complex disease mechanisms.

With the increasing prevalence of autism spectrum disorder (ASD), it is important to identify ASD patients for effective treatment and intervention, especially in early childhood. Neuroimaging techniques have been used to characterize the complex biomarkers based on the functional connectivity anomalies in the ASD. However, the diagnosis of ASD still adopts the symptom-based criteria by clinical observation. The existing computational models tend to achieve unreliable diagnostic classification on the large-scale aggregated data sets. In this work, we propose a novel graph-based classification model using the deep belief network (DBN) and the Autism Brain Imaging Data Exchange (ABIDE) database, which is a worldwide multisite functional and structural brain imaging data aggregation. The remarkable connectivity features are selected through a graph extension of K-nearest neighbors and then refined by a restricted path-based depth-first search algorithm. Thanks to the feature reduction, lower computational complexity could contribute to the shortening of the training time. The automatic hyperparameter-tuning technique is introduced to optimize the hyperparameters of the DBN by exploring the potential parameter space. The simulation experiments demonstrate the superior performance of our model, which is 6.4% higher than the best result reported on the ABIDE database. We also propose to use the data augmentation and the oversampling technique to identify further the possible subtypes within the ASD. The interpretability of our model enables the identification of the most remarkable autistic neural correlation patterns from the data-driven outcomes.

Accumulating clinical researches have shown that specific microbes with abnormal levels are closely associated with the development of various human diseases. Knowledge of microbe–disease associations can provide valuable insights for complex disease mechanism understanding as well as the prevention, diagnosis and treatment of various diseases. However, little effort has been made to predict microbial candidates for human complex diseases on a large scale. In this work, we developed a new computational model for predicting microbe–disease associations by combining two single recommendation methods. Based on the assumption that functionally similar microbes tend to get involved in the mechanism of similar disease, we adopted neighbor-based collaborative filtering and a graph-based scoring method to compute association possibility of microbe–disease pairs. The promising prediction performance could be attributed to the use of hybrid approach based on two single recommendation methods as well as the introduction of Gaussian kernel-based similarity and symptom-based disease similarity. To evaluate the performance of the proposed model, we implemented leave-one-out and fivefold cross validations on the HMDAD database, which is recently built as the first database collecting experimentally-confirmed microbe–disease associations. As a result, NGRHMDA achieved reliable results with AUCs of 0.9023 ± 0.0031 and 0.9111 in the validation frameworks of fivefold CV and LOOCV. In addition, 78.2% microbe samples and 66.7% disease samples are found to be consistent with the basic assumption of our work that microbes tend to get involved in the similar disease clusters, and vice versa. Compared with other methods, the prediction results yielded by NGRHMDA demonstrate its effective prediction performance for microbe–disease associations. It is anticipated that NGRHMDA can be used as a useful tool to search the most potential microbial candidates for various diseases, and therefore boosts the medical knowledge and drug development. The codes and dataset of our work can be downloaded from https://github.com/yahuang1991/NGRHMDA .

Objective: Deep learning (DL) techniques have been introduced to assist doctors in the interpretation of medical images by detecting image-derived phenotype abnormality. Yet the privacy-preserving policy of medical images disables the effective training of DL model using sufficiently large datasets. As a decentralized computing paradigm to address this issue, federated learning (FL) allows the training process to occur in individual institutions with local datasets, and then aggregates the resultant weights without risk of privacy leakage. Methods: We propose an effective federated multi-task learning (MTL) framework to jointly identify multiple related mental disorders based on functional magnetic resonance imaging data. A federated contrastive learning-based feature extractor is developed to extract high-level features across client models. To ease the optimization conflicts of updating shared parameters in MTL, we present a federated multi-gate mixture of expert classifier for the joint classification. The proposed framework also provides practical modules, including personalized model learning, privacy protection, and federated biomarker interpretation. Results: On real-world datasets, the proposed framework achieves robust diagnosis accuracies of 69.48 $\pm$ 1.6%, 71.44 $\pm$ 3.2%, and 83.29 $\pm$ 3.2% in autism spectrum disorder, attention deficit/hyperactivity disorder, and schizophrenia, respectively. Conclusion: The proposed framework can effectively ease the domain shift between clients via federated MTL. Significance: The current work provides insights into exploiting the advantageous knowledge shared in related mental disorders for improving the generalization capability of computer-aided detection approaches.

Neuroimaging techniques have been widely adopted to detect the neurological brain structures and functions of the nervous system. As an effective noninvasive neuroimaging technique, functional magnetic resonance imaging (fMRI) has been extensively used in computer-aided diagnosis (CAD) of mental disorders, e.g., autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). In this study, we propose a spatial–temporal co-attention learning (STCAL) model for diagnosing ASD and ADHD from fMRI data. In particular, a guided co-attention (GCA) module is developed to model the intermodal interactions of spatial and temporal signal patterns. A novel sliding cluster attention module is designed to address global feature dependency of self-attention mechanism in fMRI time series. Comprehensive experimental results demonstrate that our STCAL model can achieve competitive accuracies of 73.0 $\pm$ 4.5%, 72.0 $\pm$ 3.8%, and 72.5 $\pm$ 4.2% on the ABIDE I, ABIDE II, and ADHD-200 datasets, respectively. Moreover, the potential for feature pruning based on the co-attention scores is validated by the simulation experiment. The clinical interpretation analysis of STCAL can allow medical professionals to concentrate on the discriminative regions of interest and key time frames from fMRI data.

As post-transcriptional regulators of gene expression, micro-ribonucleic acids (miRNAs) are regarded as potential biomarkers for a variety of diseases. Hence, the prediction of miRNA-disease associations (MDAs) is of great significance for an in-depth understanding of disease pathogenesis and progression. Existing prediction models are mainly concentrated on incorporating different sources of biological information to perform the MDA prediction task while failing to consider the fully potential utility of MDA network information at the motif-level. To overcome this problem, we propose a novel motif-aware MDA prediction model, namely MotifMDA, by fusing a variety of high- and low-order structural information. In particular, we first design several motifs of interest considering their ability to characterize how miRNAs are associated with diseases through different network structural patterns. Then, MotifMDA adopts a two-layer hierarchical attention to identify novel MDAs. Specifically, the first attention layer learns high-order motif preferences based on their occurrences in the given MDA network, while the second one learns the final embeddings of miRNAs and diseases through coupling high- and low-order preferences. Experimental results on two benchmark datasets have demonstrated the superior performance of MotifMDA over several state-of-the-art prediction models. This strongly indicates that accurate MDA prediction can be achieved by relying solely on MDA network information. Furthermore, our case studies indicate that the incorporation of motif-level structure information allows MotifMDA to discover novel MDAs from different perspectives. The data and codes are available at https://github.com/stevejobws/MotifMDA.