With the increasingly available electronic medical records (EMRs), disease prediction has recently gained immense research attention, where an accurate classifier needs to be trained to map the input prediction signals (e.g., symptoms, patient demographics, etc.) to the estimated diseases for each patient. However, existing machine learning-based solutions heavily rely on abundant manually labeled EMR training data to ensure accurate prediction results, impeding their performance in the existence of rare diseases that are subject to severe data scarcity. For each rare disease, the limited EMR data can hardly offer sufficient information for a model to correctly distinguish its identity from other diseases with similar clinical symptoms. Furthermore, most existing disease prediction approaches are based on the sequential EMRs collected for every patient and are unable to handle new patients without historical EMRs, reducing their real-life practicality. In this paper, we introduce an innovative model based on Graph Neural Networks (GNNs) for disease prediction, which utilizes external knowledge bases to augment the insufficient EMR data, and learns highly representative node embeddings for patients, diseases and symptoms from the medical concept graph and patient record graph respectively constructed from the medical knowledge base and EMRs. By aggregating information from directly connected neighbor nodes, the proposed neural graph encoder can effectively generate embeddings that capture knowledge from both data sources, and is able to inductively infer the embeddings for a new patient based on the symptoms reported in her/his EMRs to allow for accurate prediction on both general diseases and rare diseases. Extensive experiments on a real-world EMR dataset have demonstrated the state-of-the-art performance of our proposed model.

Chromosome is composed of many distinct chromatin domains, referred to variably as topological domains or topologically associating domains (TADs). The domains are stable across different cell types and highly conserved across species, thus these chromatin domains have been considered as the basic units of chromosome folding and regarded as an important secondary structure in chromosome organization. However, the identification of TAD boundaries is still a great challenge due to the high cost and low resolution of Hi-C data or experiments. In this study, we propose a novel ensemble learning framework, termed as StackTADB, for predicting the boundaries of TADs. StackTADB integrates four base classifiers including Random Forest, Logistic Regression, K-NearestNeighbor and Support Vector Machine. From the analysis of a series of examinations on the data set in the previous study, it is concluded that StackTADB has optimal performance in six metrics, AUC, Accuracy, MCC, Precision, Recall and F1 score, and it is superior to the existing methods. In addition, the comparison of the performance of multiple features shows that Kmers-based features play an essential role in predicting TADs boundaries of fruit flies, and we also apply the SHapley Additive exPlanations (SHAP) framework to interpret the predictions of StackTADB to identify the reason why Kmers-based features are vital. The experimental results show that the subsequences matching the BEAF-32 motif play a crucial role in predicting the boundaries of TADs. The source code is freely available at https://github.com/HaoWuLab-Bioinformatics/StackTADB and the webserver of StackTADB is freely available at http://hwtad.sdu.edu.cn:8002/StackTADB.