Ping Zhang

Graphs & Digraphs masterfully employs student-friendly exposition, clear proofs, abundant examples, and numerous exercises to provide an essential understanding of the concepts, theorems, history, and applications of graph theory.Fully updated and thoughtfully reorganized to make reading and locating material easier for instructors and students

MOTIVATION: Graph embedding learning that aims to automatically learn low-dimensional node representations, has drawn increasing attention in recent years. To date, most recent graph embedding methods are evaluated on social and information networks and are not comprehensively studied on biomedical networks under systematic experiments and analyses. On the other hand, for a variety of biomedical network analysis tasks, traditional techniques such as matrix factorization (which can be seen as a type of graph embedding methods) have shown promising results, and hence there is a need to systematically evaluate the more recent graph embedding methods (e.g. random walk-based and neural network-based) in terms of their usability and potential to further the state-of-the-art. RESULTS: We select 11 representative graph embedding methods and conduct a systematic comparison on 3 important biomedical link prediction tasks: drug-disease association (DDA) prediction, drug-drug interaction (DDI) prediction, protein-protein interaction (PPI) prediction; and 2 node classification tasks: medical term semantic type classification, protein function prediction. Our experimental results demonstrate that the recent graph embedding methods achieve promising results and deserve more attention in the future biomedical graph analysis. Compared with three state-of-the-art methods for DDAs, DDIs and protein function predictions, the recent graph embedding methods achieve competitive performance without using any biological features and the learned embeddings can be treated as complementary representations for the biological features. By summarizing the experimental results, we provide general guidelines for properly selecting graph embedding methods and setting their hyper-parameters for different biomedical tasks. AVAILABILITY AND IMPLEMENTATION: As part of our contributions in the paper, we develop an easy-to-use Python package with detailed instructions, BioNEV, available at: https://github.com/xiangyue9607/BioNEV, including all source code and datasets, to facilitate studying various graph embedding methods on biomedical tasks. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The recent years have witnessed a surge of interests in data analytics with patient Electronic Health Records (EHR). Data-driven healthcare, which aims at effective utilization of big medical data, representing the collective learning in treating hundreds of millions of patients, to provide the best and most personalized care, is believed to be one of the most promising directions for transforming healthcare. EHR is one of the major carriers for make this data-driven healthcare revolution successful. There are many challenges on working directly with EHR, such as temporality, sparsity, noisiness, bias, etc. Thus effective feature extraction, or phenotyping from patient EHRs is a key step before any further applications. In this paper, we propose a deep learning approach for phenotyping from patient EHRs. We first represent the EHRs for every patient as a temporal matrix with time on one dimension and event on the other dimension. Then we build a four-layer convolutional neural network model for extracting phenotypes and perform prediction. The first layer is composed of those EHR matrices. The second layer is a one-side convolution layer that can extract phenotypes from the first layer. The third layer is a max pooling layer introducing sparsity on the detected phenotypes, so that only those significant phenotypes will remain. The fourth layer is a fully connected softmax prediction layer. In order to incorporate the temporal smoothness of the patient EHR, we also investigated three different temporal fusion mechanisms in the model: early fusion, late fusion and slow fusion. Finally the proposed model is validated on a real world EHR data warehouse under the specific scenario of predictive modeling of chronic diseases.

Drug-drug interaction (DDI) is an important topic for public health, and thus attracts attention from both academia and industry. Here we hypothesize that clinical side effects (SEs) provide a human phenotypic profile and can be translated into the development of computational models for predicting adverse DDIs. We propose an integrative label propagation framework to predict DDIs by integrating SEs extracted from package inserts of prescription drugs, SEs extracted from FDA Adverse Event Reporting System, and chemical structures from PubChem. Experimental results based on hold-out validation demonstrated the effectiveness of the proposed algorithm. In addition, the new algorithm also ranked drug information sources based on their contributions to the prediction, thus not only confirming that SEs are important features for DDI prediction but also paving the way for building more reliable DDI prediction models by prioritizing multiple data sources. By applying the proposed algorithm to 1,626 small-molecule drugs which have one or more SE profiles, we obtained 145,068 predicted DDIs. The predicted DDIs will help clinicians to avoid hazardous drug interactions in their prescriptions and will aid pharmaceutical companies to design large-scale clinical trial by assessing potentially hazardous drug combinations. All data sets and predicted DDIs are available at http://astro.temple.edu/~tua87106/ddi.html.

The identification of drug-target interactions (DTIs) is a key task in drug discovery, where drugs are chemical compounds and targets are proteins. Traditional DTI prediction methods are either time consuming (simulation-based methods) or heavily dependent on domain expertise (similarity-based and feature-based methods). In this work, we propose an end-to-end neural network model that predicts DTIs directly from low level representations. In addition to making predictions, our model provides biological interpretation using two-way attention mechanism. Instead of using simplified settings where a dataset is evaluated as a whole, we designed an evaluation dataset from BindingDB following more realistic settings where predictions of unobserved examples (proteins and drugs) have to be made. We experimentally compared our model with matrix factorization, similarity-based methods, and a previous deep learning approach. Overall, the results show that our model outperforms other approaches without requiring domain knowledge and feature engineering. In a case study, we illustrated the ability of our approach to provide biological insights to interpret the predictions.