Graph Representation Learning in Biomedicine

Biomedical networks are universal descriptors of systems of interacting elements, from protein interactions to disease networks, all the way to healthcare systems and scientific knowledge. With the remarkable success of representation learning in providing powerful predictions and insights, we have witnessed a rapid expansion of representation learning techniques into modeling, analyzing, and learning with such networks. In this review, we put forward an observation that long-standing principles of networks in biology and medicine -- while often unspoken in machine learning research -- can provide the conceptual grounding for representation learning, explain its current successes and limitations, and inform future advances. We synthesize a spectrum of algorithmic approaches that, at their core, leverage graph topology to embed networks into compact vector spaces, and capture the breadth of ways in which representation learning is proving useful. Areas of profound impact include identifying variants underlying complex traits, disentangling behaviors of single cells and their effects on health, assisting in diagnosis and treatment of patients, and developing safe and effective medicines

A representation learning model based on variational inference and graph autoencoder for predicting lncRNA‑disease associations

Background: Numerous studies have demonstrated that long non-coding RNAs are related to plenty of human diseases. Therefore, it is crucial to predict potential lncRNAdisease associations for disease prognosis, diagnosis and therapy. Dozens of machine learning and deep learning algorithms have been adopted to this problem, yet it is still challenging to learn efficient low-dimensional representations from high-dimensional features of lncRNAs and diseases to predict unknown lncRNA-disease associations accurately. Results: We proposed an end-to-end model, VGAELDA, which integrates variational inference and graph autoencoders for lncRNA-disease associations prediction. VGAELDA contains two kinds of graph autoencoders. Variational graph autoencoders (VGAE) infer representations from features of lncRNAs and diseases respectively, while graph autoencoders propagate labels via known lncRNA-disease associations. These two kinds of autoencoders are trained alternately by adopting variational expectation maximization algorithm. The integration of both the VGAE for graph representation learning, and the alternate training via variational inference, strengthens the capability of VGAELDA to capture efficient low-dimensional representations from high-dimensional features, and hence promotes the robustness and preciseness for predicting unknown lncRNA-disease associations. Further analysis illuminates that the designed co-training framework of lncRNA and disease for VGAELDA solves a geometric matrix completion problem for capturing efficient low-dimensional representations via a deep learning approach. Conclusion: Cross validations and numerical experiments illustrate that VGAELDA outperforms the current state-of-the-art methods in lncRNA-disease association prediction. Case studies indicate that VGAELDA is capable of detecting potential lncRNAdisease associations. The source code and data are available at https:// github. com/ zhang labNKU/ VGAEL DA

Advancing Biomedicine with Graph Representation Learning: Recent Progress, Challenges, and Future Directions

Graph representation learning (GRL) has emerged as a pivotal field that has contributed significantly to breakthroughs in various fields, including biomedicine. The objective of this survey is to review the latest advancements in GRL methods and their applications in the biomedical field. We also highlight key challenges currently faced by GRL and outline potential directions for future research.Comment: Accepted by 2023 IMIA Yearbook of Medical Informatic

Machine Learning Methods for Effectively Discovering Complex Relationships in Graph Data

Graphs are extensively employed in many systems due to their capability to capture the interactions (edges) among data (nodes) in many real-life scenarios. Social networks, biological networks and molecular graphs are some of the domains where data have inherent graph structural information. Built graphs can be used to make predictions in Machine Learning (ML) such as node classifications, link predictions, graph classifications, etc. But, existing ML algorithms hold a core assumption that data instances are independent of each other and hence prevent incorporating graph information into ML. This irregular and variable sized nature of non-Euclidean data makes learning underlying patterns of the graph more sophisticated. One approach is to convert the graph information into a lower dimensional space and use traditional learning methods on the reduced space. Meanwhile, Deep Learning has better performance than ML due to convolutional layers and recurrent layers which consider simple correlations in spatial and temporal data, respectively. This proves the importance of taking data interrelationships into account and Graph Convolutional Networks (GCNs) are inspired by this fact to exploit the structure of graphs to make better inference in both node-centric and graph-centric applications. In this dissertation, the graph based ML prediction is addressed in terms of both node classification and link prediction tasks. At first, GCN is thoroughly studied and compared with other graph embedding methods specific to biological networks. Next, we present several new GCN algorithms to improve the prediction performance related to biomedical networks and medical imaging tasks. A circularRNA (circRNA) and disease association network is modeled for both node classification and link prediction tasks to predict diseases relevant to circRNAs to demonstrate the effectiveness of graph convolutional learning. A GCN based chest X-ray image classification outperforms state-of-the-art transfer learning methods. Next, the graph representation is used to analyze the feature dependencies of data and select an optimal feature subset which respects the original data structure. Finally, the usability of this algorithm is discussed in identifying disease specific genes by exploiting gene-gene interactions