Explainable Graph Neural Network for Alzheimer's Disease And Related Dementias Risk Prediction

Alzheimer's disease and related dementias (ADRD) ranks as the sixth leading cause of death in the US, underlining the importance of accurate ADRD risk prediction. While recent advancement in ADRD risk prediction have primarily relied on imaging analysis, yet not all patients undergo medical imaging before an ADRD diagnosis. Merging machine learning with claims data can reveal additional risk factors and uncover interconnections among diverse medical codes. Our goal is to utilize Graph Neural Networks (GNNs) with claims data for ADRD risk prediction. Addressing the lack of human-interpretable reasons behind these predictions, we introduce an innovative method to evaluate relationship importance and its influence on ADRD risk prediction, ensuring comprehensive interpretation. We employed Variationally Regularized Encoder-decoder Graph Neural Network (VGNN) for estimating ADRD likelihood. We created three scenarios to assess the model's efficiency, using Random Forest and Light Gradient Boost Machine as baselines. We further used our relation importance method to clarify the key relationships for ADRD risk prediction. VGNN surpassed other baseline models by 10% in the area under the receiver operating characteristic. The integration of the GNN model and relation importance interpretation could potentially play an essential role in providing valuable insight into factors that may contribute to or delay ADRD progression. Employing a GNN approach with claims data enhances ADRD risk prediction and provides insights into the impact of interconnected medical code relationships. This methodology not only enables ADRD risk modeling but also shows potential for other image analysis predictions using claims data.

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.

In-Process Global Interpretation for Graph Learning via Distribution Matching

Graphs neural networks (GNNs) have emerged as a powerful graph learning model due to their superior capacity in capturing critical graph patterns. To gain insights about the model mechanism for interpretable graph learning, previous efforts focus on post-hoc local interpretation by extracting the data pattern that a pre-trained GNN model uses to make an individual prediction. However, recent works show that post-hoc methods are highly sensitive to model initialization and local interpretation can only explain the model prediction specific to a particular instance. In this work, we address these limitations by answering an important question that is not yet studied: how to provide global interpretation of the model training procedure? We formulate this problem as in-process global interpretation, which targets on distilling high-level and human-intelligible patterns that dominate the training procedure of GNNs. We further propose Graph Distribution Matching (GDM) to synthesize interpretive graphs by matching the distribution of the original and interpretive graphs in the feature space of the GNN as its training proceeds. These few interpretive graphs demonstrate the most informative patterns the model captures during training. Extensive experiments on graph classification datasets demonstrate multiple advantages of the proposed method, including high explanation accuracy, time efficiency and the ability to reveal class-relevant structure.

Mining On Alzheimer's Diseases Related Knowledge Graph to Identity Potential AD-related Semantic Triples for Drug Repurposing

To date, there are no effective treatments for most neurodegenerative diseases. Knowledge graphs can provide comprehensive and semantic representation for heterogeneous data, and have been successfully leveraged in many biomedical applications including drug repurposing. Our objective is to construct a knowledge graph from literature to study relations between Alzheimer's disease (AD) and chemicals, drugs and dietary supplements in order to identify opportunities to prevent or delay neurodegenerative progression. We collected biomedical annotations and extracted their relations using SemRep via SemMedDB. We used both a BERT-based classifier and rule-based methods during data preprocessing to exclude noise while preserving most AD-related semantic triples. The 1,672,110 filtered triples were used to train with knowledge graph completion algorithms (i.e., TransE, DistMult, and ComplEx) to predict candidates that might be helpful for AD treatment or prevention. Among three knowledge graph completion models, TransE outperformed the other two (MR = 13.45, Hits@1 = 0.306). We leveraged the time-slicing technique to further evaluate the prediction results. We found supporting evidence for most highly ranked candidates predicted by our model which indicates that our approach can inform reliable new knowledge. This paper shows that our graph mining model can predict reliable new relationships between AD and other entities (i.e., dietary supplements, chemicals, and drugs). The knowledge graph constructed can facilitate data-driven knowledge discoveries and the generation of novel hypotheses.

Knowledge Graph-based Neurodegenerative Diseases and Diet Relationship Discovery

To date, there are no effective treatments for most neurodegenerative diseases. However, certain foods may be associated with these diseases and bring an opportunity to prevent or delay neurodegenerative progression. Our objective is to construct a knowledge graph for neurodegenerative diseases using literature mining to study their relations with diet. We collected biomedical annotations (Disease, Chemical, Gene, Species, SNP&Mutation) in the abstracts from 4,300 publications relevant to both neurodegenerative diseases and diet using PubTator, an NIH-supported tool that can extract biomedical concepts from literature. A knowledge graph was created from these annotations. Graph embeddings were then trained with the node2vec algorithm to support potential concept clustering and similar concept identification. We found several food-related species and chemicals that might come from diet and have an impact on neurodegenerative diseases.

AutoML using Metadata Language Embeddings

As a human choosing a supervised learning algorithm, it is natural to begin by reading a text description of the dataset and documentation for the algorithms you might use. We demonstrate that the same idea improves the performance of automated machine learning methods. We use language embeddings from modern NLP to improve state-of-the-art AutoML systems by augmenting their recommendations with vector embeddings of datasets and of algorithms. We use these embeddings in a neural architecture to learn the distance between best-performing pipelines. The resulting (meta-)AutoML framework improves on the performance of existing AutoML frameworks. Our zero-shot AutoML system using dataset metadata embeddings provides good solutions instantaneously, running in under one second of computation. Performance is competitive with AutoML systems OBOE, AutoSklearn, AlphaD3M, and TPOT when each framework is allocated a minute of computation. We make our data, models, and code publicly available.