Relation Prediction over Biomedical Knowledge Bases for Drug Repositioning

Identifying new potential treatment options for medical conditions that cause human disease burden is a central task of biomedical research. Since all candidate drugs cannot be tested with animal and clinical trials, in vitro approaches are first attempted to identify promising candidates. Likewise, identifying other essential relations (e.g., causation, prevention) between biomedical entities is also critical to understand biomedical processes. Hence, it is crucial to develop automated relation prediction systems that can yield plausible biomedical relations to expedite the discovery process. In this dissertation, we demonstrate three approaches to predict treatment relations between biomedical entities for the drug repositioning task using existing biomedical knowledge bases. Our approaches can be broadly labeled as link prediction or knowledge base completion in computer science literature. Specifically, first we investigate the predictive power of graph paths connecting entities in the publicly available biomedical knowledge base, SemMedDB (the entities and relations constitute a large knowledge graph as a whole). To that end, we build logistic regression models utilizing semantic graph pattern features extracted from the SemMedDB to predict treatment and causative relations in Unified Medical Language System (UMLS) Metathesaurus. Second, we study matrix and tensor factorization algorithms for predicting drug repositioning pairs in repoDB, a general purpose gold standard database of approved and failed drug–disease indications. The idea here is to predict repoDB pairs by approximating the given input matrix/tensor structure where the value of a cell represents the existence of a relation coming from SemMedDB and UMLS knowledge bases. The essential goal is to predict the test pairs that have a blank cell in the input matrix/tensor based on the shared biomedical context among existing non-blank cells. Our final approach involves graph convolutional neural networks where entities and relation types are embedded in a vector space involving neighborhood information. Basically, we minimize an objective function to guide our model to concept/relation embeddings such that distance scores for positive relation pairs are lower than those for the negative ones. Overall, our results demonstrate that recent link prediction methods applied to automatically curated, and hence imprecise, knowledge bases can nevertheless result in high accuracy drug candidate prediction with appropriate configuration of both the methods and datasets used

Knowledge-based Biomedical Data Science 2019

Knowledge-based biomedical data science (KBDS) involves the design and implementation of computer systems that act as if they knew about biomedicine. Such systems depend on formally represented knowledge in computer systems, often in the form of knowledge graphs. Here we survey the progress in the last year in systems that use formally represented knowledge to address data science problems in both clinical and biological domains, as well as on approaches for creating knowledge graphs. Major themes include the relationships between knowledge graphs and machine learning, the use of natural language processing, and the expansion of knowledge-based approaches to novel domains, such as Chinese Traditional Medicine and biodiversity.Comment: Manuscript 43 pages with 3 tables; Supplemental material 43 pages with 3 table

Computational and human-based methods for knowledge discovery over knowledge graphs

The modern world has evolved, accompanied by the huge exploitation of data and information. Daily, increasing volumes of data from various sources and formats are stored, resulting in a challenging strategy to manage and integrate them to discover new knowledge. The appropriate use of data in various sectors of society, such as education, healthcare, e-commerce, and industry, provides advantages for decision support in these areas. However, knowledge discovery becomes challenging since data may come from heterogeneous sources with important information hidden. Thus, new approaches that adapt to the new challenges of knowledge discovery in such heterogeneous data environments are required. The semantic web and knowledge graphs (KGs) are becoming increasingly relevant on the road to knowledge discovery. This thesis tackles the problem of knowledge discovery over KGs built from heterogeneous data sources. We provide a neuro-symbolic artificial intelligence system that integrates symbolic and sub-symbolic frameworks to exploit the semantics encoded in a KG and its structure. The symbolic system relies on existing approaches of deductive databases to make explicit, implicit knowledge encoded in a KG. The proposed deductive database $DS$ can derive new statements to ego networks given an abstract target prediction. Thus, $DS$ minimizes data sparsity in KGs. In addition, a sub-symbolic system relies on knowledge graph embedding (KGE) models. KGE models are commonly applied in the KG completion task to represent entities in a KG in a low-dimensional vector space. However, KGE models are known to suffer from data sparsity, and a symbolic system assists in overcoming this fact. The proposed approach discovers knowledge given a target prediction in a KG and extracts unknown implicit information related to the target prediction. As a proof of concept, we have implemented the neuro-symbolic system on top of a KG for lung cancer to predict polypharmacy treatment effectiveness. The symbolic system implements a deductive system to deduce pharmacokinetic drug-drug interactions encoded in a set of rules through the Datalog program. Additionally, the sub-symbolic system predicts treatment effectiveness using a KGE model, which preserves the KG structure. An ablation study on the components of our approach is conducted, considering state-of-the-art KGE methods. The observed results provide evidence for the benefits of the neuro-symbolic integration of our approach, where the neuro-symbolic system for an abstract target prediction exhibits improved results. The enhancement of the results occurs because the symbolic system increases the prediction capacity of the sub-symbolic system. Moreover, the proposed neuro-symbolic artificial intelligence system in Industry 4.0 (I4.0) is evaluated, demonstrating its effectiveness in determining relatedness among standards and analyzing their properties to detect unknown relations in the I4.0KG. The results achieved allow us to conclude that the proposed neuro-symbolic approach for an abstract target prediction improves the prediction capability of KGE models by minimizing data sparsity in KGs

Mining health knowledge graph for health risk prediction

Nowadays classification models have been widely adopted in healthcare, aiming at supporting practitioners for disease diagnosis and human error reduction. The challenge is utilising effective methods to mine real-world data in the medical domain, as many different models have been proposed with varying results. A large number of researchers focus on the diversity problem of real-time data sets in classification models. Some previous works developed methods comprising of homogeneous graphs for knowledge representation and then knowledge discovery. However, such approaches are weak in discovering different relationships among elements. In this paper, we propose an innovative classification model for knowledge discovery from patients’ personal health repositories. The model discovers medical domain knowledge from the massive data in the National Health and Nutrition Examination Survey (NHANES). The knowledge is conceptualised in a heterogeneous knowledge graph. On the basis of the model, an innovative method is developed to help uncover potential diseases suffered by people and, furthermore, to classify patients’ health risk. The proposed model is evaluated by comparison to a baseline model also built on the NHANES data set in an empirical experiment. The performance of proposed model is promising. The paper makes significant contributions to the advancement of knowledge in data mining with an innovative classification model specifically crafted for domain-based data. In addition, by accessing the patterns of various observations, the research contributes to the work of practitioners by providing a multifaceted understanding of individual and public health

Patient-Centric Knowledge Graphs: A Survey of Current Methods, Challenges, and Applications

Patient-Centric Knowledge Graphs (PCKGs) represent an important shift in healthcare that focuses on individualized patient care by mapping the patient's health information in a holistic and multi-dimensional way. PCKGs integrate various types of health data to provide healthcare professionals with a comprehensive understanding of a patient's health, enabling more personalized and effective care. This literature review explores the methodologies, challenges, and opportunities associated with PCKGs, focusing on their role in integrating disparate healthcare data and enhancing patient care through a unified health perspective. In addition, this review also discusses the complexities of PCKG development, including ontology design, data integration techniques, knowledge extraction, and structured representation of knowledge. It highlights advanced techniques such as reasoning, semantic search, and inference mechanisms essential in constructing and evaluating PCKGs for actionable healthcare insights. We further explore the practical applications of PCKGs in personalized medicine, emphasizing their significance in improving disease prediction and formulating effective treatment plans. Overall, this review provides a foundational perspective on the current state-of-the-art and best practices of PCKGs, guiding future research and applications in this dynamic field

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