Dataset Information

A Method to Learn Embedding of a Probabilistic Medical Knowledge Graph: Algorithm Development.

ABSTRACT: BACKGROUND:Knowledge graph embedding is an effective semantic representation method for entities and relations in knowledge graphs. Several translation-based algorithms, including TransE, TransH, TransR, TransD, and TranSparse, have been proposed to learn effective embedding vectors from typical knowledge graphs in which the relations between head and tail entities are deterministic. However, in medical knowledge graphs, the relations between head and tail entities are inherently probabilistic. This difference introduces a challenge in embedding medical knowledge graphs. OBJECTIVE:We aimed to address the challenge of how to learn the probability values of triplets into representation vectors by making enhancements to existing TransX (where X is E, H, R, D, or Sparse) algorithms, including the following: (1) constructing a mapping function between the score value and the probability, and (2) introducing probability-based loss of triplets into the original margin-based loss function. METHODS:We performed the proposed PrTransX algorithm on a medical knowledge graph that we built from large-scale real-world electronic medical records data. We evaluated the embeddings using link prediction task. RESULTS:Compared with the corresponding TransX algorithms, the proposed PrTransX performed better than the TransX model in all evaluation indicators, achieving a higher proportion of corrected entities ranked in the top 10 and normalized discounted cumulative gain of the top 10 predicted tail entities, and lower mean rank. CONCLUSIONS:The proposed PrTransX successfully incorporated the uncertainty of the knowledge triplets into the embedding vectors.

SUBMITTER: Li L

PROVIDER: S-EPMC7273238 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A Method to Learn Embedding of a Probabilistic Medical Knowledge Graph: Algorithm Development.

Li Linfeng L Wang Peng P Wang Yao Y Wang Shenghui S Yan Jun J Jiang Jinpeng J Tang Buzhou B Wang Chengliang C Liu Yuting Y

JMIR medical informatics 20200521 5

<h4>Background</h4>Knowledge graph embedding is an effective semantic representation method for entities and relations in knowledge graphs. Several translation-based algorithms, including TransE, TransH, TransR, TransD, and TranSparse, have been proposed to learn effective embedding vectors from typical knowledge graphs in which the relations between head and tail entities are deterministic. However, in medical knowledge graphs, the relations between head and tail entities are inherently probabi ...[more]

PMID: 32436854

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Project description:Advances in machine learning and deep learning methods, together with the increasing availability of large-scale pharmacological, genomic, and chemical datasets, have created opportunities for identifying potentially useful relationships within biochemical networks. Knowledge embedding models have been found to have value in detecting knowledge-based correlations among entities, but little effort has been made to apply them to networks of biochemical entities. This is because such networks tend to be unbalanced and sparse, and knowledge embedding models do not work well on them. However, to some extent, the shortcomings of knowledge embedding models can be compensated for if they are used in association with graph embedding. In this paper, we combine knowledge embedding and graph embedding to represent biochemical entities and their relations as dense and low-dimensional vectors. We build a cascade learning framework which incorporates semantic features from the knowledge embedding model, and graph features from the graph embedding model, to score the probability of linking. The proposed method performs noticeably better than the models with which it is compared. It predicted links and entities with an accuracy of 93%, and its average hits@10 score has an average of 8.6% absolute improvement compared with original knowledge embedding model, 1.1% to 9.7% absolute improvement compared with other knowledge and graph embedding algorithm. In addition, we designed a meta-path algorithm to detect path relations in the biomedical network. Case studies further verify the value of the proposed model in finding potential relationships between diseases, drugs, genes, treatments, etc. Amongst the findings of the proposed model are the suggestion that VDR (vitamin D receptor) may be linked to prostate cancer. This is backed by evidence from medical databases and published research, supporting the suggestion that our proposed model could be of value to biomedical researchers.

Project description:BACKGROUND:Combination therapy plays an important role in the effective treatment of malignant neoplasms and precision medicine. Numerous clinical studies have been carried out to investigate combination drug therapies. Automated knowledge discovery of these combinations and their graphic representation in knowledge graphs will enable pattern recognition and identification of drug combinations used to treat a specific type of cancer, improve drug efficacy and treatment of human disorders. OBJECTIVE:This paper aims to develop an automated, visual approach to discover knowledge about combination therapies from biomedical literature, especially from those studies with high-level evidence such as clinical trial reports and clinical practice guidelines. METHODS:Based on semantic predications, which consist of a triple structure of subject-predicate-object (SPO), we proposed an automated algorithm to discover knowledge of combination drug therapies using the following rules: 1) two or more semantic predications (S1-P-O and Si-P-O, i = 2, 3…) can be extracted from one conclusive claim (sentence) in the abstract of a given publication, and 2) these predications have an identical predicate (that closely relates to human disease treatment, eg, "treat") and object (eg, disease name) but different subjects (eg, drug names). A customized knowledge graph organizes and visualizes these combinations, improving the traditional semantic triples. After automatic filtering of broad concepts such as "pharmacologic actions" and generic disease names, a set of combination drug therapies were identified and characterized through manual interpretation. RESULTS:We retrieved 22,263 clinical trial reports and 31 clinical practice guidelines from PubMed abstracts by searching "antineoplastic agents" for drug restriction (published between Jan 2009 and Oct 2019). There were 15,603 conclusive claims locally parsed using the search terms "conclusion*" and "conclude*" ready for semantic predications extraction by SemRep, and 325 candidate groups of semantic predications about combined medications were automatically discovered within 316 conclusive claims. Based on manual analysis, we determined that 255/316 claims (78.46%) were accurately identified as describing combination therapies and adopted these to construct the customized knowledge graph. We also identified two categories (and 4 subcategories) to characterize the inaccurate results: limitations of SemRep and limitations of proposal. We further learned the predominant patterns of drug combinations based on mechanism of action for new combined medication studies and discovered 4 obvious markers ("combin*," "coadministration," "co-administered," and "regimen") to identify potential combination therapies to enable development of a machine learning algorithm. CONCLUSIONS:Semantic predications from conclusive claims in the biomedical literature can be used to support automated knowledge discovery and knowledge graph construction for combination therapies. A machine learning approach is warranted to take full advantage of the identified markers and other contextual features.

Project description:BackgroundThe pharmaceutical field faces a significant challenge in validating drug target interactions (DTIs) due to the time and cost involved, leading to only a fraction being experimentally verified. To expedite drug discovery, accurate computational methods are essential for predicting potential interactions. Recently, machine learning techniques, particularly graph-based methods, have gained prominence. These methods utilize networks of drugs and targets, employing knowledge graph embedding (KGE) to represent structured information from knowledge graphs in a continuous vector space. This phenomenon highlights the growing inclination to utilize graph topologies as a means to improve the precision of predicting DTIs, hence addressing the pressing requirement for effective computational methodologies in the field of drug discovery.ResultsThe present study presents a novel approach called DTIOG for the prediction of DTIs. The methodology employed in this study involves the utilization of a KGE strategy, together with the incorporation of contextual information obtained from protein sequences. More specifically, the study makes use of Protein Bidirectional Encoder Representations from Transformers (ProtBERT) for this purpose. DTIOG utilizes a two-step process to compute embedding vectors using KGE techniques. Additionally, it employs ProtBERT to determine target-target similarity. Different similarity measures, such as Cosine similarity or Euclidean distance, are utilized in the prediction procedure. In addition to the contextual embedding, the proposed unique approach incorporates local representations obtained from the Simplified Molecular Input Line Entry Specification (SMILES) of drugs and the amino acid sequences of protein targets.ConclusionsThe effectiveness of the proposed approach was assessed through extensive experimentation on datasets pertaining to Enzymes, Ion Channels, and G-protein-coupled Receptors. The remarkable efficacy of DTIOG was showcased through the utilization of diverse similarity measures in order to calculate the similarities between drugs and targets. The combination of these factors, along with the incorporation of various classifiers, enabled the model to outperform existing algorithms in its ability to predict DTIs. The consistent observation of this advantage across all datasets underlines the robustness and accuracy of DTIOG in the domain of DTIs. Additionally, our case study suggests that the DTIOG can serve as a valuable tool for discovering new DTIs.

Dataset Information

A Method to Learn Embedding of a Probabilistic Medical Knowledge Graph: Algorithm Development.

Publications

A Method to Learn Embedding of a Probabilistic Medical Knowledge Graph: Algorithm Development.

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