Autor(es): Vilela, Joana ; Asif, Muhammad ; Marques, Ana Rita ; Santos, João Xavier ; Rasga, Célia ; Vicente, Astrid ; Martiniano, Hugo
Data: 2022
Identificador Persistente: http://hdl.handle.net/10400.18/8498
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): Autism Spectrum Disorder; Gene-disease Associations; Knowledge Graph Embedding; Personalized Medicine; Perturbações do Desenvolvimento Infantil e Saúde Mental; Autismo
Personalized medicine is a concept that has been subject of increasing interest in medical research and practice in the last few years. However, significant challenges stand in the way of practical implementations, namely in regard to extracting clinically valuable insights from the vast amount of biomedical knowledge generated in the last few years. Here, we describe an approach that uses Knowledge Graph Embedding (KGE) methods on a biomedical Knowledge Graph (KG) as a path to reasoning over the wealth of information stored in publicly accessible databases. We built a Knowledge Graph using data from DisGeNET and GO, containing relationships between genes, diseases and other biological entities. The KG contains 93,657 nodes of 5 types and 1,705,585 relationships of 59 types. We applied KGE methods to this KG, obtaining an excellent performance in predicting gene-disease associations (MR 0.13, MRR 0.96, HITS@1 0.93, HITS@3 0.99, and HITS@10 0.99). The optimal hyperparameter set was used to predict all possible novel gene-disease associations. An in-depth analysis of novel gene-disease predictions for disease terms related to Autism Spectrum Disorder (ASD) shows that this approach produces predictions consistent with known candidate genes and biological pathways and yields relevant insights into the biology of this paradigmatic complex disorder.
