Knowledge base and mini-expert platform for the diagnosis of inborn errors of metabolism

Genet Med. 2018 Jan;20(1):151-158. doi: 10.1038/gim.2017.108. Epub 2017 Jul 20.


PurposeRecognizing individuals with inherited diseases can be difficult because signs and symptoms often overlap those of common medical conditions. Focusing on inborn errors of metabolism (IEMs), we present a method that brings the knowledge of highly specialized experts to professionals involved in early diagnoses. We introduce IEMbase, an online expert-curated IEM knowledge base combined with a prototype diagnosis support (mini-expert) system.MethodsDisease-characterizing profiles of specific biochemical markers and clinical symptoms were extracted from an expert-compiled IEM database. A mini-expert system algorithm was developed using cosine similarity and semantic similarity. The system was evaluated using 190 retrospective cases with established diagnoses, collected from 15 different metabolic centers.ResultsIEMbase provides 530 well-defined IEM profiles and matches a user-provided phenotypic profile to a list of candidate diagnoses/genes. The mini-expert system matched 62% of the retrospective cases to the exact diagnosis and 86% of the cases to a correct diagnosis within the top five candidates. The use of biochemical features in IEM annotations resulted in 41% more exact phenotype matches than clinical features alone.ConclusionIEMbase offers a central IEM knowledge repository for many genetic diagnostic centers and clinical communities seeking support in the diagnosis of IEMs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Chromosome Mapping
  • Clinical Decision-Making
  • Databases, Genetic*
  • Expert Testimony*
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Knowledge Bases*
  • Medical Informatics / methods*
  • Metabolism, Inborn Errors / diagnosis*
  • Metabolism, Inborn Errors / genetics*
  • Phenotype
  • ROC Curve
  • Reproducibility of Results
  • Software*