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Open Access 01-05-2018 | Metabolomics

Integration of genomics and metabolomics for prioritization of rare disease variants: a 2018 literature review

Authors: Emma Graham, Jessica Lee, Magda Price, Maja Tarailo-Graovac, Allison Matthews, Udo Engelke, Jeffrey Tang, Leo A. J. Kluijtmans, Ron A. Wevers, Wyeth W. Wasserman, Clara D. M. van Karnebeek, Sara Mostafavi

Published in: Journal of Inherited Metabolic Disease | Issue 3/2018

Abstract

Many inborn errors of metabolism (IEMs) are amenable to treatment; therefore, early diagnosis and treatment is imperative. Despite recent advances, the genetic basis of many metabolic phenotypes remains unknown. For discovery purposes, whole exome sequencing (WES) variant prioritization coupled with clinical and bioinformatics expertise is the primary method used to identify novel disease-causing variants; however, causation is often difficult to establish due to the number of plausible variants. Integrated analysis of untargeted metabolomics (UM) and WES or whole genome sequencing (WGS) data is a promising systematic approach for identifying disease-causing variants. In this review, we provide a literature-based overview of UM methods utilizing liquid chromatography mass spectrometry (LC-MS), and assess approaches to integrating WES/WGS and LC-MS UM data for the discovery and prioritization of variants causing IEMs. To embed this integrated -omics approach in the clinic, expansion of gene-metabolite annotations and metabolomic feature-to-metabolite mapping methods are needed.

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Title: Integration of genomics and metabolomics for prioritization of rare disease variants: a 2018 literature review
Authors: Emma Graham
Jessica Lee
Magda Price
Maja Tarailo-Graovac
Allison Matthews
Udo Engelke
Jeffrey Tang
Leo A. J. Kluijtmans
Ron A. Wevers
Wyeth W. Wasserman
Clara D. M. van Karnebeek
Sara Mostafavi
Publication date: 01-05-2018
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 3/2018
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-018-0139-6

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