title: A Next Generation Multiscale View of Inborn Errors of Metabolism.
abstract: Inborn errors of metabolism (IEM) are not unlike common diseases. They often present as a spectrum of disease phenotypes that correlates poorly with the severity of the disease-causing mutations. This greatly impacts patient care and reveals fundamental gaps in our knowledge of disease modifying biology. Systems biology approaches that integrate multi-omics data into molecular networks have significantly improved our understanding of complex diseases. Similar approaches to study IEM are rare despite their complex nature. We highlight that existing common disease-derived datasets and networks can be repurposed to generate novel mechanistic insight in IEM and potentially identify candidate modifiers. While understanding disease pathophysiology will advance the IEM field, the ultimate goal should be to understand per individual how their phenotype emerges given their primary mutation on the background of their whole genome, not unlike personalized medicine. We foresee that panomics and network strategies combined with recent experimental innovations will facilitate this.
authors.affiliation: Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, New York, NY 10029, USA. Electronic address: carmen.argmann@mssm.edu.
authors.forename: Carmen A
authors.initials: CA
authors.lastname: Argmann
authors.affiliation: Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, New York, NY 10029, USA.
authors.forename: Sander M
authors.initials: SM
authors.lastname: Houten
authors.affiliation: Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, New York, NY 10029, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, New York, NY 10029, USA. Electronic address: eric.schadt@mssm.edu.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
mesh_terms: D000818:Animals; D053263:Gene Regulatory Networks; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D059467:Transcriptome
keywords: human genetic disease; metabolism; network biology; omics