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Cross-Omics: Integrating Genomics with Metabolomics in Clinical Diagnostics
| Content Provider | MDPI |
|---|---|
| Author | Kerkhofs, Marten H. P. M. Haijes, Hanneke A. Willemsen, A. Marcel Gassen, Koen L. I. Van Ham, Maria Van Der Gerrits, Johan Velden, Monique G. M. De Sain-Van Der Prinsen, Hubertus C. M. T. Deutekom, Hanneke W. M. Van Hasselt, Peter M. Van Verhoeven-Duif, Nanda M. Jans, Judith J. M. Kerkhofs, Marten |
| Copyright Year | 2020 |
| Description | Next-generation sequencing and next-generation metabolic screening are, independently, increasingly applied in clinical diagnostics of inborn errors of metabolism (IEM). Integrated into a single bioinformatic method, these two –omics technologies can potentially further improve the diagnostic yield for IEM. Here, we present cross-omics: a method that uses untargeted metabolomics results of patient’s dried blood spots (DBSs), indicated by Z-scores and mapped onto human metabolic pathways, to prioritize potentially affected genes. We demonstrate the optimization of three parameters: (1) maximum distance to the primary reaction of the affected protein, (2) an extension stringency threshold reflecting in how many reactions a metabolite can participate, to be able to extend the metabolite set associated with a certain gene, and (3) a biochemical stringency threshold reflecting paired Z-score thresholds for untargeted metabolomics results. Patients with known IEMs were included. We performed untargeted metabolomics on 168 DBSs of 97 patients with 46 different disease-causing genes, and we simulated their whole-exome sequencing results in silico. We showed that for accurate prioritization of disease-causing genes in IEM, it is essential to take into account not only the primary reaction of the affected protein but a larger network of potentially affected metabolites, multiple steps away from the primary reaction. |
| Starting Page | 206 |
| e-ISSN | 22181989 |
| DOI | 10.3390/metabo10050206 |
| Journal | Metabolites |
| Issue Number | 5 |
| Volume Number | 10 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2020-05-18 |
| Access Restriction | Open |
| Subject Keyword | Metabolites Biochemical Research Cross-omics Untargeted Metabolomics Genomics Diagnostics Data Integration Next-generation Sequencing Next-generation Metabolic Screening |
| Content Type | Text |
| Resource Type | Article |
