High-resolution metabolomics to identify urine biomarkers in corticosteroid-resistant asthmatic children  Youngja H. Park, PhD, Anne M. Fitzpatrick, PhD,

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Presentation transcript:

High-resolution metabolomics to identify urine biomarkers in corticosteroid-resistant asthmatic children  Youngja H. Park, PhD, Anne M. Fitzpatrick, PhD, Carl Angelo Medriano, MEng, Dean P. Jones, PhD  Journal of Allergy and Clinical Immunology  Volume 139, Issue 5, Pages 1518-1524.e4 (May 2017) DOI: 10.1016/j.jaci.2016.08.018 Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Schematic design for biomarker discovery and algorithm development. IM, Intramuscular. Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A, Manhattan plot between CS-R and CS-NR children using FDR q = 0.05; 30 significant features out of 8570 features. B, HCA between CS-R and CS-NR children using the significant features. Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 KEGG pathway with 30 FDR q = 0.05 significant features, a total of 21 hits on KEGG human metabolic pathways. FMN, Flavin mononucleotide. Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Two important urine biomarkers on the GSH pathway. *Significantly different (FDR q < 0.05). Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 The putative biomarkers to discriminate CS-R versus CS-NR children at visit 2. *Significantly different (FDR q < 0.05). Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Mummichog pathway analysis with significant metabolites to determine an important module between CS-R and CS-NR children. *Significantly different (FDR q < 0.05). Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Orthogonal signal correction/partial least square-discriminant analysis on children with mild-to-moderate and severe asthma. Blue, those with mild-to-moderate asthma; Red, those with severe asthma. Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Left, Manhattan plot between children with mild-to-moderate and children with severe asthma using FDR q = 0.05; 119 significant features out of 6963 features. Right, HCA between children with mild-to-moderate and children with severe asthma using the significant features. Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 KEGG pathway with FDR q = 0.05 significant features, a total of 38 hits on KEGG human metabolic pathways between children with mild-to-moderate and children with severe asthma. Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 Bar graph of the compounds between children with mild-to-moderate and children with severe asthma. Journal of Allergy and Clinical Immunology 2017 139, 1518-1524.e4DOI: (10.1016/j.jaci.2016.08.018) Copyright © 2016 American Academy of Allergy, Asthma & Immunology Terms and Conditions