Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes
Abstract Background The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disea...
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doaj-222e6d8caa7d414bab3c617c18e902122021-01-24T12:44:20ZengBMCGenome Biology1474-760X2021-01-0122112710.1186/s13059-021-02262-wIntegrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetesLeandro Balzano-Nogueira0Ricardo Ramirez1Tatyana Zamkovaya2Jordan Dailey3Alexandria N. Ardissone4Srikar Chamala5Joan Serrano-Quílez6Teresa Rubio7Michael J. Haller8Patrick Concannon9Mark A. Atkinson10Desmond A. Schatz11Eric W. Triplett12Ana Conesa13Microbiology and Cell Science Department, Institute for Food and Agricultural Sciences, University of FloridaMicrobiology and Cell Science Department, Institute for Food and Agricultural Sciences, University of FloridaMicrobiology and Cell Science Department, Institute for Food and Agricultural Sciences, University of FloridaMicrobiology and Cell Science Department, Institute for Food and Agricultural Sciences, University of FloridaMicrobiology and Cell Science Department, Institute for Food and Agricultural Sciences, University of FloridaDepartment of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes InstituteGene Expression and RNA Metabolism Laboratory, Instituto de Biomedicina de Valencia (CSIC)Laboratory of Neurobiology, Prince Felipe Research CenterDepartment of Pediatrics, University of Florida Diabetes InstituteDepartment of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes InstituteDepartment of Pediatrics, University of Florida Diabetes InstituteDepartment of Pediatrics, University of Florida Diabetes InstituteMicrobiology and Cell Science Department, Institute for Food and Agricultural Sciences, University of FloridaMicrobiology and Cell Science Department, Institute for Food and Agricultural Sciences, University of FloridaAbstract Background The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time. Results We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion. At this time, abnormalities in lipid metabolism, decreased capacity for nutrient absorption, and intracellular ROS accumulation are detected in children progressing towards IA. Additionally, extracellular matrix remodeling, inflammation, cytotoxicity, angiogenesis, and increased activity of antigen-presenting cells are observed, which may contribute to beta cell destruction. Our results indicate that altered molecular homeostasis is present in IA-developing children months before the actual detection of islet autoantibodies, which opens an interesting window of opportunity for therapeutic intervention. Conclusions The approach employed herein for assessment of the TEDDY cohort showcases the utilization of multi-omics data for the modeling of complex, multifactorial diseases, like T1D.https://doi.org/10.1186/s13059-021-02262-w |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leandro Balzano-Nogueira Ricardo Ramirez Tatyana Zamkovaya Jordan Dailey Alexandria N. Ardissone Srikar Chamala Joan Serrano-Quílez Teresa Rubio Michael J. Haller Patrick Concannon Mark A. Atkinson Desmond A. Schatz Eric W. Triplett Ana Conesa |
spellingShingle |
Leandro Balzano-Nogueira Ricardo Ramirez Tatyana Zamkovaya Jordan Dailey Alexandria N. Ardissone Srikar Chamala Joan Serrano-Quílez Teresa Rubio Michael J. Haller Patrick Concannon Mark A. Atkinson Desmond A. Schatz Eric W. Triplett Ana Conesa Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes Genome Biology |
author_facet |
Leandro Balzano-Nogueira Ricardo Ramirez Tatyana Zamkovaya Jordan Dailey Alexandria N. Ardissone Srikar Chamala Joan Serrano-Quílez Teresa Rubio Michael J. Haller Patrick Concannon Mark A. Atkinson Desmond A. Schatz Eric W. Triplett Ana Conesa |
author_sort |
Leandro Balzano-Nogueira |
title |
Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes |
title_short |
Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes |
title_full |
Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes |
title_fullStr |
Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes |
title_full_unstemmed |
Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes |
title_sort |
integrative analyses of teddy omics data reveal lipid metabolism abnormalities, increased intracellular ros and heightened inflammation prior to autoimmunity for type 1 diabetes |
publisher |
BMC |
series |
Genome Biology |
issn |
1474-760X |
publishDate |
2021-01-01 |
description |
Abstract Background The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time. Results We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion. At this time, abnormalities in lipid metabolism, decreased capacity for nutrient absorption, and intracellular ROS accumulation are detected in children progressing towards IA. Additionally, extracellular matrix remodeling, inflammation, cytotoxicity, angiogenesis, and increased activity of antigen-presenting cells are observed, which may contribute to beta cell destruction. Our results indicate that altered molecular homeostasis is present in IA-developing children months before the actual detection of islet autoantibodies, which opens an interesting window of opportunity for therapeutic intervention. Conclusions The approach employed herein for assessment of the TEDDY cohort showcases the utilization of multi-omics data for the modeling of complex, multifactorial diseases, like T1D. |
url |
https://doi.org/10.1186/s13059-021-02262-w |
work_keys_str_mv |
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