Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Feasibility of constructing multi-dimensional genomic maps of juvenile idiopathic arthritis

Lisha Zhu, Kaiyu Jiang, Laiping Wong, Michael J. Buck, Yanmin Chen, View ORCID ProfileHalima Moncrieffe, Laura A. McIntosh, Kathleen M. O’Neil, Tao Liu, Xiaoyun Xing, Daofeng Li, Ting Wang, James N. Jarvis
doi: https://doi.org/10.1101/349811
Lisha Zhu
1Department of Biochemistry, University at Buffalo, Center for Excellence in Bioinformatics and Life Sciences, 701 Ellicott St, Buffalo, NY 14203
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kaiyu Jiang
2Department of Pediatrics, Pediatric Rheumatology Research, Clinical & Translational Research Ctr, 875 Ellicott St., University at Buffalo, Buffalo, NY 14203
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laiping Wong
2Department of Pediatrics, Pediatric Rheumatology Research, Clinical & Translational Research Ctr, 875 Ellicott St., University at Buffalo, Buffalo, NY 14203
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael J. Buck
1Department of Biochemistry, University at Buffalo, Center for Excellence in Bioinformatics and Life Sciences, 701 Ellicott St, Buffalo, NY 14203
3Graduate Program in Genetics, Genomics, & Bioinformatics, University at Buffalo, Center for Excellence in Bioinformatics and Life Sciences, 701 Ellicott St, Buffalo, NY 14203
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yanmin Chen
2Department of Pediatrics, Pediatric Rheumatology Research, Clinical & Translational Research Ctr, 875 Ellicott St., University at Buffalo, Buffalo, NY 14203
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Halima Moncrieffe
4Center for Autoimmune Genomics & Etiology, Cincinnati Children’s Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229
5Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45229.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Halima Moncrieffe
Laura A. McIntosh
4Center for Autoimmune Genomics & Etiology, Cincinnati Children’s Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathleen M. O’Neil
6Department of Pediatrics, Division of Pediatric Rheumatology, 699 Riley Hospital Dr, Indianapolis, IN, 46202
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tao Liu
1Department of Biochemistry, University at Buffalo, Center for Excellence in Bioinformatics and Life Sciences, 701 Ellicott St, Buffalo, NY 14203
3Graduate Program in Genetics, Genomics, & Bioinformatics, University at Buffalo, Center for Excellence in Bioinformatics and Life Sciences, 701 Ellicott St, Buffalo, NY 14203
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jamesjar@buffalo.edu tliu4@buffalo.edu
Xiaoyun Xing
7Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Ave, St. Louis, MO 63108
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daofeng Li
7Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Ave, St. Louis, MO 63108
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ting Wang
7Department of Genetics, Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 4515 McKinley Ave, St. Louis, MO 63108
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James N. Jarvis
2Department of Pediatrics, Pediatric Rheumatology Research, Clinical & Translational Research Ctr, 875 Ellicott St., University at Buffalo, Buffalo, NY 14203
3Graduate Program in Genetics, Genomics, & Bioinformatics, University at Buffalo, Center for Excellence in Bioinformatics and Life Sciences, 701 Ellicott St, Buffalo, NY 14203
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jamesjar@buffalo.edu tliu4@buffalo.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Background Juvenile idiopathic arthritis (JIA) is one of the most common chronic conditions of childhood. Like many common chronic human illnesses, JIA likely involves complex interactions between genes and the environment, mediated by the epigenome. Such interactions are best understood through multi-dimensional genomic maps that identify critical genetic and epigenetic components of the disease. However, constructing such maps in a cost-effective way is challenging, and this challenge is further complicated by the challenge of obtaining biospecimens from pediatric patients at time of disease diagnosis, prior to therapy, as well as the limited quantity of biospecimen that can be obtained from children,particularly those who are unwell. In this paper, we demonstrate the feasibility and utility of creating multi-dimensional genomic maps for JIA from limited sample numbers.

Methods To accomplish our aims, we used an approach similar to that used in the ENCODE and Roadmap Epigenomics projects, which used only 2 replicates for each component of the genomic maps. We used genome-wide DNA methylation sequencing, whole genome sequencing on the Illumina 10x platform, RNA sequencing, and chromatin immunoprecipitation-sequencing for informative histone marks (H3K4me1 and H3K27ac) to construct a multi-dimensional map of JIA neutrophils, a cell we have shown to be important in the pathobiology of JIA.

Results The epigenomes of JIA neutrophils display numerous differences from those from healthy children. DNA methylation changes, however, had only a weak effect on differential gene expression. In contrast, H3K4me1 and H3K27ac, commonly associated with enhancer functions, strongly correlated with gene expression. Furthermore, although unique/novel enhancer marks were associated with insertion-deletion events (indels) identified on whole genome sequencing, we saw no strong association between epigenetic changes and underlying genetic variation. The initiation of treatment in JIA is associated with a re-ordering of both DNA methylation and histone modifications, demonstrating the plasticity of the epigenome in this setting.

Conclusions These findings, generated from a small number of patient samples, demonstrate how multidimensional genomic studies may yield new understandings of biology of JIA and provide insight into how therapy alters gene expression patterns.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted June 18, 2018.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Feasibility of constructing multi-dimensional genomic maps of juvenile idiopathic arthritis
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Feasibility of constructing multi-dimensional genomic maps of juvenile idiopathic arthritis
Lisha Zhu, Kaiyu Jiang, Laiping Wong, Michael J. Buck, Yanmin Chen, Halima Moncrieffe, Laura A. McIntosh, Kathleen M. O’Neil, Tao Liu, Xiaoyun Xing, Daofeng Li, Ting Wang, James N. Jarvis
bioRxiv 349811; doi: https://doi.org/10.1101/349811
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Feasibility of constructing multi-dimensional genomic maps of juvenile idiopathic arthritis
Lisha Zhu, Kaiyu Jiang, Laiping Wong, Michael J. Buck, Yanmin Chen, Halima Moncrieffe, Laura A. McIntosh, Kathleen M. O’Neil, Tao Liu, Xiaoyun Xing, Daofeng Li, Ting Wang, James N. Jarvis
bioRxiv 349811; doi: https://doi.org/10.1101/349811

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3573)
  • Biochemistry (7517)
  • Bioengineering (5479)
  • Bioinformatics (20675)
  • Biophysics (10257)
  • Cancer Biology (7931)
  • Cell Biology (11578)
  • Clinical Trials (138)
  • Developmental Biology (6563)
  • Ecology (10135)
  • Epidemiology (2065)
  • Evolutionary Biology (13537)
  • Genetics (9497)
  • Genomics (12788)
  • Immunology (7870)
  • Microbiology (19451)
  • Molecular Biology (7613)
  • Neuroscience (41871)
  • Paleontology (306)
  • Pathology (1252)
  • Pharmacology and Toxicology (2179)
  • Physiology (3249)
  • Plant Biology (7005)
  • Scientific Communication and Education (1291)
  • Synthetic Biology (1942)
  • Systems Biology (5405)
  • Zoology (1107)