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

Mapping RNA splicing variations in clinically-accessible and non-accessible tissues to facilitate Mendelian disease diagnosis using RNA-seq

View ORCID ProfileJoseph K Aicher, Paul Jewell, Jorge Vaquero-Garcia, View ORCID ProfileYoseph Barash, View ORCID ProfileElizabeth J Bhoj
doi: https://doi.org/10.1101/727586
Joseph K Aicher
1Department of Genetics, University of Pennsylvania
4Center for Applied Genomics, Children’s Hospital of Philadelphia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Joseph K Aicher
Paul Jewell
1Department of Genetics, University of Pennsylvania
2Department of Computer and Information Science, University of Pennsylvania
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jorge Vaquero-Garcia
1Department of Genetics, University of Pennsylvania
2Department of Computer and Information Science, University of Pennsylvania
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoseph Barash
1Department of Genetics, University of Pennsylvania
2Department of Computer and Information Science, University of Pennsylvania
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yoseph Barash
  • For correspondence: yosephb@upenn.edu bhoje@email.chop.edu
Elizabeth J Bhoj
1Department of Genetics, University of Pennsylvania
3Division of Human Genetics, Children’s Hospital of Philadelphia
4Center for Applied Genomics, Children’s Hospital of Philadelphia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Elizabeth J Bhoj
  • For correspondence: yosephb@upenn.edu bhoje@email.chop.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Purpose RNA-seq is a promising approach to improve diagnoses by detecting pathogenic aberrations in RNA splicing that are missed by DNA sequencing. RNA-seq is typically performed on clinically-accessible tissues (CATs) from blood and skin. RNA tissue-specificity makes it difficult to identify aberrations in relevant but non-accessible tissues (non-CATs). We determined how RNA-seq from CATs represent splicing in and across genes and non-CATs.

Methods We quantified RNA splicing in 801 RNA-seq samples from 56 different adult and fetal tissues from GTEx and ArrayExpress. We identified genes and splicing events in each non-CAT and determined when RNA-seq in each CAT would inadequately represent them. We developed an online resource, MAJIQ-CAT, for exploring our analysis for specific genes and tissues.

Results In non-CATs, 39.7% of genes have splicing that is inadequately represented by at least one CAT. 6.2% of genes have splicing inadequately represented by all CATs. A majority (52.8%) of inadequately represented genes are lowly expressed in CATs (TPM < 1), but 6.2% are inadequately represented despite being well expressed (TPM > 10).

Conclusion Many splicing events in non-CATs are inadequately evaluated using RNA-seq from CATs. MAJIQ-CAT allows users to explore which accessible tissues, if any, best represent splicing in genes and tissues of interest.

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 August 06, 2019.
Download PDF

Supplementary Material

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.
Mapping RNA splicing variations in clinically-accessible and non-accessible tissues to facilitate Mendelian disease diagnosis using RNA-seq
(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
Mapping RNA splicing variations in clinically-accessible and non-accessible tissues to facilitate Mendelian disease diagnosis using RNA-seq
Joseph K Aicher, Paul Jewell, Jorge Vaquero-Garcia, Yoseph Barash, Elizabeth J Bhoj
bioRxiv 727586; doi: https://doi.org/10.1101/727586
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Mapping RNA splicing variations in clinically-accessible and non-accessible tissues to facilitate Mendelian disease diagnosis using RNA-seq
Joseph K Aicher, Paul Jewell, Jorge Vaquero-Garcia, Yoseph Barash, Elizabeth J Bhoj
bioRxiv 727586; doi: https://doi.org/10.1101/727586

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 (3482)
  • Biochemistry (7329)
  • Bioengineering (5301)
  • Bioinformatics (20212)
  • Biophysics (9985)
  • Cancer Biology (7706)
  • Cell Biology (11273)
  • Clinical Trials (138)
  • Developmental Biology (6425)
  • Ecology (9923)
  • Epidemiology (2065)
  • Evolutionary Biology (13292)
  • Genetics (9353)
  • Genomics (12559)
  • Immunology (7681)
  • Microbiology (18964)
  • Molecular Biology (7421)
  • Neuroscience (40915)
  • Paleontology (298)
  • Pathology (1226)
  • Pharmacology and Toxicology (2130)
  • Physiology (3145)
  • Plant Biology (6842)
  • Scientific Communication and Education (1271)
  • Synthetic Biology (1893)
  • Systems Biology (5299)
  • Zoology (1086)