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

Phenogenon: Gene to Phenotype Associations for Rare Genetic Diseases

View ORCID ProfileCian Murphy, View ORCID ProfileIsmail Moghul, Nikolas Pontikos, Phenopolis consortium, UK Inherited Retinal Dystrophy consortium, UCLex consortium, Jing Yu
doi: https://doi.org/10.1101/367292
Cian Murphy
1UCL Genetics Institute, University College London, London WC1E 6BT, UK
2Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Cian Murphy
Ismail Moghul
3UCL Cancer Institute, University College London, London WC1E 6DD, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ismail Moghul
Nikolas Pontikos
1UCL Genetics Institute, University College London, London WC1E 6BT, UK
4Institute of Ophthalmology, University College London, London EC1V 9EL, UK
5Moorfields Eye Hospital, London EC1V 2PD, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jing Yu
6Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jing.yu@ndcn.ox.ac.uk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

As genome sequencing is increasingly applied to molecular diagnosis of rare Mendelian disorders, large number of patients with diverse phenotypes have their genomic and phenotypic data pooled together to uncover new genotype - phenotype relations. We introduce Phenogenon, a method that combines: the power of Human Phenotype Ontology for describing patient phenotypes, gnomAD for estimating rare variant population frequency, and CADD for variant pathogenicity prediction. By using a divide and conquer approach, we demonstrate here that Phenogenon is able to uncover true gene to phenotype relations, such as “ABCA4 – Macular dystrophy” and “SCN1A – Seizures”. Additionally, it accurately infers mode of inheritance, such as a recessive mode of inheritance in the case of the “ABCA4 – Macular dystrophy” relationship and a dominant mode of inheritance with the “SCN1A – Seizures” relationship. We also found that CADD has more power to detect early-onset rare genetic diseases than late-onset diseases. In this study, we ran Phenogenon against a diverse cohort of 3288 patients. Among the top 13 gene-phenotype relations, seven were previously known. We also highlight four potentially novel gene – phenotype relations such as “SIPA1L3 – Abnormal electroretinogram”.

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-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted July 11, 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.
Phenogenon: Gene to Phenotype Associations for Rare Genetic Diseases
(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
Phenogenon: Gene to Phenotype Associations for Rare Genetic Diseases
Cian Murphy, Ismail Moghul, Nikolas Pontikos, Phenopolis consortium, UK Inherited Retinal Dystrophy consortium, UCLex consortium, Jing Yu
bioRxiv 367292; doi: https://doi.org/10.1101/367292
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Phenogenon: Gene to Phenotype Associations for Rare Genetic Diseases
Cian Murphy, Ismail Moghul, Nikolas Pontikos, Phenopolis consortium, UK Inherited Retinal Dystrophy consortium, UCLex consortium, Jing Yu
bioRxiv 367292; doi: https://doi.org/10.1101/367292

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

  • Bioinformatics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3502)
  • Biochemistry (7343)
  • Bioengineering (5319)
  • Bioinformatics (20258)
  • Biophysics (10008)
  • Cancer Biology (7735)
  • Cell Biology (11293)
  • Clinical Trials (138)
  • Developmental Biology (6434)
  • Ecology (9947)
  • Epidemiology (2065)
  • Evolutionary Biology (13315)
  • Genetics (9359)
  • Genomics (12579)
  • Immunology (7696)
  • Microbiology (19008)
  • Molecular Biology (7437)
  • Neuroscience (41011)
  • Paleontology (300)
  • Pathology (1228)
  • Pharmacology and Toxicology (2134)
  • Physiology (3155)
  • Plant Biology (6858)
  • Scientific Communication and Education (1272)
  • Synthetic Biology (1895)
  • Systems Biology (5311)
  • Zoology (1087)