Novel Primary Immunodeficiency Candidate Genes Predicted by the Human Gene Connectome

Germline genetic mutations underlie various primary immunodeficiency (PID) diseases. Patients with rare PID diseases (like most non-PID patients and healthy individuals) carry, on average, 20,000 rare and common coding variants detected by high-throughput sequencing. It is thus a major challenge to...

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Main Authors:	Itan, Yuval, Casanova, Jean-Laurent
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381650/

id	pubmed-4381650
recordtype	oai_dc
spelling	pubmed-43816502015-04-16 Novel Primary Immunodeficiency Candidate Genes Predicted by the Human Gene Connectome Itan, Yuval Casanova, Jean-Laurent Immunology Germline genetic mutations underlie various primary immunodeficiency (PID) diseases. Patients with rare PID diseases (like most non-PID patients and healthy individuals) carry, on average, 20,000 rare and common coding variants detected by high-throughput sequencing. It is thus a major challenge to select only a few candidate disease-causing variants for experimental testing. One of the tools commonly used in the pipeline for estimating a potential PID-candidate gene is to test whether the specific gene is included in the list of genes that were already experimentally validated as PID-causing in previous studies. However, this approach is limited because it cannot detect the PID-causing mutation(s) in the many PID patients carrying causal mutations of as yet unidentified PID-causing genes. In this study, we expanded in silico the list of potential PID-causing candidate genes from 229 to 3,110. We first identified the top 1% of human genes predicted by the human genes connectome to be biologically close to the 229 known PID genes. We then further narrowed down the list of genes by retaining only the most biologically relevant genes, with functionally enriched gene ontology biological categories similar to those for the known PID genes. We validated this prediction by showing that 17 of the 21 novel PID genes published since the last IUIS classification fall into this group of 3,110 genes (p < 10−7). The resulting new extended list of 3,110 predicted PID genes should be useful for the discovery of novel PID genes in patients. Frontiers Media S.A. 2015-04-01 /pmc/articles/PMC4381650/ /pubmed/25883595 http://dx.doi.org/10.3389/fimmu.2015.00142 Text en Copyright © 2015 Itan and Casanova. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Itan, Yuval Casanova, Jean-Laurent
spellingShingle	Itan, Yuval Casanova, Jean-Laurent Novel Primary Immunodeficiency Candidate Genes Predicted by the Human Gene Connectome
author_facet	Itan, Yuval Casanova, Jean-Laurent
author_sort	Itan, Yuval
title	Novel Primary Immunodeficiency Candidate Genes Predicted by the Human Gene Connectome
title_short	Novel Primary Immunodeficiency Candidate Genes Predicted by the Human Gene Connectome
title_full	Novel Primary Immunodeficiency Candidate Genes Predicted by the Human Gene Connectome
title_fullStr	Novel Primary Immunodeficiency Candidate Genes Predicted by the Human Gene Connectome
title_full_unstemmed	Novel Primary Immunodeficiency Candidate Genes Predicted by the Human Gene Connectome
title_sort	novel primary immunodeficiency candidate genes predicted by the human gene connectome
description	Germline genetic mutations underlie various primary immunodeficiency (PID) diseases. Patients with rare PID diseases (like most non-PID patients and healthy individuals) carry, on average, 20,000 rare and common coding variants detected by high-throughput sequencing. It is thus a major challenge to select only a few candidate disease-causing variants for experimental testing. One of the tools commonly used in the pipeline for estimating a potential PID-candidate gene is to test whether the specific gene is included in the list of genes that were already experimentally validated as PID-causing in previous studies. However, this approach is limited because it cannot detect the PID-causing mutation(s) in the many PID patients carrying causal mutations of as yet unidentified PID-causing genes. In this study, we expanded in silico the list of potential PID-causing candidate genes from 229 to 3,110. We first identified the top 1% of human genes predicted by the human genes connectome to be biologically close to the 229 known PID genes. We then further narrowed down the list of genes by retaining only the most biologically relevant genes, with functionally enriched gene ontology biological categories similar to those for the known PID genes. We validated this prediction by showing that 17 of the 21 novel PID genes published since the last IUIS classification fall into this group of 3,110 genes (p < 10−7). The resulting new extended list of 3,110 predicted PID genes should be useful for the discovery of novel PID genes in patients.
publisher	Frontiers Media S.A.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4381650/
_version_	1613206294555000832

Novel Primary Immunodeficiency Candidate Genes Predicted by the Human Gene Connectome

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