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A common molecular signature in ASD gene expression: following Root 66 to autism
Several gene expression experiments on autism spectrum disorders have been conducted using both blood and brain tissue. Individually, these studies have advanced our understanding of the molecular systems involved in the molecular pathology of autism and have formed the bases of ongoing work to buil...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068868/ https://www.ncbi.nlm.nih.gov/pubmed/26731442 http://dx.doi.org/10.1038/tp.2015.112 |
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author | Diaz-Beltran, L Esteban, F J Wall, D P |
author_facet | Diaz-Beltran, L Esteban, F J Wall, D P |
author_sort | Diaz-Beltran, L |
collection | PubMed |
description | Several gene expression experiments on autism spectrum disorders have been conducted using both blood and brain tissue. Individually, these studies have advanced our understanding of the molecular systems involved in the molecular pathology of autism and have formed the bases of ongoing work to build autism biomarkers. In this study, we conducted an integrated systems biology analysis of 9 independent gene expression experiments covering 657 autism, 9 mental retardation and developmental delay and 566 control samples to determine if a common signature exists and to test whether regulatory patterns in the brain relevant to autism can also be detected in blood. We constructed a matrix of differentially expressed genes from these experiments and used a Jaccard coefficient to create a gene-based phylogeny, validated by bootstrap. As expected, experiments and tissue types clustered together with high statistical confidence. However, we discovered a statistically significant subgrouping of 3 blood and 2 brain data sets from 3 different experiments rooted by a highly correlated regulatory pattern of 66 genes. This Root 66 appeared to be non-random and of potential etiologic relevance to autism, given their enriched roles in neurological processes key for normal brain growth and function, learning and memory, neurodegeneration, social behavior and cognition. Our results suggest that there is a detectable autism signature in the blood that may be a molecular echo of autism-related dysregulation in the brain. |
format | Online Article Text |
id | pubmed-5068868 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50688682016-10-20 A common molecular signature in ASD gene expression: following Root 66 to autism Diaz-Beltran, L Esteban, F J Wall, D P Transl Psychiatry Original Article Several gene expression experiments on autism spectrum disorders have been conducted using both blood and brain tissue. Individually, these studies have advanced our understanding of the molecular systems involved in the molecular pathology of autism and have formed the bases of ongoing work to build autism biomarkers. In this study, we conducted an integrated systems biology analysis of 9 independent gene expression experiments covering 657 autism, 9 mental retardation and developmental delay and 566 control samples to determine if a common signature exists and to test whether regulatory patterns in the brain relevant to autism can also be detected in blood. We constructed a matrix of differentially expressed genes from these experiments and used a Jaccard coefficient to create a gene-based phylogeny, validated by bootstrap. As expected, experiments and tissue types clustered together with high statistical confidence. However, we discovered a statistically significant subgrouping of 3 blood and 2 brain data sets from 3 different experiments rooted by a highly correlated regulatory pattern of 66 genes. This Root 66 appeared to be non-random and of potential etiologic relevance to autism, given their enriched roles in neurological processes key for normal brain growth and function, learning and memory, neurodegeneration, social behavior and cognition. Our results suggest that there is a detectable autism signature in the blood that may be a molecular echo of autism-related dysregulation in the brain. Nature Publishing Group 2016-01 2016-01-05 /pmc/articles/PMC5068868/ /pubmed/26731442 http://dx.doi.org/10.1038/tp.2015.112 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Diaz-Beltran, L Esteban, F J Wall, D P A common molecular signature in ASD gene expression: following Root 66 to autism |
title | A common molecular signature in ASD gene expression: following Root 66 to autism |
title_full | A common molecular signature in ASD gene expression: following Root 66 to autism |
title_fullStr | A common molecular signature in ASD gene expression: following Root 66 to autism |
title_full_unstemmed | A common molecular signature in ASD gene expression: following Root 66 to autism |
title_short | A common molecular signature in ASD gene expression: following Root 66 to autism |
title_sort | common molecular signature in asd gene expression: following root 66 to autism |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5068868/ https://www.ncbi.nlm.nih.gov/pubmed/26731442 http://dx.doi.org/10.1038/tp.2015.112 |
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