Standardizing workflows in imaging transcriptomics with the abagen toolbox

Gene expression fundamentally shapes the structural and functional architecture of the human brain. Open-access transcriptomic datasets like the Allen Human Brain Atlas provide an unprecedented ability to examine these mechanisms in vivo; however, a lack of standardization across research groups has...

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Main Authors: Ross D Markello, Aurina Arnatkeviciute, Jean-Baptiste Poline, Ben D Fulcher, Alex Fornito, Bratislav Misic
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2021-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/72129
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author Ross D Markello
Aurina Arnatkeviciute
Jean-Baptiste Poline
Ben D Fulcher
Alex Fornito
Bratislav Misic
author_facet Ross D Markello
Aurina Arnatkeviciute
Jean-Baptiste Poline
Ben D Fulcher
Alex Fornito
Bratislav Misic
author_sort Ross D Markello
collection DOAJ
description Gene expression fundamentally shapes the structural and functional architecture of the human brain. Open-access transcriptomic datasets like the Allen Human Brain Atlas provide an unprecedented ability to examine these mechanisms in vivo; however, a lack of standardization across research groups has given rise to myriad processing pipelines for using these data. Here, we develop the abagen toolbox, an open-access software package for working with transcriptomic data, and use it to examine how methodological variability influences the outcomes of research using the Allen Human Brain Atlas. Applying three prototypical analyses to the outputs of 750,000 unique processing pipelines, we find that choice of pipeline has a large impact on research findings, with parameters commonly varied in the literature influencing correlations between derived gene expression and other imaging phenotypes by as much as ρ ≥ 1.0. Our results further reveal an ordering of parameter importance, with processing steps that influence gene normalization yielding the greatest impact on downstream statistical inferences and conclusions. The presented work and the development of the abagen toolbox lay the foundation for more standardized and systematic research in imaging transcriptomics, and will help to advance future understanding of the influence of gene expression in the human brain.
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spelling doaj.art-c416e6f15f4d4c81bdf3c99cab5572292022-12-22T04:32:45ZengeLife Sciences Publications LtdeLife2050-084X2021-11-011010.7554/eLife.72129Standardizing workflows in imaging transcriptomics with the abagen toolboxRoss D Markello0https://orcid.org/0000-0003-1057-1336Aurina Arnatkeviciute1Jean-Baptiste Poline2https://orcid.org/0000-0002-9794-749XBen D Fulcher3https://orcid.org/0000-0002-3003-4055Alex Fornito4Bratislav Misic5https://orcid.org/0000-0003-0307-2862McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, CanadaSchool of Psychological Sciences & Monash Biomedical Imaging, Monash University, Clayton, AustraliaMcConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, CanadaSchool of Physics, University of Sydney, Sydney, AustraliaSchool of Psychological Sciences & Monash Biomedical Imaging, Monash University, Clayton, AustraliaMcConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, CanadaGene expression fundamentally shapes the structural and functional architecture of the human brain. Open-access transcriptomic datasets like the Allen Human Brain Atlas provide an unprecedented ability to examine these mechanisms in vivo; however, a lack of standardization across research groups has given rise to myriad processing pipelines for using these data. Here, we develop the abagen toolbox, an open-access software package for working with transcriptomic data, and use it to examine how methodological variability influences the outcomes of research using the Allen Human Brain Atlas. Applying three prototypical analyses to the outputs of 750,000 unique processing pipelines, we find that choice of pipeline has a large impact on research findings, with parameters commonly varied in the literature influencing correlations between derived gene expression and other imaging phenotypes by as much as ρ ≥ 1.0. Our results further reveal an ordering of parameter importance, with processing steps that influence gene normalization yielding the greatest impact on downstream statistical inferences and conclusions. The presented work and the development of the abagen toolbox lay the foundation for more standardized and systematic research in imaging transcriptomics, and will help to advance future understanding of the influence of gene expression in the human brain.https://elifesciences.org/articles/72129transcriptomicsneuroimagingMRIprocessing variabilitysoftware
spellingShingle Ross D Markello
Aurina Arnatkeviciute
Jean-Baptiste Poline
Ben D Fulcher
Alex Fornito
Bratislav Misic
Standardizing workflows in imaging transcriptomics with the abagen toolbox
eLife
transcriptomics
neuroimaging
MRI
processing variability
software
title Standardizing workflows in imaging transcriptomics with the abagen toolbox
title_full Standardizing workflows in imaging transcriptomics with the abagen toolbox
title_fullStr Standardizing workflows in imaging transcriptomics with the abagen toolbox
title_full_unstemmed Standardizing workflows in imaging transcriptomics with the abagen toolbox
title_short Standardizing workflows in imaging transcriptomics with the abagen toolbox
title_sort standardizing workflows in imaging transcriptomics with the abagen toolbox
topic transcriptomics
neuroimaging
MRI
processing variability
software
url https://elifesciences.org/articles/72129
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