Standardizing workflows in imaging transcriptomics with the abagen toolbox.


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
16 11 2021
Historique:
received: 12 07 2021
accepted: 15 11 2021
pubmed: 17 11 2021
medline: 22 1 2022
entrez: 16 11 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34783653
doi: 10.7554/eLife.72129
pii: 72129
pmc: PMC8660024
doi:
pii:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH083320
Pays : United States
Organisme : NIMH NIH HHS
ID : RF1 MH120021
Pays : United States
Organisme : NIBIB NIH HHS
ID : P41 EB019936
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH096906
Pays : United States

Informations de copyright

© 2021, Markello et al.

Déclaration de conflit d'intérêts

RM, AA, JP, BF, AF, BM No competing interests declared

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Auteurs

Ross D Markello (RD)

McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.

Aurina Arnatkeviciute (A)

School of Psychological Sciences & Monash Biomedical Imaging, Monash University, Clayton, Australia.

Jean-Baptiste Poline (JB)

McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.

Ben D Fulcher (BD)

School of Physics, University of Sydney, Sydney, Australia.

Alex Fornito (A)

School of Psychological Sciences & Monash Biomedical Imaging, Monash University, Clayton, Australia.

Bratislav Misic (B)

McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Canada.

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