Network Enrichment Significance Testing in Brain-Phenotype Association Studies.

Autor:	Weinstein SM; Department of Epidemiology and Biostatistics, Temple University College of Public Health, Philadelphia, PA, USA., Vandekar SN; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA., Alexander-Bloch AF; Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.; Department of Child and Adolescent Psychiatry and Behavioral Science, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Raznahan A; Section on Developmental Neurogenomics, National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA., Li M; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Gur RE; Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Gur RC; Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Roalf DR; Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Park MTM; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.; Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada., Chakravarty M; Department of Psychiatry, McGill University, Montreal, QC, Canada.; Cerebral Imaging Centre, Douglas Research Centre, McGill University, Montreal, QC, Canada., Baller EB; Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Linn KA; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Satterthwaite TD; Department of Psychiatry, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA., Shinohara RT; Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 13. Date of Electronic Publication: 2023 Nov 13.
DOI:	10.1101/2023.11.10.566593
Abstrakt:	Functional networks often guide our interpretation of spatial maps of brain-phenotype associations. However, methods for assessing enrichment of associations within networks of interest have varied in terms of both scientific rigor and underlying assumptions. While some approaches have relied on subjective interpretations, others have made unrealistic assumptions about the spatial structure of imaging data, leading to inflated false positive rates. We seek to address this gap in existing methodology by borrowing insight from a method widely used in genomics research for testing enrichment of associations between a set of genes and a phenotype of interest. We propose Network Enrichment Significance Testing (NEST), a flexible framework for testing the specificity of brain-phenotype associations to functional networks or other sub-regions of the brain. We apply NEST to study phenotype associations with structural and functional brain imaging data from a large-scale neurodevelopmental cohort study. Competing Interests: Russell T. Shinohara receives consulting income from Octave Bioscience and compensation for reviewership duties from the American Medical Association. Aaron Alexander-Bloch receives consulting income from Octave Bioscience and holds equity and serves on the board of directors of Centile Biosciences. Mingyao Li receives research funding from Biogen Inc. that is unrelated to the current manuscript.
Databáze:	MEDLINE
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