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Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies

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Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies. / Murtaza, Nadeem; Cheng, Annie A; Brown, Chad O; Meka, Durga Praveen; Hong, Shuai; Uy, Jarryll A; El-Hajjar, Joelle; Pipko, Neta; Unda, Brianna K; Schwanke, Birgit; Xing, Sansi; Thiruvahindrapuram, Bhooma; Engchuan, Worrawat; Trost, Brett; Deneault, Eric; Calderon de Anda, Froylan; Doble, Bradley W; Ellis, James; Anagnostou, Evdokia; Bader, Gary D; Scherer, Stephen W; Lu, Yu; Singh, Karun K.

in: CELL REP, Jahrgang 41, Nr. 8, 111678, 22.11.2022.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Murtaza, N, Cheng, AA, Brown, CO, Meka, DP, Hong, S, Uy, JA, El-Hajjar, J, Pipko, N, Unda, BK, Schwanke, B, Xing, S, Thiruvahindrapuram, B, Engchuan, W, Trost, B, Deneault, E, Calderon de Anda, F, Doble, BW, Ellis, J, Anagnostou, E, Bader, GD, Scherer, SW, Lu, Y & Singh, KK 2022, 'Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies', CELL REP, Jg. 41, Nr. 8, 111678. https://doi.org/10.1016/j.celrep.2022.111678

APA

Murtaza, N., Cheng, A. A., Brown, C. O., Meka, D. P., Hong, S., Uy, J. A., El-Hajjar, J., Pipko, N., Unda, B. K., Schwanke, B., Xing, S., Thiruvahindrapuram, B., Engchuan, W., Trost, B., Deneault, E., Calderon de Anda, F., Doble, B. W., Ellis, J., Anagnostou, E., ... Singh, K. K. (2022). Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies. CELL REP, 41(8), [111678]. https://doi.org/10.1016/j.celrep.2022.111678

Vancouver

Murtaza N, Cheng AA, Brown CO, Meka DP, Hong S, Uy JA et al. Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies. CELL REP. 2022 Nov 22;41(8). 111678. https://doi.org/10.1016/j.celrep.2022.111678

Bibtex

@article{486a9a8ec6ec49e58c3ad6bd4cd32892,
title = "Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies",
abstract = "There are hundreds of risk genes associated with autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We use neuron-specific proximity-labeling proteomics (BioID2) to identify protein-protein interaction (PPI) networks for 41 ASD risk genes. Neuron-specific PPI networks, including synaptic transmission proteins, are disrupted by de novo missense variants. The PPI network map reveals convergent pathways, including mitochondrial/metabolic processes, Wnt signaling, and MAPK signaling. CRISPR knockout displays an association between mitochondrial activity and ASD risk genes. The PPI network shows an enrichment of 112 additional ASD risk genes and differentially expressed genes from postmortem ASD patients. Clustering of risk genes based on PPI networks identifies gene groups corresponding to clinical behavior score severity. Our data report that cell type-specific PPI networks can identify individual and convergent ASD signaling networks, provide a method to assess patient variants, and highlight biological insight into disease mechanisms and sub-cohorts of ASD.",
keywords = "Humans, Autistic Disorder/genetics, Autism Spectrum Disorder/genetics, Protein Interaction Maps/genetics, Neurons, Proteins, Wnt Signaling Pathway",
author = "Nadeem Murtaza and Cheng, {Annie A} and Brown, {Chad O} and Meka, {Durga Praveen} and Shuai Hong and Uy, {Jarryll A} and Joelle El-Hajjar and Neta Pipko and Unda, {Brianna K} and Birgit Schwanke and Sansi Xing and Bhooma Thiruvahindrapuram and Worrawat Engchuan and Brett Trost and Eric Deneault and {Calderon de Anda}, Froylan and Doble, {Bradley W} and James Ellis and Evdokia Anagnostou and Bader, {Gary D} and Scherer, {Stephen W} and Yu Lu and Singh, {Karun K}",
note = "Copyright {\textcopyright} 2022 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2022",
month = nov,
day = "22",
doi = "10.1016/j.celrep.2022.111678",
language = "English",
volume = "41",
journal = "CELL REP",
issn = "2211-1247",
publisher = "Elsevier",
number = "8",

}

RIS

TY - JOUR

T1 - Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies

AU - Murtaza, Nadeem

AU - Cheng, Annie A

AU - Brown, Chad O

AU - Meka, Durga Praveen

AU - Hong, Shuai

AU - Uy, Jarryll A

AU - El-Hajjar, Joelle

AU - Pipko, Neta

AU - Unda, Brianna K

AU - Schwanke, Birgit

AU - Xing, Sansi

AU - Thiruvahindrapuram, Bhooma

AU - Engchuan, Worrawat

AU - Trost, Brett

AU - Deneault, Eric

AU - Calderon de Anda, Froylan

AU - Doble, Bradley W

AU - Ellis, James

AU - Anagnostou, Evdokia

AU - Bader, Gary D

AU - Scherer, Stephen W

AU - Lu, Yu

AU - Singh, Karun K

N1 - Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2022/11/22

Y1 - 2022/11/22

N2 - There are hundreds of risk genes associated with autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We use neuron-specific proximity-labeling proteomics (BioID2) to identify protein-protein interaction (PPI) networks for 41 ASD risk genes. Neuron-specific PPI networks, including synaptic transmission proteins, are disrupted by de novo missense variants. The PPI network map reveals convergent pathways, including mitochondrial/metabolic processes, Wnt signaling, and MAPK signaling. CRISPR knockout displays an association between mitochondrial activity and ASD risk genes. The PPI network shows an enrichment of 112 additional ASD risk genes and differentially expressed genes from postmortem ASD patients. Clustering of risk genes based on PPI networks identifies gene groups corresponding to clinical behavior score severity. Our data report that cell type-specific PPI networks can identify individual and convergent ASD signaling networks, provide a method to assess patient variants, and highlight biological insight into disease mechanisms and sub-cohorts of ASD.

AB - There are hundreds of risk genes associated with autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We use neuron-specific proximity-labeling proteomics (BioID2) to identify protein-protein interaction (PPI) networks for 41 ASD risk genes. Neuron-specific PPI networks, including synaptic transmission proteins, are disrupted by de novo missense variants. The PPI network map reveals convergent pathways, including mitochondrial/metabolic processes, Wnt signaling, and MAPK signaling. CRISPR knockout displays an association between mitochondrial activity and ASD risk genes. The PPI network shows an enrichment of 112 additional ASD risk genes and differentially expressed genes from postmortem ASD patients. Clustering of risk genes based on PPI networks identifies gene groups corresponding to clinical behavior score severity. Our data report that cell type-specific PPI networks can identify individual and convergent ASD signaling networks, provide a method to assess patient variants, and highlight biological insight into disease mechanisms and sub-cohorts of ASD.

KW - Humans

KW - Autistic Disorder/genetics

KW - Autism Spectrum Disorder/genetics

KW - Protein Interaction Maps/genetics

KW - Neurons

KW - Proteins

KW - Wnt Signaling Pathway

U2 - 10.1016/j.celrep.2022.111678

DO - 10.1016/j.celrep.2022.111678

M3 - SCORING: Journal article

C2 - 36417873

VL - 41

JO - CELL REP

JF - CELL REP

SN - 2211-1247

IS - 8

M1 - 111678

ER -