Journal article
Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism
Nature communications, Vol.5(1), pp.3650-3650
04/11/2014
DOI: 10.1038/ncomms4650
PMCID: PMC3996537
PMID: 24722188
Abstract
Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases.
Details
- Title: Subtitle
- Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism
- Creators
- Roser Corominas - 1] Department of Psychiatry, University of California San Diego, La Jolla, California 92093, USAXinping Yang - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USAGuan Ning Lin - 1] Department of Psychiatry, University of California San Diego, La Jolla, California 92093, USAShuli Kang - 1] Department of Psychiatry, University of California San Diego, La Jolla, California 92093, USAYun Shen - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USALila Ghamsari - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USAMartin Broly - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USAMaria Rodriguez - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USAStanley Tam - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USAShelly A Trigg - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USAChangyu Fan - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USASong Yi - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USAMurat Tasan - Donnelly Centre and Departments of Molecular Genetics & Computer Science, University of Toronto, and Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada M5S 3E1Irma Lemmens - Department of Medical Protein Research, VIB, and Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent B-9000, BelgiumXingyan Kuang - Department of Computer Science and Informatics Institute, University of Missouri, Columbia, Missouri 65203, USANan Zhao - Department of Computer Science and Informatics Institute, University of Missouri, Columbia, Missouri 65203, USADheeraj Malhotra - Beyster Center for Genomics of Psychiatric Diseases and Department of Psychiatry, University of California San Diego, La Jolla, California 92093, USAJacob J Michaelson - 1] Beyster Center for Genomics of Psychiatric Diseases and Department of Psychiatry, University of California San Diego, La Jolla, California 92093, USAVladimir Vacic - New York Genome Center, New York, New York 10013, USAMichael A Calderwood - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USAFrederick P Roth - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA Donnelly Centre and Departments of Molecular Genetics & Computer Science, University of Toronto, and Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario, Canada M5S 3E1Jan Tavernier - Department of Medical Protein Research, VIB, and Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent B-9000, BelgiumSteve Horvath - Department of Human Genetics and Biostatistics, University of California, Los Angeles, California 90095, USAKourosh Salehi-Ashtiani - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USADmitry Korkin - Department of Computer Science and Informatics Institute, University of Missouri, Columbia, Missouri 65203, USAJonathan Sebat - Beyster Center for Genomics of Psychiatric Diseases and Department of Psychiatry, University of California San Diego, La Jolla, California 92093, USADavid E Hill - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USATong Hao - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USAMarc Vidal - 1] Center for Cancer Systems Biology (CCSB) and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USALilia M Iakoucheva - Department of Psychiatry, University of California San Diego, La Jolla, California 92093, USA
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.5(1), pp.3650-3650
- DOI
- 10.1038/ncomms4650
- PMID
- 24722188
- PMCID
- PMC3996537
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- England
- Grant note
- R01 HD065288 / NICHD NIH HHS R01 MH091350 / NIMH NIH HHS ARRA R01HD065288 / NICHD NIH HHS R01 HG001715 / NHGRI NIH HHS R01MH091350 / NIMH NIH HHS MH076431 / NIMH NIH HHS R01 MH076431 / NIMH NIH HHS U01 HG001715 / NHGRI NIH HHS P50 HG004233 / NHGRI NIH HHS R01HG001715 / NHGRI NIH HHS
- Language
- English
- Date published
- 04/11/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984070455002771
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