Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism

Roser Corominas, Xinping Yang, Guan Ning Lin, Shuli Kang, Yun Shen, Lila Ghamsari, Martin Broly, Maria Rodriguez, Stanley Tam, Shelly A. Wanamaker, Changyu Fan, Song Yi, Murat Tasan, Irma Lemmens, Xingyan Kuang, Nan Zhao, Dheeraj Malhotra, Jacob J. Michaelson, Vladimir Vacic, Michael A. Calderwood, Frederick P. Roth, Jan Tavernier, Steve Horvath, Kourosh Salehi-Ashtiani, Dmitry Korkin, Jonathan Sebat, David E. Hill, Tong Hao (), Marc Vidal () and Lilia M. Iakoucheva ()
Additional contact information
Roser Corominas: University of California San Diego
Xinping Yang: Dana-Farber Cancer Institute
Guan Ning Lin: University of California San Diego
Shuli Kang: University of California San Diego
Yun Shen: Dana-Farber Cancer Institute
Lila Ghamsari: Dana-Farber Cancer Institute
Martin Broly: Dana-Farber Cancer Institute
Maria Rodriguez: Dana-Farber Cancer Institute
Stanley Tam: Dana-Farber Cancer Institute
Shelly A. Wanamaker: Dana-Farber Cancer Institute
Changyu Fan: Dana-Farber Cancer Institute
Song Yi: Dana-Farber Cancer Institute
Murat Tasan: University of Toronto, and Samuel Lunenfeld Research Institute, Mt. Sinai Hospital
Irma Lemmens: VIB, Faculty of Medicine and Health Sciences, Ghent University
Xingyan Kuang: University of Missouri
Nan Zhao: University of Missouri
Dheeraj Malhotra: University of California San Diego
Jacob J. Michaelson: University of California San Diego
Vladimir Vacic: New York Genome Center
Michael A. Calderwood: Dana-Farber Cancer Institute
Frederick P. Roth: Dana-Farber Cancer Institute
Jan Tavernier: VIB, Faculty of Medicine and Health Sciences, Ghent University
Steve Horvath: University of California
Kourosh Salehi-Ashtiani: Dana-Farber Cancer Institute
Dmitry Korkin: University of Missouri
Jonathan Sebat: University of California San Diego
David E. Hill: Dana-Farber Cancer Institute
Tong Hao: Dana-Farber Cancer Institute
Marc Vidal: Dana-Farber Cancer Institute
Lilia M. Iakoucheva: University of California San Diego

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4650

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