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

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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.
Keywords
CONFERRING RISK, SCHIZOPHRENIA, COMMON VARIANTS, MENTAL-RETARDATION, STRUCTURAL VARIATION, SPECTRUM DISORDERS, GENOME-WIDE ANALYSIS, COPY-NUMBER VARIATION, DE-NOVO MUTATIONS, DUPLICATIONS

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MLA
Corominas, Roser, Xinping Yang, Guan Ning Lin, et al. “Protein Interaction Network of Alternatively Spliced Isoforms from Brain Links Genetic Risk Factors for Autism.” NATURE COMMUNICATIONS 5 (2014): n. pag. Print.
APA
Corominas, R., Yang, X., Lin, G. N., Kang, S., Shen, Y., Ghamsari, L., Broly, M., et al. (2014). Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. NATURE COMMUNICATIONS, 5.
Chicago author-date
Corominas, Roser, Xinping Yang, Guan Ning Lin, Shuli Kang, Yun Shen, Lila Ghamsari, Martin Broly, et al. 2014. “Protein Interaction Network of Alternatively Spliced Isoforms from Brain Links Genetic Risk Factors for Autism.” Nature Communications 5.
Chicago author-date (all authors)
Corominas, Roser, Xinping Yang, Guan Ning Lin, Shuli Kang, Yun Shen, Lila Ghamsari, Martin Broly, Maria Rodriguez, Stanley Tam, Shelly A Trigg, 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. 2014. “Protein Interaction Network of Alternatively Spliced Isoforms from Brain Links Genetic Risk Factors for Autism.” Nature Communications 5.
Vancouver
1.
Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, et al. Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism. NATURE COMMUNICATIONS. 2014;5.
IEEE
[1]
R. Corominas et al., “Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism,” NATURE COMMUNICATIONS, vol. 5, 2014.
@article{4431720,
  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.},
  articleno    = {3650},
  author       = {Corominas, Roser and Yang, Xinping and Lin, Guan Ning and Kang, Shuli and Shen, Yun and Ghamsari, Lila and Broly, Martin and Rodriguez, Maria and Tam, Stanley and Trigg, Shelly A and Fan, Changyu and Yi, Song and Tasan, Murat and Lemmens, Irma and Kuang, Xingyan and Zhao, Nan and Malhotra, Dheeraj and Michaelson, Jacob J and Vacic, Vladimir and Calderwood, Michael A and Roth, Frederick P and Tavernier, Jan and Horvath, Steve and Salehi-Ashtiani, Kourosh and Korkin, Dmitry and Sebat, Jonathan and Hill, David E and Hao, Tong and Vidal, Marc and Iakoucheva, Lilia M},
  issn         = {2041-1723},
  journal      = {NATURE COMMUNICATIONS},
  keywords     = {CONFERRING RISK,SCHIZOPHRENIA,COMMON VARIANTS,MENTAL-RETARDATION,STRUCTURAL VARIATION,SPECTRUM DISORDERS,GENOME-WIDE ANALYSIS,COPY-NUMBER VARIATION,DE-NOVO MUTATIONS,DUPLICATIONS},
  language     = {eng},
  pages        = {12},
  title        = {Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism},
  url          = {http://dx.doi.org/10.1038/ncomms4650},
  volume       = {5},
  year         = {2014},
}

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