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,Lila Ghamsari,Martin P. Broly,Maria J. Rodriguez,Stanley Tam,Shelly A. Trigg,Shelly A. Trigg,Changyu Fan,Song Yi,Murat Tasan,Irma Lemmens,Xingyan Kuang,Nan Zhao,Dheeraj Malhotra,Jacob J. Michaelson,Jacob J. Michaelson,Vladimir Vacic,Michael A. Calderwood,Frederick P. Roth,Frederick P. Roth,Jan Tavernier,Steve Horvath,Kourosh Salehi-Ashtiani,Kourosh Salehi-Ashtiani,Dmitry Korkin,Jonathan Sebat,David E. Hill,Tong Hao,Marc Vidal,Lilia M. Iakoucheva +34 more
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TLDR
A new interactome mapping approach is introduced by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors, demonstrating the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases.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.read more
Citations
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The BioGRID interaction database: 2015 update
Andrew Chatr-aryamontri,Bobby-Joe Breitkreutz,Rose Oughtred,Lorrie Boucher,Sven Heinicke,Daici Chen,Chris Stark,Ashton Breitkreutz,Nadine Kolas,Lara O'Donnell,Teresa Reguly,Julie Nixon,Lindsay Ramage,Andrew G. Winter,Adnane Sellam,Christie S. Chang,Jodi E. Hirschman,Chandra L. Theesfeld,Jennifer M. Rust,Michael S. Livstone,Kara Dolinski,Mike Tyers +21 more
TL;DR: The BioGRID architecture has been improved to support a broader range of interaction and post-translational modification types, to allow the representation of more complex multi-gene/protein interactions, to account for cellular phenotypes through structured ontologies, to expedite curation through semi-automated text-mining approaches, and to enhance curation quality control.
Journal ArticleDOI
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
Ryan K. C. Yuen,Daniele Merico,Matt Bookman,Jennifer L. Howe,Bhooma Thiruvahindrapuram,Rohan V. Patel,Joe Whitney,Nicole A. Deflaux,Jonathan Bingham,Zhuozhi Wang,Giovanna Pellecchia,Janet A. Buchanan,Susan Walker,Christian R. Marshall,Mohammed Uddin,Mehdi Zarrei,Eric Deneault,Lia D’Abate,Lia D’Abate,Ada J.S. Chan,Ada J.S. Chan,Stephanie Koyanagi,Tara Paton,Sergio L. Pereira,Ny Hoang,Worrawat Engchuan,Edward J Higginbotham,Karen Ho,Sylvia Lamoureux,Weili Li,Jeffrey R. MacDonald,Thomas Nalpathamkalam,Wilson W L Sung,Fiona Tsoi,John Wei,Lizhen Xu,Anne Marie Tassé,Emily Kirby,William Van Etten,Simon N. Twigger,Wendy Roberts,Irene Drmic,Sanne Jilderda,Bonnie Mackinnon Modi,Barbara Kellam,Michael J. Szego,Michael J. Szego,Cheryl Cytrynbaum,Rosanna Weksberg,Lonnie Zwaigenbaum,Marc Woodbury-Smith,Marc Woodbury-Smith,Jessica Brian,Lili Senman,Alana Iaboni,Krissy A.R. Doyle-Thomas,Ann Thompson,Christina Chrysler,Jonathan Leef,Tal Savion-Lemieux,Isabel M. Smith,Xudong Liu,Rob Nicolson,Vicki Seifer,Angie Fedele,Edwin H. Cook,Stephen R. Dager,Annette Estes,Louise Gallagher,Beth A. Malow,Jeremy R. Parr,Sarah J. Spence,Jacob A. S. Vorstman,Brendan J. Frey,James T. Robinson,Lisa J. Strug,Lisa J. Strug,Bridget A. Fernandez,Mayada Elsabbagh,Melissa T. Carter,Joachim Hallmayer,Bartha Maria Knoppers,Evdokia Anagnostou,Peter Szatmari,Peter Szatmari,Robert H. Ring,David Glazer,Mathew T. Pletcher,Stephen W. Scherer,Stephen W. Scherer +89 more
TL;DR: Se sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal that identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability.
Journal ArticleDOI
Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice
Gil Sharon,Nikki Jamie Cruz,Dae Wook Kang,Michael J. Gandal,B. D. Wang,Young-Mo Kim,Erika M. Zink,Cameron P. Casey,Bryn C. Taylor,Christianne J. Lane,Lisa M. Bramer,Nancy G. Isern,David W. Hoyt,Cecilia Noecker,Michael J. Sweredoski,Annie Moradian,Elhanan Borenstein,Janet K. Jansson,Rob Knight,Thomas O. Metz,Carlos Lois,Daniel H. Geschwind,Rosa Krajmalnik-Brown,Sarkis K. Mazmanian +23 more
TL;DR: It is proposed that the gut microbiota regulates behaviors in mice via production of neuroactive metabolites, suggesting that gut-brain connections contribute to the pathophysiology of ASD.
Journal ArticleDOI
A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains
Manuel Irimia,Manuel Irimia,Robert J. Weatheritt,Jonathan D. Ellis,Neelroop N. Parikshak,Thomas Gonatopoulos-Pournatzis,Mariana Babor,Mathieu Quesnel-Vallières,Javier Tapial,Bushra Raj,Dave O'Hanlon,Miriam Barrios-Rodiles,Michael J.E. Sternberg,Sabine P. Cordes,Frederick P. Roth,Jeffrey L. Wrana,Jeffrey L. Wrana,Daniel H. Geschwind,Benjamin J. Blencowe +18 more
TL;DR: The results reveal a highly conserved program of dynamic microexon regulation associated with the remodeling of protein-interaction networks during neurogenesis, the misregulation of which is linked to autism.
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