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ToxoNet: A high confidence map of protein-protein interactions in Toxoplasma gondii reveals novel virulence factors implicated in host cell invasion

Lakshmipuram S. Swapna, Grant C. Stevens, Aline Sardinha da Silva, Lucas Zhongming Hu, Verena Brand, Daniel D. Fusca, Xuejian Xiong, View ORCID ProfileJon P. Boyle, Michael E. Grigg, Andrew Emili, View ORCID ProfileJohn Parkinson
doi: https://doi.org/10.1101/2021.09.14.460186
Lakshmipuram S. Swapna
1Program in Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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Grant C. Stevens
1Program in Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
2Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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Aline Sardinha da Silva
3Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, 5601 Fishers Lane, MSC 9806, Bethesda, MD, 20892-9806, USA
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Lucas Zhongming Hu
2Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
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Verena Brand
1Program in Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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Daniel D. Fusca
1Program in Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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Xuejian Xiong
1Program in Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
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Jon P. Boyle
4Department of Biological Sciences, Dietrich School of Arts and Sciences, University of Pittsburgh, Pittsburgh. Pennsylvania, 15260, USA
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Michael E. Grigg
3Molecular Parasitology Section, Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, 5601 Fishers Lane, MSC 9806, Bethesda, MD, 20892-9806, USA
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Andrew Emili
2Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
5Department of Biology and Biochemistry, Boston University, Boston, Massachusetts, USA
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John Parkinson
1Program in Molecular Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
2Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada
6Departments of Biochemistry and Computer Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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  • For correspondence: john.parkinson@utoronto.ca
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ABSTRACT

The apicomplexan intracellular parasite Toxoplasma gondii is a major food borne pathogen with significant impact in children and during pregnancy. The majority of the T. gondii proteome remains uncharacterized and the organization of proteins into complexes is unclear. To overcome this knowledge gap, we utilize a biochemical fractionation strategy coupled with mass spectrometry to predict interactions by correlation profiling. Key to this approach is the integration of additional datasets based on gene co-expression as well as phylogenetic profiles that eliminate poorly supported interactions and reduce the number of false positive interactions. In addition to a supervised machine learning strategy, we employed an unsupervised approach in data integration, based on similarity network fusion, to overcome the deficit of high-quality training data in non-model organisms. The resulting high confidence network, we term ToxoNet, comprises 2,063 interactions connecting 652 proteins. Clustering of this network identifies 93 protein complexes, predicting both novel complexes as well as new components for previously known complexes. In particular, we identified clusters enriched in mitochondrial machinery that include previously uncharacterized proteins that likely represent novel adaptations to oxidative phosphorylation. Furthermore, complexes enriched in proteins localized to secretory organelles and the inner membrane complex, predict additional novel components representing novel targets for detailed functional characterization. We present ToxoNet as a publicly available resource with the expectation that it will help drive future hypotheses within the research community.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 15, 2021.
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ToxoNet: A high confidence map of protein-protein interactions in Toxoplasma gondii reveals novel virulence factors implicated in host cell invasion
Lakshmipuram S. Swapna, Grant C. Stevens, Aline Sardinha da Silva, Lucas Zhongming Hu, Verena Brand, Daniel D. Fusca, Xuejian Xiong, Jon P. Boyle, Michael E. Grigg, Andrew Emili, John Parkinson
bioRxiv 2021.09.14.460186; doi: https://doi.org/10.1101/2021.09.14.460186
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ToxoNet: A high confidence map of protein-protein interactions in Toxoplasma gondii reveals novel virulence factors implicated in host cell invasion
Lakshmipuram S. Swapna, Grant C. Stevens, Aline Sardinha da Silva, Lucas Zhongming Hu, Verena Brand, Daniel D. Fusca, Xuejian Xiong, Jon P. Boyle, Michael E. Grigg, Andrew Emili, John Parkinson
bioRxiv 2021.09.14.460186; doi: https://doi.org/10.1101/2021.09.14.460186

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