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TripletGO: Integrating Transcript Expression Profiles with Protein Homology Inferences for High-Accuracy Gene Function Annotations

View ORCID ProfileYi-Heng Zhu, View ORCID ProfileChengxin Zhang, View ORCID ProfileYan Liu, View ORCID ProfileGilbert S. Omenn, View ORCID ProfilePeter L. Freddolino, View ORCID ProfileDong-Jun Yu, View ORCID ProfileYang Zhang
doi: https://doi.org/10.1101/2021.11.25.470058
Yi-Heng Zhu
1School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China
2Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA
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Chengxin Zhang
2Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA
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Yan Liu
1School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China
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Gilbert S. Omenn
2Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA
3Departments of Internal Medicine, Human Genetics, and School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA
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Peter L. Freddolino
2Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA
4Department of Biological Chemistry, University of Michigan, University of Michigan, Ann Arbor, MI, 48109, USA
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Dong-Jun Yu
1School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China
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  • For correspondence: zhng@umich.edu njyudj@njust.edu.cn
Yang Zhang
2Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA
4Department of Biological Chemistry, University of Michigan, University of Michigan, Ann Arbor, MI, 48109, USA
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  • For correspondence: zhng@umich.edu njyudj@njust.edu.cn
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Abstract

Gene Ontology (GO) has been widely used to annotate functions of genes and gene products. We proposed a new method (TripletGO) to deduce GO terms of protein-coding and non-coding genes, through the integration of four complementary pipelines built on transcript expression profiling, genetic sequence alignment, protein sequence alignment and naïve probability, respectively. TripletGO was tested on a large set of 5,754 genes from 8 species (human, mouse, arabidopsis, rat, fly, budding yeast, fission yeast, and nematoda) and 2,433 proteins with available expression data from the CAFA3 experiment and achieved function annotation accuracy significantly beyond the current state-of-the-art approaches. Detailed analyses show that the major advantage of TripletGO lies in the coupling of a new triplet-network based profiling method with the feature space mapping technique which can accurately recognize function patterns from transcript expressions. Meanwhile, the combination of multiple complementary models, especially those from transcript expression and protein-level alignments, improves the coverage and accuracy of the final GO annotation results. The standalone package and an online server of TripletGO are freely available at https://zhanglab.ccmb.med.umich.edu/TripletGO/.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • E-mail: yihzhu{at}umich.edu (Zhu Y), zcx{at}umich.edu (Zhang C), yanliu{at}njust.edu.cn (Liu Y), gomenn{at}med.umich.edu (Omenn G), petefred{at}umich.edu (Freddolino P).

  • https://zhanglab.ccmb.med.umich.edu/TripletGO/

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Posted November 27, 2021.
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TripletGO: Integrating Transcript Expression Profiles with Protein Homology Inferences for High-Accuracy Gene Function Annotations
Yi-Heng Zhu, Chengxin Zhang, Yan Liu, Gilbert S. Omenn, Peter L. Freddolino, Dong-Jun Yu, Yang Zhang
bioRxiv 2021.11.25.470058; doi: https://doi.org/10.1101/2021.11.25.470058
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TripletGO: Integrating Transcript Expression Profiles with Protein Homology Inferences for High-Accuracy Gene Function Annotations
Yi-Heng Zhu, Chengxin Zhang, Yan Liu, Gilbert S. Omenn, Peter L. Freddolino, Dong-Jun Yu, Yang Zhang
bioRxiv 2021.11.25.470058; doi: https://doi.org/10.1101/2021.11.25.470058

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