Network Propagation for the Analysis of Multi-omics Data

Author(s):  
Minwoo Pak ◽  
Dabin Jeong ◽  
Ji Hwan Moon ◽  
Hongryul Ann ◽  
Benjamin Hur ◽  
...  
2020 ◽  
Author(s):  
Bihai Zhao ◽  
Zhihong Zhang ◽  
Meiping Jiang ◽  
Sai Hu ◽  
Yingchun Luo ◽  
...  

Abstract Background: The accurate annotation of protein functions is of great significance in elucidating the phenomena of life, disease treatment and new drug development. Various methods have been developed to facilitate the prediction of functions by combining protein interaction networks (PINs) with multi-omics data. However, how to make full use of multiple biological data to improve the performance of functions annotation is still a dilemma. Results We presented NPF (Network Propagation for Functions prediction), an integrative protein function predicting framework assisted by network propagation and functional module detection, for discovering interacting partners with similar functions to target proteins. NPF leverages knowledge of the protein interaction network architecture and multi-omics data, such as domain annotation and protein complex information, to augment protein-protein functional similarity in a propagation manner. We have verified the great potential of NPF for accurately inferring protein functions. Comprehensive evaluation of NPF indicates that NPF archived higher performance than competing methods in terms of leave-one-out cross-validation and ten-fold cross validation. Conclusions: We demonstrated that network propagation combined with multi-omics data can not only discover more partners with similar function, but also effectively free from the constraints of the "small-world" feature of protein interaction networks. We conclude that the performance of function prediction depends greatly on whether we can extract and exploit proper functional similarity information from protein correlations.


2020 ◽  
Author(s):  
bihai zhao ◽  
Zhihong Zhang ◽  
Meiping Jiang ◽  
Sai Hu ◽  
Yingchun Luo ◽  
...  

Abstract Background: The accurate annotation of protein functions is of great significance in elucidating the phenomena of life, disease treatment and new drug development. Various methods have been developed to facilitate the prediction of functions by combining protein interaction networks (PINs) with multi-omics data. However, how to make full use of multiple biological data to improve the performance of functions annotation is still a dilemma.Results: We presented NPF (Network Propagation for Functions prediction), an integrative protein function predicting framework assisted by network propagation and functional module detection, for discovering interacting partners with similar functions to target proteins. NPF leverages knowledge of the protein interaction network architecture and multi-omics data, such as domain annotation and protein complex information, to augment protein-protein functional similarity in a propagation manner. We have verified the great potential of NPF for accurately inferring protein functions. Comprehensive evaluation of NPF indicates that NPF archived higher performance than competing methods in terms of leave-one-out cross-validation and ten-fold cross validation.Conclusions: We demonstrated that network propagation combined with multi-omics data can not only discover more partners with similar function, but also effectively free from the constraints of the "small-world" feature of protein interaction networks. We conclude that the performance of function prediction depends greatly on whether we can extract and exploit proper functional similarity information from protein correlations.


2021 ◽  
Vol 17 (11) ◽  
pp. e1009161
Author(s):  
Konstantina Charmpi ◽  
Manopriya Chokkalingam ◽  
Ronja Johnen ◽  
Andreas Beyer

Network propagation refers to a class of algorithms that integrate information from input data across connected nodes in a given network. These algorithms have wide applications in systems biology, protein function prediction, inferring condition-specifically altered sub-networks, and prioritizing disease genes. Despite the popularity of network propagation, there is a lack of comparative analyses of different algorithms on real data and little guidance on how to select and parameterize the various algorithms. Here, we address this problem by analyzing different combinations of network normalization and propagation methods and by demonstrating schemes for the identification of optimal parameter settings on real proteome and transcriptome data. Our work highlights the risk of a ‘topology bias’ caused by the incorrect use of network normalization approaches. Capitalizing on the fact that network propagation is a regularization approach, we show that minimizing the bias-variance tradeoff can be utilized for selecting optimal parameters. The application to real multi-omics data demonstrated that optimal parameters could also be obtained by either maximizing the agreement between different omics layers (e.g. proteome and transcriptome) or by maximizing the consistency between biological replicates. Furthermore, we exemplified the utility and robustness of network propagation on multi-omics datasets for identifying ageing-associated genes in brain and liver tissues of rats and for elucidating molecular mechanisms underlying prostate cancer progression. Overall, this work compares different network propagation approaches and it presents strategies for how to use network propagation algorithms to optimally address a specific research question at hand.


2020 ◽  
Author(s):  
bihai zhao ◽  
Zhihong Zhang ◽  
Meiping Jiang ◽  
Sai Hu ◽  
Yingchun Luo ◽  
...  

Abstract Background: The accurate annotation of protein functions is of great significance in elucidating the phenomena of life, treating disease and developing new medicines. Various methods have been developed to facilitate the prediction of these functions by combining protein interaction networks (PINs) with multi-omics data. However, it is still challenging to make full use of multiple biological to improve the performance of functions annotation.Results: We presented NPF (Network Propagation for Functions prediction), an integrative protein function predicting framework assisted by network propagation and functional module detection, for discovering interacting partners with similar functions to target proteins. NPF leverages knowledge of the protein interaction network architecture and multi-omics data, such as domain annotation and protein complex information, to augment protein-protein functional similarity in a propagation manner. We have verified the great potential of NPF for accurately inferring protein functions. According to the comprehensive evaluation of NPF, it delivered a better performance than other competing methods in terms of leave-one-out cross-validation and ten-fold cross validation.Conclusions: We demonstrated that network propagation, together with multi-omics data, can both discover more partners with similar function, and is unconstricted by the “small-world” feature of protein interaction networks. We conclude that the performance of function prediction depends greatly on whether we can extract and exploit proper functional information of similarity from protein correlations.


2021 ◽  
Author(s):  
Konstantina Charmpi ◽  
Manopriya Chokkalingam ◽  
Ronja Johnen ◽  
Andreas Beyer

Network propagation refers to a class of algorithms that integrate information from input data across connected nodes in a given network. These algorithms have wide applications in systems biology, protein function prediction, inferring condition-specifically altered sub-networks, and prioritizing disease genes. Despite the popularity of network propagation, there is a lack of comparative analyses of different algorithms on real data and little guidance on how to select and parameterize the various algorithms. Here, we address this problem by analyzing different combinations of network normalization and propagation methods and by demonstrating schemes for the identification of optimal parameter settings on real proteome and transcriptome data. Our work highlights the risk of a ‘topology bias’ caused by the incorrect use of network normalization approaches. Capitalizing on the fact that network propagation is a regularization approach, we show that minimizing the bias-variance tradeoff can be utilized for selecting optimal parameters. The application to real multi-omics data demonstrated that optimal parameters could also be obtained by either maximizing the agreement between different omics layers (e.g. proteome and transcriptome) or by maximizing the consistency between biological replicates. Furthermore, we exemplified the utility and robustness of network propagation on multi-omics datasets for identifying ageing-associated genes in brain and liver tissues of rats and for elucidating molecular mechanisms underlying prostate cancer progression. Overall, this work compares different network propagation approaches and it presents strategies for how to use network propagation algorithms to optimally address a specific research question at hand.


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