scholarly journals Multi-task learning for the simultaneous reconstruction of the human and mouse gene regulatory networks

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Paolo Mignone ◽  
Gianvito Pio ◽  
Sašo Džeroski ◽  
Michelangelo Ceci

AbstractThe reconstruction of Gene Regulatory Networks (GRNs) from gene expression data, supported by machine learning approaches, has received increasing attention in recent years. The task at hand is to identify regulatory links between genes in a network. However, existing methods often suffer when the number of labeled examples is low or when no negative examples are available. In this paper we propose a multi-task method that is able to simultaneously reconstruct the human and the mouse GRNs using the similarities between the two. This is done by exploiting, in a transfer learning approach, possible dependencies that may exist among them. Simultaneously, we solve the issues arising from the limited availability of examples of links by relying on a novel clustering-based approach, able to estimate the degree of certainty of unlabeled examples of links, so that they can be exploited during the training together with the labeled examples. Our experiments show that the proposed method can reconstruct both the human and the mouse GRNs more effectively compared to reconstructing each network separately. Moreover, it significantly outperforms three state-of-the-art transfer learning approaches that, analogously to our method, can exploit the knowledge coming from both organisms. Finally, a specific robustness analysis reveals that, even when the number of labeled examples is very low with respect to the number of unlabeled examples, the proposed method is almost always able to outperform its single-task counterpart.

Author(s):  
Paolo Mignone ◽  
Gianvito Pio ◽  
Domenica D’Elia ◽  
Michelangelo Ceci

Abstract Motivation The reconstruction of gene regulatory networks (GRNs) from gene expression data has received increasing attention in recent years, due to its usefulness in the understanding of regulatory mechanisms involved in human diseases. Most of the existing methods reconstruct the network through machine learning approaches, by analyzing known examples of interactions. However, (i) they often produce poor results when the amount of labeled examples is limited, or when no negative example is available and (ii) they are not able to exploit information extracted from GRNs of other (better studied) related organisms, when this information is available. Results In this paper, we propose a novel machine learning method that overcomes these limitations, by exploiting the knowledge about the GRN of a source organism for the reconstruction of the GRN of the target organism, by means of a novel transfer learning technique. Moreover, the proposed method is natively able to work in the positive-unlabeled setting, where no negative example is available, by fruitfully exploiting a (possibly large) set of unlabeled examples. In our experiments, we reconstructed the human GRN, by exploiting the knowledge of the GRN of Mus musculus. Results showed that the proposed method outperforms state-of-the-art approaches and identifies previously unknown functional relationships among the analyzed genes. Availability and implementation http://www.di.uniba.it/∼mignone/systems/biosfer/index.html. Supplementary information Supplementary data are available at Bioinformatics online.


RSC Advances ◽  
2017 ◽  
Vol 7 (37) ◽  
pp. 23222-23233 ◽  
Author(s):  
Wei Liu ◽  
Wen Zhu ◽  
Bo Liao ◽  
Haowen Chen ◽  
Siqi Ren ◽  
...  

Inferring gene regulatory networks from expression data is a central problem in systems biology.


Biotechnology ◽  
2019 ◽  
pp. 265-304
Author(s):  
David Correa Martins Jr. ◽  
Fabricio Martins Lopes ◽  
Shubhra Sankar Ray

The inference of Gene Regulatory Networks (GRNs) is a very challenging problem which has attracted increasing attention since the development of high-throughput sequencing and gene expression measurement technologies. Many models and algorithms have been developed to identify GRNs using mainly gene expression profile as data source. As the gene expression data usually has limited number of samples and inherent noise, the integration of gene expression with several other sources of information can be vital for accurately inferring GRNs. For instance, some prior information about the overall topological structure of the GRN can guide inference techniques toward better results. In addition to gene expression data, recently biological information from heterogeneous data sources have been integrated by GRN inference methods as well. The objective of this chapter is to present an overview of GRN inference models and techniques with focus on incorporation of prior information such as, global and local topological features and integration of several heterogeneous data sources.


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