Exploiting transfer learning for the reconstruction of the human gene regulatory network

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.

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):  
Gourab Ghosh Roy ◽  
Nicholas Geard ◽  
Karin Verspoor ◽  
Shan He

Abstract Motivation Inferring gene regulatory networks (GRNs) from expression data is a significant systems biology problem. A useful inference algorithm should not only unveil the global structure of the regulatory mechanisms but also the details of regulatory interactions such as edge direction (from regulator to target) and sign (activation/inhibition). Many popular GRN inference algorithms cannot infer edge signs, and those that can infer signed GRNs cannot simultaneously infer edge directions or network cycles. Results To address these limitations of existing algorithms, we propose Polynomial Lasso Bagging (PoLoBag) for signed GRN inference with both edge directions and network cycles. PoLoBag is an ensemble regression algorithm in a bagging framework where Lasso weights estimated on bootstrap samples are averaged. These bootstrap samples incorporate polynomial features to capture higher-order interactions. Results demonstrate that PoLoBag is consistently more accurate for signed inference than state-of-the-art algorithms on simulated and real-world expression datasets. Availability and implementation Algorithm and data are freely available at https://github.com/gourabghoshroy/PoLoBag. Supplementary information Supplementary data are available at Bioinformatics online.


Author(s):  
Prashant Singh ◽  
Fredrik Wrede ◽  
Andreas Hellander

Abstract Summary Discrete stochastic models of gene regulatory networks are fundamental tools for in silico study of stochastic gene regulatory networks. Likelihood-free inference and model exploration are critical applications to study a system using such models. However, the massive computational cost of complex, high-dimensional and stochastic modelling currently limits systematic investigation to relatively simple systems. Recently, machine-learning-assisted methods have shown great promise to handle larger, more complex models. To support both ease-of-use of this new class of methods, as well as their further development, we have developed the scalable inference, optimization and parameter exploration (Sciope) toolbox. Sciope is designed to support new algorithms for machine-learning-assisted model exploration and likelihood-free inference. Moreover, it is built ground up to easily leverage distributed and heterogeneous computational resources for convenient parallelism across platforms from workstations to clouds. Availability and implementation The Sciope Python3 toolbox is freely available on https://github.com/Sciope/Sciope, and has been tested on Linux, Windows and macOS platforms. Supplementary information Supplementary information is 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.


Author(s):  
Ali Fakhry

The applications of Deep Q-Networks are seen throughout the field of reinforcement learning, a large subsect of machine learning. Using a classic environment from OpenAI, CarRacing-v0, a 2D car racing environment, alongside a custom based modification of the environment, a DQN, Deep Q-Network, was created to solve both the classic and custom environments. The environments are tested using custom made CNN architectures and applying transfer learning from Resnet18. While DQNs were state of the art years ago, using it for CarRacing-v0 appears somewhat unappealing and not as effective as other reinforcement learning techniques. Overall, while the model did train and the agent learned various parts of the environment, attempting to reach the reward threshold for the environment with this reinforcement learning technique seems problematic and difficult as other techniques would be more useful.


Sign in / Sign up

Export Citation Format

Share Document