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2023 | OriginalPaper | Buchkapitel

Gene Networks Inference by Reinforcement Learning

verfasst von : Rodrigo Cesar Bonini, David Correa Martins-Jr

Erschienen in: Advances in Bioinformatics and Computational Biology

Verlag: Springer Nature Switzerland

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Abstract

Gene Regulatory Networks inference from gene expression data is an important problem in systems biology field, involving the estimation of gene-gene indirect dependencies and the regulatory functions among these interactions to provide a model that explains the gene expression dataset. The main goal is to comprehend the global molecular mechanisms underlying diseases for the development of medical treatments and drugs. However, such a problem is considered an open problem, since it is difficult to obtain a satisfactory estimation of the dependencies given a very limited number of samples subject to experimental noises. Many gene networks inference methods exist in the literature, where some of them use heuristics or model based algorithms to find interesting networks that explain the data by codifying whole networks as solutions. However, in general, these models are slow, not scalable to real sized networks (thousands of genes), or require many parameters, the knowledge from an specialist or a large number of samples to be feasible. Reinforcement Learning is an adaptable goal oriented approach that does not require large labeled datasets and many parameters; can give good quality solutions in a feasible execution time; and can work automatically without the need of a specialist for a long time. Therefore, we here propose a way to adapt Reinforcement Learning to the Gene Regulatory Networks inference domain in order to get networks with quality comparable to one achieved by exhaustive search, but in much smaller execution time. Our experimental evaluation shows that our proposal is promising in learning and successfully finding good solutions across different tasks automatically in a reasonable time. However, scalabilty to networks with thousands of genes remains as limitation of our RL approach due to excessive memory consuming, although we foresee some possible improvements that could deal with this limitation in future versions of our proposed method.

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Literatur
1.
Zurück zum Zitat Akutsu, T., Miyano, S., Kuhara, S., et al.: Identification of genetic networks from a small number of gene expression patterns under the Boolean network model. In: Proceedings of the Pacific Symposium on Biocomputing (PSB), vol. 4, pp. 17–28 (1999) Akutsu, T., Miyano, S., Kuhara, S., et al.: Identification of genetic networks from a small number of gene expression patterns under the Boolean network model. In: Proceedings of the Pacific Symposium on Biocomputing (PSB), vol. 4, pp. 17–28 (1999)
2.
Zurück zum Zitat Anastassiou, D.: Computational analysis of the synergy among multiple interacting genes. Mole. Syst. Biol. 3, 83 (2007)CrossRef Anastassiou, D.: Computational analysis of the synergy among multiple interacting genes. Mole. Syst. Biol. 3, 83 (2007)CrossRef
3.
Zurück zum Zitat Barrera, J., et al.: Constructing probabilistic genetic networks of Plasmodium falciparum from dynamical expression signals of the intraerythrocytic development cycle. In: McConnell, P., Lin, S.M., Hurban, P. (eds.) Methods of Microarray Data Analysis, pp. 11–26. Springer, Boston, MA (2007). https://doi.org/10.1007/978-0-387-34569-7_2 Barrera, J., et al.: Constructing probabilistic genetic networks of Plasmodium falciparum from dynamical expression signals of the intraerythrocytic development cycle. In: McConnell, P., Lin, S.M., Hurban, P. (eds.) Methods of Microarray Data Analysis, pp. 11–26. Springer, Boston, MA (2007). https://​doi.​org/​10.​1007/​978-0-387-34569-7_​2
4.
Zurück zum Zitat Bonini, R., Da Silva, F.L., Glatt, R., Spina, E., Costa, A.H.R.: A framework to discover and reuse object-oriented options in reinforcement learning. In: 2018 7th Brazilian Conference on Intelligent Systems (BRACIS), pp. 109–114. IEEE (2018) Bonini, R., Da Silva, F.L., Glatt, R., Spina, E., Costa, A.H.R.: A framework to discover and reuse object-oriented options in reinforcement learning. In: 2018 7th Brazilian Conference on Intelligent Systems (BRACIS), pp. 109–114. IEEE (2018)
5.
Zurück zum Zitat Bonini, R.C., Silva, F.L., Spina, E., Costa, A.H.R.: Using options to accelerate learning of new tasks according to human preferences. In: AAAI Workshop Human-Machine Collaborative Learning, pp. 1–8 (2017) Bonini, R.C., Silva, F.L., Spina, E., Costa, A.H.R.: Using options to accelerate learning of new tasks according to human preferences. In: AAAI Workshop Human-Machine Collaborative Learning, pp. 1–8 (2017)
6.
Zurück zum Zitat Brazhnik, P., Fuente, A., Mendes, P.: Gene networks: how to put the function in genomics. Trends Biotechnol. 20(11), 467–472 (2002)CrossRefPubMed Brazhnik, P., Fuente, A., Mendes, P.: Gene networks: how to put the function in genomics. Trends Biotechnol. 20(11), 467–472 (2002)CrossRefPubMed
7.
Zurück zum Zitat Cover, T.M., Van-Campenhout, J.M.: On the possible orderings in the measurement selection problem. IEEE Trans. Syst. Man Cybern. 7(9), 657–661 (1977)CrossRef Cover, T.M., Van-Campenhout, J.M.: On the possible orderings in the measurement selection problem. IEEE Trans. Syst. Man Cybern. 7(9), 657–661 (1977)CrossRef
8.
Zurück zum Zitat Da Silva, F.L., Nishida, C.E., Roijers, D.M., Costa, A.H.R.: Coordination of electric vehicle charging through multiagent reinforcement learning. IEEE Trans. Smart Grid 11(3), 2347–2356 (2019)CrossRef Da Silva, F.L., Nishida, C.E., Roijers, D.M., Costa, A.H.R.: Coordination of electric vehicle charging through multiagent reinforcement learning. IEEE Trans. Smart Grid 11(3), 2347–2356 (2019)CrossRef
9.
Zurück zum Zitat De Jong, H.: Modeling and simulation of genetic regulatory systems: a literature review. J. Comput. Biol. 9(1), 67–103 (2002)CrossRefPubMed De Jong, H.: Modeling and simulation of genetic regulatory systems: a literature review. J. Comput. Biol. 9(1), 67–103 (2002)CrossRefPubMed
10.
Zurück zum Zitat D’haeseleer, P., Liang, S., Somgyi, R.: Tutorial: gene expression data analysis and modeling. In: Pacific Symposium on Biocomputing. Hawaii, January 1999 D’haeseleer, P., Liang, S., Somgyi, R.: Tutorial: gene expression data analysis and modeling. In: Pacific Symposium on Biocomputing. Hawaii, January 1999
11.
Zurück zum Zitat Dougherty, E.R., Xiao, Y.: Design of probabilistic Boolean networks under the requirement of contextual data consistency. IEEE Trans. Signal Process. 54(9), 3603–3613 (2006)CrossRef Dougherty, E.R., Xiao, Y.: Design of probabilistic Boolean networks under the requirement of contextual data consistency. IEEE Trans. Signal Process. 54(9), 3603–3613 (2006)CrossRef
12.
Zurück zum Zitat Eberwine, J., Sul, J., Bartfai, T., Kim, J.: The promise of single-cell sequencing. Nat. Methods 11, 25–27 (2014)CrossRefPubMed Eberwine, J., Sul, J., Bartfai, T., Kim, J.: The promise of single-cell sequencing. Nat. Methods 11, 25–27 (2014)CrossRefPubMed
13.
Zurück zum Zitat Erdös, P., Rényi, A.: On random graphs. Publ. Math. Debrecen 6, 290–297 (1959)CrossRef Erdös, P., Rényi, A.: On random graphs. Publ. Math. Debrecen 6, 290–297 (1959)CrossRef
14.
Zurück zum Zitat Hecker, M., Lambeck, S., Toepfer, S., van Someren, E., Guthke, R.: Gene regulatory network inference: data integration in dynamic models-a review. Biosystems 96, 86–103 (2009)CrossRefPubMed Hecker, M., Lambeck, S., Toepfer, S., van Someren, E., Guthke, R.: Gene regulatory network inference: data integration in dynamic models-a review. Biosystems 96, 86–103 (2009)CrossRefPubMed
15.
Zurück zum Zitat Jacomini, R.S., Martins-Jr, D.C., Silva, F.L., Costa, A.H.R.: GeNICE: a novel framework for gene network inference by clustering, exhaustive search, and multivariate analysis. J. Comput. Biol. 24(8), 809–830 (2017)CrossRef Jacomini, R.S., Martins-Jr, D.C., Silva, F.L., Costa, A.H.R.: GeNICE: a novel framework for gene network inference by clustering, exhaustive search, and multivariate analysis. J. Comput. Biol. 24(8), 809–830 (2017)CrossRef
16.
Zurück zum Zitat Jimenez, R.D., Martins-Jr, D.C., Santos, C.S.: One genetic algorithm per gene to infer gene networks from expression data. Netw. Modeling Anal. Health Inform. Bioinform. 4, 1–22 (2015) Jimenez, R.D., Martins-Jr, D.C., Santos, C.S.: One genetic algorithm per gene to infer gene networks from expression data. Netw. Modeling Anal. Health Inform. Bioinform. 4, 1–22 (2015)
17.
Zurück zum Zitat Kauffman, S.A.: Homeostasis and differentiation in random genetic control networks. Nature 224(215), 177–178 (1969)CrossRefPubMed Kauffman, S.A.: Homeostasis and differentiation in random genetic control networks. Nature 224(215), 177–178 (1969)CrossRefPubMed
18.
Zurück zum Zitat Liang, S., Fuhrman, S., Somogyi, R.: Reveal, a general reverse engineering algorithm for inference of genetic network architectures. In: Pacific Symposium on Biocomputing, vol. 3, pp. 18–29 (1998) Liang, S., Fuhrman, S., Somogyi, R.: Reveal, a general reverse engineering algorithm for inference of genetic network architectures. In: Pacific Symposium on Biocomputing, vol. 3, pp. 18–29 (1998)
19.
Zurück zum Zitat Lopes, F.M., Martins-Jr, D.C., Barrera, J., Cesar-Jr, R.M.: A feature selection technique for inference of graphs from their known topological properties: revealing scale-free gene regulatory networks. Inf. Sci. 272, 1–15 (2014)CrossRef Lopes, F.M., Martins-Jr, D.C., Barrera, J., Cesar-Jr, R.M.: A feature selection technique for inference of graphs from their known topological properties: revealing scale-free gene regulatory networks. Inf. Sci. 272, 1–15 (2014)CrossRef
20.
Zurück zum Zitat Marbach, D., Prill, R.J., Schaffter, T., Mattiussi, C., Floreano, D., Stolovitzky, G.: Revealing strengths and weaknesses of methods for gene network inference. Proc. Natl. Acad. Sci. 107(14), 6286–6291 (2010)CrossRefPubMedPubMedCentral Marbach, D., Prill, R.J., Schaffter, T., Mattiussi, C., Floreano, D., Stolovitzky, G.: Revealing strengths and weaknesses of methods for gene network inference. Proc. Natl. Acad. Sci. 107(14), 6286–6291 (2010)CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Martins-Jr, D.C., Braga-Neto, U., Hashimoto, R.F., Dougherty, E.R., Bittner, M.L.: Intrinsically multivariate predictive genes. IEEE J. Sel. Top. Signal Process. 2(3), 424–439 (2008)CrossRef Martins-Jr, D.C., Braga-Neto, U., Hashimoto, R.F., Dougherty, E.R., Bittner, M.L.: Intrinsically multivariate predictive genes. IEEE J. Sel. Top. Signal Process. 2(3), 424–439 (2008)CrossRef
22.
Zurück zum Zitat Nam, D., Seo, S., Kim, S.: An efficient top-down search algorithm for learning Boolean networks of gene expression. Mach. Learn. 65, 229–245 (2006)CrossRef Nam, D., Seo, S., Kim, S.: An efficient top-down search algorithm for learning Boolean networks of gene expression. Mach. Learn. 65, 229–245 (2006)CrossRef
23.
Zurück zum Zitat Pratapa, A., Jalihal, A.P., Law, J.N., Bharadwaj, A., Murali, T.: Benchmarking algorithms for gene regulatory network inference from single-cell transcriptomic data. Nat. Methods 17(2), 147–154 (2020)CrossRefPubMedPubMedCentral Pratapa, A., Jalihal, A.P., Law, J.N., Bharadwaj, A., Murali, T.: Benchmarking algorithms for gene regulatory network inference from single-cell transcriptomic data. Nat. Methods 17(2), 147–154 (2020)CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Shalon, D., Smith, S.J., Brown, P.O.: A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. Genome Res. 6, 639–45 (1996)CrossRefPubMed Shalon, D., Smith, S.J., Brown, P.O.: A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. Genome Res. 6, 639–45 (1996)CrossRefPubMed
25.
Zurück zum Zitat Shmulevich, I., Dougherty, E.R., Kim, S., Zhang, W.: Probabilistic Boolean networks: a rule-based uncertainty model for gene regulatory networks. Bioinformatics 18(2), 261–274 (2002)CrossRefPubMed Shmulevich, I., Dougherty, E.R., Kim, S., Zhang, W.: Probabilistic Boolean networks: a rule-based uncertainty model for gene regulatory networks. Bioinformatics 18(2), 261–274 (2002)CrossRefPubMed
26.
Zurück zum Zitat Silva, F.L., Taylor, M.E., Costa, A.H.R.: Autonomously reusing knowledge in multiagent reinforcement learning. In: IJCAI (2018) Silva, F.L., Taylor, M.E., Costa, A.H.R.: Autonomously reusing knowledge in multiagent reinforcement learning. In: IJCAI (2018)
27.
Zurück zum Zitat Snoep, J.L., Westerhoff, H.V.: From isolation to integration, a systems biology approach for building the silicon cell. Top. Curr. Genet. 13, 13–30 (2005)CrossRef Snoep, J.L., Westerhoff, H.V.: From isolation to integration, a systems biology approach for building the silicon cell. Top. Curr. Genet. 13, 13–30 (2005)CrossRef
28.
Zurück zum Zitat Sutton, R.S., Barto, A.G.: Reinforcement Learning: An Introduction, 1st edn. MIT Press, Cambridge (1998) Sutton, R.S., Barto, A.G.: Reinforcement Learning: An Introduction, 1st edn. MIT Press, Cambridge (1998)
29.
Zurück zum Zitat Velculescu, V.E., Zhang, L., Vogelstein, B., Kinzler, K.W.: Serial analysis of gene expression. Science 270, 484–487 (1995)CrossRefPubMed Velculescu, V.E., Zhang, L., Vogelstein, B., Kinzler, K.W.: Serial analysis of gene expression. Science 270, 484–487 (1995)CrossRefPubMed
31.
Zurück zum Zitat Watkins, C.J., Dayan, P.: Q-learning. Mach. Learn. 8(3), 279–292 (1992)CrossRef Watkins, C.J., Dayan, P.: Q-learning. Mach. Learn. 8(3), 279–292 (1992)CrossRef
32.
Zurück zum Zitat Yerudkar, A., Chatzaroulas, E., Del Vecchio, C., Moschoyiannis, S.: Sampled-data control of probabilistic Boolean control networks: a deep reinforcement learning approach. Inf. Sci. 619, 374–389 (2023)CrossRef Yerudkar, A., Chatzaroulas, E., Del Vecchio, C., Moschoyiannis, S.: Sampled-data control of probabilistic Boolean control networks: a deep reinforcement learning approach. Inf. Sci. 619, 374–389 (2023)CrossRef
33.
Zurück zum Zitat Zhang, Y., Chang, X., Liu, X.: Inference of gene regulatory networks using pseudo-time series data. Bioinformatics 37(16), 2423–2431 (2021)CrossRefPubMed Zhang, Y., Chang, X., Liu, X.: Inference of gene regulatory networks using pseudo-time series data. Bioinformatics 37(16), 2423–2431 (2021)CrossRefPubMed
Metadaten
Titel
Gene Networks Inference by Reinforcement Learning
verfasst von
Rodrigo Cesar Bonini
David Correa Martins-Jr
Copyright-Jahr
2023
DOI
https://doi.org/10.1007/978-3-031-42715-2_13

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