Abstract
Transcriptomics response of SK-N-AS cells to methamidophos (an acetylcholine esterase inhibitor) exposure was measured at 10 time points between 0.5 and 48 h. The data was analyzed using a combination of traditional statistical methods, machine learning techniques, and methods to infer causal relations between time profiles. We identified several processes that appeared to be upregulated in cells treated with methamidophos including: unfolded protein response, response to cAMP, calcium ion response, and cell-cell signaling. The data confirmed the expected consequence of acetylcholine buildup. Transcripts with potentially key roles were identified by anomaly detection using convolutional autoencoders and Generative Adversarial Networks, and causal networks relating these transcripts were inferred using Siamese convolutional networks and time warp causal inference.
Sponsored by the US Army Research Office and the Defense Advanced Research Projects Agency; accomplished under Cooperative Agreement W911NF-14-2-0020.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Notes
- 1.
Disclaimer. Research was sponsored by the U.S. Army Research Office and the Defense Advanced Research Projects Agency and was accomplished under Cooperative Agreement Number W911NF-14-2-0020. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office, DARPA, or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation hereon.
References
Bromley, J., Guyon, I., LeCun, Y., Säckinger, E., Shah, R.: Signature verification using a “siamese” time delay neural network. In: Cowan, J.D., Tesauro, G., Alspector, J. (eds.) Advances in Neural Information Processing Systems, vol. 6, pp. 737–744. Morgan-Kaufmann (1994)
Goodfellow, I.J., et al.: Generative adversarial nets. In: Proceedings of the 27th International Conference on Neural Information Processing Systems, NIPS 2014, vol. 2, pp. 2672–2680. MIT Press (2014)
Li, D., Zhang, H., Zhong, Y.: Hepatic GDF15 is regulated by CHOP of the unfolded protein response and alleviates NAFLD progression in obese mice. Biochem. Biophys. Res. Commun. 498, 388–394 (2018)
Mi, H., et al.: PANTHER version 11: expanded annotation data from gene ontology and reactome pathways, and data analysis tool enhancements. Nucleic Acids Res. 45(D1), D183–D189 (2017)
Needleman, S.B., Wunsch, C.D.: A general method applicable to the search for similarities in the amino acid sequence of two proteins. J. Mol. Biol. 48(3), 443–453 (1970)
Stehr, M.O., et al.: Learning causality: synthesis of large-scale causal networks from high-dimensional time series data. CoRR abs/1905.02291 (2019). http://arxiv.org/abs/1905.02291
Talcott, C., et al.: Transcriptional response of SK-N-AS cells to methamidophos: extended version (2019). http://www.csl.sri.com/users/clt/XYZ/methamidophosX.pdf
Vertes, A., et al.: Inferring mechanism of action of an unknown compound from time series omics data. In: Češka, M., Šafránek, D. (eds.) CMSB 2018. LNCS, vol. 11095, pp. 238–255. Springer, Cham (2018). https://doi.org/10.1007/978-3-319-99429-1_14
Willoughby, D., Cooper, D.M.F.: Organization and Ca++ regulation of adenylyl cyclases in camp microdomains. Physiol. Rev. 87(3), 965–1010 (2007)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this paper
Cite this paper
Vertes, A. et al. (2019). Transcriptional Response of SK-N-AS Cells to Methamidophos (Extended Abstract). In: Bortolussi, L., Sanguinetti, G. (eds) Computational Methods in Systems Biology. CMSB 2019. Lecture Notes in Computer Science(), vol 11773. Springer, Cham. https://doi.org/10.1007/978-3-030-31304-3_29
Download citation
DOI: https://doi.org/10.1007/978-3-030-31304-3_29
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-31303-6
Online ISBN: 978-3-030-31304-3
eBook Packages: Computer ScienceComputer Science (R0)