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      Conditional Generative Adversarial Networks for Individualized Treatment Effect Estimation and Treatment Selection

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          Abstract

          Treatment response is heterogeneous. However, the classical methods treat the treatment response as homogeneous and estimate the average treatment effects. The traditional methods are difficult to apply to precision oncology. Artificial intelligence (AI) is a powerful tool for precision oncology. It can accurately estimate the individualized treatment effects and learn optimal treatment choices. Therefore, the AI approach can substantially improve progress and treatment outcomes of patients. One AI approach, conditional generative adversarial nets for inference of individualized treatment effects (GANITE) has been developed. However, GANITE can only deal with binary treatment and does not provide a tool for optimal treatment selection. To overcome these limitations, we modify conditional generative adversarial networks (MCGANs) to allow estimation of individualized effects of any types of treatments including binary, categorical and continuous treatments. We propose to use sparse techniques for selection of biomarkers that predict the best treatment for each patient. Simulations show that MCGANs outperform seven other state-of-the-art methods: linear regression (LR), Bayesian linear ridge regression (BLR), k-Nearest Neighbor (KNN), random forest classification [RF (C)], random forest regression [RF (R)], logistic regression (LogR), and support vector machine (SVM). To illustrate their applications, the proposed MCGANs were applied to 256 patients with newly diagnosed acute myeloid leukemia (AML) who were treated with high dose ara-C (HDAC), Idarubicin (IDA) and both of these two treatments (HDAC+IDA) at M. D. Anderson Cancer Center. Our results showed that MCGAN can more accurately and robustly estimate the individualized treatment effects than other state-of-the art methods. Several biomarkers such as GSK3, BILIRUBIN, SMAC are identified and a total of 30 biomarkers can explain 36.8% of treatment effect variation.

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            The central role of the propensity score in observational studies for causal effects

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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                11 December 2020
                2020
                : 11
                : 585804
                Affiliations
                [1] 1Department of Biostatistics and Data Science, School of Public Health, The University of Texas Health Science Center at Houston , Houston, TX, United States
                [2] 2School of Mathematical Sciences, Fudan University , Shanghai, China
                [3] 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [4] 4Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, United States
                [5] 5Department of Medical Genetics, University of Wisconsin-Madison , Madison, WI, United States
                Author notes

                Edited by: Chao Xu, University of Oklahoma Health Sciences Center, United States

                Reviewed by: Shuangxi Ji, University of Texas MD Anderson Cancer Center, United States; Chuan Qiu, Tulane University, United States

                *Correspondence: Momiao Xiong momiao.xiong@ 123456uth.tmc.edu

                This article was submitted to Statistical Genetics and Methodology, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2020.585804
                7759680
                33362849
                747f65e7-5d14-4256-b1e4-be5809cd6c97
                Copyright © 2020 Ge, Huang, Fang, Guo, Liu, Lin and Xiong.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 July 2020
                : 18 November 2020
                Page count
                Figures: 7, Tables: 7, Equations: 28, References: 47, Pages: 17, Words: 10396
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 11925103
                Funded by: National Key Research and Development Program of China Stem Cell and Translational Research 10.13039/501100013290
                Award ID: 2018YFC0116600
                Categories
                Genetics
                Methods

                Genetics
                causal inference,generative adversarial networks,counterfactuals,treatment estimation,precision medicine

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