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      Application of Artificial Intelligence Modeling Technology Based on Fluid Biopsy to Diagnose Alzheimer’s Disease

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          Abstract

          Background: There are no obvious clinical signs and symptoms in the early stages of Alzheimer’s disease (AD), and most patients usually have mild cognitive impairment (MCI) before diagnosis. Therefore, early diagnosis of AD is very critical. This paper mainly discusses the blood biomarkers of AD patients and uses machine learning methods to study the changes of blood transcriptome during the development of AD and to search for potential blood biomarkers for AD.

          Methods: Individualized blood mRNA expression data of 711 patients were downloaded from the GEO database, including the control group (CON) (238 patients), MCI (189 patients), and AD (284 patients). Firstly, we analyzed the subcellular localization, protein types and enrichment pathways of the differentially expressed mRNAs in each group, and established an artificial intelligence individualized diagnostic model. Furthermore, the XCell tool was used to analyze the blood mRNA expression data and obtain blood cell composition and quantitative data. Ratio characteristics were established for mRNA and XCell data. Feature engineering operations such as collinearity and importance analysis were performed on all features to obtain the best feature solicitation. Finally, four machine learning algorithms, including linear support vector machine (SVM), Adaboost, random forest and artificial neural network, were used to model the optimal feature combinations and evaluate their classification performance in the test set.

          Results: Through feature engineering screening, the best feature collection was obtained. Moreover, the artificial intelligence individualized diagnosis model established based on this method achieved a classification accuracy of 91.59% in the test set. The area under curve (AUC) of CON, MCI, and AD were 0.9746, 0.9536, and 0.9807, respectively.

          Conclusion: The results of cell homeostasis analysis suggested that the homeostasis of Natural killer T cell (NKT) might be related to AD, and the homeostasis of Granulocyte macrophage progenitor (GMP) might be one of the reasons for AD.

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          Most cited references37

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          Support-vector networks

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            xCell: digitally portraying the tissue cellular heterogeneity landscape

            Tissues are complex milieus consisting of numerous cell types. Several recent methods have attempted to enumerate cell subsets from transcriptomes. However, the available methods have used limited sources for training and give only a partial portrayal of the full cellular landscape. Here we present xCell, a novel gene signature-based method, and use it to infer 64 immune and stromal cell types. We harmonized 1822 pure human cell type transcriptomes from various sources and employed a curve fitting approach for linear comparison of cell types and introduced a novel spillover compensation technique for separating them. Using extensive in silico analyses and comparison to cytometry immunophenotyping, we show that xCell outperforms other methods. xCell is available at http://xCell.ucsf.edu/. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1349-1) contains supplementary material, which is available to authorized users.
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              Causal analysis approaches in Ingenuity Pathway Analysis

              Motivation: Prior biological knowledge greatly facilitates the meaningful interpretation of gene-expression data. Causal networks constructed from individual relationships curated from the literature are particularly suited for this task, since they create mechanistic hypotheses that explain the expression changes observed in datasets. Results: We present and discuss a suite of algorithms and tools for inferring and scoring regulator networks upstream of gene-expression data based on a large-scale causal network derived from the Ingenuity Knowledge Base. We extend the method to predict downstream effects on biological functions and diseases and demonstrate the validity of our approach by applying it to example datasets. Availability: The causal analytics tools ‘Upstream Regulator Analysis', ‘Mechanistic Networks', ‘Causal Network Analysis' and ‘Downstream Effects Analysis' are implemented and available within Ingenuity Pathway Analysis (IPA, http://www.ingenuity.com). Supplementary information: Supplementary material is available at Bioinformatics online.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                03 December 2021
                2021
                : 13
                : 768229
                Affiliations
                [1] 1Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University , Fuzhou, China
                [2] 2China National Center for Bioinformation , Beijing, China
                [3] 3Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences , Beijing, China
                [4] 4Chinese Academy of Sciences Key Laboratory of Standardization and Measurement for Nanotechnology, Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Chinese Academy of Sciences Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China , Beijing, China
                [5] 5School of Nanoscience and Technology, Sino-Danish College, University of Chinese Academy of Sciences , Beijing, China
                [6] 6School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology , Wuhan, China
                Author notes

                Edited by: Xiuqin Jia, Capital Medical University, China

                Reviewed by: Ke Du, China Medical University, China; Fuzhou Hua, Second Affiliated Hospital of Nanchang University, China; Kewei Chen, Banner Alzheimer’s Institute, United States

                *Correspondence: Xiuli Zhang, zhxiuli@ 123456gmail.com

                These authors have contributed equally to this work

                This article was submitted to Alzheimer’s Disease and Related Dementias, a section of the journal Frontiers in Aging Neuroscience

                Article
                10.3389/fnagi.2021.768229
                8679840
                34924996
                368fe1bc-1a57-4e9c-abb8-73ea496a509a
                Copyright © 2021 Sh, Liu, Zhang, Zhou, Hu and Zhang.

                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
                : 31 August 2021
                : 15 October 2021
                Page count
                Figures: 5, Tables: 1, Equations: 3, References: 37, Pages: 12, Words: 7585
                Categories
                Aging Neuroscience
                Original Research

                Neurosciences
                alzheimer’s disease,mild cognitive impairment,artificial intelligence,predictive diagnostics,blood biomarkers

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