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pmid:33335112
Detecting methylation signatures in neurodegenerative disease by density-based clustering of applications with reducing noise.
Saurav Mallik · Zhongming Zhao
Scientific reports · 2020 doi:10.1038/s41598-020-78463-3
Paper
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Experiment
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Data
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Analysis
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Execution
absent
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Complete file
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However, analysis of such data often suffers from detecting the outliers of the samples, which subsequently affects the extraction of the true biological signals involved in the disease. To address this critical issue, we developed a novel framework for identifying methylation signatures using consecutive adaptation of a well-known outlier detection algorithm, density based clustering of applications with reducing noise (DBSCAN) followed by hierarchical clustering. We applied the framework to two representative neurodegenerative diseases, Alzheimer's disease (AD) and Down syndrome (DS), using DNA methylation datasets from public sources (Gene Expression Omnibus, GEO accession ID: GSE74486). We first applied DBSCAN algorithm to eliminate outliers, and then used Limma statistical method to determine differentially methylated genes. Next, hierarchical clustering technique was applied to detect gene modules. Our analysis identified a methylation signature comprising 21 genes for AD and a methylation signature comprising 89 genes for DS, respectively. Our evaluation indicated that these two signatures could lead to high classification accuracy values (92% and 70%) for these two diseases. 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"caption": "Top significant KEGG pathways and GO terms enriched with Down syndrome specific genes.", "rows": [["\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {Gsig}^{\\text{a}}$$\\end{document}Gsiga", "KEGG pathway or GO \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\hbox {term}^{\\text{b}}$$\\end{document}termb", "Enrichment p value"], ["ADH1B", "KEGG pathway: hsa05204: Chemical carcinogenesis", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$3.24\\times 10^{-3}$$\\end{document}3.24×10-3"], ["KEGG pathway: hsa00982: Drug metabolism-cytochrome P450", "0.011"], ["CALML6", "KEGG pathway: hsa04740: Olfactory transduction", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5.51\\times 10^{-5}$$\\end{document}5.51×10-5"], ["CD33", "GO-MF: GO:0004872 Receptor activity", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$2.21\\times 10^{-5}$$\\end{document}2.21×10-5"], ["CLEC2B", "GO-MF: GO:0030246 Carbohydrate binding", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5.26\\times 10^{-9}$$\\end{document}5.26×10-9"], ["CX3CR1", "GO-BP: GO:0006935 Chemotaxis", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$8.73\\times 10^{-6}$$\\end{document}8.73×10-6"], ["GO-BP: GO:0070098 Chemokine-mediated signaling pathway", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$2.60\\times 10^{-5}$$\\end{document}2.60×10-5"], ["KEGG pathway: hsa04060: Cytokine–cytokine receptor interaction", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$7.49\\times 10^{-4}$$\\end{document}7.49×10-4"], ["KEGG pathway: hsa04062: Chemokine signaling pathway", "0.044"], ["HAMP", "GO-BP: GO:0006955 Immune response", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$3.25\\times 10^{-10}$$\\end{document}3.25×10-10"], ["LCE3A", "GO-BP: GO:0030216 Keratinocyte differentiation", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$9.70\\times 10^{-4}$$\\end{document}9.70×10-4"], ["OR8G1", "KEGG pathway: hsa04740: Olfactory transduction", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5.51\\times 10^{-5}$$\\end{document}5.51×10-5"], ["OR52H1", "KEGG pathway: hsa04740: Olfactory transduction", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5.51\\times 10^{-5}$$\\end{document}5.51×10-5"], ["PGLYRP1", "GO-BP: GO:0006955 Immune response", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$3.25\\times 10^{-10}$$\\end{document}3.25×10-10"], ["GO-CC: GO:0005576 Extracellular region", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$2.40\\times 10^{-9}$$\\end{document}2.40×10-9"], ["RARRES1", "GO-CC: GO:0016021 Integral component of membrane", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$1.59\\times 10^{-11}$$\\end{document}1.59×10-11"], ["TAS2R41", "GO-BP: GO:0001580 Detection of chemical stimulus involved in sensory perception of bitter taste", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} 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\\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$3.24\\times 10^{-3}$$\\end{document}3.24×10-3"], ["KEGG pathway: hsa00982: Drug metabolism-cytochrome P450", "0.011"], ["CALML6", "KEGG pathway: hsa04740: Olfactory transduction", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5.51\\times 10^{-5}$$\\end{document}5.51×10-5"], ["CD33", "GO-MF: GO:0004872 Receptor activity", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$2.21\\times 10^{-5}$$\\end{document}2.21×10-5"], ["CLEC2B", "GO-MF: GO:0030246 Carbohydrate 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hsa04060: Cytokine–cytokine receptor interaction", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$7.49\\times 10^{-4}$$\\end{document}7.49×10-4"], ["KEGG pathway: hsa04062: Chemokine signaling pathway", "0.044"], ["HAMP", "GO-BP: GO:0006955 Immune response", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$3.25\\times 10^{-10}$$\\end{document}3.25×10-10"], ["LCE3A", "GO-BP: GO:0030216 Keratinocyte differentiation", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$9.70\\times 10^{-4}$$\\end{document}9.70×10-4"], ["OR8G1", "KEGG pathway: hsa04740: Olfactory transduction", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5.51\\times 10^{-5}$$\\end{document}5.51×10-5"], ["OR52H1", "KEGG pathway: hsa04740: Olfactory transduction", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$5.51\\times 10^{-5}$$\\end{document}5.51×10-5"], ["PGLYRP1", "GO-BP: GO:0006955 Immune response", "\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} 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