08eb3f88a13bbfb5913a83fe02350982 antibiotics_a2021v10n2p97.pdf 730161977fd4e011d79400b3a3e968ae7af0842f antibiotics_a2021v10n2p97.pdf 8cfc7eea05e3b591d0cd468c573a88a84cf7a8c4510b005018c05d40becf69f1 antibiotics_a2021v10n2p97.pdf Title: Weighted Gene Co-Expression Network Analysis Identifies Key Modules and Hub Genes Associated with Mycobacterial Infection of Human Macrophages Subject: Tuberculosis (TB) is still a leading cause of death worldwide. Treatments remain unsatisfactory due to an incomplete understanding of the underlying host–pathogen interactions during infection. In the present study, weighted gene co-expression network analysis (WGCNA) was conducted to identify key macrophage modules and hub genes associated with mycobacterial infection. WGCNA was performed combining our own transcriptomic results using Mycobacterium aurum-infected human monocytic macrophages (THP1) with publicly accessible datasets obtained from three types of macrophages infected with seven different mycobacterial strains in various one-to-one combinations. A hierarchical clustering tree of 11,533 genes was built from 198 samples, and 47 distinct modules were revealed. We identified a module, consisting of 226 genes, which represented the common response of host macrophages to different mycobacterial infections that showed significant enrichment in innate immune stimulation, bacterial pattern recognition, and leukocyte chemotaxis. Moreover, by network analysis applied to the 74 genes with the best correlation with mycobacteria infection, we identified the top 10 hub-connecting genes: NAMPT, IRAK2, SOCS3, PTGS2, CCL20, IL1B, ZC3H12A, ABTB2, GFPT2, and ELOVL7. Interestingly, apart from the well-known Toll-like receptor and inflammation-associated genes, other genes may serve as novel TB diagnosis markers and potential therapeutic targets. Keywords: mycobacterium; macrophage; WGCNA; transcriptome; network analysis Author: Lu Lu, RanLei Wei, Sanjib Bhakta, Simon J. Waddell and Ester Boix Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Jan 20 10:52:18 2021 CET ModDate: Wed Jan 20 11:30:53 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4057344 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- TLGRFU+VnURWPalladioL Type 1 Custom yes yes no 10 0 ZQVPWY+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 GKHATZ+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 PHKEQA+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 YYFPCJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 33 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 55 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 59 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 63 0 JBTTSN+VnURWPalladioL-Italic Type 1 Custom yes yes no 78 0 CBSRZX+EURM10 Type 1 Builtin yes yes no 85 0 GDDFBL+PalatinoLinotype CID TrueType Identity-H yes yes yes 99 0 GDDFCN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 105 0 GDDFBK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 108 0 GDDFBM+PalatinoLinotype TrueType WinAnsi yes yes no 111 0 GDDFCN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 125 0 GDDFBK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 128 0 GDDFBM+PalatinoLinotype TrueType WinAnsi yes yes no 131 0 GDDFCN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 150 0 GDDFBK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 153 0 GDDFBM+PalatinoLinotype TrueType WinAnsi yes yes no 156 0 GDDFCN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 178 0 GDDFBK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 181 0 GDDFBM+PalatinoLinotype TrueType WinAnsi yes yes no 184 0 GDDFCN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 202 0 GDDFBK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 205 0 GDDFBM+PalatinoLinotype TrueType WinAnsi yes yes no 208 0 GDDFBK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 223 0 GDDFBM+PalatinoLinotype TrueType WinAnsi yes yes no 226 0 GDDFCN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 229 0 GDDFCN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 249 0 GDDFBK+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 252 0 GDDFBM+PalatinoLinotype TrueType WinAnsi yes yes no 255 0 OCXAOJ+PazoMath-Italic Type 1 Builtin yes yes no 265 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2021-02-11 02:18:49 CET RepresentationInformation: antibiotics_a2021v10n2p97.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-02-01 13:26:57 CET Size: 4057344 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 515 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Construction of Weighted Co-Expression Network Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Correlation between Modules and Identification of Key Modules Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Functional Enrichment and Identification of Hub Genes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Children: Item: Title: RNA Sequencing of Human Monocyte-Derived Macrophage (THP-1) Infected with M. Aurum Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Data Collection and Sample Processing for WGCNA Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Construction of Weighted Gene Co-Expressed Networks Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Functional Enrichment of Recurrence-Associated Modules Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Identification of Hub Genes in Key Modules Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Info: Title: Weighted Gene Co-Expression Network Analysis Identifies Key Modules and Hub Genes Associated with Mycobacterial Infection of Human Macrophages Author: Lu Lu, RanLei Wei, Sanjib Bhakta, Simon J. Waddell and Ester Boix Subject: Tuberculosis (TB) is still a leading cause of death worldwide. Treatments remain unsatisfactory due to an incomplete understanding of the underlying host pathogen interactions during infection. In the present study, weighted gene co-expression network analysis (WGCNA) was conducted to identify key macrophage modules and hub genes associated with mycobacterial infection. WGCNA was performed combining our own transcriptomic results using Mycobacterium aurum-infected human monocytic macrophages (THP1) with publicly accessible datasets obtained from three types of macrophages infected with seven different mycobacterial strains in various one-to-one combinations. A hierarchical clustering tree of 11,533 genes was built from 198 samples, and 47 distinct modules were revealed. We identified a module, consisting of 226 genes, which represented the common response of host macrophages to different mycobacterial infections that showed significant enrichment in innate immune stimulation, bacterial pattern recognition, and leukocyte chemotaxis. Moreover, by network analysis applied to the 74 genes with the best correlation with mycobacteria infection, we identified the top 10 hub-connecting genes: NAMPT, IRAK2, SOCS3, PTGS2, CCL20, IL1B, ZC3H12A, ABTB2, GFPT2, and ELOVL7. Interestingly, apart from the well-known Toll-like receptor and inflammation-associated genes, other genes may serve as novel TB diagnosis markers and potential therapeutic targets. 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