{"data":{"id":"10.5061/dryad.3tx95x6s3","type":"dois","attributes":{"doi":"10.5061/dryad.3tx95x6s3","prefix":"10.5061","suffix":"dryad.3tx95x6s3","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Li, Haizhou","nameType":"Personal","givenName":"Haizhou","familyName":"Li","affiliation":["Guangzhou Medical University"],"nameIdentifiers":[{"schemeUri":"https://orcid.org","nameIdentifier":"https://orcid.org/0009-0006-9469-864X","nameIdentifierScheme":"ORCID"}]},{"name":"Kang, Wen-Tyng","nameType":"Personal","givenName":"Wen-Tyng","familyName":"Kang","affiliation":["Guangzhou Medical University"],"nameIdentifiers":[]},{"name":"Zheng, Yujiahui","nameType":"Personal","givenName":"Yujiahui","familyName":"Zheng","affiliation":["Guangzhou Medical University"],"nameIdentifiers":[]},{"name":"He, Yonglv","nameType":"Personal","givenName":"Yonglv","familyName":"He","affiliation":["Guangzhou Medical University"],"nameIdentifiers":[]},{"name":"Zhong, Rongcui","nameType":"Personal","givenName":"Rongcui","familyName":"Zhong","affiliation":["Guangzhou Medical University"],"nameIdentifiers":[]},{"name":"Fang, Shanfang","nameType":"Personal","givenName":"Shanfang","familyName":"Fang","affiliation":["Guangzhou Medical University"],"nameIdentifiers":[]},{"name":"Wen, Weijie","nameType":"Personal","givenName":"Weijie","familyName":"Wen","affiliation":["Guangzhou Medical University"],"nameIdentifiers":[]},{"name":"Liu, Shouping","nameType":"Personal","givenName":"Shouping","familyName":"Liu","affiliation":["Guangzhou Medical University"],"nameIdentifiers":[]},{"name":"Lin, Shuimu","nameType":"Personal","givenName":"Shuimu","familyName":"Lin","affiliation":["Guangzhou Medical University"],"nameIdentifiers":[]}],"titles":[{"title":"Development of xanthone derivatives as effective broad-spectrum antimicrobials: Disrupting cell wall and inhibiting DNA synthesis"}],"publisher":"Dryad","container":{},"publicationYear":2025,"subjects":[{"subject":"FOS: Basic medicine","schemeUri":"https://web-archive.oecd.org/2012-06-15/138575-38235147.pdf","subjectScheme":"fos"},{"subject":"FOS: Basic medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"RNA-seq"},{"subject":"Xanthone"},{"subject":"Antibacterial"},{"subject":"drug-resistant bacteria"}],"contributors":[],"dates":[{"date":"2025-01-06T16:28:40Z","dateType":"Created"},{"date":"2025-01-30T15:47:39Z","dateType":"Submitted"},{"date":"2025-02-10T00:00:00Z","dateType":"Issued"},{"date":"2025-02-10T00:00:00Z","dateType":"Available"}],"language":"en","types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsCitedBy","relatedIdentifier":"10.1126/sciadv.adt4723","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["1076937 bytes"],"formats":[],"version":"4","rightsList":[{"rights":"Creative Commons Zero v1.0 Universal","rightsUri":"https://creativecommons.org/publicdomain/zero/1.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc0-1.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Discovering potent antibiotics is of critical importance due to the\n substantial increases of microbial resistance. Xanthones are intriguing\n sources of antimicrobials, despite a scarcity of extensive investigations\n into their mechanisms of action. Here, we reported the development of a\n series of xanthone derivatives, among which compound XT17 displayed strong\n broad-spectrum antibacterial activity, weak hemolytic activity and low\n cytotoxicity against mammalian cell lines, low frequencies of drug\n resistance, and potent in vivo efficacy in Staphylococcu aureus or\n Pseudomonas aeruginosa induced murine corneal infection models. Compound\n XT17 presented a multifaceted mode of actions, involving the disruption of\n cell wall by interacting with lipoteichoic acid or lipopolysaccharides and\n the suppression of DNA synthesis. A further docking study confirmed the\n capability of compound XT17 to form a stable complex with the bacterial\n gyrase enzyme. This work could offer an innovative design strategy for\n developing broad-spectrum therapeutic agents against drug-resistant\n bacteria.","descriptionType":"Abstract"},{"description":"A series of xanthone derived antimicrobial agents were designed\n and synthesized. The xanthone scaffold serves as the core precursor for a\n further chemically modification at its phenolic hydroxyl positions to\n improve the pharmacological properties of xanthone derivatives against\n both Gram-positive and Gram-negative bacteria. The candidate compound\n XT17, identified through a structure-activity relationship (SAR) study of\n these synthesized compounds, showed strong bactericidal properties and\n potent in vitro efficacy. A comprehensive transcriptomic analysis of the\n candidate compound XT17 was assessed using the high-throughput RNA-seq\n technique to gain insight into the antibacterial mechanisms. This efficacy\n stems from a dual-action mechanism: cell wall destruction and DNA gyrase\n inhibition. \u003cstrong\u003eGrowth condition and total\n RNA extraction\u003c/strong\u003e For the challenge\n experiments, 5 ml of \u003cem\u003eE. coli\u003c/em\u003e ATCC 25922 at an\n OD\u003csub\u003e600\u003c/sub\u003e of 0.5, representing the mid-log phase, was\n exposed to compound XT17 (4× MIC) for 2 h in a biological duplicate.\n Cultures treated with 4× MIC ciprofloxacin and without antibiotics served\n as positive and negative controls, respectively. After exposure, 1 ml\n aliquots of cells were immediately pelleted at 4 °C by centrifugation for\n 2 min at 2000 rpm. The supernatants were removed and immediately frozen in\n liquid nitrogen. The samples were stored at −80 °C for later total RNA\n isolation. Total RNA was extracted using the bacterial RNA kit (Omega\n Bio-Tek, USA) according to the manufacturer’s instructions. The RNA\n Integrity Number (RIN) values were obtained to assess RNA quality using an\n Agilent Genomics 2200 Tape Station instrument.\n \u003cstrong\u003eTranscriptome sequencing \u003c/strong\u003e\n A total amount of 2–5 ng of the RNA per sample was executed as\n the input material to construct each cDNA library for RNA sequencing using\n the NEBNext Ultra Directional RNA Library prep kit from Illumina. The\n quality of the resulting libraries was checked using Agilent High\n Sensitivity DNA chips to ensure proper library size distribution and the\n absence of small adapters. Libraries were quantified and normalized by\n qPCR before being sequenced at 150 cycles with the NextSeq 500 High Output\n Kit, yielding approximately 9 million, 75 bp, and paired-end reads for\n each library. \u003cstrong\u003eBioinformatics\n analysis\u003c/strong\u003e Read mapping was aligned using\n Bowtie2. HTSeq v0.6.1 was used for quantification of expression levels.\n DESeq2 on the R package (v1.12.4) was used to calculate differentially\n expressed genes. Differential expression was computed using edgeR:\n exactTest for each treatment versus the untreated control. The\n \u003cem\u003eE. coli\u003c/em\u003e database used for mapping was\n GCF_017357505.1_ASM1735750v1_genomic.fna. Both the Gene Ontology (GO), and\n Kyoto Encyclopedia of Genes and Genomes (KEGG Ortholog database)\n enrichment analyses were done with Fisher’s exact test. All\n \u003cem\u003eP\u003c/em\u003e values were adjusted with the Benjamini-Hochberg\n procedure to generate false-discovery rates (FDRs; adjusted\n \u003cem\u003eP\u003c/em\u003e values). GO enrichment analysis was carried out\n using the clusterProfiler package on the R platform. KEGG pathway mapping\n and figure generation were performed with the PathView website. Clusters\n of Orthologous Groups (COG) of protein databases with an E-value of 1\n e\u003csup\u003e-5\u003c/sup\u003e. For hierarchal clustering analysis of gene\n expression, the gene expression levels were normalized to z-scores of\n log\u003csub\u003e10 \u003c/sub\u003e(FPKM + 1), where FPKM is fragments per\n kilobase per million. For hierarchal clustering analysis of the regulation\n of transcription factors, the UMPGA method was used as the clustering\n method. Transcription of genes that were not notably regulated was\n considered unchanged. Volcano plots were generated by plot_volcano from\n soothsayer (https://github.com/jolespin/soothsayer) in Python v.3.6.6.\n Directed networks (DiNetwork) were constructed and plotted using NetworkX\n and Matplotlib Python packages, respectively. Hierarchical clustering\n analysis and heatmap calculation were performed with the pheatmap package\n on R platform. The umap package on the R platform was used for UMAP\n analysis of FPKM vectors of each transcriptome. The figures were created\n via ggplot2 package.","descriptionType":"Methods"},{"description":"# Development of xanthone derivatives as effective broad-spectrum\n antimicrobials: Disrupting cell wall and inhibiting DNA synthesis\n [https://doi.org/10.5061/dryad.3tx95x6s3\n ](https://doi.org/10.5061/dryad.3tx95x6s3) ## Description of the data and\n file structure ### Files and variables #### File:\n CPF\\_vs\\_CONTROL.gene\\_DE.signi.addAnno.xlsx **Description:**  The\n transcriptome changes on Ciprofloxacin (CPF)-treated *E. coli* ATCC 25922\n via RNA sequencing (RNA-seq) technology. ##### Variables * Mean\n TPM, log2FoldChange, p Value, q Value  #### File:\n XT17\\_vs\\_CONTROL.gene\\_DE.signi.addAnno.xlsx **Description:** The\n transcriptome changes on compound **XT17**-treated *E. coli* ATCC 25922\n via RNA sequencing (RNA-seq) technology. ##### Variables Mean\n TPM, log2FoldChange, p Value, q Value  | **abbreviation** |\n **description** | | :--------------- |\n :---------------------------------------------------------------------------------------------------------------------- | | Gene id | Gene Identifier | | down | down regulated genes | | up | up regulated genes | | MeanTPM | Mean Transcripts Per Million | | log2FoldChange | Representing the ratio of expression levels between two samples | | pValue | Used to evaluate whether the differences between samples are significant | | qValue | Statistical measure for controlling false positive rate | | GO | Gene Ontology | | KEGG | ‌Kyoto Encyclopedia of Genes and Genomes | | COG | Cluster of Orthologous Groups | | - | Indicating that there is no relevant annotation information for this gene or protein under a specific GO/KEGG/COG term. | ## Code/software Read mapping was aligned using Bowtie2. HTSeq v0.6.1 was used for quantification of expression levels. DESeq2 on the R package (v1.12.4) was used to calculate differentially expressed genes. Differential expression was computed using edgeR: exactTest for each treatment versus the untreated control. Volcano plots were generated by plot_volcano from soothsayer ([https://github.com/jolespin/soothsayer](https://github.com/jolespin/soothsayer)) in Python v.3.6.6. Directed networks (DiNetwork) were constructed and plotted using NetworkX and Matplotlib Python packages, respectively. Hierarchical clustering analysis and heatmap calculation were performed with the pheatmap package on R platform. The umap package on the R platform was used for UMAP analysis of FPKM vectors of each transcriptome. The figures were created via ggplot2 package.","descriptionType":"TechnicalInfo"}],"geoLocations":[],"fundingReferences":[{"schemeUri":"https://ror.org","funderName":"National Natural Science Foundation of China","awardNumber":"22277016","funderIdentifier":"https://ror.org/01h0zpd94","funderIdentifierType":"ROR"},{"schemeUri":"https://ror.org","funderName":"National Natural Science Foundation of China","awardNumber":"21907019","funderIdentifier":"https://ror.org/01h0zpd94","funderIdentifierType":"ROR"}],"xml":"<?xml version="1.0" encoding="UTF-8"?>
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  <identifier identifierType="DOI">10.5061/DRYAD.3TX95X6S3</identifier>
  <creators>
    <creator>
      <creatorName nameType="Personal">Li, Haizhou</creatorName>
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      <affiliation affiliationIdentifier="https://ror.org/00zat6v61" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Guangzhou Medical University</affiliation>
    </creator>
    <creator>
      <creatorName nameType="Personal">Kang, Wen-Tyng</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00zat6v61" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Guangzhou Medical University</affiliation>
    </creator>
    <creator>
      <creatorName nameType="Personal">Zheng, Yujiahui</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00zat6v61" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Guangzhou Medical University</affiliation>
    </creator>
    <creator>
      <creatorName nameType="Personal">He, Yonglv</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00zat6v61" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Guangzhou Medical University</affiliation>
    </creator>
    <creator>
      <creatorName nameType="Personal">Zhong, Rongcui</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00zat6v61" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Guangzhou Medical University</affiliation>
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      <creatorName nameType="Personal">Fang, Shanfang</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00zat6v61" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Guangzhou Medical University</affiliation>
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    <creator>
      <creatorName nameType="Personal">Wen, Weijie</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00zat6v61" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Guangzhou Medical University</affiliation>
    </creator>
    <creator>
      <creatorName nameType="Personal">Liu, Shouping</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00zat6v61" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Guangzhou Medical University</affiliation>
    </creator>
    <creator>
      <creatorName nameType="Personal">Lin, Shuimu</creatorName>
      <affiliation affiliationIdentifier="https://ror.org/00zat6v61" affiliationIdentifierScheme="ROR" schemeURI="https://ror.org">Guangzhou Medical University</affiliation>
    </creator>
  </creators>
  <titles>
    <title>
      Development of xanthone derivatives as effective broad-spectrum
      antimicrobials: Disrupting cell wall and inhibiting DNA synthesis
    </title>
  </titles>
  <publisher publisherIdentifier="https://ror.org/00x6h5n95" publisherIdentifierScheme="ROR" schemeURI="https://ror.org/">Dryad</publisher>
  <resourceType resourceTypeGeneral="Dataset">dataset</resourceType>
  <publicationYear>2025</publicationYear>
  <subjects>
    <subject subjectScheme="fos" schemeURI="https://web-archive.oecd.org/2012-06-15/138575-38235147.pdf">FOS: Basic medicine</subject>
    <subject>RNA-seq</subject>
    <subject>Xanthone</subject>
    <subject>Antibacterial</subject>
    <subject>drug-resistant bacteria</subject>
  </subjects>
  <fundingReferences>
    <fundingReference>
      <funderName>National Natural Science Foundation of China</funderName>
      <funderIdentifier funderIdentifierType="ROR">https://ror.org/01h0zpd94</funderIdentifier>
      <awardNumber>22277016</awardNumber>
    </fundingReference>
    <fundingReference>
      <funderName>National Natural Science Foundation of China</funderName>
      <funderIdentifier funderIdentifierType="ROR">https://ror.org/01h0zpd94</funderIdentifier>
      <awardNumber>21907019</awardNumber>
    </fundingReference>
  </fundingReferences>
  <dates>
    <date dateType="Created">2025-01-06T16:28:40Z</date>
    <date dateType="Submitted">2025-01-30T15:47:39Z</date>
    <date dateType="Issued">2025-02-10T00:00:00Z</date>
    <date dateType="Available">2025-02-10T00:00:00Z</date>
  </dates>
  <language>en</language>
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  <descriptions>
    <description descriptionType="Abstract">
      Discovering potent antibiotics is of critical importance due to the
      substantial increases of microbial resistance. Xanthones are intriguing
      sources of antimicrobials, despite a scarcity of extensive investigations
      into their mechanisms of action. Here, we reported the development of a
      series of xanthone derivatives, among which compound XT17 displayed strong
      broad-spectrum antibacterial activity, weak hemolytic activity and low
      cytotoxicity against mammalian cell lines, low frequencies of drug
      resistance, and potent in vivo efficacy in Staphylococcu aureus or
      Pseudomonas aeruginosa induced murine corneal infection models. Compound
      XT17 presented a multifaceted mode of actions, involving the disruption of
      cell wall by interacting with lipoteichoic acid or lipopolysaccharides and
      the suppression of DNA synthesis. A further docking study confirmed the
      capability of compound XT17 to form a stable complex with the bacterial
      gyrase enzyme. This work could offer an innovative design strategy for
      developing broad-spectrum therapeutic agents against drug-resistant
      bacteria.
    </description>
    <description descriptionType="Methods">
      &lt;p&gt;A series of xanthone derived antimicrobial agents were designed
      and synthesized. The xanthone scaffold serves as the core precursor for a
      further chemically modification at its phenolic hydroxyl positions to
      improve the pharmacological properties of xanthone derivatives against
      both Gram-positive and Gram-negative bacteria. The candidate compound
      XT17, identified through a structure-activity relationship (SAR) study of
      these synthesized compounds, showed strong bactericidal properties and
      potent in vitro efficacy. A comprehensive transcriptomic analysis of the
      candidate compound XT17 was assessed using the high-throughput RNA-seq
      technique to gain insight into the antibacterial mechanisms. This efficacy
      stems from a dual-action mechanism: cell wall destruction and DNA gyrase
      inhibition.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Growth condition and total
      RNA extraction&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;For the challenge
      experiments, 5 ml of &lt;em&gt;E. coli&lt;/em&gt; ATCC 25922 at an
      OD&lt;sub&gt;600&lt;/sub&gt; of 0.5, representing the mid-log phase, was
      exposed to compound XT17 (4× MIC) for 2 h in a biological duplicate.
      Cultures treated with 4× MIC ciprofloxacin and without antibiotics served
      as positive and negative controls, respectively. After exposure, 1 ml
      aliquots of cells were immediately pelleted at 4 °C by centrifugation for
      2 min at 2000 rpm. The supernatants were removed and immediately frozen in
      liquid nitrogen. The samples were stored at −80 °C for later total RNA
      isolation. Total RNA was extracted using the bacterial RNA kit (Omega
      Bio-Tek, USA) according to the manufacturer’s instructions. The RNA
      Integrity Number (RIN) values were obtained to assess RNA quality using an
      Agilent Genomics 2200 Tape Station instrument.&lt;/p&gt;
      &lt;p&gt;&lt;strong&gt;Transcriptome sequencing &lt;/strong&gt;&lt;/p&gt;
      &lt;p&gt;A total amount of 2–5 ng of the RNA per sample was executed as
      the input material to construct each cDNA library for RNA sequencing using
      the NEBNext Ultra Directional RNA Library prep kit from Illumina. The
      quality of the resulting libraries was checked using Agilent High
      Sensitivity DNA chips to ensure proper library size distribution and the
      absence of small adapters. Libraries were quantified and normalized by
      qPCR before being sequenced at 150 cycles with the NextSeq 500 High Output
      Kit, yielding approximately 9 million, 75 bp, and paired-end reads for
      each library.&lt;/p&gt; &lt;p&gt;&lt;strong&gt;Bioinformatics
      analysis&lt;/strong&gt;&lt;/p&gt; &lt;p&gt;Read mapping was aligned using
      Bowtie2. HTSeq v0.6.1 was used for quantification of expression levels.
      DESeq2 on the R package (v1.12.4) was used to calculate differentially
      expressed genes. Differential expression was computed using edgeR:
      exactTest for each treatment versus the untreated control. The
      &lt;em&gt;E. coli&lt;/em&gt; database used for mapping was
      GCF_017357505.1_ASM1735750v1_genomic.fna. Both the Gene Ontology (GO), and
      Kyoto Encyclopedia of Genes and Genomes (KEGG Ortholog database)
      enrichment analyses were done with Fisher’s exact test. All
      &lt;em&gt;P&lt;/em&gt; values were adjusted with the Benjamini-Hochberg
      procedure to generate false-discovery rates (FDRs; adjusted
      &lt;em&gt;P&lt;/em&gt; values). GO enrichment analysis was carried out
      using the clusterProfiler package on the R platform. KEGG pathway mapping
      and figure generation were performed with the PathView website. Clusters
      of Orthologous Groups (COG) of protein databases with an E-value of 1
      e&lt;sup&gt;-5&lt;/sup&gt;. For hierarchal clustering analysis of gene
      expression, the gene expression levels were normalized to z-scores of
      log&lt;sub&gt;10 &lt;/sub&gt;(FPKM + 1), where FPKM is fragments per
      kilobase per million. For hierarchal clustering analysis of the regulation
      of transcription factors, the UMPGA method was used as the clustering
      method. Transcription of genes that were not notably regulated was
      considered unchanged. Volcano plots were generated by plot_volcano from
      soothsayer (https://github.com/jolespin/soothsayer) in Python v.3.6.6.
      Directed networks (DiNetwork) were constructed and plotted using NetworkX
      and Matplotlib Python packages, respectively. Hierarchical clustering
      analysis and heatmap calculation were performed with the pheatmap package
      on R platform. The umap package on the R platform was used for UMAP
      analysis of FPKM vectors of each transcriptome. The figures were created
      via ggplot2 package.&lt;/p&gt;
    </description>
    <description descriptionType="TechnicalInfo">
      # Development of xanthone derivatives as effective broad-spectrum
      antimicrobials: Disrupting cell wall and inhibiting DNA synthesis
      [https://doi.org/10.5061/dryad.3tx95x6s3
      ](https://doi.org/10.5061/dryad.3tx95x6s3) ## Description of the data and
      file structure ### Files and variables #### File:
      CPF\_vs\_CONTROL.gene\_DE.signi.addAnno.xlsx **Description:**  The
      transcriptome changes on Ciprofloxacin (CPF)-treated *E. coli* ATCC 25922
      via RNA sequencing (RNA-seq) technology. ##### Variables * Mean
      TPM, log2FoldChange, p Value, q Value  #### File:
      XT17\_vs\_CONTROL.gene\_DE.signi.addAnno.xlsx **Description:** The
      transcriptome changes on compound **XT17**-treated *E. coli* ATCC 25922
      via RNA sequencing (RNA-seq) technology. ##### Variables Mean
      TPM, log2FoldChange, p Value, q Value  | **abbreviation** |
      **description** | | :--------------- |
      :---------------------------------------------------------------------------------------------------------------------- | | Gene id | Gene Identifier | | down | down regulated genes | | up | up regulated genes | | MeanTPM | Mean Transcripts Per Million | | log2FoldChange | Representing the ratio of expression levels between two samples | | pValue | Used to evaluate whether the differences between samples are significant | | qValue | Statistical measure for controlling false positive rate | | GO | Gene Ontology | | KEGG | ‌Kyoto Encyclopedia of Genes and Genomes | | COG | Cluster of Orthologous Groups | | - | Indicating that there is no relevant annotation information for this gene or protein under a specific GO/KEGG/COG term. | ## Code/software Read mapping was aligned using Bowtie2. HTSeq v0.6.1 was used for quantification of expression levels. DESeq2 on the R package (v1.12.4) was used to calculate differentially expressed genes. Differential expression was computed using edgeR: exactTest for each treatment versus the untreated control. Volcano plots were generated by plot_volcano from soothsayer ([https://github.com/jolespin/soothsayer](https://github.com/jolespin/soothsayer)) in Python v.3.6.6. Directed networks (DiNetwork) were constructed and plotted using NetworkX and Matplotlib Python packages, respectively. Hierarchical clustering analysis and heatmap calculation were performed with the pheatmap package on R platform. The umap package on the R platform was used for UMAP analysis of FPKM vectors of each transcriptome. The figures were created via ggplot2 package.
    </description>
  </descriptions>
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