PreprintCited by 18Genomics and Phylogenetic StudiesPneumonia and Respiratory InfectionsBacterial Genetics and Biotechnology

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PneumoBrowse 2: An integrated visual platform for curated genome annotation and multiomics data analysis of Streptococcus pneumoniae

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Preprint — published as 10.1093/nar/gkae923 · Paper page

Abstract

Streptococcus pneumoniae is an opportunistic human pathogen responsible for high morbidity and mortality rates. Extensive genome sequencing revealed its large pangenome, serotype diversity, and provided insight into genome dynamics. However, functional genome analysis has lagged behind, as that requires detailed and time-consuming manual curation of genome annotations, and integration of genomic and phenotypic data. To remedy this, PneumoBrowse was presented in 2018; a user-friendly interactive online platform, which provided the detailed annotation of the S. pneumoniae D39V genome, alongside transcriptomic data. Since 2018, many new studies on S. pneumoniae genome biology and protein functioning have been performed. Here, we present PneumoBrowse 2 ( https://veeninglab.com/pneumobrowse ) , fully rebuilt in JBrowse 2. We updated annotations for transcribed and transcriptional regulatory features in the D39V genome. We added genome-wide data tracks for high-resolution chromosome conformation capture (Hi-C) data, chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-Seq), ribosome profiling, CRISPRi-seq gene essentiality data and more. Additionally, we included 18 phylogenetically diverse S. pneumoniae genomes and their annotations. By providing easy access to diverse high-quality genome annotations, and links to other databases (including UniProt and AlphaFold), PneumoBrowse 2 will further accelerate research and development into preventive and treatment strategies, through increased understanding of the pneumococcal genome. Graphical abstract:

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Graphical Abstract CC BY · PubMed Central
Figure 1. Genome-wide data tracks for D39V in PneumoBrowse 2. (A) A genome-wide data track for the normalized intensities of ribosome profiling under control conditions has been added for D39V (14). The data track includes the score for the positive strand (upwards, red), and the negative strand (downwards, blue). (B) Genome-wide data tracks for methylated bases in the chromosome of D39V and GC content. The annotations of the methylated sites indicate the type and strand-specificity of the methylated bases. A track for the calculation of GC content (using customizable settings) is provided through the NucContent plugin.
Figure 1. Genome-wide data tracks for D39V in PneumoBrowse 2. (A) A genome-wide data track for the normalized intensities of ribosome profiling under control conditions has been added for D39V (14). The data track includes the score for the positive strand (upwards, red), and the negative strand (downwards, blue). (B) Genome-wide data tracks for methylated bases in the chromosome of D39V and GC content. The annotations of the methylated sites indicate the type and strand-specificity of the methylated bases. A track for the calculation of GC content (using customizable settings) is provided through the NucContent plugin.CC BY · PubMed Central
Figure 2. Tracks with ChIP-Seq data for chromosomal protein binding and Hi-C conformation capture data in PneumoBrowse 2. (A) Genome-wide data tracks representing ChIP-Seq results for HU and RpoB binding to the chromosome. The plotted values indicate the ratio of the signal between the immunoprecipitated and the control experiments at a resolution of 50 bp. MACS2-called peaks in the RpoB- and HU-binding data indicate regions of enriched binding (15). (B) Hi-C chromosome conformation capture data of the first 500,000 nucleotides, with a resolution of 1000 bp, showing the interactions this part of the chromosome on a diagonal line, with interactions marked in red (15).
Figure 2. Tracks with ChIP-Seq data for chromosomal protein binding and Hi-C conformation capture data in PneumoBrowse 2. (A) Genome-wide data tracks representing ChIP-Seq results for HU and RpoB binding to the chromosome. The plotted values indicate the ratio of the signal between the immunoprecipitated and the control experiments at a resolution of 50 bp. MACS2-called peaks in the RpoB- and HU-binding data indicate regions of enriched binding (15). (B) Hi-C chromosome conformation capture data of the first 500,000 nucleotides, with a resolution of 1000 bp, showing the interactions this part of the chromosome on a diagonal line, with interactions marked in red (15).CC BY · PubMed Central
Figure 3. Position of sgRNAs binding sites and detailed information of annotated features for the D39V genome in PneumoBrowse 2. (A) A genome-wide data track displaying the position of the sgRNAs included in the CRISPRi-Seq library for D39V (12,13). The positions of the 20-nucleotide long sgRNA spacers are on the non-template strand of the targeted coding feature. (B) Overview of the information available for each coding feature in the D39V annotation: the information for galU (SPV_1919) is shown. Information for each coding sequence includes links to external resources (AlphaFold, PneumoWiki, UniProt, amongst others), gene essentiality data, and expression data (12) (de Bakker and Veening, data to be published). (C) The predicted AlphaFold structure of GalU that is available through the AlphaFold and UniProt links in PneumoBrowse, is shown.
Figure 3. Position of sgRNAs binding sites and detailed information of annotated features for the D39V genome in PneumoBrowse 2. (A) A genome-wide data track displaying the position of the sgRNAs included in the CRISPRi-Seq library for D39V (12,13). The positions of the 20-nucleotide long sgRNA spacers are on the non-template strand of the targeted coding feature. (B) Overview of the information available for each coding feature in the D39V annotation: the information for galU (SPV_1919) is shown. Information for each coding sequence includes links to external resources (AlphaFold, PneumoWiki, UniProt, amongst others), gene essentiality data, and expression data (12) (de Bakker and Veening, data to be published). (C) The predicted AlphaFold structure of GalU that is available through the AlphaFold and UniProt links in PneumoBrowse, is shown.CC BY · PubMed Central
Figure 4. Addition of 18 phylogenetically diverse pneumococcal genomes besides D39V to PneumoBrowse 2. (A) A mid-point-rooted maximum likelihood phylogenetic tree based on the core genome alignment of the genome sequences presented here, and genomes representing the phylogenetic diversity within the S. pneumoniae species, based on a recombination-corrected core genome alignment (42). Genomes included in PneumoBrowse 2 are highlighted in orange boldface text. (B) For the 18 genomes besides D39V, tracks describing the following are available: the reference sequence; genomic annotation; predicted Rho-independent terminator sequences; predicted binding sites for ComE, ComX and ParB; and methylated genomic bases (not available for SN7572 and R1501). A track for the calculation (using customizable settings) of GC content is provided through the NucContent plugin. (C) Genome wide alignments between all genomes included in PneumoBrowse 2 are available through the data track from each individual genome panel, or through the linear synteny and dotplot alignment views panels. The linear synteny view and dotplot view of the alignment between D39V and DP1322 show the large inversion previously identified in D39V (5).
Figure 4. Addition of 18 phylogenetically diverse pneumococcal genomes besides D39V to PneumoBrowse 2. (A) A mid-point-rooted maximum likelihood phylogenetic tree based on the core genome alignment of the genome sequences presented here, and genomes representing the phylogenetic diversity within the S. pneumoniae species, based on a recombination-corrected core genome alignment (42). Genomes included in PneumoBrowse 2 are highlighted in orange boldface text. (B) For the 18 genomes besides D39V, tracks describing the following are available: the reference sequence; genomic annotation; predicted Rho-independent terminator sequences; predicted binding sites for ComE, ComX and ParB; and methylated genomic bases (not available for SN7572 and R1501). A track for the calculation (using customizable settings) of GC content is provided through the NucContent plugin. (C) Genome wide alignments between all genomes included in PneumoBrowse 2 are available through the data track from each individual genome panel, or through the linear synteny and dotplot alignment views panels. The linear synteny view and dotplot view of the alignment between D39V and DP1322 show the large inversion previously identified in D39V (5).CC BY · PubMed Central

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Metadata

Authors
Janssen, A. B., Gibson, P. S., Bravo, A. M., de Bakker, V., Slager, J., & Veening, J.-W.
Affiliations
  • University of Lausanne (CH)
  • University Medical Center Groningen (NL)
Corresponding author
Veening, Jan-Willem
Venue
Nucleic Acids Research
Publisher
openRxiv
Published
2024-08-07
Volume
53
Issue
D1
Pages
D839-D851
ISSN
0305-1048 (ISSN-L)
OpenAlex
W4403646540
Cited by
18
References
1
Citations by year
2026: 8 · 2025: 10
FWCI
2.45
Type
journal article
Language
en
Open access
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion, cc-by)
  • IRIS (submittedVersion, cc-by)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
  • National Science Foundation
  • Università degli Studi di Siena
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310 030_192 517, TMPFP3_210 202, 51NF40_180 541 792, 310 030_200)
  • Karolinska Institutet
  • Université de Lausanne
  • RWTH Aachen University
  • Universität Greifswald
  • National Center for Chronic Disease Prevention and Health Promotion (R36 DP001322)
  • Faculté de Biologie et de Médecine, Université de Lausanne
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Health Sciences › Medicine › Epidemiology › Pneumonia and Respiratory Infections
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
Streptococcus pneumoniae, genome annotation, multi-omics integration, JBrowse, Hi-C, ChIP-seq, ribosome profiling, gene essentiality, transcriptional regulation, pan-genome, serotype diversity
MeSH terms
Multiomics, Humans, Software, Streptococcus pneumoniae, Genome, Bacterial, Genomics, Databases, Genetic, Molecular Sequence Annotation

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Janssen, A. B., Gibson, P. S., Bravo, A. M., de Bakker, V., Slager, J., & Veening, J.-W. (2024). PneumoBrowse 2: An integrated visual platform for curated genome annotation and multiomics data analysis of Streptococcus pneumoniae. Nucleic Acids Research. https://doi.org/10.1101/2024.08.07.606308