MetaHiC phage-bacteria infection network reveals active cycling phages of the healthy human gut

  1. Martial Marbouty  Is a corresponding author
  2. Agnès Thierry
  3. Gaël A Millot
  4. Romain Koszul  Is a corresponding author
  1. Institut Pasteur, Unité Régulation Spatiale des Génomes, CNRS, UMR 3525, France
  2. Institut Pasteur, Bioinformatics and Biostatistics Hub, CNRS, USR 3756, France
5 figures, 1 table and 7 additional files

Figures

Figure 1 with 3 supplements
Binning of human gut microbiota using 3C and HiC protocols I and II.

(a) Sex, ID, and age of the 10 individuals investigated in this study. The colors indicate the proximity ligation protocol used to generate the libraries. (b) Computational pipeline of paired-end …

Figure 1—figure supplement 1
Comparisons of 3C and Hi-C protocols I and II.

(a) Bar plot of 3D signal ratio calculated for each constructed library. The 3D ratio is defined as the ratio of the paired-end (PE) reads that link unambiguously two contigs together compared to …

Figure 1—figure supplement 2
Relation between abundance and completion/contamination for the retrieved metagenomic assembled genomes (MAGs).

(a) Plot of the completion (Y-axis) in function of abundance (X-axis; log2) for the 1100 retrieved MAGs (i.e. bins >500 kb). (b) Plot of the contamination (Y-axis) in function of abundance (X-axis; …

Figure 1—figure supplement 3
Comparisons of metagenomic assembled genomes (MAGs) obtained using meta3C, metaHiC protocol I, or metaHiC protocol II.

(a) Venn diagram of the MAGs obtained using meta3C, metaHiC protocol I, or metaHiC protocol II data for the samples #8015, #9010, and #16016. We compared the different retrieved MAGs using the …

Figure 2 with 2 supplements
Metagenomic assembled genomes (MAGs) recovered using meta3C/metaHiC applied on 10 healthy human gut samples.

Phylogenetic tree comprising the 715 reconstructed MAGs with a completion above 50% and a contamination below 10% (691 different species at a threshold of 95% identity). A very long branch was cut …

Figure 2—figure supplement 1
Phylogenetic tree for the 10 processed samples.

Only metagenomic assembled genomes (MAGs) with a completion above 50% and a contamination below 10% are integrated in each tree. Colors of the inner six layers indicate the taxonomy of the MAG …

Figure 2—figure supplement 2
Comparisons of metagenomic assembled genomes (MAGs) taxonomic abundance and reads taxonomic abundance.

Bar charts of MAGs taxonomic abundance (left) and reads taxonomic abundance using Kaiju (Menzel et al., 2016) (right) for each sample. Different taxonomic levels are shown (upper: phylum; middle: …

Figure 3 with 2 supplements
Phage-bacteria network of interactions in human gut.

(a) Pie chart of phages contigs distribution among the different classes (see 'Materials and methods' and Figure 3—figure supplement 1). (b) Gaussian smoothed heatmap of the sequence distance …

Figure 3—figure supplement 1
Classification of phages contigs.

Scheme of the followed process to classify phage contigs in the three classes (A, B, C), as described in the 'Materials and methods' section. Red stars point to the 10 recursive Louvain iterations …

Figure 3—figure supplement 2
Comparison of phages and their characterized hosts between samples.

(a) Circos representation of the 454 pairs of phages belonging to the same genus. The different circles represent the different characterized hosts at different taxonomic levels (from inside to …

Figure 4 with 1 supplement
Phages-host ratio in human intestinal tract.

(a) Boxplot of the coverage ratio between different classes of contigs and the mean coverage of their associated MAGs. From left to right, coverage ratio of: (1) all binned contigs into metagenomic …

Figure 4—figure supplement 1
Phages-hosts ratio.

(a) Boxplot of the coverage ratio between phage contigs and their associated metagenomic assembled genome (MAG) (log2 scale) for the 10 samples. Dashed red lines indicate a ratio of 1. (b) Left: …

Figure 5 with 1 supplement
CrAss-like phages and their associated hosts.

Phylogenetic tree of crAss-like phages contigs found in the 10 assemblies. Representatives of the 10 genera of crAss-like phages described by Guerin et al. are included (in italic blue). Names of …

Figure 5—figure supplement 1
CrAss-like phages contact maps.

Raw contact matrices of the different crAss-like phage contigs found in the 10 assemblies. Each contact map is displayed using 5 kb bins (one pixel = 5 kb). Arrow in the upper right corner indicates …

Tables

Key resources table
Reagent type (species) or resourceDesignationSource or referenceIdentifiersAdditional information
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 17006–19 yo – femaleFreshly frozen from healthy donor
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 16026–20 yo – maleFreshly frozen from healthy donor
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 16021–28 yo – femaleFreshly frozen from healthy donor
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 7016–64 yo – maleFreshly frozen from healthy donor
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 10015–26 yo – femaleFreshly frozen from healthy donor
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 8016–69 femaleFreshly frozen from healthy donor
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 7020–73 yo – maleFreshly frozen from healthy donor
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 16016–35 yo – femaleFreshly frozen from healthy donor
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 8015–64 yo – femaleFreshly frozen from healthy donor
Biological sample (human)Frozen human fecal samplesInstitut Pasteur Biobanque (ICAReB)Patient 9010–60 yo - femaleFreshly frozen from healthy donor
Chemical compound, drugFormaldehyde (35–37%)Sigma AldrichF8775(also contain methanol as stabilizer – 15%)
Chemical compound, drugMyOne streptavidin beadsLife Science
Chemical compound, drugdCTP-14 BiotinLife Science
Software, algorithmCutadaptMartin, 2011v.1.9.1
Software, algorithmFastQCAndrews, 2010v.0.10.1
Software, algorithmMEGAHITLi et al., 2015v.1.1.1.2
Software, algorithmQuastGurevich et al., 2013v.2.2
Software, algorithmbowtie2Langmead and Salzberg, 2012v.2.2.3
Software, algorithmMetaTOR PipelineBaudry et al., 2019
Software, algorithmMetaBatKang et al., 2015
Software, algorithmCheckMParks et al., 2015v1.1.2
Software, algorithmGTDB-TkChaumeil et al., 2020release 0.95
Software, algorithmseqtkseqt, 2020; https://github.com/lh3/seqtk
Software, algorithmhicstuffMatthey-Doret, 2020; https://github.com/koszullab/hicstuff
Software, algorithmLASThttp://last.cbrc.jp/
Software, algorithmitol https://itol.embl.de/
Software, algorithmVirSorterRoux et al., 2015v.1.0.3
Software, algorithmVIBRANTKieft et al., 2020v.1.0.1
Software, algorithmMashOndov et al., 2016v.2.0
Software, algorithmPILER-CREdgar, 2007
Software, algorithmProdigalHyatt et al., 2010v.2.6.3
Software, algorithmMUSCLEEdgar, 2004
Software, algorithmAMASBorowiec, 2016
Software, algorithmIQ-TREENguyen et al., 2015v.1.5.5
Software, algorithmR environmentR Development Core Team, 2020
OtherCovaris S220CovarisAFA tubes
OtherPrecellys TUBEBertin TechnologyVK05 + VK01 glass beads

Additional files

Supplementary file 1

Assembly statistics.

Table indicating different metrics of the 10 sample and the resulting libraries and assemblies.

https://cdn.elifesciences.org/articles/60608/elife-60608-supp1-v2.xlsx
Supplementary file 2

Mapping statistics.

Table indicating different statistics on PE reads mapping and 3D ratio.

https://cdn.elifesciences.org/articles/60608/elife-60608-supp2-v2.xlsx
Supplementary file 3

CrAss-like phages contigs.

Table containing informations on the different detected crAss-like phage contigs.

https://cdn.elifesciences.org/articles/60608/elife-60608-supp3-v2.xlsx
Supplementary file 4

Metagenomic assembled genomes (MAGs) data.

Comma separated file describing the MAGs called in the study: sample, bin ID, bin size, bin mean GC%, bin mean coverage, taxonomy (seven levels), completion, contamination, contigs number, N50, mean contig size, longest contig, coding density.

https://cdn.elifesciences.org/articles/60608/elife-60608-supp4-v2.zip
Supplementary file 5

Contigs data.

Comma separated file describing all the binned contigs present in MAGs: sample, contig ID, contig size, contig coverage, contig GC%, associated bin.

https://cdn.elifesciences.org/articles/60608/elife-60608-supp5-v2.zip
Supplementary file 6

Phages contigs data.

Comma separated file describing all the phages’ contigs associated to MAGs: sample, contig ID, associated bin.

https://cdn.elifesciences.org/articles/60608/elife-60608-supp6-v2.zip
Transparent reporting form
https://cdn.elifesciences.org/articles/60608/elife-60608-transrepform-v2.pdf

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