Home › Studies › PRJNA649316
PRJNA649316 SRP274124

Longitudinal gut Hi-C, neutropenic antibiotic patients

Hi-C and metagenomic sequencing of neutropenic patient microbiomes

43 longitudinal gut microbiome samples from adults, including neutropenic patients undergoing antibiotic treatment, using Hi-C and metagenomic sequencing to link bacterial taxa to mobile antibiotic resistance genes. machine-written summary

43 samples · 43 runs · US · Adult · 2020 · 11.14 Gbp / sample

Sources
✓Sequence archive 215○Abstract / description✓Full text 43○Supplementary tables–External resources–User contribution–Human verified

Checked this project's papers and archive records yourself? Mark it human-verified.

what each source gave
✓ Sequence archive215 sample values (collection date, health condition, health condition detail, subject id, timepoint)
○ Abstract / descriptionread; no usable statement
✓ Full text43 sample values (country) · PMC7463002, PMC8294855
○ Supplementary tablesfiles read; no table could be matched to the samples
– External resourcesnot covered by the external resources we ingest
– User contributionnothing uploaded yet
– Human verifiednot yet checked by a person · I checked this project — verify it
Interventions

intervention — arms not resolved

Antibiotic given as the study intervention (incl. eradication therapy design observational_with_procedure · population transplant_or_immunocompromised · Multiple courses of antibiotics during HSCT hospitalization in neutropenic patients

“receive multiple courses of antibiotics” — bioproject.description (study level; per-sample arms are in the intervention column below)

Samples at a glance
1 country
Age
adult43
Condition
transplant_or_immunocompromised33
healthy_control10
Country
US43
Body site
primary43
Collected 2016–2019
2016: 33 samples2019: 10 samples20162019
Sequencing depth per sample · this project all projects
all projects, 0–0.03 Gbp: 25,080 samples (4 %)all projects, 0.03–0.1 Gbp: 17,066 samples (3 %)all projects, 0.1–0.3 Gbp: 29,179 samples (5 %)all projects, 0.3–1 Gbp: 47,044 samples (8 %)all projects, 1–3 Gbp: 124,983 samples (22 %)all projects, 3–10 Gbp: 253,728 samples (44 %)this project, 3–10 Gbp: 19 samplesall projects, 10–30 Gbp: 72,533 samples (13 %)this project, 10–30 Gbp: 22 samplesall projects, 30–100 Gbp: 3,024 samples (1 %)this project, 30–100 Gbp: 2 samplesall projects, 100–300 Gbp: 106 samples (0 %)all projects, ≥ 300 Gbp: 9 samples (0 %)project median 11.14 Gbp per sample0130Gbp
Sampling design and relatedness

longitudinal — not resolved

9 of 9 people sampled more than once (43 samples; median 5, up to 7 per person). Schedule stated by the source: “Samples collected over a 2–3-week period; for patients, from admission for transplant through hospitalization until neutrophil engraftment” (time origin: admission).

How longitudinal and relatedness information is derived

Community composition
Bacteroides 9.7%Phocaeicola 7.3%Streptococcus 4.6%Alistipes 4.2%Blautia_A 3.8%Roseburia 3.8%Veillonella 3.2%Prevotella 3.1%Faecalibacterium 3.1%Parabacteroides 2.4%Lactobacillus 2.0%Anaerostipes 1.9%not assigned to a genus 3.6%other genera 47.4%

Genera, mean relative abundance over 37 profiled gut samples of this project (Sandpiper SingleM profiles, GTDB R232; low-depth and non-metagenome profiles left out).

Field coverage
fieldsamplescoverageR1R2R3R4
age_category43 100%
country43 100%43
health_condition43 100%43
subject_id43 100%43
collection_date43 100%43
health_condition_detail43 100%43
timepoint_label43 100%43
Papers (3)
  • Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C. 2020 PMID 32873785 PMC7463002 own_data
  • Linking plasmid-based beta-lactamases to their bacterial hosts using single-cell fusion PCR. 2021 PMID 34282723 PMC8294855 own_data
  • Noise reduction strategies in metagenomic chromosome confirmation capture to link antibiotic resistance genes to microbial hosts. 2023 PMID 37272920 PMC10327510 unsure
Details
Archive description

The gut microbiome harbors a silent reservoir of antibiotic resistance (AR) genes that is thought to contribute to the emergence of multidrug-resistant pathogens through the process of horizontal gene transfer (HGT). To counteract the spread of AR genes, it is paramount to know which organisms harbor mobile AR genes and with which organisms they engage in HGT. Despite methods to characterize the bulk presence, abundance and function of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) and their concomitant AR genes. Here, we apply and evaluate a high-throughput, culture-independent method for surveilling the bacterial carriage of MGEs, based on bacterial Hi-C protocols. We compare two healthy individuals with a cohort of seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics throughout their prolonged hospitalizations, and are thus acutely vulnerable to the threat of multidrug-resistant infections. We find that the networks of HGT are surprisingly distinct between individuals, yet AR and mobile genes are more dispersed across taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT is occurring throughout the course of treatment in the microbiomes of neutropenic patients and within the guts of healthy individuals over a similar timeframe. Whereas most efforts to understand the spread of AR genes have focused on pathogenic species, our findings shed light on the role of the human gut microbiome in this process.

How this project entered the registry

Classified as human gut / stool shotgun DNA metagenome of adult by deterministic_prior with confidence 0.90. Assay shotgun_dna.

  • host external_curation.infant_catalog · “infant triage reason_code age_adult_only”
  • body site study.description · “The gut microbiome harbors a”
  • body site external_curation.infant_catalog · “body_site_call gut”
  • life stage external_curation.infant_catalog · “infant triage reason_code age_adult_only”
Evidence examples (one per field × route)
samplefieldvaluerouteconf.sourcequote
SAMN15663441collection_date2016/2017R10.90biosample.attribute:collection_date2016/2017
SAMN15663441countryUSR30.70paper.fulltext.methodsBone Marrow Transplantation Unit at New York Presbyterian Hospital
SAMN15663441health_conditiontransplant_or_immunocompromisedR10.85biosample.attribute:TITLETITLE: neutropenic patient stool sample
SAMN15663441health_condition_detailneutropenic patient stool sampleR10.85biosample.attribute:TITLETITLE: neutropenic patient stool sample
SAMN15663441subject_idB314R10.85sample.attr.host_subject_idB314
SAMN15663441timepoint_label1R10.70sample.name_rule:sample_aliasB314-1
Sequencing

43 runs over 43 samples · mean 12.66 Gbp per run (median 11.14 Gbp, total 544.19 Gbp; 43 runs with a base count) · layout PAIRED 43 · platform ILLUMINA 43 · models Illumina NovaSeq 6000 (43) · 86% of runs with a Sandpiper profile · first public 2020-07-30

Authors (31)

Kent AG first · Vill AC · Shi Q · Satlin MJ · Brito IL last · Diebold PJ first · New FN · Hovan M · McCallum GE first · Rossiter AE · Quraishi MN · Iqbal TH · Kuehne SA · van Schaik W last · Argentini C first · Lugli GA · Tarracchini C · Fontana F · Mancabelli L · Viappiani A · Anzalone R · Angelini L · Alessandri G · Longhi G · Bianchi MG · Taurino G · Bussolati O · Milani C · van Sinderen D · Turroni F · Ventura M last

Downloads

PRJNA649316.csv.gz (2.0 KB) · parquet (70.7 KB) — all 43 samples, every field with route and confidence · PRJNA649316_determinations.csv.gz (2.5 KB) — 258 evidence rows

Samples (43 · every field this project has values for · hover a cell for its source)
Loading the sample table…