Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women

Study information

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

29765068

DOI Digital object identifier for electronic documents.

10.1038/s41598-018-25879-7

URI

Authors

Łaniewski P, Barnes D, Goulder A, Cui H, Roe DJ, Chase DM, Herbst-Kralovetz MM

Journal

Scientific reports

Year

2018

While high-risk human papillomavirus (HPV) infection is a well-established risk factor for cervical cancer, there are likely other factors within the local microenvironment that contribute to cervical carcinogenesis. Here we investigated relationships between HPV, vaginal pH, vaginal microbiota (VMB) composition, level of genital immune mediators and severity of cervical neoplasm. We enrolled women with low- and high-grade cervical dysplasia (LGD, HGD), invasive cervical carcinoma (ICC), and healthy controls. HPV16, HPV45, HPV58, and HPV31 were the most prevalent in our cohort with HPV16 and HPV31 genotypes more prevalent in Hispanics. Vaginal pH was associated with ethnicity and severity of cervical neoplasm. Lactobacillus dominance decreased with the severity of cervical neoplasm, which correlated with elevated vaginal pH. Hispanic ethnicity was also associated with decreased Lactobacillus dominance. Furthermore, Sneathia was enriched in all precancerous groups, ICC, abnormal pH and Hispanic origin. Patients with ICC, but not LGD and HGD, exhibited increased genital inflammatory scores and elevated specific immune mediators. Notably, IL-36γ was significantly associated with ICC. Our study revealed local, host immune and microbial signatures associated with cervical carcinogenesis and provides an initial step to understanding the complex interplay between mucosal inflammation, HPV persistence and the VMB.

Experiment 1

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Subjects

Location of subjects

United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.

Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology

Vagina Distal oviductal region,Distal portion of oviduct,Vaginae,Vagina,vagina

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Group 0 name Corresponds to the control (unexposed) group for case-control studies

HPV-

Group 1 name Corresponds to the case (exposed) group for case-control studies

HPV+

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

HPV+ determined by the Linear Array HPV Genotyping Tests

Group 0 sample size Number of subjects in the control (unexposed) group

20

Group 1 sample size Number of subjects in the case (exposed) group

31

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)

3 months

Lab analysis

Sequencing type

16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).

raw counts

Statistical test

DESeq2

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)

0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?

Yes

Signature 1

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Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the HPV+ group when compared to HPV-negative control prior to adjusting

Abundance in Group 1: increased abundance in HPV+

NCBI	Quality Control	Links
Prevotella
Sneathia sanguinegens

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

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Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the HPV+ group when compared to HPV-negative control prior to adjusting

Abundance in Group 1: decreased abundance in HPV+

NCBI	Quality Control	Links
Actinomyces
Anaerococcus lactolyticus
Bifidobacterium
Dialister
Fenollaria massiliensis
Fusobacterium nucleatum
Gardnerella
Lactobacillus
Lactobacillus gasseri
Mobiluncus mulieris
Peptoniphilus grossensis
Streptococcus anginosus

Revision editor(s): WikiWorks, ChiomaBlessing

Experiment 2

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Cervical glandular intraepithelial neoplasia Cervical glandular intraepithelial neoplasia,cervical glandular intraepithelial neoplasia

Group 1 name Corresponds to the case (exposed) group for case-control studies

low grade dysplasia

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

low grade dysplasia confirmed by histology of colonoscopy-directed biopsy

Group 1 sample size Number of subjects in the case (exposed) group

12

Lab analysis

Statistical Analysis

Signature 1

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Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the low grade dysplasia group when compared to HPV-negative control prior to adjusting

Abundance in Group 1: increased abundance in low grade dysplasia

NCBI	Quality Control	Links
Fannyhessea vaginae
Gemelliphila asaccharolytica
Mobiluncus mulieris
Parvimonas
Sneathia sanguinegens

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

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Source: Figure 4

Description: Enrichment in bacterial taxa in the low grade dysplasia group when compared to HPV-negative control prior to adjusting

Abundance in Group 1: decreased abundance in low grade dysplasia

NCBI	Quality Control	Links
Anaerococcus obesiensis
Brenneria
Campylobacter ureolyticus
Escherichia
Finegoldia magna
Fusobacterium nucleatum
Lactobacillus
Lactobacillus crispatus
Lactobacillus gasseri
Peptoniphilus
Aedoeadaptatus coxii
Peptoniphilus duerdenii
Peptoniphilus grossensis
Shigella
Streptococcus
Streptococcus anginosus

Revision editor(s): WikiWorks, ChiomaBlessing

Experiment 3

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

high grade dysplasia

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

high grade dysplasia confirmed by histology of colonoscopy-directed biopsy

Group 1 sample size Number of subjects in the case (exposed) group

27

Lab analysis

Statistical Analysis

Signature 1

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Source: Figure 4

Description: Enrichment in bacterial taxa in the high grade dysplasia group when compared to HPV-negative control prior to adjusting

Abundance in Group 1: increased abundance in high grade dysplasia

NCBI	Quality Control	Links
Atopobium
Clostridium
Fannyhessea vaginae
Gardnerella
Hoylesella buccalis
Megasphaera
Parvimonas
Prevotella amnii
Shuttleworthella
Sneathia
Sneathia sanguinegens
Streptococcus agalactiae

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

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Curated date: 2021/01/10

Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the high grade dysplasia group when compared to HPV-negative control prior to adjusting

Abundance in Group 1: decreased abundance in high grade dysplasia

NCBI	Quality Control	Links
Anaerococcus lactolyticus
Anaerococcus obesiensis
Bifidobacterium
Dialister
Dialister propionicifaciens
Fenollaria massiliensis
Finegoldia magna
Lactobacillus
Lactobacillus gasseri
Aedoeadaptatus coxii
Peptoniphilus duerdenii
Peptoniphilus grossensis
Peptoniphilus lacrimalis
Porphyromonas
Prevotella bivia
Prevotella corporis
Prevotella disiens
Streptococcus
Ureaplasma

Revision editor(s): WikiWorks, ChiomaBlessing

Experiment 4

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Cervical carcinoma

Group 1 name Corresponds to the case (exposed) group for case-control studies

invasive cervical carcinoma

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

invasive cervical carcinoma confirmed by histology of colonoscopy-directed biopsy

Group 1 sample size Number of subjects in the case (exposed) group

10

Lab analysis

Statistical Analysis

Signature 1

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Curated date: 2021/01/10

Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the invasive cervical carcinoma group when compared to HPV-negative control prior to adjusting

Abundance in Group 1: increased abundance in invasive cervical carcinoma

NCBI	Quality Control	Links
Sneathia sanguinegens

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

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Curated date: 2021/01/10

Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the invasive cervical carcinoma group when compared to HPV-negative control prior to adjusting

Abundance in Group 1: decreased abundance in invasive cervical carcinoma

NCBI	Quality Control	Links
Anaerococcus lactolyticus
Bifidobacterium
Brenneria
Corynebacterium
Dialister
Dialister propionicifaciens
Escherichia
Fenollaria massiliensis
Fusobacterium nucleatum
Howardella
Lactobacillus
Lactobacillus crispatus
Lactobacillus gasseri
Aedoeadaptatus coxii
Peptoniphilus duerdenii
Peptoniphilus grossensis
Prevotella bivia
Prevotella corporis
Shigella
Streptococcus
Streptococcus anginosus
Ureaplasma
Winkia neuii subsp. anitrata

Revision editor(s): WikiWorks, ChiomaBlessing

Experiment 5

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Group 1 name Corresponds to the case (exposed) group for case-control studies

HPV+

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

HPV+ determined by the Linear Array HPV Genotyping Tests

Group 1 sample size Number of subjects in the case (exposed) group

31

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment

age, body mass index, ethnic group

Signature 1

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Curated date: 2021/01/10

Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the HPV+ group when compared to HPV-negative control after adjusting for age, BMI and ethnicity

Abundance in Group 1: increased abundance in HPV+

NCBI	Quality Control	Links
Lactobacillus
Megasphaera
Olsenella
Peptostreptococcus anaerobius
Prevotella
Shuttleworthella

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

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Curated date: 2021/01/10

Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the HPV+ group when compared to HPV-negative control after adjusting for age, BMI and ethnicity

Abundance in Group 1: decreased abundance in HPV+

NCBI	Quality Control	Links
Aerococcus
Anaerococcus
Anaerococcus obesiensis
Bifidobacterium
Gardnerella
Hoylesella timonensis
Peptoniphilus grossensis
Prevotella bivia

Revision editor(s): WikiWorks, ChiomaBlessing

Experiment 6

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Cervical glandular intraepithelial neoplasia Cervical glandular intraepithelial neoplasia,cervical glandular intraepithelial neoplasia

Group 1 name Corresponds to the case (exposed) group for case-control studies

low grade dysplasia

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

low grade dysplasia confirmed by histology of colonoscopy-directed biopsy

Group 1 sample size Number of subjects in the case (exposed) group

12

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, ChiomaBlessing

Source: Figure 4

Description: Enrichment in bacterial taxa in the low grade dysplasia group when compared to HPV-negative control after adjusting for age, BMI and ethnicity

Abundance in Group 1: increased abundance in low grade dysplasia

NCBI	Quality Control	Links
Anaerococcus lactolyticus
Bifidobacterium
Clostridium
Dialister
Gemelliphila asaccharolytica
Hoylesella buccalis
Lactobacillus
Lactobacillus gasseri
Lactobacillus iners
Mobiluncus mulieris
Peptostreptococcus anaerobius
Porphyromonas
Prevotella
Prevotella amnii
Prevotella disiens
Sneathia
Sneathia sanguinegens
Winkia neuii subsp. anitrata

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

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Mark reviewed

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Curated date: 2021/01/10

Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the low grade dysplasia group when compared to HPV-negative control after adjusting for age, BMI and ethnicity

Abundance in Group 1: decreased abundance in low grade dysplasia

NCBI	Quality Control	Links
Lactobacillus
Lactobacillus crispatus
Aedoeadaptatus coxii

Revision editor(s): WikiWorks, ChiomaBlessing

Experiment 7

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

high grade dysplasia

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

high grade dysplasia confirmed by histology of colonoscopy-directed biopsy

Group 1 sample size Number of subjects in the case (exposed) group

27

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, ChiomaBlessing

Source: Figure 4

Description: Enrichment in bacterial taxa in the high grade dysplasia group when compared to HPV-negative control after adjusting for age, BMI and ethnicity

Abundance in Group 1: increased abundance in high grade dysplasia

NCBI	Quality Control	Links
Clostridium
Gardnerella
Lactobacillus iners
Megasphaera
Parvimonas
Prevotella amnii
Shuttleworthella
Sneathia
Sneathia sanguinegens

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

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Curated date: 2021/01/10

Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in the high grade dysplasia group when compared to HPV-negative control after adjusting for age, BMI and ethnicity

Abundance in Group 1: decreased abundance in high grade dysplasia

NCBI	Quality Control	Links
Actinotignum schaalii
Aerococcus
Anaerococcus
Anaerococcus lactolyticus
Anaerococcus obesiensis
Bifidobacterium
Campylobacter ureolyticus
Corynebacterium coyleae
Dialister
Ezakiella coagulans
Fenollaria massiliensis
Gallicola
Gardnerella
Howardella
Hoylesella buccalis
Hoylesella timonensis
Aedoeadaptatus coxii
Peptoniphilus duerdenii
Peptoniphilus grossensis
Peptoniphilus lacrimalis
Porphyromonas
Prevotella bivia

Revision editor(s): Fatima, WikiWorks, ChiomaBlessing

Experiment 8

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Cervical carcinoma

Group 1 name Corresponds to the case (exposed) group for case-control studies

invasive cervical carcinoma

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

invasive cervical carcinoma confirmed by histology of colonoscopy-directed biopsy

Group 1 sample size Number of subjects in the case (exposed) group

10

Lab analysis

Statistical Analysis

Signature 1

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Curated date: 2021/01/10

Curator: Cynthia Anderson

Revision editor(s): WikiWorks, Lwaldron, Cynthia Anderson, ChiomaBlessing

Source: Figure 4

Description: Enrichment in bacterial taxa in the invasive cervical carcinoma group when compared to HPV-negative control after adjusting for age, BMI, and ethnicity

Abundance in Group 1: decreased abundance in invasive cervical carcinoma

NCBI	Quality Control	Links
Anaerococcus
Bifidobacterium
Gardnerella
Lactobacillus
Lactobacillus crispatus
Moryella
Peptoniphilus grossensis
Prevotella bivia

Revision editor(s): WikiWorks, Lwaldron, Cynthia Anderson, ChiomaBlessing

Experiment 9

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Cervical carcinoma

Group 0 name Corresponds to the control (unexposed) group for case-control studies

abnormal pH

Group 1 name Corresponds to the case (exposed) group for case-control studies

normal pH

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

HPV+ determined by the Linear Array HPV Genotyping Tests, low grade dysplasia,high grade dysplasia, invasive cervical carcinoma confirmed by histology of colonoscopy-directed biopsy,

Group 1 sample size Number of subjects in the case (exposed) group

74

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment

Not specified

Signature 1

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Source: Figure 4

Description: Enrichment in bacterial taxa in patients with abnormal pH vs. normal pH

Abundance in Group 1: increased abundance in normal pH

NCBI	Quality Control	Links
Atopobium
Bifidobacterium
Clostridium
Enterococcus
Fusobacterium nucleatum
Gardnerella
Gemella
Megasphaera
Metamycoplasma hominis
Mobiluncus mulieris
Moryella
Parvimonas
Peptostreptococcus
Prevotella
Prevotella amnii
Prevotella disiens
Shuttleworthella
Sneathia
Sneathia sanguinegens
Staphylococcus
Streptococcus
Streptococcus agalactiae
Veillonella
Veillonella montpellierensis

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

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Curated date: 2021/01/10

Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in patients with abnormal pH vs. normal pH

Abundance in Group 1: decreased abundance in normal pH

NCBI	Quality Control	Links
Brenneria
Clostridium
Escherichia
Lactobacillus
Lactobacillus gasseri
Shigella

Revision editor(s): WikiWorks, ChiomaBlessing

Experiment 10

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Reviewed Marked as Reviewed by Fatima Zohra on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Group 0 name Corresponds to the control (unexposed) group for case-control studies

non-Hispanic

Group 1 name Corresponds to the case (exposed) group for case-control studies

Hispanic

Group 0 sample size Number of subjects in the control (unexposed) group

53

Group 1 sample size Number of subjects in the case (exposed) group

47

Lab analysis

Statistical Analysis

Signature 1

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Source: Figure 4

Description: Enrichment in bacterial taxa in Hispanic vs. non-Hispanic group

Abundance in Group 1: increased abundance in Hispanic

NCBI	Quality Control	Links
Aerococcus
Atopobium
Enterococcus
Fannyhessea vaginae
Gardnerella
Megasphaera
Mobiluncus mulieris
Moryella
Porphyromonas
Shuttleworthella
Sneathia
Sneathia sanguinegens
Streptococcus
Streptococcus anginosus
Veillonella
Veillonella montpellierensis

Revision editor(s): WikiWorks, ChiomaBlessing

Signature 2

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Curated date: 2021/01/10

Curator: Cynthia Anderson

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Source: Figure 4

Description: Enrichment in bacterial taxa in Hispanic vs. non-Hispanic group

Abundance in Group 1: decreased abundance in Hispanic

NCBI	Quality Control	Links
Anaerococcus vaginalis
Hoylesella buccalis
Lactobacillus
Lactobacillus gasseri

Revision editor(s): WikiWorks, ChiomaBlessing