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Human Microbiome Project: A Community Resource 2016 HIV Microbiome Workshop November 17, 2016 Lita M. Proctor, Ph.D. Coordinator, Human Microbiome Project NHGRI/NIH

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Human Microbiome Project: A Community Resource

2016 HIV Microbiome Workshop November 17, 2016

Lita M. Proctor, Ph.D.Coordinator, Human Microbiome Project

NHGRI/NIH

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Human Microbiome Project: 2007 to 2017Building a community resource

Clinically-examined300 male/female

18-40 y.o.

5 major body regions(18 body sites)

Up to 3 visits in 2 yrs

No antibiotics, probiotics, immunomodulators

ii. Disease/disorder cohorts:Skin: eczema, psoriasis, acneGI/oral: esophageal adenocarcinoma, necrotizing enterocolitis, pediatric IBS, ulcerative colitis, Crohn’s DiseaseUrogenital: bacterial vaginosis, circumcision, sexual histories

NIH Human Microbiome Project $215M community resource

Phase 1: Survey of the microbiome “Who’s there?”

Phase 2: Integrative HMP “iHMP” “What are they doing?”

i. Pregnancy and Preterm Birth cohort: Vaginal & gut microbiomes and host (mother, infant)

ii. IBD Dynamics cohort: GI microbiome and host

iii. Type 2 Diabetes Dynamics cohort: GI & nasal microbiomes and host

i. Healthy cohort (case/control): Exemplar human-microbiome conditions:

Longitudinal studies Biological properties of host & microbiome

over time:

Gene expression profiles

Protein profilesMetabolite profilesOther host/microbiome phenotype profiles

Spanogiannopoulos et al. (2016)

Known roles of microbial metabolism for many classes of drugs:increase bioavailabilitydecreases bioavailabilityincreases toxicity

Gut microbiota can play direct and indirect roles in drug metabolism

Data-mining HMP Metagenomic Data to Discover Important Molecules or Pathways

Data-mining HMP Metagenomic Data to Discover Important Molecules or Pathways

10% of HMP gut microbiota synthesize neurotransmitter tryptamine

Will

iam

s e

t al

. (2

01

4)

Prevalence of AR genes across gut metagenomes, including HMP

Fors

lun

de

t al

. (2

01

4)

Donia et al. (2014)

Distribution of novel antibiotics in HMP metagenomes, across multiple body regions

OralGut Vaginal

iHMP: Dynamics of Pregnancy and Preterm Birth(http://vmc.vcu.edu/momspi)

iHMP: Dynamics of IBD Onset(http://ibdmdb.org)

iHMP: Dynamics of Type 2 Diabetes Onset(http://med.stanford.edu/ipop.html)

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*Blue represents data from the microbiome, red from the host, black represents global data (host +microbiome)

Public Repositories for Primary iHMP Multi-omic Data*

• All HMP primary data, tools, pipelines, analytical walk-throughs• Owen White (PI, UMD School of Medicine)

HMP Data Coordination Center (www.hmp2dcc.org)

iHMP DCC

OSDF

OSDFAPI

SubjectsSamples

Omics data

T2D

Preterm birth

IBD

OSDFAPI

SubjectsSamples

Omics data

OSDFAPI

SubjectsSamples

Omics data

AnadanaOSDFAPI

SubjectsSamples

Sequences

Biosample/SRA

GEO

PRIDE, MW

OSDFAPI

RNA sequences

OSDFAPI

Mass-Spec, LC data

• Uniform submissions thanks to common software and metadata standards.

• Repository submissions performed by data manager at each iHMP site.

• Data also shared with the iHMP DCC.

iHMP DCC Data Import and Export

iHMP Microbiome Multi-omic Framework

Framework will link the three iHMP studies and provide user-friendly access to:

Study design, number of subjects, timepoints, clinical metadata

Primary data and processed data, etc. Data processing pipelines Derived data such as community profiles, gene expression

profiles, predicted metabolic pathways, etc. Analytical pipelines for derived data

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HMP Data & Tools in NIH Cloud Commons

NIH Data Commons:cloud-based resource

HMP data & tools as pilot for Commons

HMP phase 1 data & tools in the cloud ~2017

HMP phase 2 data & tools in the cloud ~2018-2019-2020

2012-2013: $100-150M/yr and 18 ICOs invested in the human microbiome

Trans-NIH Microbiome Working Group (TMWG) established 2012

Extramural program staff only, membership from 18 ICOs

LM Proctor (NHGRI), TMWG chair

Mission: Forum for microbiome-related investments at NIH• Identify, gaps, needs, challenges and

opportunities• Share upcoming FOAs, develop joint

FOAs; coordinate joint funding of applications

• Develop microbiome review panel at CSR

• Organize NIH-wide meetings• Serve as central resource for

external community

TMWG (external page):www.commonfund.nih.gov/hmp/related_activities

(http://www.nist.gov/mml/microbiome-standards.cfm)

NIST*- NIH Workshop: Standards for Microbiome Measurements

The webcast recording posted online http://go.usa.gov/cw8dT.

Special issue in prep., BMC Standards in Genomic Sciences

*NIST = Natl. Institute of Standards & Technology

“The Human Microbiome: Emerging Themes at the Horizon of the 21st Century”

NIH-wide human microbiome workshop, organized by TMWG 40+ speakers, 500 participants; August 16-18, 2017 Open floor discussion each day Workshop closes with joint agency panel: NIH, FDA, CDC, NIST, USDA

Workshop goals: Identify knowledge gaps, technical hurdles, new approaches

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Questions?

[email protected]