the exposome - a systems approach for discovery in … · 2016-05-17 · national institutes of...

National Institutes of Health • U.S. Department of Health and Human Services

The Exposome - A Systems Approach for

Discovery in Environmental Health

Yuxia Cui, PhD

Contract Scientific Program Analyst National Institute of Environmental Health Sciences

National Institutes of Health U.S. Department of Health and Human Services

The Exposome (Wild): The totality of exposure an individual is subjected to from conception to death…the ‘environmental’ correlate to the genome.


http://www.nature.com/ki/journal/v62/n5/fig_tab/4493262f1.html

The Exposome

http://www.nature.com/ki/journal/v62/n5/fig_tab/4493262f1.html


The NIEHS strategic plan (2012-2017)

Strategic Goal 3: Transform exposure science by enabling consideration of the totality of human exposures and links to biological pathways and create a blueprint for incorporating exposure science into human health studies.

– Advance characterization of environmental exposures through improved exposure assessment at both the individual and population levels

– Define and disseminate the concept of the exposome

– Create tools and technologies, and the research capacity, needed to characterize the exposome


Exposome activities supported by NIEHS

• Sensor development – The Exposure Biology Program

– SBIR

– Superfund Program

• The HERCULES Exposome Center (2013)

• The Exposure Science and Exposome Webinar Series (2014-)

• The NIEHS Exposome Workshop (2015) • Children's Health Exposure Analysis Resource (2015)


The NIEHS Exposome Workshop - More than an in-person workshop

• Five pre-meeting workgroups formed in summer 2014 – External exposure assessment

– Biomonitoring

– Biological impact and consequences

– Epidemiology

– Data science and informatics

• At-meeting workgroups, January 14-15, 2015 – Integrate/prioritize recommendations

– Use-cases


A resource to facilitate and promote exposome research

(1) Exposome clearinghouse

Tools and technologies

User Gateway

Resources

Data repository

Sample registry

Standards and protocols


(2) Improve methods and technologies

Chen et al, Cell, 2012 Nieuwenhuijsen et al. Int. J. Environ. Res. Public Health 2014, 11, 7805

Patel et al PLOS1, 2010


• Identification of use cases

• Secondary analyses of banked samples

• Establishing policies to promote data sharing

• Education and training

(3) Practical considerations and exposome promotion strategies

A series of EHP commentaries will be coming soon.


0

10

20

30

40

50

60

70

80

90

100

1.E-07 1.E-06 1.E-05 1.E-04 1.E-03 1.E-02 1.E-01 1.E+00 1.E+01 1.E+02 1.E+03 1.E+04 1.E+05

Cum

ulat

ive

perc

ent

Blood concentration (µM)

DrugsFoodsPollutantsEndogenous

Venlafaxine

Aspirin

Simvastatin

Digoxin

Estradiol

Testosterone

Cortisol

Homocysteine

Cholesterol

Malondialdehyde Benzene

Lead

DDE Arsenic

PCB 170

Perfluorononanoic acid

Hexachlorocyclohexane

BDE 100

Cotinine

OCDD

Trichloromethane

Acetaldehyde

Folic acid, Vitamin D3

Sulforaphane

Trimethylamine-N-oxide

γ-Tocopherol

Ethanol

Solanidine

β-Carotene

Caffeine

Aflatoxin B1

Genistein

Normal blood concentrations

(1,561 chemicals)

1,000-fold

Rappaport et al., Environ Health Perspect, 2014 SM


0

10

20

30

40

50

60

70

80

90

100

1.E-07 1.E-06 1.E-05 1.E-04 1.E-03 1.E-02 1.E-01 1.E+00 1.E+01 1.E+02 1.E+03 1.E+04 1.E+05

Cum

ulat

ive

perc

ent

Blood concentration (µM)

DrugsFoodsPollutantsEndogenous

Simvastatin

Digoxin

Estradiol

Testosterone

Benzene

DDE Arsenic

PCB 170

Perfluorononanoic acid

Hexachlorocyclohexane

BDE 100

Cotinine

OCDD

Trichloromethane

Folic acid, Vitamin D3

Solanidine

Aflatoxin B1

Genistein

Untargeted methods not currently suitable for serum concentrations < 0.1 µM

Rappaport et al., Environ Health Perspect, 2014 SM


SNP-trait associations with p-value ≤ 5×10-8 from 2000+ GWAS studies

http://www.ebi.ac.uk/fgpt/gwas/

Less than 300 chemicals are being reported in NHANES

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

Totalregisteredchemicals

Widecommercial

use

NHANES


CHEAR at NIEHS

• Purpose

– Provide infrastructure for adding or expanding exposure analysis to studies involving research in children’s health

– Promote incorporation of environmental exposure factors in studies of children’s health and development

• Time line

– RFAs announced in February 26, 2015

– Applications due April 30, 2015

– Plan to fund in September 2015


The CHEAR Infrastructure

Scientific Consulting Panel

Steering Committee

Coordinating Center

National Exposure Assessment Laboratory Network

Hub 1

Hub 2

Hub 3

Hub 4

Data Repository, Analysis and Science Center


The CHEAR work flow Pre-submission

consultation & design conducted with

Coordinating Center

Project proposal submitted

Project proposal reviewed & evaluated

Samples submitted to National Exposure

Assessment Laboratory Network

Samples processed Data sent to Data

Repository, Analysis and Science Center

Data deposited into CHEAR repository

Investigator accesses data in repository

Data analysis and consultation


CHEAR Coordinating Center

Interactions between

CHEAR and users

Manage CHEAR internal

workflow

Governance and

administrative support

Resources for the broader community


National Exposure Assessment Laboratory Network

Hub Admin Core

Targeted Untargeted

Response

Clarification: Analysis of exogenous and endogenous analytes


Data Repository, Analysis and Science Center Statistical

Services and Methods

Development Resource

Data Repository and Management

Core Data Science

Resource

Admin Core


Outcomes

• Create a public resource of children’s exposures across the country

• Expand the number of studies that include environmental exposure

• Develop data and metadata standards to facilitate data sharing and meta data analysis


Measuring the exposome is just the first step

Sanchez, Exposome informatics, J Am Med Inform Assoc, 2014


?

The NIEHS Exposure Science and the Exposome Webinar Series Registration @ http://tools.niehs.nih.gov/conference/exposome_webinar/ Email: [email protected]

Thanks!

CHEAR: http://www.niehs.nih.gov/research/supported/dert/programs/chear/index.cfm Email: [email protected]

To learn more

http://tools.niehs.nih.gov/conference/exposome_webinar/

http://tools.niehs.nih.gov/conference/exposome_webinar/

http://www.niehs.nih.gov/research/supported/dert/programs/chear/index.cfm



the exposome - a systems approach for discovery in … · 2016-05-17 · national institutes of...

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