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National Tuberculosis Archive: Integrating Science, Medicine, and Public Health

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Integrating Science, Medicine, and Public Health. Joshua Lederberg ... High-throughput, e.g., Illumina/Solexa: 1 Gb in 3 days. NCGR: 25 Gb since August 2007 ... – PowerPoint PPT presentation

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Title: National Tuberculosis Archive: Integrating Science, Medicine, and Public Health


1
National Tuberculosis ArchiveIntegrating
Science, Medicine, andPublic Health
  • Damian Gessler, Ph.D.
  • National Center for Genome Resources
  • Santa Fe, NM
  • ddg_at_ncgr.org

Gary Simpson, M.D., Ph.D.,M.P.H. State of New
Mexico, Dept. of Health - Emeritus Santa Fe,
NM garyl.simpson_at_comcast.net
2
An Update
  • Integrating Science, Medicine, and Public Health
  • Joshua Lederberg
  • Beadle, Tatum Lederberg 1958 Noble Prize
  • Gessler et al. 2006 Science

Authors Institutions
3
The Context
  • HIV
  • Hantavirus
  • 1993 As an example of Lederbergs observation
  • TB
  • Diminishing cases
  • Low, diminishing incidence
  • Increasing drug resistance
  • Increasing medical complexity
  • Globalization of the disease

4
The Threat
  • January 1990 - August 1993
  • 43 Months - 8,021 Cases
  • 357 Patients with W strain tuberculosis
  • All resistant to first line drugs
  • 86 HIV infected
  • gt90 Mortality
  • 160 Patients identified since study
  • 22 Patients identified outside of NYC

Bifani et al., JAMA 1996275452. Munsiff et al.,
JID 2003188356.
Courtesy B. Kreiswirth, Sevilleta 2006
5
The Gap
  • Labor-intensive contact investigation in light of
    diminishing incidence
  • Ad hoc GIS-based decision-making tools for the
    rank-and-file
  • Investments in genomic, epidemiological, and
    clinical resources are not sufficiently
    integrated and available for effective on-demand,
    evidence-based, decision making.

One looks to turn data into actionable
information.
6
The Need
  • Rapid, evidence-based decision making support
  • Public health professionals to have time access
    to aggregated and integrated information
  • Tighten the feedback between Science, Medicine,
    and Public Health to leverage resources across
    the disciplines.

Do this for a disease that is slowly changing
from being one that is common and treatable, to
one that is becoming uncommon and increasingly
difficult to treat.
7
Addressing the Need to fill the Gap
  • Bring secure, web-based decision-support
    infrastructure to decision-makers (from policy
    makers to field offices)
  • Integrate disparate data via centralized
    resources to deliver value-add to distributed
    clients
  • Tighten the feedback between Science, Medicine,
    and Public Health to leverage resources across
    the disciplines.

Often over-looked non-trivial
8
National Tuberculosis Archive
  • Dont let the name fool youthis is much more
    than a deep freeze but it does recognize the
    absolute importance of archiving etiological
    materials as part of a comprehensive solution
  • Endorsed by over two dozen experts and
    professionals from the nations top Science,
    Medicine, and Public Health institutions
    (Harvard, Denver Health, CDC, and many others)
  • To tighten the feedback between Science,
    Medicine, and Public Health to leverage resources
    across the disciplines, it is comprised of two
    parts 1) Architecture 2) Client

A unique model to deliver on the Need
9
National Tuberculosis ArchiveArchitecture
10
National Tuberculosis ArchiveClient Data Cube
Data model
Ill complete this over the weekend Itll be a
few slides and at the core of what separates us
from OTIS and TB GIMS
Data source
11
National Tuberculosis ArchiveTechnologies
  • Sequencing
  • High-throughput, e.g., Illumina/Solexa 1 Gb in
    3 days
  • NCGR 25 Gb since August 2007
  • Sanger 200 human genome pilot project as part
    of a 1,000 human genome project. Est. time 2-3
    yrs.
  • TB Seven genomes/run for lt10K. Use this for
    phylogenetic anchoring to complement CDC
    Universal Genotyping.
  • Archiving
  • University of New Mexico
  • Second largest tissue archive in the world
    (600,000 samples)
  • Redundant, computerized, secure
  • Informatics
  • Chado, SSWAP, AJAX ready technologies for
    deployment.

Over the next 2-3 yrs, this cost/through-put will
improve by 10-100x
12
Operational Steps
  • Acquiring and archiving isolates
  • Acquiring epidemiological and clinical data
  • Generating phylogenetic data
  • Integrating genomic, epidemiological, clinical,
    and phylogenetic data
  • Delivering integrated data
  • Supplying research isolates

13
Operational Steps
  • 1. Acquiring and archiving isolates
  • Forwarded from California and Michigan
  • Archive and DNA bank

14
Operational Steps
  • 2. Acquiring epidemiological and clinical data
  • Based on Report of Verified Case Tuberculosis
  • In coordination with CDC.

15
Operational Steps
  • 3. Generating phylogenetic data
  • Create comprehensive phylogeny of TB in the US
  • Based on Universal Genotyping data
  • Augmented as needed with ancillary sequencing

16
Operational Steps
  • 4. Integrating genomic, epidemiological,
    clinical, and phylogenetic data
  • Data cube data model and data views
  • Three tiered architecture segregating RDBMS,
    business logic, and presentation layer
  • Web services to specialized data providers such
    as TB GIMS.

17
Operational Steps
  • 5. Delivering integrated data
  • Credentialed web access
  • Search and browse across jurisdictional and
    temporal boundaries via epidemiological,
    clinical, genomic (BLAST), and phylogenetic
    characteristics.
  • Data cube presentation layer

18
Operational Steps
  • 6. Supplying research isolates
  • Select research isolates from the repository of
    field isolates based on web searching on
    epidemiological, clinical, genomic, and
    phylogenetic criteria.
  • Shepherd requests to the CDC and USPHS
  • Candidate model for further systematic pathogen
    repositories and etiological distribution control.

19
Patient Confidentiality
  • Top Priority. We institute a suite of
    architectural and technological design principles
    to safe-guard patient confidentially
  • Data is pathogen-centric, not patient-centric.
  • Names, addresses, etc. from RVCT are neither
    stored nor accessible via the NTBA
  • NTBA has a dual-accession numbering system
  • RVCT number (stored at CDC and state Health
    departments)
  • linked to a private (hidden) NTBA record number,
    which is
  • linked to a public isolate accession number
  • Credentialed access via data views
  • Public data (e.g., OTIS) over HTTP
  • State/federal TB control programs (e.g., TB GIMS)
    via HTTPS
  • Variable data resolution
  • Geographic suppression

OTIS Online Tuberculosis Information System TB
GIMS TB Genotyping Information Management System
20
Collaborators
Active contributors in terms of
authorship, signatory, or funding initiatives
  • Dr. Marcos Burgos, University of New Mexico
  • Dr. Richard Chaisson, Johns Hopkins University
  • Dr. Vojo Deretic, University of New Mexico
  • Dr. Christopher Dye, World Health Organization
  • Dr. Paul Farmer, Harvard Medical School
  • Dr. Sebastien Gagneux, Institute for Systems
    Biology
  • Dr. Lee Hood, Institute for Systems Biology
  • Dr. Philip Hopewell, University of California,
    San Francisco
  • Dr. Stephen Kingsmore, National Center for Genome
    Resources
  • Dr. Thomas Kindt, National Institutes of Health,
    Emeritus
  • Dr. Barry Kreiswirth, Public Health Research
    Institute
  • Dr. Midori Kato-Maeda, University of California,
    San Francisco
  • Dr. Barun Mathema, Public Health Research
    Institute
  • Dr. Patrick Moonan, Centers for Disease Control
    and Prevention
  • Dr. Megan Murray, Harvard School of Public Health
  • Dr. James Musser, The Methodist Hospital Research
    Institute
  • Dr. Thomas Navin, Centers for Disease Control and
    Prevention
  • Dr. Lee Reichman, University of Medicine and
    Dentistry of New Jersey

21
Capabilities
  • University of New Mexico (UNM)
  • Built and manages the worlds 2nd largest archive
  • Active and deployed in the 1993 Hantavirus
    outbreak
  • Computerized and proven
  • Active TB researchers as part of 140M Health
    Sciences Center
  • National Center for Genome Resources (NCGR)
  • One of the nations most established non-profit
    bioinformatic centers (1993)
  • Built and maintained numerous information
    resources (TAIR, LIS, ISYS, SSWAP)
  • New Mexico Genome Sequencing Center for high
    throughput (Gb/day) sequencing
  • Earth Data Analysis Center (EDAC)
  • Founded in 1964 from NASA
  • Desktop and Online Geospatial Application
    Development
  • Geospatial data management, integration, and
    delivery
  • Partners at LANL (TB research), Sandia
    (informatic security), NMSU (Bovine TB), NMDOH
    (border state)

22
Commitments
  • University of New Mexico in-kind donation of
    BSL-2 and BSL-3 space for three years
  • Transfer of up to 25,000 isolates from the Public
    Health Research Institute TB Center, courtesy of
    Dr. B. Kreiswirth
  • NCGR informatic design and implementation
    expertise
  • CDC Universal Genotyping Program coordination

23
Acknowledgements
  • Dr. Marcos Burgos, University of New Mexico
  • Dr. Richard Chaisson, Johns Hopkins University
  • Dr. Vojo Deretic, University of New Mexico
  • Dr. Christopher Dye, World Health Organization
  • Dr. Paul Farmer, Harvard Medical School
  • Dr. Sebastien Gagneux, Institute for Systems
    Biology
  • Dr. Lee Hood, Institute for Systems Biology
  • Dr. Philip Hopewell, University of California,
    San Francisco
  • Dr. Stephen Kingsmore, National Center for Genome
    Resources
  • Dr. Thomas Kindt, National Institutes of Health,
    Emeritus
  • Dr. Barry Kreiswirth, Public Health Research
    Institute
  • Dr. Midori Kato-Maeda, University of California,
    San Francisco
  • Dr. Barun Mathema, Public Health Research
    Institute
  • Dr. Patrick Moonan, Centers for Disease Control
    and Prevention
  • Dr. Megan Murray, Harvard School of Public Health
  • Dr. James Musser, The Methodist Hospital Research
    Institute
  • Dr. Thomas Navin, Centers for Disease Control and
    Prevention
  • Dr. Lee Reichman, University of Medicine and
    Dentistry of New Jersey

Thanks to our many collaborators
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