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AIDS CLINICAL ROUNDS
The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease clinicians, physicians and
researchers. The goal of these presentations is to provide the most
current research, clinical practices and trends in HIV, HBV, HCV, TB
and other infectious diseases of global significance.

The slides from the AIDS Clinical Rounds presentation that you are
about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.
Open Source Software Solutions for
Clinical Research: Applications for
HIV Research



Jason A. Young, Ph.D
Assistant Professor
Department of Medicine, UCSD




                               AIDS Clinical Rounds - 8.3.12
UCSD CFAR BIT Core
    Bioinformatics and Information Technologies (BIT) Core
Aims
• Provide bio/informatics expertise
• To be agile, interactive, affordable
• Committed to open source



Resources
• The BIT Core team!
• 24/7, secure web & data servers
• 500+ node compute cluster
• A collection of open source
software solutions and services          Website: https://cfar.ucsd.edu/bit
                                         E-mail: bitcore@ucsd.edu
                                         GitHub: http://github.com/beastcore
Clients
• Center For AIDS Research (CFAR)        • IAVI Neutralizing Antibody Consortium (IAVI-NAC)
• AntiViral Research Center (AVRC)       • California Collaborative Treatment Group (CCTG)
• AIDS Research Institute (ARI)          • ... other research investigators and growing ...
Outline


  1. Web and Mobile Research Services


  2. Clinical Data Management


  3. Bioinformatics Expertise
Outline


  1. Web and Mobile Research Services


  2. Clinical Data Management


  3. Bioinformatics Expertise
Web and Mobile Research Services
                                                  “A powerful, flexible open source
                                                   Content Management System”
Accessible:
Non-technical users can create websites and maintain content
using only a web browser. Comes with built-in workflows,
permissions, etc.

Widely deployed:
Broad user base includes NASA, Nokia, Novell, and major
universities (Harvard, MIT and Penn State).

Large development and support base:
340 core developers and >300 solution providers in 57
countries.

Mature:
First released in 2001. Provides developers a robust framework
for custom product development.

Secure:
Best security record of any major CMS.

Extensible:
Over 1900 projects extending core functionality currently
available.
Web and Mobile Research Services
                       ARI - ari.ucsd.edu
                       CFAR - cfar.ucsd.edu
                       AVRC - avrc.ucsd.edu
                       HIVe - hive.ucsd.edu
                       ET - theearlytest.ucsd.edu
                       LTW - leadthewaysd.com




                             Doug Richman (UCSD)
Web and Mobile Research Services
                       ARI - ari.ucsd.edu
                       CFAR - cfar.ucsd.edu
                       AVRC - avrc.ucsd.edu
                       HIVe - hive.ucsd.edu
                       ET - theearlytest.ucsd.edu
                       LTW - leadthewaysd.com




                             Doug Richman (UCSD)
Web and Mobile Research Services
                       ARI - ari.ucsd.edu
                       CFAR - cfar.ucsd.edu
                       AVRC - avrc.ucsd.edu
                       HIVe - hive.ucsd.edu
                       ET - theearlytest.ucsd.edu
                       LTW - leadthewaysd.com




                             Doug Richman (UCSD)
Web and Mobile Research Services
                                            ARI - ari.ucsd.edu
                                            CFAR - cfar.ucsd.edu
                                            AVRC - avrc.ucsd.edu
                                            HIVe - hive.ucsd.edu
                                            ET - theearlytest.ucsd.edu
                                            LTW - leadthewaysd.com




•   Core Service Request Forms
•   Feedback Forms
•   Developmental Grant Submission System
•   Laboratory Experiment Tracking System
•   Retroviral Seminar Series Calendar
                                                  Doug Richman (UCSD)
Web and Mobile Research Services
                       ARI - ari.ucsd.edu
                       CFAR - cfar.ucsd.edu
                       AVRC - avrc.ucsd.edu
                       HIVe - hive.ucsd.edu
                       ET - theearlytest.ucsd.edu
                       LTW - leadthewaysd.com




                         Constance Benson (UCSD)
Web and Mobile Research Services
                                       ARI - ari.ucsd.edu
                                       CFAR - cfar.ucsd.edu
                                       AVRC - avrc.ucsd.edu
                                       HIVe - hive.ucsd.edu
                                       ET - theearlytest.ucsd.edu
                                       LTW - leadthewaysd.com




•   Clinical trial information
•   Events calendar
•   AIDS rounds presentation slides*
                                         Constance Benson (UCSD)
Web and Mobile Research Services
HIVe: HIV e-resource (hive.ucsd.edu)           ARI - ari.ucsd.edu
•   Acute and Early HIV (AEH) cohort network   CFAR - cfar.ucsd.edu
•   Data standardization and sharing           AVRC - avrc.ucsd.edu
•   3 active & 7 legacy AEH sites              HIVe - hive.ucsd.edu
                                               ET - theearlytest.ucsd.edu
                                               LTW - leadthewaysd.com




                                    UCSD   UCSF      MGH                AIED


                                       AIEDRP AIEDRP AIEDRP AIEDRP


                                                    AIEDRP AIEDRP
Web and Mobile Research Services
HIVe: HIV e-resource (hive.ucsd.edu)           ARI - ari.ucsd.edu
•   Acute and Early HIV (AEH) cohort network   CFAR - cfar.ucsd.edu
•   Data standardization and sharing           AVRC - avrc.ucsd.edu
•   3 active & 7 legacy AEH sites              HIVe - hive.ucsd.edu
                                               ET - theearlytest.ucsd.edu
        hive.ucsd.edu                          LTW - leadthewaysd.com


      ucsd.hive.ucsd.edu
                                    UCSD   UCSF      MGH                AIED
      ucsf.hive.ucsd.edu
                                       AIEDRP AIEDRP AIEDRP AIEDRP
      mgh.hive.ucsd.edu
                                                    AIEDRP AIEDRP
Web and Mobile Research Services
San Diego Primary Infection Cohort (SDPIC)
                                              ARI - ari.ucsd.edu
(1996 - Present)
                                              CFAR - cfar.ucsd.edu
•   2 Screening Programs (~12k screens)
                                              AVRC - avrc.ucsd.edu
•   7 Research Studies (~2.5k enrollments)
                                              HIVe - hive.ucsd.edu
• Data: Demographics, risk factors, partner
                                             ET - theearlytest.ucsd.edu
information, labs, viral sequences, and much
more...                                      LTW - leadthewaysd.com
•   Specimen: Over 200k


                                  UCSD       UCSF   MGH               AIED

        ucsd.hive.ucsd.edu
                                      AIEDRP AIEDRP AIEDRP AIEDRP


Susan Little (UCSD)                                 AIEDRP AIEDRP
Web and Mobile Research Services
                         ARI - ari.ucsd.edu
                         CFAR - cfar.ucsd.edu
                         AVRC - avrc.ucsd.edu
                         HIVe - hive.ucsd.edu
                         ET - theearlytest.ucsd.edu
                         LTW - leadthewaysd.com




                     Susan Little & Davey Smith (UCSD)
Web and Mobile Research Services
                                              ARI - ari.ucsd.edu
                                              CFAR - cfar.ucsd.edu
                                              AVRC - avrc.ucsd.edu
                                              HIVe - hive.ucsd.edu
                                              ET - theearlytest.ucsd.edu
                                              LTW - leadthewaysd.com




•   AEH screening program (Rapid/NAT)
•   Obtain NAT results online or over the phone in two weeks

                                          Susan Little & Davey Smith (UCSD)
Web and Mobile Research Services
                       ARI - ari.ucsd.edu
                       CFAR - cfar.ucsd.edu
                       AVRC - avrc.ucsd.edu
                       HIVe - hive.ucsd.edu
                       ET - theearlytest.ucsd.edu
                       LTW - leadthewaysd.com




                                Susan Little (UCSD)
Web and Mobile Research Services
                                              ARI - ari.ucsd.edu
                                              CFAR - cfar.ucsd.edu
                                              AVRC - avrc.ucsd.edu
                                              HIVe - hive.ucsd.edu
                                              ET - theearlytest.ucsd.edu
                                              LTW - leadthewaysd.com




•   Hyper-local (92103/92104) HIV testing campaign (Rapid/NAT)
•   Public media advertising campaign
•   Storefront & door-to-door testing
•   Goal: What are the barriers to testing?            Susan Little (UCSD)
Web and Mobile Research Services
                       ARI - ari.ucsd.edu
                       CFAR - cfar.ucsd.edu
                       AVRC - avrc.ucsd.edu
                       HIVe - hive.ucsd.edu
                       ET - theearlytest.ucsd.edu
                       LTW - leadthewaysd.com




                                Susan Little (UCSD)
Web and Mobile Research Services
                       ARI - ari.ucsd.edu
                       CFAR - cfar.ucsd.edu
                       AVRC - avrc.ucsd.edu
                       HIVe - hive.ucsd.edu
                       ET - theearlytest.ucsd.edu
                       LTW - leadthewaysd.com




                                Susan Little (UCSD)
Web and Mobile Research Services
                                                 ARI - ari.ucsd.edu
                                                 CFAR - cfar.ucsd.edu
                                                 AVRC - avrc.ucsd.edu
                                                 HIVe - hive.ucsd.edu
                                                 ET - theearlytest.ucsd.edu
                                                 LTW - leadthewaysd.com




•   Hyper-local (92103/92104) HIV testing campaign (Rapid/NAT)
•   Public media advertising campaign
•   Storefront & door-to-door testing
•   Aim: What are the barriers to HIV testing?            Susan Little (UCSD)
Web and Mobile Research Services
 iFormBuilder
 iOS Mobile Data
Collection Platform
Web and Mobile Research Services
 iFormBuilder
 iOS Mobile Data      Functionality
Collection Platform   •   Runs on all iOS devices
                      •   25+ field widgets
                      •   Flexible skip logic
                      •   GPS functionality
                      •   HIPAA compliant
                      •   Encrypted data upload to cloud
Web and Mobile Research Services
 iFormBuilder
 iOS Mobile Data      Functionality
Collection Platform   •   Runs on all iOS devices
                      •   25+ field widgets
                      •   Flexible skip logic
                      •   GPS functionality
                      •   HIPAA compliant
                      •   Encrypted data upload to cloud


                      One year for LTW...
                      •   1317 iPad administered surveys
                      •   1062 individuals tested for HIV
                      •   24 newly diagnosed HIV(+) cases
Outline


  1. Web and Mobile Research Services


  2. Clinical Data Management


  3. Bioinformatics Expertise
Clinical Data Management
Open source Clinical Content Analysis and Management System
 OCCAMS: Designed to handle all aspects of complex and evolving clinical research studies




                                                            William of Ockham (1288-1347)
Clinical Data Management
Open source Clinical Content Analysis and Management System
 OCCAMS: Designed to handle all aspects of complex and evolving clinical research studies

  June 1996              ~15 years                April 2010
SDPIC Infection   Numerous data management         OCCAMS
Cohort Begins       solutions and providers   development begins




                                                                   William of Ockham (1288-1347)
Clinical Data Management
Open source Clinical Content Analysis and Management System
 OCCAMS: Designed to handle all aspects of complex and evolving clinical research studies

  June 1996              ~15 years                April 2010
SDPIC Infection   Numerous data management         OCCAMS
Cohort Begins       solutions and providers   development begins




 1. Web-accessible (eCRFs)
 2. Patient centric (no data duplication)
 3. Broad data support
 4. Integrated specimen handling
 5. QA workflows and auditing reports
 6. PHI-compliant with granular permissions
 7. Modular, flexible and extensible
                                                                   William of Ockham (1288-1347)
 8. Open source (Plone/Python-powered)
Clinical Data Management
Open source Clinical Content Analysis and Management System
 OCCAMS: Designed to handle all aspects of complex and evolving clinical research studies

  June 1996              ~15 years                April 2010       September 2010              Present
SDPIC Infection   Numerous data management         OCCAMS             Alpha version      +2.5k AEH enrollments
Cohort Begins       solutions and providers   development begins   launched for SDPIC      +12k AEH screens




 1. Web-accessible (eCRFs)
 2. Patient centric (no data duplication)
 3. Broad data support
 4. Integrated specimen handling
 5. QA workflows and auditing reports
 6. PHI-compliant with granular permissions
 7. Modular, flexible and extensible
                                                                        William of Ockham (1288-1347)
 8. Open source (Plone/Python-powered)
Clinical Data Management
SDPIC pre-OCCAMS workflow...
1. Nurse sees patient, completes    3. CRF and source documentation consistency checked
          source docs                                  by AVRC staff




   2. Nurse completes case report form (CRF)   4. CRF entered into database by students
Clinical Data Management
SDPIC pre-OCCAMS workflow...             Challenges
                              1. Rooms full of paper and binders.
                              2. Lag time between source doc,
                              CRF, and CRF database entry
                              completion make reporting difficult
                              and incomplete.
                              3. Several opportunities for
                              transcription errors.
                              4. No QC after students entered CRF
                              to database.
                              5. Data duplication in cases where
                              patients on multiple studies.
                              6. CRF changes not automatically
                              reflected in database.
                              7. Arduous auditing process.
Clinical Data Management
SDPIC pre-OCCAMS workflow...             Challenges
                              1. Rooms full of paper and binders.
                              2. Lag time between source doc,
                              CRF, and CRF database entry
                              completion make reporting difficult
                              and incomplete.
                              3. Several opportunities for
                              transcription errors.
                              4. No QC after students entered CRF
                              to database.
                              5. Data duplication in cases where
                              patients on multiple studies.
                              6. CRF changes not automatically
                              reflected in database.
                              7. Arduous auditing process.
Clinical Data Management
SDPIC pre-OCCAMS workflow...             Challenges
                              1. Rooms full of paper and binders.
                              2. Lag time between source doc,
                              CRF, and CRF database entry
                              completion make reporting difficult
                              and incomplete.
                              3. Several opportunities for
                              transcription errors.
                              4. No QC after students entered CRF
                              to database.
                              5. Data duplication in cases where
                              patients on multiple studies.
                              6. CRF changes not automatically
                              reflected in database.
                              7. Arduous auditing process.
Clinical Data Management
SDPIC pre-OCCAMS workflow...             Challenges
                              1. Rooms full of paper and binders.
                              2. Lag time between source doc,
                              CRF, and CRF database entry
                              completion make reporting difficult
                              and incomplete.
                              3. Several opportunities for
                              transcription errors.
                              4. No QC after students entered CRF
                              to database.
                              5. Data duplication in cases where
                              patients on multiple studies.
                              6. CRF changes not automatically
                              reflected in database.
                              7. Arduous auditing process.
Clinical Data Management
SDPIC pre-OCCAMS workflow...             Challenges
                              1. Rooms full of paper and binders.
                              2. Lag time between source doc,
                              CRF, and CRF database entry
                              completion make reporting difficult
                              and incomplete.
                              3. Several opportunities for
                              transcription errors.
                              4. No QC after students entered CRF
                              to database.
                              5. Data duplication in cases where
                              patients on multiple studies.
                              6. CRF changes not automatically
                              reflected in database.
                              7. Arduous auditing process.
Clinical Data Management
SDPIC pre-OCCAMS workflow...             Challenges
                              1. Rooms full of paper and binders.
                              2. Lag time between source doc,
                              CRF, and CRF database entry
                              completion make reporting difficult
                              and incomplete.
                              3. Several opportunities for
                              transcription errors.
                              4. No QC after students entered CRF
                              to database.
                              5. Data duplication in cases where
                              patients on multiple studies.
                              6. CRF changes not automatically
                              reflected in database.
                              7. Arduous auditing process.
Clinical Data Management
SDPIC pre-OCCAMS workflow...             Challenges
                              1. Rooms full of paper and binders.
                              2. Lag time between source doc,
                              CRF, and CRF database entry
                              completion make reporting difficult
                              and incomplete.
                              3. Several opportunities for
                              transcription errors.
                              4. No QC after students entered CRF
                              to database.
                              5. Data duplication in cases where
                              patients on multiple studies.
                              6. CRF changes not automatically
                              reflected in database.
                              7. Arduous auditing process.
Clinical Data Management
SDPIC post-OCCAMS workflow...
1. Nurse sees patient, completes          3. Workflow notifies AVRC staff eCRF ready for QC
          source docs




   2. Nurse direct enters data via eCRF
  that is automatically generated based               4. High volume eCRFs entered by
          on study and visit week                                 students
Clinical Data Management

                                  Challenges
                      1. Rooms full of paper and binders.
                      2. Lag time between source doc,
                      CRF, and CRF database entry
                      completion make reporting difficult
                      and incomplete.
                      3. Several opportunities for
                      transcription errors.
                      4. No QC after students entered CRF
                      to database.
                      5. Data duplication in cases where
                      patients on multiple studies.
                      6. CRF changes not automatically
                      reflected in database.
                      7. Arduous auditing process.
Clinical Data Management

                                  Challenges
                      1. Rooms full of paper and binders.
                      2. Lag time between source doc,
                      CRF, and CRF database entry
                      completion make reporting difficult
                      and incomplete.
                      3. Several opportunities for
                      transcription errors.
                      4. No QC after students entered CRF
                      to database.
                      5. Data duplication in cases where
                      patients on multiple studies.
                      6. CRF changes not automatically
                      reflected in database.
                      7. Arduous auditing process.
Clinical Data Management

                                  Challenges
                      1. Rooms full of paper and binders.
                      2. Lag time between source doc,
                      CRF, and CRF database entry
                      completion make reporting difficult
                      and incomplete.
                      3. Several opportunities for
                      transcription errors.
                      4. No QC after students entered CRF
                      to database.
                      5. Data duplication in cases where
                      patients on multiple studies.
                      6. CRF changes not automatically
                      reflected in database.
                      7. Arduous auditing process.
Clinical Data Management

                                  Challenges
                      1. Rooms full of paper and binders.
                      2. Lag time between source doc,
                      CRF, and CRF database entry
                      completion make reporting difficult
                      and incomplete.
                      3. Several opportunities for
                      transcription errors.
                      4. No QC after students entered CRF
                      to database.
                      5. Data duplication in cases where
                      patients on multiple studies.
                      6. CRF changes not automatically
                      reflected in database.
                      7. Arduous auditing process.
Clinical Data Management

                                  Challenges
                      1. Rooms full of paper and binders.
                      2. Lag time between source doc,
                      CRF, and CRF database entry
                      completion make reporting difficult
                      and incomplete.
                      3. Several opportunities for
                      transcription errors.
                      4. No QC after students entered CRF
                      to database.
                      5. Data duplication in cases where
                      patients on multiple studies.
                      6. CRF changes not automatically
                      reflected in database.
                      7. Arduous auditing process.
Clinical Data Management

                                  Challenges
                      1. Rooms full of paper and binders.
                      2. Lag time between source doc,
                      CRF, and CRF database entry
                      completion make reporting difficult
                      and incomplete.
                      3. Several opportunities for
                      transcription errors.
                      4. No QC after students entered CRF
                      to database.
                      5. Data duplication in cases where
                      patients on multiple studies.
                      6. CRF changes not automatically
                      reflected in database.
                      7. Arduous auditing process.
Clinical Data Management
            OCCAMS Modular Development

        Core
    occams.clinical

   occams.datastore

     occams.form

    occams.export

    occams.import
Clinical Data Management
            OCCAMS Modular Development

        Core
    occams.clinical

   occams.datastore

     occams.form

    occams.export

    occams.import
Clinical Data Management
            OCCAMS Modular Development

        Core           •   EAV Database Structure
                            ~60 SQL tables total
    occams.clinical
                       •   Robust versioning support
   occams.datastore         Data versioning (audit trail)
                            Form versioning (revision history)
     occams.form

    occams.export

    occams.import
Clinical Data Management
         Form Versioning with OCCAMS
Clinical Data Management
         Form Versioning with OCCAMS
Clinical Data Management
         Form Versioning with OCCAMS


                  Version 1
                 1/2010 - ...

                   A=
                   B=
                   C=
Clinical Data Management
         Form Versioning with OCCAMS


                  Version 1      Version 2
                 1/2010 - ...   7/2010 - ...

                   A=             A=
                   B=             B=
                   C=             D=
Clinical Data Management
         Form Versioning with OCCAMS


                  Version 1      Version 2      Version 3
                 1/2010 - ...   7/2010 - ...   10/2010 - ...

                   A=             A=             A=
                   B=             B=             B=
                   C=             D=             E=
Clinical Data Management
         Form Versioning with OCCAMS


                  Version 1            Version 2       Version 3
                 1/2010 - ...         7/2010 - ...    10/2010 - ...

                   A=                   A=                 A=
                   B=                   B=                 B=
                   C=                   D=                 E=


                                  Which Form to Use?
                                Example. Visit on 8/2010
Clinical Data Management
         Form Versioning with OCCAMS


                  Version 1           Version 2        Version 3
                 1/2010 - ...      7/2010 - Retract   10/2010 - ...

                   A=                   A=                 A=
                   B=                   B=                 B=
                   C=                   D=                 E=


                                  Which Form to Use?
                                Example. Visit on 8/2010
Clinical Data Management
         Form Versioning with OCCAMS


                  Version 1           Version 2         Version 3
                 1/2010 - ...      7/2010 - Retract    10/2010 - ...

                     A=                 A=                A=
                     B=                 B=                B=
                     C=                 D=                E=



                 •   Multiple versions of a form can exist simultaneously
                 •   The correct form for a visit date is auto-presented
                 •   Draft forms can be created and edited concurrently
Clinical Data Management
            OCCAMS Modular Development

        Core                        Add-ons
    occams.clinical                 occams.lab

   occams.datastore              occams.sequence

     occams.form                 occams.symptom

    occams.export                  occams.drug

    occams.import                 occams.partner

                                    occams.edi

                                occams.transmission
Clinical Data Management
                    OCCAMS Modular Development

               Core                          Add-ons
         occams.clinical                     occams.lab

       occams.datastore                   occams.sequence

          occams.form                     occams.symptom

         occams.export                      occams.drug

         occams.import                     occams.partner

 • Currently undergoing finalization of       occams.edi
 remaining core features and testing
 •Public Beta release aimed for first     occams.transmission
 half of 2013
Outline


  1. Web and Mobile Research Services


  2. Clinical Data Management


  3. Bioinformatics Expertise
Bioinformatics Expertise
 HyPhy (hyphy.org)
 A molecular evolution and statistical sequence analysis software package
 • Positive/Negative selection detection
 • Recombination analysis
 • Nucleotide, protein and codon model selection
 Some of the most popular functions are implemented in a webserver hosted at
 datamonkey.org

 Galaxy (galaxy.psu.edu)
 A web-based, scalable, framework for genomic tools, data integration, and reproducible
 analyses.
 • Filter sequences obtained from public databases by specific traits, i.e. find exons with the
 greatest number of SNPs.
 • Deep sequencing analysis tools (read mapping, chip-SEQ, metagenomic taxonomic
 breakdowns).

 Custom Bioinformatics Services
 Examples...
 • Sequence analysis (traditional and NGS)
 • Network analysis
 • Machine Learning
Bioinformatics Expertise
 HyPhy (hyphy.org)
 A molecular evolution and statistical sequence analysis software package
 • Positive/Negative selection detection
 • Recombination analysis
 • Nucleotide, protein and codon model selection
 Some of the most popular functions are implemented in a webserver hosted at
 datamonkey.org

 Galaxy (galaxy.psu.edu)
 A web-based, scalable, framework for genomic tools, data integration, and reproducible
 analyses.
 • Filter sequences obtained from public databases by specific traits, i.e. find exons with the
 greatest number of SNPs.
 • Deep sequencing analysis tools (read mapping, chip-SEQ, metagenomic taxonomic
 breakdowns).

 Custom Bioinformatics Services
 Examples...
 • Sequence analysis (traditional and NGS)
 • Network analysis
 • Machine Learning
Bioinformatics Expertise
                  Network Analysis
         Example: SDPIC Transmission Network

     Screening                          Observational
     Programs                             Studies
                                           AEH
        ET                                 Study
      NAT/Rapid
       Testing          AEH                Partner
                                         Counseling &
                      Infection            Referral
                     NAT(+)/Rapid(-)
                                           Services
                        <70 EDI
                                           (PCRS)
       LTW
     NAT/Rapid                             Partner
      Testing                              Study
Bioinformatics Expertise
                     SDPIC Transmission Network

   Epidemological Link                   Phylogenetic Link
   Partner Counseling and Referral         Genetic distance between
  Services (PCRS) results in index to   HIV pol sequences isolated from
    partner linkage being identified           any two individuals
   (both persons enrolled on study)                is <= 1%
Bioinformatics Expertise
                     SDPIC Transmission Network

   Epidemological Link                   Phylogenetic Link
   Partner Counseling and Referral         Genetic distance between
  Services (PCRS) results in index to   HIV pol sequences isolated from
    partner linkage being identified           any two individuals
   (both persons enrolled on study)                is <= 1%
Bioinformatics Expertise
                      SDPIC Transmission Network

   Epidemological Link                            Phylogenetic Link
    Partner Counseling and Referral                Genetic distance between
   Services (PCRS) results in index to          HIV pol sequences isolated from
     partner linkage being identified                  any two individuals
    (both persons enrolled on study)                       is <= 1%



AEH Study        AEH                                 Partner Study
                                                HIV (-)   AEH      Chronic




                                   “Epilinks”
Bioinformatics Expertise
                     SDPIC Transmission Network

   Epidemological Link                   Phylogenetic Link
   Partner Counseling and Referral         Genetic distance between
  Services (PCRS) results in index to   HIV pol sequences isolated from
    partner linkage being identified           any two individuals
   (both persons enrolled on study)                is <= 1%
Bioinformatics Expertise
                      SDPIC Transmission Network

   Epidemological Link                             Phylogenetic Link
    Partner Counseling and Referral                 Genetic distance between
   Services (PCRS) results in index to           HIV pol sequences isolated from
     partner linkage being identified                   any two individuals
    (both persons enrolled on study)                        is <= 1%



AEH Study        AEH                                  Partner Study
                                                 HIV (-)   AEH      Chronic




                                  “Phylolinks”
Bioinformatics Expertise
                     SDPIC Transmission Network

   Epidemological Link                       Phylogenetic Link
   Partner Counseling and Referral             Genetic distance between
  Services (PCRS) results in index to       HIV pol sequences isolated from
    partner linkage being identified               any two individuals
   (both persons enrolled on study)                    is <= 1%




  1. How effective is PCRS in an AEH setting?
  2. What is the structure of the SDPIC transmission network?
  3. Do HIV(+) reported partners represent likely transmission links?
Bioinformatics Expertise
  1. How effective is PCRS in an AEH setting?
                                            Number Needed To Interview
                                            Previous PCRS studies report...
                                            NNTI: 11-15
                                            A single AEH PCRS study reports...
                                            NNTI: 25 (25/1)
                                            SDPIC...
                                            NNTI: 5.9




                                            Sheldon Morris & Susan Little
Bioinformatics Expertise
  1. How effective is PCRS in an AEH setting?
                                            Number Needed To Interview
                                            Previous PCRS studies report...
                                            NNTI: 11-15
                                            A single AEH PCRS study reports...
                                            NNTI: 25 (25/1)
                                            SDPIC...
                                            NNTI: 5.9




                                            Sheldon Morris & Susan Little
Bioinformatics Expertise
  1. How effective is PCRS in an AEH setting?
                                            Number Needed To Interview
                                            Previous PCRS studies report...
                                            NNTI: 11-15
                                            A single AEH PCRS study reports...
                                            NNTI: 25 (25/1)
                                            SDPIC...
                                            NNTI: 5.9




                                            Sheldon Morris & Susan Little
Bioinformatics Expertise
  1. How effective is PCRS in an AEH setting?
                                            Number Needed To Interview
                                            Previous PCRS studies report...
                                            NNTI: 11-15
                                            A single AEH PCRS study reports...
                                            NNTI: 25 (25/1)
                                            SDPIC...
                                            NNTI: 5.9




                                            Sheldon Morris & Susan Little
Bioinformatics Expertise
  2. What is the structure of the SDPIC transmission network?
                                            Number Needed To Interview
                                            Previous PCRS studies report...
                                            NNTI: 11-15
                                            A single AEH PCRS study reports...
                                            NNTI: 25 (25/1)
                                            SDPIC...
                                            NNTI: 5.9

                                            Scale-free network structure
                                            • Highly-connected nodes critical




                                            Sheldon Morris & Susan Little
Bioinformatics Expertise
  3. Do HIV(+) reported partners represent actual transmission links?
                                             Number Needed To Interview
                                             Previous PCRS studies report...
                                             NNTI: 11-15
                                             A single AEH PCRS study reports...
                                             NNTI: 25 (25/1)
                                             SDPIC...
                                             NNTI: 5.9

                                             Scale-free network structure
                                             • Highly-connected nodes critical


                                             Only ~34% of seroconcordant epi-
                                             linked pairs are also phylo-linked




                                             Sheldon Morris & Susan Little
Bioinformatics Expertise
                   Machine Learning
Example: HIV bnAb epitope and bnAb resistance prediction




                                      Lance Hepler & IAVI NAC
Bioinformatics Expertise
                           Machine Learning
 Example: HIV bnAb epitope and bnAb resistance prediction

IDEPI: IDentify EPItopes
  A pipeline for predicting HIV-1 bnAb epitopes from bnAb neutralization
  titers matched with gp160 sequences.


CARTAS: ComputAional Real Time Antibody Surveillance
  IDEPI extended to predict HIV resistance to bnAb using gp160 sequences
  Input:
     IDEPI inferred predictive model based on neutralization titers
     23.5k HIV-1 group M gp160 sequences from Los Alamos HIV-1 database


                                                    Lance Hepler & IAVI NAC
Bioinformatics Expertise
                           Machine Learning
 Example: HIV bnAb epitope and bnAb resistance prediction

IDEPI: IDentify EPItopes
  A pipeline for predicting HIV-1 bnAb epitopes from bnAb neutralization
  titers matched with gp160 sequences.


CARTAS: ComputAional Real Time Antibody Surveillance
  IDEPI extended to predict HIV resistance to bnAb using gp160 sequences
  Input:
     IDEPI inferred predictive model based on neutralization titers
     23.5k HIV-1 group M gp160 sequences from Los Alamos HIV-1 database


                                                    Lance Hepler & IAVI NAC
Bioinformatics Expertise
                           Machine Learning
 Example: HIV bnAb epitope and bnAb resistance prediction

IDEPI: IDentify EPItopes
  A pipeline for predicting HIV-1 bnAb epitopes from bnAb neutralization
  titers matched with gp160 sequences.


CARTAS: ComputAional Real Time Antibody Surveillance
  IDEPI extended to predict HIV resistance to bnAb using gp160 sequences
  Input:
     IDEPI inferred predictive model based on neutralization titers
     23.5k HIV-1 group M gp160 sequences from Los Alamos HIV-1 database


                                                    Lance Hepler & IAVI NAC
Bioinformatics Expertise
      HIV bnAb epitope and bnAb resistance prediction

                                                    2F5




          Learn More: http://cfar.ucsd.edu/research/croi
Bioinformatics Expertise
      HIV bnAb epitope and bnAb resistance prediction


                                                           B12




          Learn More: http://cfar.ucsd.edu/research/croi
Bioinformatics Expertise
      HIV bnAb epitope and bnAb resistance prediction




                                                   2F5 + B12




          Learn More: http://cfar.ucsd.edu/research/croi
Bioinformatics Expertise
      HIV bnAb epitope and bnAb resistance prediction




                                                   2F5 + B12




                                           Near real-time surveillance

          Learn More: http://cfar.ucsd.edu/research/croi
Acknowledgements
          BIT Core                               CFAR
Sergei Pond                        Doug Richman
Dave Mote                          Kim Schaffer
Marco Martinez                     Bryna Block
Jennifer Rodriguez-Mueller
Steve Weaver                                     AVRC
Konrad Scheffler                     Susan Little
Joel Wertheim                      Sheldon Morris
Lance Hepler                       Richard Haubrich
Martin Smith                       Connie Benson
                                   Davey Smith
         IAVI NAC                  Sanjay Mehta
Pascal Poignard                    ... and all the other superheros ...
           Website: http://cfar.ucsd.edu/bit
           Twitter: @ucsdbit
           Email: bitcore@ucsd.edu
           GitHub: http://github.com/beastcore

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Open Source Software Solutions for Clinical Research: Applications for HIV Research

  • 1. AIDS CLINICAL ROUNDS The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission.
  • 2. Open Source Software Solutions for Clinical Research: Applications for HIV Research Jason A. Young, Ph.D Assistant Professor Department of Medicine, UCSD AIDS Clinical Rounds - 8.3.12
  • 3. UCSD CFAR BIT Core Bioinformatics and Information Technologies (BIT) Core Aims • Provide bio/informatics expertise • To be agile, interactive, affordable • Committed to open source Resources • The BIT Core team! • 24/7, secure web & data servers • 500+ node compute cluster • A collection of open source software solutions and services Website: https://cfar.ucsd.edu/bit E-mail: bitcore@ucsd.edu GitHub: http://github.com/beastcore Clients • Center For AIDS Research (CFAR) • IAVI Neutralizing Antibody Consortium (IAVI-NAC) • AntiViral Research Center (AVRC) • California Collaborative Treatment Group (CCTG) • AIDS Research Institute (ARI) • ... other research investigators and growing ...
  • 4. Outline 1. Web and Mobile Research Services 2. Clinical Data Management 3. Bioinformatics Expertise
  • 5. Outline 1. Web and Mobile Research Services 2. Clinical Data Management 3. Bioinformatics Expertise
  • 6. Web and Mobile Research Services “A powerful, flexible open source Content Management System” Accessible: Non-technical users can create websites and maintain content using only a web browser. Comes with built-in workflows, permissions, etc. Widely deployed: Broad user base includes NASA, Nokia, Novell, and major universities (Harvard, MIT and Penn State). Large development and support base: 340 core developers and >300 solution providers in 57 countries. Mature: First released in 2001. Provides developers a robust framework for custom product development. Secure: Best security record of any major CMS. Extensible: Over 1900 projects extending core functionality currently available.
  • 7. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com Doug Richman (UCSD)
  • 8. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com Doug Richman (UCSD)
  • 9. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com Doug Richman (UCSD)
  • 10. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com • Core Service Request Forms • Feedback Forms • Developmental Grant Submission System • Laboratory Experiment Tracking System • Retroviral Seminar Series Calendar Doug Richman (UCSD)
  • 11. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com Constance Benson (UCSD)
  • 12. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com • Clinical trial information • Events calendar • AIDS rounds presentation slides* Constance Benson (UCSD)
  • 13. Web and Mobile Research Services HIVe: HIV e-resource (hive.ucsd.edu) ARI - ari.ucsd.edu • Acute and Early HIV (AEH) cohort network CFAR - cfar.ucsd.edu • Data standardization and sharing AVRC - avrc.ucsd.edu • 3 active & 7 legacy AEH sites HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com UCSD UCSF MGH AIED AIEDRP AIEDRP AIEDRP AIEDRP AIEDRP AIEDRP
  • 14. Web and Mobile Research Services HIVe: HIV e-resource (hive.ucsd.edu) ARI - ari.ucsd.edu • Acute and Early HIV (AEH) cohort network CFAR - cfar.ucsd.edu • Data standardization and sharing AVRC - avrc.ucsd.edu • 3 active & 7 legacy AEH sites HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu hive.ucsd.edu LTW - leadthewaysd.com ucsd.hive.ucsd.edu UCSD UCSF MGH AIED ucsf.hive.ucsd.edu AIEDRP AIEDRP AIEDRP AIEDRP mgh.hive.ucsd.edu AIEDRP AIEDRP
  • 15. Web and Mobile Research Services San Diego Primary Infection Cohort (SDPIC) ARI - ari.ucsd.edu (1996 - Present) CFAR - cfar.ucsd.edu • 2 Screening Programs (~12k screens) AVRC - avrc.ucsd.edu • 7 Research Studies (~2.5k enrollments) HIVe - hive.ucsd.edu • Data: Demographics, risk factors, partner ET - theearlytest.ucsd.edu information, labs, viral sequences, and much more... LTW - leadthewaysd.com • Specimen: Over 200k UCSD UCSF MGH AIED ucsd.hive.ucsd.edu AIEDRP AIEDRP AIEDRP AIEDRP Susan Little (UCSD) AIEDRP AIEDRP
  • 16. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com Susan Little & Davey Smith (UCSD)
  • 17. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com • AEH screening program (Rapid/NAT) • Obtain NAT results online or over the phone in two weeks Susan Little & Davey Smith (UCSD)
  • 18. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com Susan Little (UCSD)
  • 19. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com • Hyper-local (92103/92104) HIV testing campaign (Rapid/NAT) • Public media advertising campaign • Storefront & door-to-door testing • Goal: What are the barriers to testing? Susan Little (UCSD)
  • 20. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com Susan Little (UCSD)
  • 21. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com Susan Little (UCSD)
  • 22. Web and Mobile Research Services ARI - ari.ucsd.edu CFAR - cfar.ucsd.edu AVRC - avrc.ucsd.edu HIVe - hive.ucsd.edu ET - theearlytest.ucsd.edu LTW - leadthewaysd.com • Hyper-local (92103/92104) HIV testing campaign (Rapid/NAT) • Public media advertising campaign • Storefront & door-to-door testing • Aim: What are the barriers to HIV testing? Susan Little (UCSD)
  • 23. Web and Mobile Research Services iFormBuilder iOS Mobile Data Collection Platform
  • 24. Web and Mobile Research Services iFormBuilder iOS Mobile Data Functionality Collection Platform • Runs on all iOS devices • 25+ field widgets • Flexible skip logic • GPS functionality • HIPAA compliant • Encrypted data upload to cloud
  • 25. Web and Mobile Research Services iFormBuilder iOS Mobile Data Functionality Collection Platform • Runs on all iOS devices • 25+ field widgets • Flexible skip logic • GPS functionality • HIPAA compliant • Encrypted data upload to cloud One year for LTW... • 1317 iPad administered surveys • 1062 individuals tested for HIV • 24 newly diagnosed HIV(+) cases
  • 26. Outline 1. Web and Mobile Research Services 2. Clinical Data Management 3. Bioinformatics Expertise
  • 27. Clinical Data Management Open source Clinical Content Analysis and Management System OCCAMS: Designed to handle all aspects of complex and evolving clinical research studies William of Ockham (1288-1347)
  • 28. Clinical Data Management Open source Clinical Content Analysis and Management System OCCAMS: Designed to handle all aspects of complex and evolving clinical research studies June 1996 ~15 years April 2010 SDPIC Infection Numerous data management OCCAMS Cohort Begins solutions and providers development begins William of Ockham (1288-1347)
  • 29. Clinical Data Management Open source Clinical Content Analysis and Management System OCCAMS: Designed to handle all aspects of complex and evolving clinical research studies June 1996 ~15 years April 2010 SDPIC Infection Numerous data management OCCAMS Cohort Begins solutions and providers development begins 1. Web-accessible (eCRFs) 2. Patient centric (no data duplication) 3. Broad data support 4. Integrated specimen handling 5. QA workflows and auditing reports 6. PHI-compliant with granular permissions 7. Modular, flexible and extensible William of Ockham (1288-1347) 8. Open source (Plone/Python-powered)
  • 30. Clinical Data Management Open source Clinical Content Analysis and Management System OCCAMS: Designed to handle all aspects of complex and evolving clinical research studies June 1996 ~15 years April 2010 September 2010 Present SDPIC Infection Numerous data management OCCAMS Alpha version +2.5k AEH enrollments Cohort Begins solutions and providers development begins launched for SDPIC +12k AEH screens 1. Web-accessible (eCRFs) 2. Patient centric (no data duplication) 3. Broad data support 4. Integrated specimen handling 5. QA workflows and auditing reports 6. PHI-compliant with granular permissions 7. Modular, flexible and extensible William of Ockham (1288-1347) 8. Open source (Plone/Python-powered)
  • 31. Clinical Data Management SDPIC pre-OCCAMS workflow... 1. Nurse sees patient, completes 3. CRF and source documentation consistency checked source docs by AVRC staff 2. Nurse completes case report form (CRF) 4. CRF entered into database by students
  • 32. Clinical Data Management SDPIC pre-OCCAMS workflow... Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 33. Clinical Data Management SDPIC pre-OCCAMS workflow... Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 34. Clinical Data Management SDPIC pre-OCCAMS workflow... Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 35. Clinical Data Management SDPIC pre-OCCAMS workflow... Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 36. Clinical Data Management SDPIC pre-OCCAMS workflow... Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 37. Clinical Data Management SDPIC pre-OCCAMS workflow... Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 38. Clinical Data Management SDPIC pre-OCCAMS workflow... Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 39. Clinical Data Management SDPIC post-OCCAMS workflow... 1. Nurse sees patient, completes 3. Workflow notifies AVRC staff eCRF ready for QC source docs 2. Nurse direct enters data via eCRF that is automatically generated based 4. High volume eCRFs entered by on study and visit week students
  • 40. Clinical Data Management Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 41. Clinical Data Management Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 42. Clinical Data Management Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 43. Clinical Data Management Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 44. Clinical Data Management Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 45. Clinical Data Management Challenges 1. Rooms full of paper and binders. 2. Lag time between source doc, CRF, and CRF database entry completion make reporting difficult and incomplete. 3. Several opportunities for transcription errors. 4. No QC after students entered CRF to database. 5. Data duplication in cases where patients on multiple studies. 6. CRF changes not automatically reflected in database. 7. Arduous auditing process.
  • 46. Clinical Data Management OCCAMS Modular Development Core occams.clinical occams.datastore occams.form occams.export occams.import
  • 47. Clinical Data Management OCCAMS Modular Development Core occams.clinical occams.datastore occams.form occams.export occams.import
  • 48. Clinical Data Management OCCAMS Modular Development Core • EAV Database Structure ~60 SQL tables total occams.clinical • Robust versioning support occams.datastore Data versioning (audit trail) Form versioning (revision history) occams.form occams.export occams.import
  • 49. Clinical Data Management Form Versioning with OCCAMS
  • 50. Clinical Data Management Form Versioning with OCCAMS
  • 51. Clinical Data Management Form Versioning with OCCAMS Version 1 1/2010 - ... A= B= C=
  • 52. Clinical Data Management Form Versioning with OCCAMS Version 1 Version 2 1/2010 - ... 7/2010 - ... A= A= B= B= C= D=
  • 53. Clinical Data Management Form Versioning with OCCAMS Version 1 Version 2 Version 3 1/2010 - ... 7/2010 - ... 10/2010 - ... A= A= A= B= B= B= C= D= E=
  • 54. Clinical Data Management Form Versioning with OCCAMS Version 1 Version 2 Version 3 1/2010 - ... 7/2010 - ... 10/2010 - ... A= A= A= B= B= B= C= D= E= Which Form to Use? Example. Visit on 8/2010
  • 55. Clinical Data Management Form Versioning with OCCAMS Version 1 Version 2 Version 3 1/2010 - ... 7/2010 - Retract 10/2010 - ... A= A= A= B= B= B= C= D= E= Which Form to Use? Example. Visit on 8/2010
  • 56. Clinical Data Management Form Versioning with OCCAMS Version 1 Version 2 Version 3 1/2010 - ... 7/2010 - Retract 10/2010 - ... A= A= A= B= B= B= C= D= E= • Multiple versions of a form can exist simultaneously • The correct form for a visit date is auto-presented • Draft forms can be created and edited concurrently
  • 57. Clinical Data Management OCCAMS Modular Development Core Add-ons occams.clinical occams.lab occams.datastore occams.sequence occams.form occams.symptom occams.export occams.drug occams.import occams.partner occams.edi occams.transmission
  • 58. Clinical Data Management OCCAMS Modular Development Core Add-ons occams.clinical occams.lab occams.datastore occams.sequence occams.form occams.symptom occams.export occams.drug occams.import occams.partner • Currently undergoing finalization of occams.edi remaining core features and testing •Public Beta release aimed for first occams.transmission half of 2013
  • 59. Outline 1. Web and Mobile Research Services 2. Clinical Data Management 3. Bioinformatics Expertise
  • 60. Bioinformatics Expertise HyPhy (hyphy.org) A molecular evolution and statistical sequence analysis software package • Positive/Negative selection detection • Recombination analysis • Nucleotide, protein and codon model selection Some of the most popular functions are implemented in a webserver hosted at datamonkey.org Galaxy (galaxy.psu.edu) A web-based, scalable, framework for genomic tools, data integration, and reproducible analyses. • Filter sequences obtained from public databases by specific traits, i.e. find exons with the greatest number of SNPs. • Deep sequencing analysis tools (read mapping, chip-SEQ, metagenomic taxonomic breakdowns). Custom Bioinformatics Services Examples... • Sequence analysis (traditional and NGS) • Network analysis • Machine Learning
  • 61. Bioinformatics Expertise HyPhy (hyphy.org) A molecular evolution and statistical sequence analysis software package • Positive/Negative selection detection • Recombination analysis • Nucleotide, protein and codon model selection Some of the most popular functions are implemented in a webserver hosted at datamonkey.org Galaxy (galaxy.psu.edu) A web-based, scalable, framework for genomic tools, data integration, and reproducible analyses. • Filter sequences obtained from public databases by specific traits, i.e. find exons with the greatest number of SNPs. • Deep sequencing analysis tools (read mapping, chip-SEQ, metagenomic taxonomic breakdowns). Custom Bioinformatics Services Examples... • Sequence analysis (traditional and NGS) • Network analysis • Machine Learning
  • 62. Bioinformatics Expertise Network Analysis Example: SDPIC Transmission Network Screening Observational Programs Studies AEH ET Study NAT/Rapid Testing AEH Partner Counseling & Infection Referral NAT(+)/Rapid(-) Services <70 EDI (PCRS) LTW NAT/Rapid Partner Testing Study
  • 63. Bioinformatics Expertise SDPIC Transmission Network Epidemological Link Phylogenetic Link Partner Counseling and Referral Genetic distance between Services (PCRS) results in index to HIV pol sequences isolated from partner linkage being identified any two individuals (both persons enrolled on study) is <= 1%
  • 64. Bioinformatics Expertise SDPIC Transmission Network Epidemological Link Phylogenetic Link Partner Counseling and Referral Genetic distance between Services (PCRS) results in index to HIV pol sequences isolated from partner linkage being identified any two individuals (both persons enrolled on study) is <= 1%
  • 65. Bioinformatics Expertise SDPIC Transmission Network Epidemological Link Phylogenetic Link Partner Counseling and Referral Genetic distance between Services (PCRS) results in index to HIV pol sequences isolated from partner linkage being identified any two individuals (both persons enrolled on study) is <= 1% AEH Study AEH Partner Study HIV (-) AEH Chronic “Epilinks”
  • 66. Bioinformatics Expertise SDPIC Transmission Network Epidemological Link Phylogenetic Link Partner Counseling and Referral Genetic distance between Services (PCRS) results in index to HIV pol sequences isolated from partner linkage being identified any two individuals (both persons enrolled on study) is <= 1%
  • 67. Bioinformatics Expertise SDPIC Transmission Network Epidemological Link Phylogenetic Link Partner Counseling and Referral Genetic distance between Services (PCRS) results in index to HIV pol sequences isolated from partner linkage being identified any two individuals (both persons enrolled on study) is <= 1% AEH Study AEH Partner Study HIV (-) AEH Chronic “Phylolinks”
  • 68. Bioinformatics Expertise SDPIC Transmission Network Epidemological Link Phylogenetic Link Partner Counseling and Referral Genetic distance between Services (PCRS) results in index to HIV pol sequences isolated from partner linkage being identified any two individuals (both persons enrolled on study) is <= 1% 1. How effective is PCRS in an AEH setting? 2. What is the structure of the SDPIC transmission network? 3. Do HIV(+) reported partners represent likely transmission links?
  • 69. Bioinformatics Expertise 1. How effective is PCRS in an AEH setting? Number Needed To Interview Previous PCRS studies report... NNTI: 11-15 A single AEH PCRS study reports... NNTI: 25 (25/1) SDPIC... NNTI: 5.9 Sheldon Morris & Susan Little
  • 70. Bioinformatics Expertise 1. How effective is PCRS in an AEH setting? Number Needed To Interview Previous PCRS studies report... NNTI: 11-15 A single AEH PCRS study reports... NNTI: 25 (25/1) SDPIC... NNTI: 5.9 Sheldon Morris & Susan Little
  • 71. Bioinformatics Expertise 1. How effective is PCRS in an AEH setting? Number Needed To Interview Previous PCRS studies report... NNTI: 11-15 A single AEH PCRS study reports... NNTI: 25 (25/1) SDPIC... NNTI: 5.9 Sheldon Morris & Susan Little
  • 72. Bioinformatics Expertise 1. How effective is PCRS in an AEH setting? Number Needed To Interview Previous PCRS studies report... NNTI: 11-15 A single AEH PCRS study reports... NNTI: 25 (25/1) SDPIC... NNTI: 5.9 Sheldon Morris & Susan Little
  • 73. Bioinformatics Expertise 2. What is the structure of the SDPIC transmission network? Number Needed To Interview Previous PCRS studies report... NNTI: 11-15 A single AEH PCRS study reports... NNTI: 25 (25/1) SDPIC... NNTI: 5.9 Scale-free network structure • Highly-connected nodes critical Sheldon Morris & Susan Little
  • 74. Bioinformatics Expertise 3. Do HIV(+) reported partners represent actual transmission links? Number Needed To Interview Previous PCRS studies report... NNTI: 11-15 A single AEH PCRS study reports... NNTI: 25 (25/1) SDPIC... NNTI: 5.9 Scale-free network structure • Highly-connected nodes critical Only ~34% of seroconcordant epi- linked pairs are also phylo-linked Sheldon Morris & Susan Little
  • 75. Bioinformatics Expertise Machine Learning Example: HIV bnAb epitope and bnAb resistance prediction Lance Hepler & IAVI NAC
  • 76. Bioinformatics Expertise Machine Learning Example: HIV bnAb epitope and bnAb resistance prediction IDEPI: IDentify EPItopes A pipeline for predicting HIV-1 bnAb epitopes from bnAb neutralization titers matched with gp160 sequences. CARTAS: ComputAional Real Time Antibody Surveillance IDEPI extended to predict HIV resistance to bnAb using gp160 sequences Input: IDEPI inferred predictive model based on neutralization titers 23.5k HIV-1 group M gp160 sequences from Los Alamos HIV-1 database Lance Hepler & IAVI NAC
  • 77. Bioinformatics Expertise Machine Learning Example: HIV bnAb epitope and bnAb resistance prediction IDEPI: IDentify EPItopes A pipeline for predicting HIV-1 bnAb epitopes from bnAb neutralization titers matched with gp160 sequences. CARTAS: ComputAional Real Time Antibody Surveillance IDEPI extended to predict HIV resistance to bnAb using gp160 sequences Input: IDEPI inferred predictive model based on neutralization titers 23.5k HIV-1 group M gp160 sequences from Los Alamos HIV-1 database Lance Hepler & IAVI NAC
  • 78. Bioinformatics Expertise Machine Learning Example: HIV bnAb epitope and bnAb resistance prediction IDEPI: IDentify EPItopes A pipeline for predicting HIV-1 bnAb epitopes from bnAb neutralization titers matched with gp160 sequences. CARTAS: ComputAional Real Time Antibody Surveillance IDEPI extended to predict HIV resistance to bnAb using gp160 sequences Input: IDEPI inferred predictive model based on neutralization titers 23.5k HIV-1 group M gp160 sequences from Los Alamos HIV-1 database Lance Hepler & IAVI NAC
  • 79. Bioinformatics Expertise HIV bnAb epitope and bnAb resistance prediction 2F5 Learn More: http://cfar.ucsd.edu/research/croi
  • 80. Bioinformatics Expertise HIV bnAb epitope and bnAb resistance prediction B12 Learn More: http://cfar.ucsd.edu/research/croi
  • 81. Bioinformatics Expertise HIV bnAb epitope and bnAb resistance prediction 2F5 + B12 Learn More: http://cfar.ucsd.edu/research/croi
  • 82. Bioinformatics Expertise HIV bnAb epitope and bnAb resistance prediction 2F5 + B12 Near real-time surveillance Learn More: http://cfar.ucsd.edu/research/croi
  • 83. Acknowledgements BIT Core CFAR Sergei Pond Doug Richman Dave Mote Kim Schaffer Marco Martinez Bryna Block Jennifer Rodriguez-Mueller Steve Weaver AVRC Konrad Scheffler Susan Little Joel Wertheim Sheldon Morris Lance Hepler Richard Haubrich Martin Smith Connie Benson Davey Smith IAVI NAC Sanjay Mehta Pascal Poignard ... and all the other superheros ... Website: http://cfar.ucsd.edu/bit Twitter: @ucsdbit Email: bitcore@ucsd.edu GitHub: http://github.com/beastcore