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The PhenX Toolkit: Standard Measures for Collaborative Research - Wayne Huggins


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Introduction and Background: The Web-based PhenX Toolkit (consensus measures for Phenotypes and eXposures, https://www. is a catalog of standard measures designed to facilitate collaborative biomedical research. PhenX measures help ensure that phenotypes from different studies are collected and represented in a consistent format. This consistency can enable data comparability across sites in large cohorts (e.g., Precision Medicine Initiative) and facilitates combining data to validate clinically actionable variants, increase statistical power (e.g., studies of rare genetic conditions or gene-enviroment interactions), or compare treatments and outcomes between patients.

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The PhenX Toolkit: Standard Measures for Collaborative Research - Wayne Huggins

  1. 1. RTI International is a trade name of Research Triangle Institute The PhenX Toolkit: Standard Measures for Collaborative Research Human Variome Project June 2, 2016 Wayne Huggins, PhD 1
  2. 2. PhenX: consensus measures for Phenotypes and eXposures • PhenX is funded by the National Human Genome Research Institute (NHGRI), Project Scientist, Dr. Erin Ramos with co-funding from the National Institute on Drug Abuse (NIDA) • In September 2007, RTI International was awarded a Cooperative Agreement (U01) to select and define high priority measures for GWAS (phase 1) • In July 2013, RTI International was awarded a Genomics Resource grant (U41) to expand the Toolkit, review existing measure and add features (phase 2) • PhenX uses an established consensus based process and is driven by the scientific community • Initially focused on measures for genome-wide association studies, the scope has broadened to clinical, translational and epidemiological research
  3. 3. Why Use Standard Measures? • Increased sample size provides greater statistical power – For GWAS, to identify moderate associations and more complex interactions – For other types of studies, increases statistical confidence in results • Study findings require validation – Initial findings need to be replicated, standard measures aid comparisons • Cross-study analyses increase the impact of individual studies – Many diseases and conditions share common risk factors – Use of standard (common) measures facilitates cross-study analyses
  4. 4. PhenX Project Organization 4
  5. 5. Criteria for Selecting PhenX Measures • Clearly defined • Well established • Broadly applicable • Validated • Reproducible • Specific • Reliable • Standard measurement protocols exist • Criteria defined by the PhenX Steering Committee • Working Groups select measures to be included in the Toolkit
  6. 6. • Alcohol, Tobacco, and Other Substances • Anthropometrics • Cancer • Cardiovascular • Demographics • Diabetes • Environmental Exposures • Gastrointestinal • Geriatrics • Infectious Diseases and Immunity • Neurology • Nutrition and Dietary Supplements • Obesity • Ocular • Oral Health • Physical Activity and Physical Fitness • Pregnancy • Psychiatric • Psychosocial • Rare Genetic Conditions • Reproductive Health • Respiratory • Skin, Bone, Muscle, and Joint • Social Environments • Speech and Hearing PhenX - Research Domains
  7. 7. PhenX Supplements - adding depth to the Toolkit • PhenX Measures for Sickle Cell Disease Research (funded by NHLBI) – Ellen Werner, Project Scientist – Sickle Cell Disease Research and Scientific Panel (SRSP) – Collaborating with H3Africa (Human Heredity and Health in Africa) on a Sickle Cell Disease ontology • PhenX Measures for Mental Health Research (funded by NIMH) – Greg Farber, Project Scientist – Mental Health Research Scientific Panel (MHRP) • PhenX Measures for Tobacco Regulatory Science (funded by TRSP) – Kay Wanke, Project Scientist – Tobacco Regulatory Research Scientific Panel (TRRP) • PhenX Measures for Substance Abuse and Addiction (funded by NIDA) – Kevin Conway, Project Scientist – Substance Abuse and Addiction Scientific Panel (SSP)
  8. 8. 8
  9. 9. Toolkit Features • Browse or Search entire Toolkit – Browse by “Domain”, “Measure,” or “Collection” – Search using “Smart Query Tool” • Add measures to “My Toolkit” – Identifies “Essential Measures” – Recommends “Related Measures” – Registration allows users to save and share multiple Toolkits • Download information about selected measures – Custom Reports – Custom Data Collection Worksheets (DCW) – Data Dictionaries (DD) support data submission to dbGaP – REDCap zip instrument files to upload to studies in REDCap • Translations – Spanish and Chinese coming soon 9
  10. 10. PhenX Measures are Connected to Standards and Resources 10
  11. 11. PhenX Collaborations - dbGaP 11 • Goal: Identify dbGaP studies that can be combined with PhenX measures for potential use in cross-study analysis • Annotate use of PhenX measures Data submission • Mapping PhenX variables to dbGaP study variables retrospectively (PhenX has relatively small number of variables compared to dbGaP) • PhenX in dbGaP advanced search • dbGaP adding PhenX in Faceted Browsing (in design phase)
  12. 12. 12 Mapping to retrospective studies
  13. 13. PhenX Collaborations - REDCap • Research Electronic Data Capture (REDCap) application allows users to build and manage online surveys and databases quickly and securely • Web-based data collection for PhenX protocols • All PhenX protocols have REDCap Zip Instruments, which can be uploaded directly to REDCap • Accessible at both REDCap (a link to PhenX) and PhenX sites • REDCap available for use on mobile devices 13
  14. 14. RTI International is a trade name of Research Triangle Institute
  15. 15. PhenX Collaborations - Translations Translated protocols – Sharing Spanish translations in the Toolkit – Template for other languages e.g. Chinese – Spanish • Major sources include NHANES, CDC, GAIN, NHLBI, NSDUH • To date, we retrieved 59 of 194 – Chinese • Dr. Jim Zhang, Director, Shanghai Key Laboratory of Children’s Environmental Health, Institute of Translational Medicine SJTU • Chinese translation for all 21 domains, received 2 domains, expect remaining in May – Toolkit navigation is in English 16
  16. 16. PhenX Collaborations – H3Africa • H3Africa – Sickle Cell Disease Ontology – African population-specific protocols for the Toolkit? 17
  17. 17. Registered Users and FOAs Recommending PhenX Measures Over Time 18
  18. 18. Summary - PhenX and HVP • PhenX for epidemiology, clinical and translational research as well as genomics – PhenX Measures for Rare Genetic Conditions – Supplements • Most PhenX measures are agnostic, but provide information that leads to diagnoses – Diagnostic criteria change – Modular approach, multiple measures may be needed to make a “diagnoses” • Expansion of PhenX Ontology – Compatible with HPO and Monarch – Collaboration with H3Africa on SCD ontology • Adoption of standard vocabulary (e.g. UMLS) and definitions (e.g. MeSH) 19
  19. 19. Acknowledgements • NHGRI – Erin Ramos (Project Scientist) – Brenda Iglesias (Program Analyst) • PhenX Steering Committee – Mary Marazita, Co-Chair – Cathy McCarty, Co-Chair • WG Chairs / Members • NIH Liaisons • Other Liaisons, HHS, DoD, CDC, FDA, VA • NIDA lead – Kevin Conway • TRSP lead – Kay Wanke • NIMH lead – Greg Farber • NHLBI lead – Ellen Werner • RTI Team – Carol Hamilton (Principal Investigator) – Tabitha Hendershot (Co- Investigator) – Amanda Riley (Project Manager) – Darigg Brown – Wayne Huggins – Debbie Maiese – Destiney Nettles – Helen Pan – Mike Phillips – Toolkit team – Communications team – Logistics team – Collaborators
  20. 20. 21 Questions?
  21. 21. Resources • – Find PhenX measures for inclusion in your study – Quick Start guide – Tutorial • – Provides general information about the PhenX project – Register to receive periodic updates via e-mail of the PhenX Newsletter and notification of new surveys
  22. 22. 23
  23. 23. 24
  24. 24. PhenX Terminology • DOMAIN: Topical area with a unifying theme • COLLECTION: A collection of measures with a shared characteristic, target population or topic. The measures included in a Collection may cut across research Domains • MEASURE: A certain characteristic of, or related to, a study subject • PROTOCOL: Standard procedure recommended by a Working Group to collect and record a PhenX measure
  25. 25. RTI International is a trade name of Research Triangle Institute Cross-reference table for PhenX measures and variables PhenX variable PhenX ID dbGaP variable LOINC code Current Age PXV010101020000 phv00023938.v1 phv00024004.v1 21612-7 Ethnicity PXV010501010000 phv00023941.v1 phv00024007.v1 56050-8 Gender PXV010701010000 phv00023939.v1 phv00024005.v1 46607-8 P3G variable* Age Ethnicity Gender eMERGE variable caDSR CDE Age 2423393 Ethnicity 2200284 Gender 2179640 * P3G DataShaPER doesn’t distinguish between “exact” and “similar” mappings to PhenX measures
  26. 26. New Frontiers for PMI – and PhenX • Hand-held devices for gathering data • PhenX in EHRs / Linking to EHRs • Inclusion in patient portals • 23andMe etc 27
  27. 27. PhenX Measures Being Included in Current Initiatives and NIH-Funded Studies 28 NIH Research Initiative/Study Number of PhenX Measures Sample size Adolescent Brain Cognitive Development (ABCD) Study 43 10,000* Precision Medicine Initiative (PMI) 16 1 million* Population Assessment of Tobacco and Health (PATH) 16 46,000 Tobacco Centers of Regulatory Science (TCORS) 38 unknown Environmental influences on Child Health Outcomes: Patient Reported Outcomes Research Resource Center Core (ECHO PRO Core) PhenX recommended in RFA 50,000* Data Coordinating Center for Sickle Cell Disease Implementation Consortium (SCDIC): PhenX recommended in RFA 2,100* * Planned
  28. 28. PhenX Measures Enable Cross-Study Analysis 29
  29. 29. • Review each of 21 original domains to ensure measures still reflect current science – ERP 1 – Anthropometrics, Diabetes, Nutrition and Dietary Supplements, & Physical Activity and Physical Fitness – ERP 2 – Demographics, Environmental Exposures, Social Environments – ERP 3 – Alcohol, Tobacco, and Other Substances, Substance Abuse and Addiction Collections – ERP 4 – Psychiatric, Neurology, Psychosocial – ERP 5 – Reproductive Health Expert Review Panels (ERPs) 30
  30. 30. 1. Ataxia Rating Scale 2. Body Proportions 3. Bone Age 4. Child Oral Health Pain 5. Complete Blood Count (CBC) 6. Disability Index 7. Disease Progression and Regression 8. Disorders of Respiratory Control with Inherent Autonomic Dysregulation 9. Echocardiography Phenotypes 10. Family Health History 11. Growth Charts 12. Quality of Life 13. Scale of Developmental Domains of Early Childhood 14. Scoliosis - Physical Assessment 15. Scoliosis - Quality of Life 16. Sweat Chloride Test Rare Genetic Conditions 31