NIST: Mission, Metrology, and Standards. NBMC Workshop Blood, Sweat, & Tears III November 2-3, 2016

Transcription

1 NIST: Mission, Metrology, and Standards NBMC Workshop Blood, Sweat, & Tears III November 2-3, 2016 Peter M. Vallone, Ph.D. Leader, Applied Genetics Group NIST Gaithersburg, MD USA

2 WHY AM I HERE PRECISION MEDICINE Precision medicine (PM) is a medical model that proposes the customization of healthcare, with medical decisions, practices, and/or products being tailored to the individual patient. Right drug, at the right time, for the right patient It s health care tailored to you Many definitions exist

3 Why am I here? One aspect of the President s Precision Medicine Initiative Cohort Program ( sensors mentioned over 60 times) should consider the use and integration of select wireless sensors, either worn or employed in the home, that have been validated and that would provide useful health data for specific subgroups of the PMI cohort. These sensors may include research grade or commercial grade wrist-worn accelerometers, wireless weight scales, movement sensors in the home, continuous heart rate and pulse oxygen monitors, respiration monitors, glucometers, spirometers, and other FDA approved wireless medical monitoring devices used in the home.

4 NIST - DEPARTMENT OF COMMERCE Mission: To promote U.S. innovation and industrial competitiveness by advancing measurement science, standards, and technology in ways that enhance economic security and improve the quality of life. Economic drivers get quality products to market efficiently Don t lose US ideas to foreign markets NIST is a non-regulatory agency NIST exists to support industry 28 miles away

5 Laboratories at NIST Communications Technology Laboratory (CTL) Engineering Laboratory Information Technology Laboratory Material Measurement Laboratory Physical Measurement Laboratory

6 STAKEHOLDERS DRIVE OUR STANDARDS Who are our customers? Academic Industrial Regulatory Other Government Agencies Lieber Institute: Automated algorithm for picking good stem cell colonies Bad Good

7 NIST Solve the Missing Middle high F u n d i n g / I n v e s t m e n t Basic R&D Valley of Death Manufacturing low Basic Materials Research Academia Government Proof of concept Academia Government Laboratoryscale production??? Capacity to produce prototype??? Capability in production environment Private sector Demonstration of production rates Private sector

8 What is Metrology? Metrology is the science of measurements It s a key element in Trade Product development/design Improvement in health Protection of the environment Innovation Prototype kilogram Metrology is primarily concerned with: Establishing the units of a measurement, ensuring uniformity of the measurements Developing methods of measurement Errors associated with measurements Accuracy of measurements The establishment of traceability chains by determining and documenting the value and accuracy of a measurement and disseminating that knowledge The formal system that tells us how well we trust data measurements

9 METROLOGY CHEAT-SHEET Traceability Back to known reference point Allows comparison of results Method validation Does an assay accurately measure what is intended? Is assay robust? Uncertainty How good is the result? How good does it need to be? Limits of detection, equipment comparability, comparability and interoperability across space and time, innovative measurement techniques.trying to stay a step ahead. Examples: ERCC Spike-in Controls for gene expression studies NIST mab reference material Reference data for mass spec profiles of metabolites, etc. EDRN collaboration to validate biomarkers for cancer diagnostics DNA forensics Quantitative Imaging Protocols Comparative study of cell-counting instrumentation Cell line ID protocols

10 NIST Standard Reference Materials Over 1,300 available These materials are used to perform instrument calibrations in units as part of overall quality assurance programs Verify the accuracy of specific measurements Support the development of new measurement methods.

11 NIST Standard Reference Materials Over 1,300 available These materials are used to perform instrument calibrations in units as part of overall quality assurance programs Verify the accuracy of specific measurements Support the development of new measurement methods. Fatty acids, Cholesterol, Amino acids, vitamins, clinical markers, etc

12 AN EXAMPLE OF A STANDARD REFERENCE MATERIAL SRM 2391c PCR-Based DNA Profiling Standard Purpose: Forensic DNA labs characterize the material to ensure accuracy of their DNA typing methods and validate their procedures Commercial companies use the material to develop and characterize their test kits Required by the FBI for all lab submitting DNA results SRM 2391c Harmonization of DNA typing results in the US and abroad SRM 2391c PCR based DNA Profiling Standard

13 SRM 2391C PCR BASED DNA PROFILING STANDARD SRM 2391c Acquire genomic DNA samples (blood bank, cell lines) Characterized (sequenced) by various methods at NIST (Sanger sequencing and next-generation sequencing) Materials bottled and tested for homogeneity and stability Sold with a certificate with certified sequence values

14 Confidence in Genomics Measurements Genome in a Bottle NIST led consortium with more than 75 public, private, academic partners Developing whole genome reference materials and bioinformatics tools for quality assurance of whole genome sequencing technologies (next gen and next/next gen). FDA used this to approve the first highthroughput DNA sequencer. NY Times (5/14/15): The federal government (NIST and FDA) opened a new era of genetic medicine on Thursday by introducing a standard way to ensure the accuracy of DNA tests used to tailor treatments for individual patients. RM 8398 Human DNA for Whole-Genome Variant Assessment (Daughter of Utah/European Ancestry)

15 Confidence in Microbiome Measurements Announced by the White House, May 2016 RM 8375 Microbial Genomic DNA Standards for Sequencing Performance Assessment Standards for Microbiome Measurements NIST workshop August 9-10, 2016 Dr. Scott Jackson, organizer Web announcement:

16 NISTmAb Reference Material 8671 Target Industry: Biomanufacturing Intended Use: Supplement in-house reference standard program as material for evaluating methods that determine physicochemical and biophysical attributes of monoclonal antibodies. Developed from: 2014 to 2016 Discussions with Industry Stakeholders Industry Donation of Reference Material Extensive Characterization of the Reference Material Packaging / Stability Testing/Intern al Review Release as NIST RM/SRM Examples of use- Streamline implementation of new technology Assist method qualification Widely available historical data Harmonize approaches to well characterize products Assess method applicability, variability & utility

17 CRM to Support Metabolomics Identification, measurement and interpretation of the fingerprint of metabolites or metabolome in various cells, biological tissues and fluids that representthe constituentsof biochemical cellular processes The metabolome represents the identity and concentration of metabolites at a given point in time Profiles are dynamic Reflects phenotype Range in the 1000s Technical Contacts: Johanna Camara, Katrice Lippa SRM 1950 Metabolites in Human Plasma was designed to represent a normal human plasma and to be used for method validation in metabolomics studies Value assignment of over 90 individual constituents (cholesterol, creatinine, hormones, fatty acids, amino acids, vitamins, trace elements and electrolytes)

18 The NIST/EPA/NIH Mass Spectral Library (SRD1A) Reference Standard Mass Spectra for Molecular Identification Basis: Fragments of charged molecules provide reproducible, distinguishable fingerprints for molecules in complex mixtures Usage World s most widely used MS library >5,000 NEW installations per year Integrated into instrument vendor software systems Content NIST2014 -evaluated spectra for 212,961 compounds Accompanying chemical name(s) and identifiers Chemical structures and retention information Validated software for spectrum matching Industry customers Biotechnology Biomedical Research Homeland Security Forensics Environmental Analysis Food Analysis Peptide Library 500,000 peptides for 8 species NIST/EPA/NIH Mass Spectral Library EI spectra of 212K compounds IgG Library Peptides Glycopeptide Glycans Small Molecule Tandem MS 7K compounds Ion trap/ Collision cell NIST2017 version will be released in spring of 2017 with many more additional spectra added.

19 TECHNOLOGY

20 Sensor calibration? The need for standards to validate and benchmark wearable devices

21 Acknowledgements Kelley Rogers Katrice Lippa Jeanita Pritchett Christopher Soles