Next Steps for
Functional Genomics
PROCEEDINGS OF A WORKSHOP
Robert Pool, Steven M. Moss, and Frances Sharples, Rapporteurs
Board on Life Sciences
Division on Earth and Life Studies
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by the National Science Foundation under Award Number 1927620. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-67673-1
International Standard Book Number-10: 0-309-67673-8
Digital Object Identifier: https://doi.org/10.17226/25780
Additional copies of this publication are available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.
Copyright 2020 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2020. Next Steps for Functional Genomics: Proceedings of a Workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/25780.
The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Marcia McNutt is president.
The National Academy of Engineering was established in 1964 under the charter of the National Academy of Sciences to bring the practices of engineering to advising the nation. Members are elected by their peers for extraordinary contributions to engineering. Dr. John L. Anderson is president.
The National Academy of Medicine (formerly the Institute of Medicine) was established in 1970 under the charter of the National Academy of Sciences to advise the nation on medical and health issues. Members are elected by their peers for distinguished contributions to medicine and health. Dr. Victor J. Dzau is president.
The three Academies work together as the National Academies of Sciences, Engineering, and Medicine to provide independent, objective analysis and advice to the nation and conduct other activities to solve complex problems and inform public policy decisions. The Academies also encourage education and research, recognize outstanding contributions to knowledge, and increase public understanding in matters of science, engineering, and medicine.
Learn more about the National Academies of Sciences, Engineering, and Medicine at www.nationalacademies.org.
Consensus Study Reports published by the National Academies of Sciences, Engineering, and Medicine document the evidence-based consensus on the study’s statement of task by an authoring committee of experts. Reports typically include findings, conclusions, and recommendations based on information gathered by the committee and the committee’s deliberations. Each report has been subjected to a rigorous and independent peer-review process and it represents the position of the National Academies on the statement of task.
Proceedings published by the National Academies of Sciences, Engineering, and Medicine chronicle the presentations and discussions at a workshop, symposium, or other event convened by the National Academies. The statements and opinions contained in proceedings are those of the participants and are not endorsed by other participants, the planning committee, or the National Academies.
For information about other products and activities of the National Academies, please visit www.nationalacademies.org/about/whatwedo.
PLANNING COMMITTEE ON NEXT STEPS FOR FUNCTIONAL GENOMICS: A WORKSHOP
GENE E. ROBINSON (NAS, NAM), Chair, University of Illinois at Urbana-Champaign
PHILIP N. BENFEY (NAS), Duke University
CHARLES DANKO, Cornell University
EMMA FARLEY, University of California, San Diego
TRUDY F. C. MACKAY (NAS), Clemson University
TERRY MAGNUSON (NAM), University of North Carolina at Chapel Hill
LAUREN O’CONNELL, Stanford University
ANDREA SWEIGART, University of Georgia
Staff
STEVEN M. MOSS, Associate Program Officer, Board on Life Sciences
FRANCES SHARPLES, Board Director, Board on Life Sciences
KOSSANA YOUNG, Senior Program Assistant, Board on Life Sciences
BOARD ON LIFE SCIENCES
JAMES P. COLLINS, Chair, Arizona State University
A. ALONSO AGUIRRE, George Mason University
VALERIE H. BONHAM, Ropes & Gray LLP
DOMINIQUE BROSSARD, University of Wisconsin–Madison
NANCY D. CONNELL, Johns Hopkins Center for Health Security
SEAN M. DECATUR, Kenyon College
JOSEPH R. ECKER, Salk Institute for Biological Studies
SCOTT V. EDWARDS, Harvard University
GERALD EPSTEIN, National Defense University
ROBERT J. FULL, University of California, Berkeley
MARY E. MAXON, Lawrence Berkeley National Laboratory
ROBERT NEWMAN, Independent Consultant
STEPHEN J. O’BRIEN, Nova Southeastern University
LUCILA OHNO-MACHADO, University of California, San Diego
CLAIRE POMEROY, Albert and Mary Lasker Foundation
MARY E. POWER, University of California, Berkeley
SUSAN RUNDELL SINGER, Rollins College
LANA SKIRBOLL, Sanofi
DAVID R. WALT, Harvard Medical School
PHYLLIS M. WISE, University of Colorado Boulder
Staff
FRANCES SHARPLES, Director
KATIE BOWMAN, Senior Program Officer
ANDREA HODGSON, Program Officer
JO HUSBANDS, Senior Scholar
KEEGAN SAWYER, Senior Program Officer
AUDREY THEVENON, Program Officer
STEVEN M. MOSS, Associate Program Officer
JESSICA DE MOUY, Senior Program Assistant
KOSSANA YOUNG, Senior Program Assistant
Reviewers
This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
JULIA BAILEY-SERRES, University of California, Riverside
EMMA FARLEY, University of California, San Diego
MARC HALFON, University at Buffalo-SUNY
STEVEN HENIKOFF, Fred Hutchinson Cancer Research Center
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by JASPER RINE, University of California, Berkeley. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
This page intentionally left blank.
Contents
Importance of Functional Genomics
Workshop Outline and Objectives
2 THE GENOTYPE–PHENOTYPE CHALLENGE
Concluding Remarks and Summary
3 CASE STUDIES ON BUILDING FUNCTIONAL GENOMICS TOOLS IN DIVERSE SYSTEMS
Understanding the Genotype–Phenotype Connection in Monkeyflowers
Microbial Communities and Their Interactions on Cheese Rinds
Neurogenetics of Sociality and Relationships
Genetic Interrogation of Diverse Plants
4 UNDERSTANDING THE CONTRIBUTIONS OF NON-PROTEIN-CODING DNA TO PHENOTYPE
Functional Genomics of Adaptation in Sticklebacks
Phylogenetics of Flightless Birds
Role of Chromatin Folding in Gene Expression
5 ADVANCING RESEARCH ON THE ENVIRONMENTAL REGULATION OF GENE FUNCTION
Factors Shaping Variation in Social Behavior
How Environmental Factors Influence a Complex Phenotype
Environmental Regulation of Gene Function in Agriculture
Environmental Factors Affecting Quantitative Traits in Drosophila
6 PREDICTING CURRENT AND FUTURE SOURCES OF VARIATION IN QUANTITATIVE TRAITS
Discovering the Genetic Basis of a Change: An Example
Exploring the Regulation of Gene Expression
7 INTERPRETING AND VALIDATING RESULTS FROM HIGH-THROUGHPUT SCREENING APPROACHES
Lessons on Design and Validation from a CRISPR Loss-of-Function Screen on KRAS-Mutant Cancers
Using Functional Genomics to Understand Development
Validating Results from High-Throughput Enhancer Screens
Harnessing Genetic Diversity to Understand Maintenance of Pluripotency in Embryonic Stem Cells
8 LARGE DATABASES AND CONSORTIA
ChRO-seq: A New Technique for Interpreting Genome Sequence
Using Gene Expression to Understand the Genetics of Disease
A Cloud-Based Platform for Genomics Data Mining
9 BIG-PICTURE CHALLENGES IN RESEARCH, EDUCATION, AND TRAINING
Determining and Defining “Model” Systems
Societal and Ethical Implications of Functional Genomics Research
10 FUTURE OF FUNCTIONAL GENOMICS
Breakout Group Discussions on the Future of Functional Genomics
Comments from the Town Hall Discussion
Closing Remarks and Final Overview
This page intentionally left blank.
7-3 Display of how the sequences of the enhancers ETS and GATA encode for tissue-specific expression
7-4 Mediation analysis, called the “steps method,” which contains four logical statements
8-1 Representation of ChRO-seq data and interpretation of those data
8-2 Representation of how to identify “anchors” across datasets
9-1 Ethical dimensions of consideration behind choosing a research organism