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DEFINING THE MANDATE OF PROTEOMICS
IN THE POST-GENOMICS ERA
WORKSHOP REPORT
STEERING COMMITTEE FOR DEFINING THE MANDATE OF PROTEOMICS IN THE PosT-GENoM~cs ERA
U.S. National Committee for the International Union of Biochemistry and Molecular Biology
Board on International Scientific Organizations
Policy and Global Affairs Division
and
Board on Life Sciences
Division of Earth and Life Studies
NATIONAL RESEARCH COUNCIL
OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, D.C.
www.nap.edu
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THE NATIONAL ACADEMIES PRESS 500 Fifth Street, N.W. Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of
the National Research Council, whose members are drawn from the councils of the National
Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The
members of the committee responsible for the report were chosen for their special competences
and with regard for appropriate balance.
This study was supported mostly by industry contributions (see Acknowledgments) and by
Contract/Grant No. 0222688 between the National Academy of Sciences and the National
Science Foundation and Contract/Grant No. N01-OD-4-2139 between the National Academy of
Sciences and the National Institutes of Health. Any opinions, findings, conclusions, or
recommendations expressed in this publication are those of the authoress and do not necessarily
reflect the views of the organizations or agencies that provided support for the project.
This report is available online at http://www.nap.edu
Copyright 2002 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
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THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, an`Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in
scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general
welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to
advise the federal government on scientific and technical matters. Dr. Bruce M. Alberts is president of the National Academy of
Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a
parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing
with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of
Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and
recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent
members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts
under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal
government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is
president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community
of science and technology with the Academy's purposes of furthering knowledge and advising the federal government.
Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating
agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the
government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies
and the Institute of Medicine. Dr. Bruce M. Alberts and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National
Research Council.
www.national-academies.org
.
. . .
111
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STEERING COMMITTEE FOR DEFINING THE MANDATE OF PROTEOMICS
IN THE POST-GENOMICS ERA
George Kenyon
University ofMichigan, Chair
David M. DeMarini
U.S. Environmental Protection Agency
Elaine Fuchs
Rockefeller University
David Galas
Keck Graduate Institute of Applied Life
Sciences
Jack Kirsch
University of California, Berkeley
Contributing author: Thomas Leyh
Albert Einstein College of Medicine
National Research Council Stag
Board on International Scientif c Organizations
Laura Sheahan
Program Officer
Scott Spaulding
Program Officer
Pamela Gamble
Senior Program Assistant
Walter Moos
MitoKor
Gregory Petsko
Brandeis University
Dagmar Ringe
Brandeis University
Gerald Rubin
Howard Hughes Medical institute
Wendy White
Director
Lois Peterson
Assistant Director
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ACKNOWLEDGMENTS
The U.S. National Committee for the International Union of Biochemistry and Molecular
Biology (USNC/TUBMB) and the Board on Life Sciences of the National Research Council
(NRC) are grateful to the many individuals whose efforts made possible the symposium and the
report. The symposium was supported by grants from the National Institute of General Medical
Sciences/National Institutes of Health and the National Science Foundation, as well as by
generous support from industry: ActiviX Biosciences, Applied Biosystems, Aventis
Pharmaceuticals, DuPont Pharmaceuticals, Genentech, GeneProt, Large Scale Biology, Lynx
Therapeutics, Micromass UK, MitoKor, Oxford GlycoSciences, Pfizer, Phylos, Prolinx,
Proteome Systems., Structural Bioinformatics, and Structural GenomiX. The American
Chemical Society also helped to support the symposium. People who were especially helpful in
preparing for this meeting included Pamela Gamble, Laura Sheahan, Scott Spaulding, Lois
Peterson, and Wendy White, all of the Board of International Scientific Organizations (BISO) of
the NRC.
George Kenyon, chair of both the U.S. National Committee for the International Union of
Biochemistry and Molecular Biology (USN/lUBMB) and the ad hoc symposium steering
committee, conceived of the workshop in an effort to encourage discussion about the future of
proteomics, similar to the preliminary meetings held for the Human Genome Project. The
workshop was organized by an ad hoc steering committee derived from two committees of the
National Research Council (NRC): the USNC/lUBMB and the Board on Life Sciences. The
steering committee selected the speakers and some of its members wrote the workshop report.
The committee members are George Kenyon (Chair), David DeMarini, Elaine Fuchs, David
Galas, Jack Kirsch, Walter Moos, Gregory Petsko, Dagmar Ringe, and Gerald Rubin. Breakout
session chair, Tom Leyh, Albert Einstein College of Medicine was the only renort nllthor not
part of the original steering committee.
~ ~ _# 1
meetings held for the Human Genome Project.
, · ·,, . · . ~ . · . .
. ~ · _ ,
~~~ ~ Or -- - —I---__ ___
This report has been reviewed in draft form by individuals chosen for their diverse
perspectives and technical expertise, in accordance with procedures approved by the NRC's
Report Review Committee. The purpose of this independent review is to provide candid and
critical comments that will assist the institution in making its published report as sound as
possible and to ensure that the report meets institutional standards for objectivity and evidence.
The review comments and draft manuscript remain confidential to protect the integrity of the
deliberative process.
We wish to thank the following individuals for their review of this report: Cheryl
Arrowsmith, University of Toronto; Patricia Babbitt, University of California, San Francisco;
David Baker, University of Washington; Samir Hanash, University of Michigan; John
Quakenbush, Institute for Genomic Research, and Russell Thomas, Kalypsys, Inc. Although the
reviewers listed above have provided many constructive comments and suggestions, they were
not asked to endorse the content of the report, nor did they see the final draft before its release.
The review of this report was overseen by Cynthia Beall, Case Western Reserve University, who
was responsible for making certain that an independent examination of this report was carried
out in accordance with institutional procedures and that all review comments were carefully
considered. Responsibility for the final content of this report rests entirely with the authoring
committee and the institution.
. .
V11
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CONTENTS
Summary eve
Introduction en 1
Proteomics
~ 2
Discussion of General Topics Covered at the Symposium 4
Lessons Learned from the Human Genome Project
Sources of Proteins.......
Protein Separation e 9
Protein Identification 12
Data Collection 14
Proteomics and the Problem of Function 17
. 1 9
...20
Bioinformatics.........
Structural Proteomics.
Cellular Function.....
Applications.......
Samples..
Ethical Considerations.......
Development of Diagnostics
Computational Methods and Bioinformatics................
Database infrastructure and interface design......
Development of new methods....
Protein Structural Initiative.
Research Coll:ahorntinn
Conclusion
References.......
..... 23
... 23
................. 25
................ 27
.......................................... 27
Proteomics: A Coordinated International Effort 27
28
28
. 30
.................................................................... 31
1X
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BOXES
BOX 1 Symposium Speakers and Affiliations.
BOX 2 Comments from Francis Collins.......
FIGURES
Figure 1: Potential plasma proteins observable at various concentration ranges... 10
Figure 2: The Molecular Scanner 13
Figure 3: Technologies for (quantitative) global analysis 14
Figure 4: Isotope coded affinity tags (ICAT) 15
Figure 5: The Basic TCAT Approach 16
Figure 6: Selective identification of differentially expressed proteins 17
APPENDIXES
A Speaker Biographies............................
B Symposium Agenda and Breakout Sessions.
C Workshop Participants..........................
x
.31
36
................................................... 40
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