Selected Reaction Monitoring Mass Spectrometry (SRM-MS) in Proteomics: A Comprehensive View

296 Pages·2020·11.901 MB·English

by  Mahmud Hossain

Mahmud Hossain
Selected Reaction
Monitoring Mass
Spectrometry
(SRM-MS) in
Proteomics
A Comprehensive View
Selected Reaction Monitoring Mass Spectrometry
(SRM-MS) in Proteomics
Mahmud Hossain
Selected Reaction
Monitoring Mass
Spectrometry (SRM-MS)
in Proteomics
A Comprehensive View
Mahmud Hossain
Sanofi Genzyme
Framingham, MA, USA
ISBN 978-3-030-53432-5 ISBN 978-3-030-53433-2 (eBook)
https://doi.org/10.1007/978-3-030-53433-2
© Springer Nature Switzerland AG 2020
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To my academic mentors
Richard D. Smith, PhD
Battelle Fellow & Chief Scientist, Biological
Sciences Division, Pacific Northwest
National Laboratory (PNNL), Richland, WA,
USA
Professor Fred W. McLafferty
Peter J.W. Debye Professor, Emeritus, Dept.
of Chemistry, Cornell University, NY, USA
Professor Patrick A. Limbach
Vice President for Research & Professor of
Chemistry, University of Cincinnati, OH,
USA
Professor J. Ricky Cox
Anna S. Brown & Ruth B. Logan Endowed
Chair, Dept. of Chemistry, Murray State
University,
Murray, KY, USA
Professor Mustafizur Rahman (in memory
of)
Department of Biochemistry & Molecular
Biology, University of Dhaka, Bangladesh
To my virtual mentors (for targeted
proteomics, especially for SRM-MS)
Professor Ruedi Aebersold
Dept. of Biology, Institute of Molecular
Systems Biology, ETH Zurich, Switzerland
Steven A. Carr, PhD
Senior Director of Proteomics, Institute
Scientist, Broad Institute of MIT & Harvard,
USA
To my lifelong mentors (my parents)
M. Amir Hossain & Fatema Begum
Hopkinton, Massachusetts, USA
The end of one journey is simply the start of another. You have to see what you missed the first
time, see again what you already saw, see in springtime what you saw in summer, in daylight what
you saw at night, see the sun shining where you saw the rain falling, see the crops growing, the fruit
ripen, the stone which has moved, the shadow that was not there before. You have to go back to the
footsteps already taken, to go over them again or add fresh ones alongside them. You have to start
the journey anew. Always.
Nobel laureate Jose’ Saramago in his Journey to Portugal
vii
Preface
Mass spectrometry (MS)-based proteomic research, mostly facilitated by the advent
of electrospray and MALDI ionization as well as by the significant advancements in
MS technology, has been developed tremendously over the last two decades for
both qualitative and quantitative analyses. Two major approaches have been utilized
for this purpose – shotgun or discovery and targeted methodologies.
In the last decade, selected reaction monitoring mass spectrometry (SRM-MS, aka,
multiple reaction monitoring mass spectrometry or MRM-MS) has emerged as the most
mature MS-based targeted proteomics platform for the consistent detection and accurate
quantification of preselected proteins in complex biological matrices which utilized the
capability of triple quadrupole (QqQ) or quadrupole ion trap (QTrap) mass spectrome-
ters to selectively isolate target peptide ion and to monitor its paired selected fragment
ion together, known as transition, that identify and quantify a peptide, and through infer-
ence, the cognate protein in proteome, sub-proteome, tissue, or cellular protease digests.
Upon initial development, these assays can be applied to wide-ranging biological or
biomedical studies across laboratories in a highly multiplexed form with high-sensitiv-
ity and great reproducibility for high-throughput protein detection and quantification
with a wide dynamic range of up to five orders of magnitude. With its utmost signifi-
cance, Nature Methods declared SRM-MS as the “Method of the Year” for 2012.
Despite all its competitive advantages, a significant effort is needed to develop a
highly efficient SRM assay which includes selection of proteins, proteotypic pep-
tides and transitions, optimization of LC-MS parameters, validation of transitions,
among others, with sequential, sometimes lengthy and iterative steps that often limit
the broader applications. As a biological mass spectrometry researcher of more than
a decade, I personally felt for a book on SRM-MS that would provide a wide-
ranging aspect of this “gold-standard” targeted proteomics method including some
fundamentals, method development, instrumentation, data acquisition and analysis,
public data storage and reuse, future directions, and so on. In this book, mostly
SRM-MS on targeted proteomics has been discussed, although there are other appli-
cations available on small molecules/other biomolecules. This book is aimed at aca-
demics and researchers from undergraduate to postgraduate and beyond of mass
spectrometry and/or biomedical area, and at any general mass spectrometry and/or
proteomics enthusiast as well.
ix
x Preface
First two chapters of this book is related to general mass spectrometry. History
of mass spectrometry – from the time of J.J. Thompson to current period – has been
described in Chap. 1 which mentioned how mass spectrometry, with its continued
innovation, always played a distinct role in contemporary Sciences – first in Physics/
Nuclear Physics, then in Chemistry, now in Biology – over the years. In Chap. 2,
major components of mass spectrometers – ion source, mass analyzers, detectors,
and vacuum systems – are described. Besides, tandem mass spectrometry and vari-
ous dissociation methods, including collision induced dissociation (CID), that are
used nowadays have been discussed. Chapter 3 starts with different proteomics
approaches where SRM-MS and other targeted MS-based proteomics approaches
are described and compared. In Chap. 4, the development of an SRM-MS assay has
been discussed which includes general workflow, selection of protein, peptide, tran-
sition and its validation, assay optimization, and quality control. In Chap. 5, avail-
able bioinformatics tools, both for preacquisition or method development and
post-MS acquisition data analysis, have been described. SRM-MS has become a
prominent technique for precise quantification of targeted proteins. Both relative,
label-free and label-based quantification and absolute quantification techniques,
using AQUA, QconCAT, and PSAQ, with SRM have been mentioned in Chap. 6.
Major applications are described in Chaps. 7 and 8. In Chap. 7, some selected pro-
teomics applications, such as general proteomics, biomarkers, and clinical area, are
cited. In Chap. 8, posttranslational modifications (PTMs) and analysis of different
PTMs using SRM with selected examples have been discussed. The book concludes
with Chap. 9 in which current challenges, contemporary trends, and future direc-
tions are stated. It is neither intended nor possible to describe every topic of
SRM-MS in great details in this book; however, with chapter-end references and in
bibliography with the list of review articles, interested readers will find plenty of
resources for further readings.
For the last decade, field of SRM-MS on proteomics has been shaped, enriched,
and guided by the research groups of Ruedi Aebersold, Richard Smith, Steven Carr,
Michael MacCoss, Christoph Borchers, and Amanda Paulovich, to name a few. I am
deeply honored and privileged to work/discuss with several of these finest scientists.
I am a big fan of their research and ideas. Many thanks to Professor
M. Waheeduzzaman of Austin Peay State University, TN, my uncle, and his fam-
ily – Sabina, Nadeem, and Naveed Zaman – for their enduring love and affection for
me. It took several years to prepare this manuscript. During this process, my wife
Khodeja Fatema Hossain and my daughter Fariha Fardin Hossain provided tremen-
dous encouragement and endless support, and of course, sacrificed their valuable
family time for me. I sincerely appreciate the extraordinary help and continued sup-
port provided by Maria David (Project Coordinator) and, especially, Merry Stuber
(Senior Editor) of Springer Nature. In fact, without their inspiration, and reminder,
it would probably take me forever to complete. Thank you Khodeja, Fariha, Maria,
and Merry from the bottom of my heart! Thanks in advance to all my readers. I will
be greatly honored if anyone in anyway is benefited from this book.
Framingham, MA, USA Mahmud Hossain
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Introduction to Mass Spectrometry . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.1 Mass Spectrometer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.2 Mass Spectrum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.2 General Applications of Mass Spectrometry . . . . . . . . . . . . . . . . . . 3
1.2.1 Proteomics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.2.2 Other Biological Applications . . . . . . . . . . . . . . . . . . . . . . . 4
1.2.3 Pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.2.4 Clinical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.2.5 Environmental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.2.6 Geological . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.3 History of Mass Spectrometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.3.1 The Early Years of Mass Spectrometry . . . . . . . . . . . . . . . . 6
1.3.2 Use of Mass Spectrometry Pre– and Post–World
War II Era . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.3.3 Beginning of Biomolecule Research
by Mass Spectrometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.3.4 Paradigm Shift in Mass Spectrometry Analysis . . . . . . . . . . 11
1.3.5 The Development of Proteomics . . . . . . . . . . . . . . . . . . . . . 12
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
2 The Mass Spectrometer and Its Components. . . . . . . . . . . . . . . . . . . . 17
2.1 Major Components of the Mass Spectrometer . . . . . . . . . . . . . . . . . 17
2.1.1 Ion Source . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.2 Mass Analyzers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
2.1.3 Detectors of Mass Spectrometry . . . . . . . . . . . . . . . . . . . . . 32
2.1.4 Other Components of Mass Spectrometer:
Vacuum System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
2.2 Tandem Mass Spectrometry (MS/MS) . . . . . . . . . . . . . . . . . . . . . . 39
2.2.1 MS/MS Instrumentation . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
2.2.2 Scan Modes in Tandem Mass Spectrometry . . . . . . . . . . . . 40
xi