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 COMPREHENSIVE
CHEMOMETRICS: CHEMICAL
AND BIOCHEMICAL
DATA ANALYSIS

SECOND EDITION
This page intentionally left blank
 COMPREHENSIVE
CHEMOMETRICS: CHEMICAL
AND BIOCHEMICAL
DATA ANALYSIS

SECOND EDITION
EDITORS IN CHIEF
Steven Brown
Department of Chemistry and Biochemistry
University of Michigan
USA
Romà Tauler
Department of Environmental Chemistry
Institute of Environmental Assessment and Water Research (IDÆA)
SPANISH COUNCIL OF SCIENTIFIC RESEARCH (CSIC)
Spain
Beata Walczak
Department of Analytical Chemistry
Institute of Chemistry
Silesian University
Poland

VOLUME 1
Elsevier
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EDITORS IN CHIEF

Steven Brown obtained PhD in analytical chemistry from the University of Washington in 1978,
where he worked with Bruce Kowalski. That year he was appointed Assistant Professor at the University
of California, Berkeley, with a joint appointment at Lawrence Berkeley Laboratory. In 1981, he moved
to Washington State University, and in 1986 to the Department of Chemistry and Biochemistry at the
University of Delaware, where he is presently Willis F. Harrington Professor.
He has served as a Section President of the American Chemical Society from 1982–1984, as Chair
of the Department of Chemistry and Biochemistry at the University of Delaware from 1997–2002, and
as President of the North American Chapter of the International Chemometrics Society from 1986–
1988. He has served on the Editorial Staff of the Journal of Chemometrics since its inception, first as
a founding Editor and then as Editor in Chief before stepping down as Editor in Chief in 2007. He
now serves on the journal’s editorial board.
His research interests concern a wide range of problems in chemometrics and machine learning,
with over 300 publications in the scientific literature. He has edited several books, including the first
edition of the four-volume set Comprehensive Chemometrics, published by Elsevier in 2009. A focus of
his research has been on the development of new instrumental methods through use of multivariate
mathematical methods for multicomponent analysis, including calibration transfer, and the novel
use of data fusion methods. He was winner of the first EAS Award in Chemometrics in 1996 and the Kowalski Award in 2015. His work
has had applications in biomedical analysis, food science, plant science, forensic science, pharmaceutical characterization, and process
chemistry.

Romà Tauler (Barcelona, Spain, 1955) is research professor at IDAEA-CSIC. He obtained his doctorate
in Analytical Chemistry at the University of Barcelona in 1977. He was Assistant and Associate Professor
of the University of Barcelona (1978–2002) and has been CSIC Research Full Professor since 2003. He
is Chief Editor of Journal of Chemometrics and Intelligent Laboratory Systems and of the Comprehensive
Chemometrics major reference work. He has achieved an Award for Achievements in Chemometrics,
Eastern Analytical Symposium, and in 2009 the Kowalski Prize from J. of Chemometrics, Wiley, 2009.
He served as the President of the Catalan Chemistry Society, 2008–2013, and was the recipient of
the Eu-ERC Advanced Grant award Nr. 320337, 2013–2018, CHEMAGEB project. Romà Tauler
has published more than 430 research publications and 60 book chapters, with more than 16,000
citations and h-índex 63. His main research field is Chemometrics and its applications to
Environmental Chemistry, Omic Sciences, and Bioanalytical Chemistry.

v
vi Editors in Chief

Prof. Beata Walczak graduated in chemistry from the Faculty of Mathematics, Physics and Chemistry,
Silesian University, Katowice, Poland, in 1979. Since then she has been working in the Institute of
Chemistry, Silesian University, where now she is the Head of the Department of Analytical Chemistry.
Meanwhile, she stayed as a postdoc at the University of Orleans (France) and at the Graz University of
Technology (Austria). She also held a post of a visiting professor at Vrije Universitiet Brussel
(Belgium), at Rome Univeristy “La Sapienza” (Italy), at AgroParisTech University (France), at the
University of Modena and Reggio Emilia(Italy), and at Radboud University (The Netherlands).
From the early 1990s she has been involved in chemometrics, and her main scientific interests are
in all aspects of data exploration and modeling (dealing with missing and censored data, dealing with
outliers, data representativity, enhancement of instrumental signals, signal warping, data compression,
linear and nonlinear projections, development of modeling approaches, feature selection techniques,
etc.). She authored and coauthored ca. 170 scientific papers, 400 conference papers, and delivered
many invited lectures at the numerous international chemistry meetings. She acted as an editor and
coauthor of the book Wavelets in Chemistry, Vol. 22, in the series “Data Handling in Science and Tech-
nology,” Elsevier, Amsterdam, 2000, and as an coeditor of four-volume Comprehensive Chemometrics,
Elsevier, Amsterdam, 2009. Currently she acts as Editor of the journal Chemometrics and Intelligent
Laboratory Systems and of “Data Handling in Chemistry and Technology” (the Elsevier book series), and also as a member of the editorial
boards of Talanta, Analytical Letters, J. of Chemometrics, and Acta Chromatographica.
SECTION EDITORS

Richard Brereton did his BA, MA, PhD and postdoc in the University of Cambridge, after which time
he moved to the staff of the University of Bristol where he was successively Lecturer, Reader,
Professor and Emeritus. He is Fellow of the Royal Society of Chemistry, Royal Statistical Society
and Royal Society of Medicine and a Chartered Chemist. He is Editor-in-Chief of the journal Heritage
Science, columnist for J Chemometrics, and editorial board member for several journals. He has given
around 200 invited lectures in over 30 countries, been main / sole supervisor of 33 PhD and 6
research masters students, on around 50 conference organising committees, and acted as expert
witness in 13 court cases. He has published over 400 recorded articles, including 8 books, 209 papers
in Web of Knowledge, 20 book chapters, 32 book reviews, 9 conference papers, almost all as main or
sole author. His papers have been cited over 5000 times according to Web of Knowledge, and his
books over 3000 times according to Google Scholar. He has published the most cited paper in J Che-
mometrics over the last decade, and the eighth most cited paper in the Analyst since 2000.

Marina Cocchi currently serves as an associate professor in Analytical Chemistry-Chemometrics, at

the Department of Chemical and Geological Sciences of the University of Modena and Reggio Emilia
(Italy), teaching chemometrics at undergraduate and graduate levels. She holds a degree (cum
Laude) and a Ph.D. in Chemical Sciences from the University of Modena. As a part of his Ph.D.
he worked with Professor S. Wold on development of chemometrics approaches for 3D QSAR.
She has published more than 100 papers in international journals and books covering a range of
topics embracing Multivariate, Multi-way and Multiset methods; Data Fusion; 2D WT in Multivariate
Images Analysis for fault detection and pattern recognition; algorithms for features selection in
Wavelet Domain; MSPC; Food Authenticity; Chemical fingerprinting by spectroscopy (MIR, NIR,
NMR) and chromatography.
She has supervised twelve PhD Thesis in chemometrics. She has been in the board of Italian Che-
mometrics Group from 2001 to 2015, acting as President in 2007-11. Since 2010 she has been
member of the editorial board of Chemometrics and Intelligent Laboratory Systems. She has been
Editor of the book Data Fusion: Methods and Applications, Data Handling in Science and Tech-
nology series, vol.31, Elsevier 2019.

Anna de Juan is an associate professor at the Department of Chemical Engineering and Analytical
Chemistry at the University of Barcelona since 2003, teaching chemometrics at undergraduate and
graduate levels. She holds a degree and PhD in Chemistry from the University of Barcelona (UB)
and her expertise is in Multivariate Curve Resolution (MCR) methods: theoretical development
and application to bioanalytical and analytical problems. Since 2002 she is member of the Editorial
Advisory Board of Chemometrics and Intelligent Laboratory systems and since 2006 of Analytica
Chimica Acta. Recently, it has acted as section editor for the reference work Comprehensive Chemo-
metrics, Elsevier (2009). She has stayed in the framework of research collaborations in Vrije Univer-
siteit Brussel, Brussels (1995), Virginia Commonwealth University, Richmond, US (1998), The
University of Newcastle, Australia (2002), Université des Sciences et Technologies de Lille, France
(2004) and the University of Dalhousie, Canada (2016). In 2004 she received the 4th Chemometrics
Elsevier Award together with Karl Booksh. She has published more than 130 papers in international
journals and books and has given more than 180 presentations in different international confer-
ences, 50 of them plenary or keynote lectures, basically on design of chemometric tools and multi-
variate curve resolution developments and related methods and on applications to process analysis,
hyperspectral image analysis and general analytical applications.

vii
viii Section editors

Rafael Cela Torrijos is a professor of analytical chemistry in the University of Santiago de Compos-
tela, Spain, and the Head of Laboratory for Analytical Chemistry in the Research institute of Chem-
ical and Biological Analyses (IAQBUS), in the same university. Previously, he was at the Universities
of Madrid (Complutense) and Cádiz, belonging to the group of analytical chemists that started the
development of chemometrics by the 1980s in Spain. His research has focused on the analytical
applications of separation science, and particularly, the development and optimization of sample
preparation techniques in chromatographic analysis, including experimental designs and develop-
ment of computer-assisted chromatographic methods, being the author of the Mchrom Scout soft-
ware, distributed by Mestrelab Research S.L. Currently, he is the author or co-author of more than
300 scientific papers and several textbooks.

Riccardo Leardi was born in Novi Ligure (Italy) on October 17, 1959.
In 1983 he graduated cum laude in Pharmaceutical Chemistry and Technology at the Faculty of
Pharmacy of the University of Genova..
His actual position is Associate Professor at the Department of Pharmacy of the School of
Medical and Pharmaceutical Sciences of the University of Genoa. In 2013 he got the qualification
for full professor in Analytical Chemistry.
Since 1985 he has been working in the section of Analytic Chemistry of the Department of Phar-
macy of the University of Genova, and his research field is Chemometrics.
His interests are mainly devoted to problems of classification and regression (applied especially
to food, environmental and clinical data), experimental design, process optimization, multivariate
process monitoring and multivariate quality control.
His original research focused mainly on genetic algorithms, especially in their application to the
problem of variable selection, and three-way methods.
He developed the chemometrical softwares CAT (Chemometric Agile Tool) and BasiCAT, both
freely downloadable from the site http://gruppochemiometria.it/index.php/software.
He is author of almost 150 papers and more than 130 communications in national and interna-
tional meetings, several of which as invited speaker; he was invited to give talks and courses in several
industries and research centers.
He organizes two schools of Chemometrics (Multivariate Analysis; Experimental Design), each
held twice a year at the University of Genoa.
Since November 2002 he started his activity of chemometric consultancy.

Prof. Federico Marini was born in Rome, Italy, in 1977 and he received his MSc (2000) and PhD
(2004) from Sapienza University of Rome. He is currently associate professor of Chemometrics at
Sapienza University of Rome. In 2006, he was awarded the Young Researcher Prize from Italian
Chemical Society and in 2012 he won the Chemometrics and Intelligent Laboratory Systems Award
“for his achievements in chemometrics”. He has been visiting researcher in various Universities
(Copenhagen, Stellenbosch, Silesia, Lille). His research activity is focused on all aspects of chemo-
metrics, ranging from the application of existing methods to real world problems in different fields
to the design and development of novel algorithms. He is author of more than 150 papers in inter-
national journals, and recently he edited and coauthored the book Chemometrics in food chemistry
(Elsevier). He is member of the Editorial boards of Chemolab, Analytica Chimica Acta, J. of Chemo-
metrics, J. of NIR Spectroscopy, J. of Spectral Imaging and he serves as Associate Editor for Chemo-
metrics in Wiley’s Encyclopedia of Analytical Chemistry. He is the past coordinator of the
Chemometric group of the Italian Chemical Society and the coordinator of the Chemometric study
group of EUCheMS.
 Section editors ix

Alejandro C. Olivieri was born in Rosario, Argentina (07/28/1958). He obtained his B.Sc. from the
Catholic University (1982), and his Ph.D. from the National University of Rosario (1986). He did
Postdoctoral Research at the University of Illinois, Urbana-Champaign, USA. In 1990, he returned
to the University of Rosario, and joined the National Research Council (CONICET). He founded
a research group in chemometrics in analytical chemistry, publishing about 250 papers in interna-
tional journals, books and book chapters, and supervised nine Ph.D. theses. He received several
national and international awards, including the John Simon Guggenheim Memorial Foundation
fellowship (2001–2002). In 2018 he published “Introduction to multivariate calibration. A practical
approach”, a book which was selected by Choice, from the Association of College and Research
Libraries (ACRL) as one of the Outstanding Academic Titles for 2019.

Dr. William Rayens is Professor and the Dr. Bing Zhang Endowed Department Chair in the Depart-
ment of Statistics at the University of Kentucky. Rayens has an extensive research record focused
primarily on the development of multivariate and multi-way statistical methodologies, mostly
related to problems in chemistry and the neurosciences. He has mentored several Ph.D. students
and has been honored at both the College and the University level as an outstanding teacher. Rayens
also served as Assistant Provost for General Education during which time he was tasked with imple-
menting new general education reforms at the University of Kentucky, the first changes to that
program in almost 30 years. He designed the one-of-a-kind Technologically Enhanced Active
Learning rooms in the University’s multi-million dollar Jacobs Science Building. Dr. Rayens received
his Ph.D. in mathematics from Duke University in 1986.

Luis A. Sarabia received his Ph.D. in Statistics from de University of Valladolid (Spain) in 1979.
Since 1974, he has been teaching Statistics, Mathematics and Design of Experiments mostly to grad-
uate and postgraduate students of Chemistry. In 2000 he reached the position of professor at the
University of Burgos. He is currently director of the Department of Mathematics and Computation
and a member of the research group Chemometrics and Qualimetrics (officially recognized as
consolidated research group, UIC-237). He is author and co-author of around 140 papers, 7 chapter
of book and approximately 160 communications in international meetings. He was co-founder of
Colloquium Chemiometricum Mediterraneum. His research interest are in multivariate statistics,
n-way procedures, evolutionary algorithms for multiresponse optimization, design of experiments,
QbD and PAT with application to regulated chemical analysis, food safety, food characterization and
fraud detection.
This page intentionally left blank
IN MEMORY OF ROGER PHAN TAN LUU

“Science evolves by means of research. Scientific research is based on experiments (Galileo Galilei, Two new
sciences, 1638). With time experiments have becoming more and more complex. So scientists used “experi-
mental design (DOE, design of experiments)” as a useful tool. Only 40 years ago Roger Phan Tan Luu suggested
that DOE is the core of the Methodology of experimental research, much more than a tool, a philosophy.
The research work of Roger Phan Tan Luu includes new tools, the organization of design for complex
experiments, and a lot of applications. To perform research work on a real problem it is necessary to know very
well the problem. Obvious. When the expert of the problem asks for the help of the expert of design, the
problem expert must know just some base elements of the Methodology. The expert of Methodology instead
must study to have a deep knowledge of the problem, in much detail. In this way Roger accumulated knowl-
edge, i.e., experience, in many fields of research. The result of nearly 50 years of activity was a complete scientist,
from theory to new tools, to applications.
A complete scientist is always a teacher. Roger was a great teacher, not only in his Aix-Marseille University, but
throughout the world. He had the rare ability to capture the attention of student, transforming a boring heavy
sequence of theorems into a compelling, instructive show. For the students a pleasure, not a pain.
This description is that of the public man.
The private man was (outside the family) a loner. Only in the last 20 years of the past century did he make
contact in the organization of schools (Eurochemometrics, Erasmus stages) of chemometrics and experimental
design for some people of large affinity. With these people, he opened himself to friendship. As one of his
friends, I received from him very much. It was possible for me to appreciate his generosity, his humor, his speed
to answer to invitation (and of course to work together).
Friendship details are very intimate, not ready to be described. For friends the final separation is a very
hard continuous sentiment. Memories help. As a friend, as a common scientist, always I will remember.
Michele Forina

xi
This page intentionally left blank
CONTRIBUTORS TO VOLUME 1

BW Bader Jasper Engel

Sandia National Laboratories, Albuquerque, NM, USA
A Beal
NemrodW SAS, Marseille, France
JM Bernardo
Universitat de València, Valencia, Spain
Andrey Bogomolov
Endress þ Hauser Liquid Analysis GmbH þ Co. KG,
Gerlingen, Germany; and Samara State Technical
University, Samara, Russia
Richard G Brereton
School of Chemistry, University of Bristol, Bristol,
United Kingdom
B Campisi
Department of Economics, Business, Mathematics and
Statistics, University of Trieste, Trieste, Italy
Johan E Carlson
Department of Computer Science and Electrical
Engineering, Luleå University of Technology, Luleå,
Sweden
Biometris, Wageningen University & Research,
Wageningen, The Netherlands
KH Esbensen
KHE Consulting, Copenhagen, Denmark
Bernard Francq
Institute of Statistics, Biostatistics and Actuarial Sciences
(ISBA), Louvain Institute for Data Analysis and
Modeling (LIDAM), Université catholique de Louvain
(UCLouvain), Louvain-la-Neuve, Belgium; and
CMC Statistical Sciences, GSK Vaccines, Rixensart,
Belgium
Bernadette Govaerts
Institute of Statistics, Biostatistics and Actuarial Sciences
(ISBA), Louvain Institute for Data Analysis and
Modeling (LIDAM), Université catholique de Louvain
(UCLouvain), Louvain-la-Neuve, Belgium
Ana Herrero
Departamento de Química, Facultad de Ciencias,
Universidad de Burgos, Burgos, Spain

Rolf Carlson HCJ Hoefsloot

Department of Chemistry, Faculty of Science, University University of Amsterdam, Amsterdam, Netherlands
of Tromsoe, Tromsoe, Norway
Kas J Houthuijs
Georgia Charkoftaki Analytical Chemistry, Institute for Molecules and
Department of Environmental Health Sciences, Yale Materials, Radboud University Nijmegen, Nijmegen,
School of Public Health Yale University, New Haven, The Netherlands
CT, United States
Mia Hubert
Bieke Dejaegher Department of Mathematics, KU Leuven, Leuven,
Analytical Chemistry, Applied Chemometrics and Belgium
Molecular Modelling, Vrije Universiteit Brussel e VUB,
JJ Jansen
Brussels, Belgium
Netherlands Institute for Ecology, Heteren, Netherlands
Paul HC Eilers
LP Julius
Department of Biostatistics, Erasmus University Medical
Glycom A/S, Esbjerg, Denmark
Center Rotterdam, The Netherlands
Riccardo Leardi
SLR Ellison Department of Pharmacy, University of Genoa, Genoa,
LGC Limited, Teddington, Middlesex, United Kingdom Italy

xiii
xiv Contributors to Volume 1
Federico Marini
Department of Chemistry, University of Rome La
Sapienza, Rome, Italy
Rebecca Marion
Institute of Statistics, Biostatistics and Actuarial Sciences
(ISBA), Louvain Institute for Data Analysis and
Modeling (LIDAM), Université catholique de Louvain
(UCLouvain), Louvain-la-Neuve, Belgium
Manon Martin
Institute of Statistics, Biostatistics and Actuarial Sciences
(ISBA), Louvain Institute for Data Analysis and
Modeling (LIDAM), Université catholique de Louvain
(UCLouvain), Louvain-la-Neuve, Belgium; and Fond
National de le Recherche Scientifique, Brussels, Belgium
M Cruz Ortiz
Departamento de Química, Facultad de Ciencias,
Universidad de Burgos, Burgos, Spain
M Pavan
Joint Research Centre, European Commission, Ispra,
Italy
R Phan-Tan-Luu
NemrodW SAS, Marseille, France; and University Paul
Cezanne, Marseille Cedex, France
FF Pitard
Francis Pitard Sampling Consultants, Broomfield, CO,
USA
M Sagrario Sánchez
Departamento de Matemáticas y Computación, Facultad
de Ciencias, Universidad de Burgos, Burgos, Spain
Luis A Sarabia
Departamento de Matemáticas y Computación, Facultad
de Ciencias, Universidad de Burgos, Burgos, Spain
AK Smilde
University of Amsterdam, Amsterdam, Netherlands
Michel Thiel
Institute of Statistics, Biostatistics and Actuarial Sciences
(ISBA), Louvain Institute for Data Analysis and
Modeling (LIDAM), Université catholique de Louvain
(UCLouvain), Louvain-la-Neuve, Belgium; and
Statistics and Decision Sciences, Janssen
Pharmaceutical, Beerse, Belgium
M Thompson
Birkbeck College, University of London, London, United
Kingdom
R Todeschini
University of MilanoeBicocca, Milan, Italy
Rafael Cela Torrijos
CRLF University of Santiago de Compostela, Santiago,
Spain
Yvan Vander Heyden
Analytical Chemistry, Applied Chemometrics and
Molecular Modelling, Vrije Universiteit Brussel e VUB,
Brussels, Belgium
Vasilis Vasiliou
Department of Environmental Health Sciences, Yale
School of Public Health Yale University, New Haven,
CT, United States
DJ Vis
University of Amsterdam, Amsterdam, Netherlands
D Voinovich
Department of Chemical and Pharmaceutical Sciences,
University of Trieste, Trieste, Italy
Beata Walczak
Institute of Chemistry, University of Silesia, Katowice,
Poland
JA Westerhuis
University of Amsterdam, Amsterdam, Netherlands
SUBJECT CLASSIFICATION

Statistics
Quality of Analytical Measurements: Statistical Methods for Internal Validation
Proficiency Testing in Analytical Chemistry
Quality of Analytical Measurements: Univariate Regression
Robust and Nonparametric Statistical Methods
Bayesian Methodology in Statistics
Robust multivariate statistical methods
An Introduction to the Theory of Sampling: An Essential Part of Total Quality Management
Representative Sampling, Data Quality, Validation: A Necessary Trinity in Chemometrics

Experimental Design
Introduction: Experimental Designs
Screening Strategies
The Study of Experimental Factors
Response Surface Methodology
Experimental Design for Mixture Studies
Nonclassical Experimental Designs
Designing a multicomponent calibration experiment: basic principles and diagonal approach

Analysis of Variance
General Linear Models
Multiset Data Analysis: ANOVA Simultaneous Component Analysis and Related Methods
Regularized Manova
ANOVAdTP

Optimization
Constrained and Unconstrained Optimization
Sequential Optimization Methods
Optimization: Steepest Ascent, Steepest Descent, and Gradient Methods
Multicriteria Decision-Making Methods
Genetic Algorithms in Chemistry
A Guided Tour of Penalties
Particle Swarm Optimization

Linear Soft-Modeling
Linear Soft-Modeling: Introduction
Principal Component Analysis: Concept, Geometrical Interpretation, Mathematical Background, Algorithms, History, Practice
Principal Component Analysis

xv
xvi Subject Classification

Independent Component Analysis

Independent component analysis in Analytical Chemistry
Introduction to Multivariate Curve Resolution
Two-Way Data Analysis: Evolving Factor Analysis
Two-Way Data Analysis: Detection of Purest Variables
Two-Way Data Analysis: Multivariate Curve Resolution j Noniterative Resolution Methods
Two-Way Data Analysis: Multivariate Curve Resolution j Iterative Resolution Methods
Two-Way Data Analysis: Multivariate Curve Resolution j Error in Curve Resolution
Estimation of feasible bands in Multivariate Curve Resolution
Multiway Data Analysis: Eigenvector-Based Methods
Multilinear Models: Iterative Methods
Multiset Data Analysis: Extended Multivariate Curve Resolution
Tensor Similarity in Chemometrics
Bayesian Methods for Factor Analysis in Chemometrics
Time Series Modeling
Other Topics in Soft-Modeling: Maximum Likelihood-Based Soft-Modeling Methods
Figures of Merit

Unsupervised Learning
Unsupervised Data Mining: Introduction
Data Mapping: Linear Methods versus Nonlinear Techniques
Tree-Based Clustering and Extensions
Model-Based Clustering
Common Clustering Algorithms
Density-Based Clustering Methods

Other Problems With Data Analysis

Feature Selection: Introduction
Feature Selection in the Wavelet Domain: Adaptive Wavelets
Missing Data
Compositional Data Analysis in Chemometrics
Sparse Methods

Data Preprocessing
Preprocessing Methods
Evaluation of Preprocessing Methods
Model-based preprocessing in vibrational spectroscopy
Normalization and Closure
Variable Shift and Alignment
Background Estimation, Denoising, and Preprocessing
Denoising and Signal-to-Noise Ratio Enhancement: Classical Filtering
Denoising and Signal-to-Noise Ratio Enhancement: Derivatives
Denoising and Signal-to-Noise Ratio Enhancement: Splines
Data Quality and Denoising: a Review
Model-Based Preprocessing and Background Elimination: OSC, OPLS, and O2PLS

Regression and Classification

Calibration Methodologies
Variable Selection
Partial Least Squares
Multivariate Approaches: UVE-PLS
Data Fusion
Multiblock and Three-Way Data Analysis
 Subject Classification xvii

Transfer of Multivariate Calibration Models

Robust Multivariate Methods in Chemometrics/Robust and Sparse Multivariate Methods in Chemometrics
Regression Diagnostics
Model-Based Data Fitting
Linear Approaches for Nonlinear Modeling
Computationally Intensive Nonlinear Regression Methods
Neural Networks
Feedforward Neural Networks
Kernel Methods
Classification: Basic Concepts
Validation of Classifiers
Statistical Discriminant Analysis
Soft Independent Modeling by Class Analogy
Decision Tree Modeling in Classification
Random Forest and Ensemble Methods
Multivariate Approaches to Classification Using Genetic Algorithms
Multiway Classification
Deep Learning Theoretical Chapter for chemometrician

Applications
Chemometrics in Electrochemistry
Chemometrics in the Pharmaceutical Industry
Environmental Chemometrics
Resampling and Testing in Regression Models with Environmetrical Applications
Application of Chemometrics in the Food Sciences
Chemometrics in Forensics
Chemometric Analysis of Sensory Data
Smart Sensors
Statistical Control of Measures and Processes
Best Practice and Performance of Hardware in Process Analytical Technology (PAT)dA Prerequisite to Avoid
Pitfalls in Data Analytics
Multivariate Statistical Process Control and Process Control, Using Latent Variables
Batch Process Modeling and MSPC
Chemometrics in Raman spectroscopy
Chemometrics in NIR Hyperspectral ImagingdTheory and Applications in the Agricultural Crops and Products Sector
Mass Spectroscopic Imaging: Chemometric Data Analysis
Fast analysis, Processing, and Modeling of Hyperspectral Videos: Challenges and Possible Solutions
Image Processing
Chemometrics Analysis of Big Data
Systems Biology
Analysis of Metabolomics Data
Data Processing for RNA/DNA Sequencing
Analysis of Megavariate Data in Functional Omics
Spectral Map Analysis of Microarray Data
Chemometrics in Flow Cytometry
Chemometrics for QSAR Modeling
Chemoinformatics
High-Performance GRID Computing in Chemoinformatics
This page intentionally left blank
PREFACE

Some 50 years ago, the first publications appeared on the use of computer-aided mathematics to analyze
chemical data. With those publications, the modern field of chemometrics was launched. Both the speed and
power of computers and the sophistication of analytical instrumentation have made great leaps in the inter-
vening time. The ready availability of chemometric software, coupled with the increasing need for rigorous,
systematic examination of ever-larger and more sophisticated sets of measurements from instrumentation has
generated strong interest in reliable methods for converting the mountains of measurements into more
manageable piles of results, and for converting those results into nuggets of useful information. Interest in
application of chemometrics has spread well beyond chemists with a need to understand and interpret their
measurements; now chemometrics is helping to make important contributions in process engineering, in
systems biology, in environmental science, and other disciplines that rely on chemical instrumentation, to name
only a few areas.
In the 12 years since the first edition of this book appeared, there has been considerable change in the fields
of data science and of chemometrics. As applications of chemometrics continue to grow, so too does is the
methodology of chemometrics. After 50 years, chemometrics is a scientific field with mature areas, but it is also
a field where change continues to occur at a rapid pace, driven both by advances in chemical instrumentation
and measurement and by close connection of chemometrics with the data science, machine learning, statistics
and signal processing research communities. The interfacial location of chemometrics, falling between
measurements on the one side and statistical and computational theory and methods on the other, poses
a challenge to the new practitioner: gaining sufficient breadth and depth of understanding in data science and
learning in what ways data science connects with measurement chemistry, in order to use chemometrics
effectively.
The four volumes of Comprehensive Chemometrics, 2nd Ed. are the result of a meeting in Oxford in January,
2017, where the editors planned a revised work that would update most of the work covered in the first edition
and would cover emerging areas of chemometric research, while providing a sampling of current applications.
Our goal was to bring our reference work current with the advances in chemometrics that have occurred since
2006, with a treatment that would serve both the new and the experienced practitioner.
What has resulted from this collaboration is a resource that captures the practice of chemometrics now. The
four volumes in the revised work now include 119 chapters, with 33 new, 35 reprinted and 51 updated chapters,
making this the most wide-reaching and detailed overview of the field of chemometrics ever published.
Comprehensive Chemometrics 2nd Ed. offers depth and rigor to the new practitioner entering the field, and breadth
and varied perspectives on current literature to more experienced practitioners aiming to expand their horizons.
Software and datasets, both of which are especially valuable to those learning the methods, are provided in
some chapters. The coverage is not only comprehensive, it is authoritative as well; authors contributing to
Comprehensive Chemometrics 2nd Ed. are among the most distinguished practitioners of the field.
Comprehensive Chemometrics 2nd Ed. would not have been possible without the considerable help of the
Editorial Board, who assisted in selecting authors and reviewing chapters. For this edition, our Board included
Richard Brereton, Marina Cocchi, Anna De Juan, Riccardo Leardi, Roger Phan Tan Lu, Federico Marini, William
Rayens, Luis Sarabia, Alejandro Olivieri and Rafael Cela.
This new edition would not have been possible without the hard work of the staff at Elsevier. We also owe
thanks to Rachel Conway, Senior Acquisitions Editor at Elsevier, for supporting the project and seeing the
project off, to Sean Simms, who took over the task of Acquisitions Editor in 2019, to Dhivya Karunagaran and
Brinda Subramanian for their help in ensuring that submissions met the requirements for publication, and

xix
xx Preface

especially to Paula Davies, our Content Project Manager, for overseeing the entire project, keeping track of the
due dates and submissions, encouraging authors as needed, and helping us to keep to the production schedule.
Finally, we extend special thanks to all of our authors whose efforts have made the work the valuable reference
that it is.

Steven Brown
Romà Tauler
Beata Walczak
March, 2020
CONTENTS OF ALL VOLUMES

Editors in Chief v
Section Editors vii
In memory of Roger Phan Tan Luu xi
Contributors to Volume 1 xiii
Subject Classification xv
Preface xix

VOLUME 1

1.01 Quality of Analytical Measurements: Statistical Methods for Internal Validation 1

M Cruz Ortiz, Luis A Sarabia, M Sagrario Sánchez, and Ana Herrero
1.02 Proficiency Testing in Analytical Chemistry 53
M Thompson and SLR Ellison
1.03 Quality of Analytical Measurements: Univariate Regression 71
MC Ortiz, MS Sánchez, and LA Sarabia
1.04 Robust Multivariate Statistical Methods 107
Mia Hubert
1.05 Bayesian Methodology in Statistics 123
JM Bernardo
1.06 Robust Methods for High-Dimensional Data 149
Mia Hubert
1.07 An Introduction to the Theory of Sampling: An Essential Part of Total Quality Management 173
FF Pitard
1.08 Representative Sampling, Data Quality, ValidationdA Necessary Trinity in Chemometrics 185
KH Esbensen and LP Julius
1.09 Introduction Experimental Designs 205
R Cela and R Phan-Tan-Luu

xxi
xxii Contents of All Volumes

1.10 Screening Strategies 209

Rafael Cela Torrijos and Roger Phan-Tan-Luu
1.11 The Study of Experimental Factors 251
Rolf Carlson and Johan E Carlson
1.12 Response Surface Methodology 287
Luis A Sarabia, M Cruz Ortiz, and M Sagrario Sánchez
1.13 Experimental Design for Mixture Studies 327
D Voinovich, B Campisi, R Phan-Tan-Luu, and A Beal
1.14 Nonclassical Experimental Designs 385
Aurélie Beal and Roger Phan-Tan-Luu
1.15 Designing a Multi-Component Calibration Experiment: Basic Principles and Diagonal Approach 411
Andrey Bogomolov
1.16 The Essentials on Linear Regression, ANOVA, General Linear and Linear Mixed Models for the
Chemist 431
Bernadette Govaerts, Bernard Francq, Rebecca Marion, Manon Martin, and Michel Thiel
1.17 Multiset Data Analysis: ANOVA Simultaneous Component Analysis and Related Methods 465
HCJ Hoefsloot, DJ Vis, JA Westerhuis, AK Smilde, and JJ Jansen
1.18 Regularized Multivariate Analysis of Variance 479
Jasper Engel, Kas J Houthuijs, Vasilis Vasiliou, and Georgia Charkoftaki
1.19 ANOVA-Target Projection (ANOVA-TP) 495
Federico Marini and Beata Walczak
1.20 Constrained and Unconstrained Optimization 521
BW Bader
1.21 Sequential Optimization Methods 553
Bieke Dejaegher and Yvan Vander Heyden
1.22 Optimisation: Steepest Ascent, Steepest Descent and Gradient Methods 573
Richard G Brereton
1.23 Multicriteria Decision-Making Methods 585
M Pavan and R Todeschini
1.24 Genetic Algorithms in Chemistry 617
Riccardo Leardi
1.25 A Guided Tour of Penalties 635
Paul HC Eilers
1.26 Particle Swarm Optimization 649
Federico Marini and Beata Walczak

VOLUME 2

2.01 Introduction to Linear Soft-Modeling 1

Anna de Juan and Romà Tauler
 Contents of All Volumes xxiii

2.02 Principal Component Analysis: Concept, Geometrical Interpretation, Mathematical Background,

Algorithms, History, Practice 3
KH Esbensen and P Geladi
2.03 Principal Component Analysis 17
Paul Geladi and Johan Linderholm
2.04 Independent Component Analysis 39
F Westad and M Kermit
2.05 Independent Component Analysis in Analytical Chemistry 57
Hadi Parastar
2.06 Introduction to Multivariate Curve Resolution 85
Sarah C Rutan, Anna de Juan, and Romà Tauler
2.07 Two-Way Data Analysis: Evolving Factor Analysis 95
M Maeder and A de Juan
2.08 Two-Way Data Analysis: Detection of Purest Variables 107
Willem Windig, Andrey Bogomolov, and Sergey Kucheryavskiy
2.09 Two-Way Data Analysis: Multivariate Curve Resolution: Noniterative Resolution Methods 137
Zhimin Zhang, Pan Ma, and Hongmei Lu
2.10 Two-Way Data Analysis: Multivariate Curve Resolution, Iterative Methods 153
Anna de Juan, Sarah C Rutan, and Romà Tauler
2.11 Multivariate Curve ResolutiondError in Curve Resolution 173
Romà Tauler and Marcel Maeder
2.12 On the Ambiguity Underlying Multivariate Curve Resolution Methods 199
Mathias Sawall, Henning Schröder, Denise Meinhardt, and Klaus Neymeyr
2.13 Multiway Data Analysis: Eigenvector-Based Methods 233
J Ferré, R Boqué, and NM Faber
2.14 Multilinear Models, Iterative Methods 267
Giorgio Tomasi, Evrim Acar, and Rasmus Bro
2.15 Multiset Data Analysis: Extended Multivariate Curve Resolution 305
Romà Tauler, Marcel Maeder, and Anna de Juan
2.16 Tensor Similarity in Chemometrics 337
Frederik Van Eeghem and Lieven De Lathauwer
2.17 Bayesian Methods for Factor Analysis in Chemometrics 355
Eun Sug Park and Romà Tauler
2.18 Time Series Analysis Methods in Chemometrics 371
Steven D Brown
2.19 Other Topics in Soft-Modeling: Maximum Likelihood-Based Soft-Modeling Methods 399
PD Wentzell
2.20 Figures of Merit 441
Franco Allegrini and Alejandro C Olivieri
2.21 Unsupervised Data Mining: Introduction 465
D Coomans, C Smyth, I Lee, T Hancock, and J Yang
xxiv Contents of All Volumes

2.22 Data Mapping: Linear Methods versus Nonlinear Techniques 479

R Wehrens
2.23 Tree-Based Clustering and Extensions 491
T Hancock and C Smyth
2.24 Model-Based Clustering 509
GJ McLachlan, SI Rathnayake, and SX Lee
2.25 Common Clustering Algorithms 531
Ickjai Lee and Jianhua Yang
2.26 Density-Based Clustering Methods 565
M Daszykowski and B Walczak
2.27 Feature Selection: Introduction 581
BK Lavine
2.28 Feature Selection in the Wavelet Domain: Adaptive Wavelets 587
DA Donald, YL Everingham, LW McKinna, and D Coomans
2.29 Missing Data 615
F Arteaga, A Folch-Fortuny, and A Ferrer
2.30 Compositional Data Analysis in Chemometrics 641
Peter Filzmoser and Karel Hron
2.31 Sparse Methods 663
Ahmad Mani-Varnosfaderani

VOLUME 3

3.01 Pre-processing Methods 1

Jean-Michel Roger, Jean-Claude Boulet, Magida Zeaiter, and Douglas N Rutledge
3.02 Evaluation of Preprocessing Methods 77
H Jonsson and J Gabrielsson
3.03 Model-Based Pre-Processing in Vibrational Spectroscopy 83
Achim Kohler, Johanne Heitmann Solheim, Valeria Tafintseva, Boris Zimmermann, and Volha Shapaval
3.04 Normalization and Closure 101
M Bylesjö, O Cloarec, and M Rantalainen
3.05 Variable Shift and Alignment 115
Renger H Jellema, Abel Folch-Fortuny, and Margriet MWB Hendriks
3.06 Background Estimation, Denoising, and Preprocessing 137
J Trygg, J Gabrielsson, and T Lundstedt
3.07 Denoising and Signal-to-Noise Ratio Enhancement: Classical Filtering 143
DF Thekkudan and SC Rutan
3.08 Denoising and Signal-to-Noise Ratio Enhancement: Derivatives 157
V-M Taavitsainen
 Contents of All Volumes xxv

3.09 Denoising and Signal-to-Noise Ratio Enhancement: Splines 165

V-M Taavitsainen
3.10 Data Quality and Denoising: A Review 179
MS Reis, PM Saraiva, and BR Bakshi
3.11 Model Based Preprocessing and Background Elimination: OSC, OPLS, and O2PLS 205
M Bylesjö and M Rantalainen
3.12 Calibration Methodologies 213
John H Kalivas and Steven D Brown
3.13 Linear Regression Modeling: Variable Selection 249
Roberto Kawakami Harrop Galvão, Mário César Ugulino de Araújo, and
Sófacles Figueredo Carreiro Soares
3.14 An Elemental Perspective on Partial Least Squares 295
William S Rayens
3.15 Multivariate Approaches: UVE-PLS 309
V Centner
3.16 Data and Model Fusion in Chemometrics 317
Steven D Brown
3.17 Multi-Block and Three-Way Data Analysis 341
Mohamed Hanafi, El Mostafa Qannari, and Benoit Jaillais
3.18 Transfer of Multivariate Calibration Models 359
Steven D Brown
3.19 Robust Multivariate Methods in Chemometrics 393
Peter Filzmoser, Sven Serneels, Ricardo Maronna, and Christophe Croux
3.20 Regression Diagnostics 431
Joan Ferré Baldrich
3.21 Model-Based Data Fitting 477
M Maeder, N McCann, S Clifford, and G Puxty
3.22 Linear Approaches for Nonlinear Modeling 497
H Chen and BR Bakshi
3.23 Computationally Intensive Nonlinear Regression Methods 505
Bin Li, Bhavik R Bakshi, and Prem Goel
3.24 Non-linear Modeling: Neural Networks 519
Federico Marini
3.25 Feed-Forward Neural Networks 543
BK Lavine and TR Blank
3.26 Kernel Methods 555
J Suykens
3.27 Classification: Basic Concepts 567
BK Lavine and WS Rayens
3.28 Validation of Classifiers 575
BK Lavine
xxvi Contents of All Volumes

3.29 Statistical Discriminant Analysis 585

BK Lavine and WS Rayens
3.30 Soft Independent Modeling by Class Analogy 605
Alexey L Pomerantsev and Oxana Ye Rodionova
3.31 Decision Tree Modeling 625
Steven D Brown and Anthony J Myles
3.32 Random Forest and Ensemble Methods 661
George Stavropoulos, Robert van Voorstenbosch, Frederik-Jan van Schooten, and Agnieszka Smolinska
3.33 Genetic Algorithms for Variable Selection and Pattern Recognition 673
Barry K Lavine, Collin G White, and Charles E Davidson
3.34 Multi Way Classification 701
Marina Cocchi, Mario Li Vigni, and Caterina Durante
3.35 Deep Learning Theoretical Chapter for Chemometrician 723
Robert van Vorstenbosch, Agnieszka Smolinska, and Lionel Blanchet

VOLUME 4

4.01 Chemometrics in Electrochemistry 1

M Esteban, C Ariño, and JM Díaz-Cruz
4.02 Chemometrics in the Pharmaceutical Industry 33
Benoît Igne, Christian Airiau, Sameer Talwar, and Elyse Towns
4.03 Environmental Chemometrics 69
Philip K Hopke
4.04 Resampling and Testing in Regression Models with Environmetrical Applications 87
J Roca-Pardiñas, C Cadarso-Suárez, and W González-Manteiga
4.05 Application of Chemometrics in the Food Sciences 99
Paolo Oliveri, Cristina Malegori, Eleonora Mustorgi, and Monica Casale
4.06 Chemometrics in Forensics 113
Marcelo M Sena, Werickson FC Rocha, Jez WB Braga, Carolina S Silva, and Aaron Urbas
4.07 Chemometric Analysis of Sensory Data 149
D Brynn Hibbert
4.08 Smart Sensors 193
Jordi Fonollosa
4.09 Statistical Control of Measures and Processes 215
AJ Ferrer-Riquelme
4.10 Best Practice and Performance of Hardware in Process Analytical Technology (PAT) 237
Rudolf W Kessler and Waltraud Kessler
4.11 Multivariate Statistical Process Control and Process Control, Using Latent Variables 275
T Kourti
 Contents of All Volumes xxvii

4.12 Batch Process Modeling and MSPC 305

S Wold, N Kettaneh-Wold, JF MacGregor, and KG Dunn
4.13 Comprehensive Chemometrics 333
Shuxia Guo, Oleg Ryabchykov, Nairveen Ali, Rola Houhou, and Thomas Bocklitz
4.14 Chemometrics in NIR Hyperspectral Imaging: Theory and Applications in the Agricultural
Crops and Products Sector 361
Juan Antonio Fernández Pierna, Philippe Vermeulen, Damien Eylenbosch, James Burger,
Bernard Bodson, Pierre Dardenne, and Vincent Baeten
4.15 Mass Spectrometry Imaging: Chemometric Data Analysis 381
Joaquim Jaumot and Carmen Bedia
4.16 Fast Analysis, Processing and Modeling of Hyperspectral Videos: Challenges and
Possible Solutions 395
Raffaele Vitale, Petter Stefansson, Federico Marini, Cyril Ruckebusch, Ingunn Burud,
and Harald Martens
4.17 Image Processing in Chemometrics 411
Siewert Hugelier, Raffaele Vitale, and Cyril Ruckebusch
4.18 Chemometrics Analysis of Big Data 437
José Camacho and Edoardo Saccenti
4.19 Systems Biology 459
L Coulier, S Wopereis, C Rubingh, H Hendriks, M Radonjic, and RH Jellema
4.20 Analysis of Metabolomics DatadA Chemometrics Perspective 483
Julien Boccard and Serge Rudaz
4.21 Data Processing for RNA/DNA Sequencing 507
Inmaculada Fuertes, Maria Vila-Costa, Jana Asselman, Benjamín Piña, and Carlos Barata
4.22 Analysis of Megavariate Data in Functional Omics 515
EF Mosleth, A McLeod, I Rud, L Axelsson, LE Solberg, B Moen, KME Gilman, EM Færgestad,
A Lysenko, C Rawlings, SN Dankel, G Mellgren, F Barajas-Olmos, LS Orozco, S Sæbø, L Gidskehaug,
A Oust, A Kohler, H Martens, and KH Liland
4.23 Spectral Map Analysis of Microarray Data 569
L Bijnens, R Verbeeck, HW Göhlmann, W Talloen, RA Ion, PJ Lewi, and L Wouters
4.24 Chemometrics in Flow Cytometry 585
Gerjen H Tinnevelt and Jeroen J Jansen
4.25 Chemometrics for QSAR Modeling 599
Roberto Todeschini, Viviana Consonni, Davide Ballabio, and Francesca Grisoni
4.26 Chemoinformatics 635
J Polanski
4.27 High-Performance GRID Computing in Chemoinformatics 677
N Sim, D Konovalov, and D Coomans

Index 703
This page intentionally left blank
 1.01 Quality of Analytical Measurements: Statistical Methods for
Internal Validationq
M Cruz Ortiz, Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Burgos, Spain
Luis A Sarabia and M Sagrario Sánchez, Departamento de Matemáticas y Computación, Facultad de Ciencias, Universidad de
Burgos, Burgos, Spain
Ana Herrero, Departamento de Química, Facultad de Ciencias, Universidad de Burgos, Burgos, Spain
© 2020 Elsevier B.V. All rights reserved.
This is an update of M.C. Ortiz, L.A. Sarabia, M.S. Sánchez, A. Herrero, 1.02 - Quality of Analytical Measurements: Statistical Methods for Internal
Validation, in Comprehensive Chemometrics, edited by Steven D. Brown, Romá Tauler, Beata Walczak, Elsevier, 2009, https://doi.org/10.1016/B978-
044452701-1.00090-9.

1.01.1 Introduction 3
1.01.2 Confidence and Tolerance Intervals 7
1.01.2.1 Confidence Interval 8
1.01.2.2 Confidence Interval on the Mean of a Normal Distribution 9
1.01.2.2.1 Case 1: Known variance 9
1.01.2.2.2 Case 2: Unknown variance 10
1.01.2.3 Confidence Interval on the Variance of a Normal Distribution 10
1.01.2.4 Confidence Interval on the Difference in Two Means 11
1.01.2.4.1 Case 1: Known variances 11
1.01.2.4.2 Case 2: Unknown variances 11
1.01.2.4.3 Case 3: Confidence interval for paired samples 12
1.01.2.5 Confidence Interval on the Ratio of Variances of Two Normal Distributions 12
1.01.2.6 Confidence Interval on the Median 13
1.01.2.7 Joint Confidence Intervals 13
1.01.2.8 Tolerance Intervals 13
1.01.2.8.1 Case 1: b-content tolerance interval 13
1.01.2.8.2 Case 2: b-expectation tolerance interval 14
1.01.2.8.3 Case 3: Distribution free intervals 14
1.01.3 Hypothesis Tests 15
1.01.3.1 Elements of a Hypothesis Test 15
1.01.3.2 Hypothesis Test on the Mean of a Normal Distribution 19
1.01.3.2.1 Case 1: Known variance 19
1.01.3.2.2 Case 2: Unknown variance 19
1.01.3.2.3 Case 3: The paired t-test 19
1.01.3.3 Hypothesis Test on the Variance of a Normal Distribution 20
1.01.3.4 Hypothesis Test on the Difference in Two Means 20
1.01.3.4.1 Case 1: Known variances 20
1.01.3.4.2 Case 2: Unknown variances 21
1.01.3.5 Test Based on Intervals 22
1.01.3.6 Hypothesis Test on the Variances of Two Normal Distributions 23
1.01.3.7 Hypothesis Test on the Comparison of Several Independent Variances 24
1.01.3.7.1 Case 1: Cochran’s test 24
1.01.3.7.2 Case 2: Bartlett’s test 25
1.01.3.7.3 Case 3: Levene’s test 25
1.01.3.8 Goodness-of-Fit Tests: Normality Tests 26
1.01.3.8.1 Case 1: Chi-square test 26
1.01.3.8.2 Case 2: D’Agostino normality test 27
1.01.4 One-Way Analysis of Variance 28
1.01.4.1 The Fixed Effects Model 28
1.01.4.2 Power of the Fixed Effects ANOVA model 30
1.01.4.3 Uncertainty and Testing of the Estimated Parameters in the Fixed Effects Model 31
1.01.4.3.1 Case 1: Orthogonal contrasts 32
1.01.4.3.2 Case 2: Comparison of several means 32
1.01.4.4 The Random Effects Model 33

q
Change History: October 2019. M. Cruz Ortiz, Luis A. Sarabia, M. Sagrario Sánchez, Ana Herrero added MATLAB live-scripts for the computations; re-written
introduction to tolerance intervals; corrected estimates in Table 13; updated texts; corrected mistakes and updated references.

Comprehensive Chemometrics, 2nd edition, Volume 1 https://doi.org/10.1016/B978-0-12-409547-2.14746-8 1

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 Yours, &c. in Him,

G. W.

LETTER MCCLXXXV.
To Mr. K――n.

Leith, May 14, 1763.

My dear old steady Friend,

W HY so fearful of writing a longer letter? The longer the better. Blessed

be God, though disappointed in embarking, by reason of sickness, I
can read, and write, and hope (notwithstanding a little cold, which threw me
somewhat back this week) soon to get upon my throne again. The news
about the congregations, you may well guess rejoiced my poor heart.
Surely Mr. H―― will not get to heaven before me too. What an age do we
live in! Children thus to take the lead of their parents. Heavenly Father, not
my will, but thine be done! I expect to-morrow’s interview. A single eye will
carry us through all. A catholic spirit is the plague of bigots. Lord Jesus,
cure them of their bad distemper! I rejoice to hear that good Lady H――n is
so supported. Pray remember me in the kindest manner to dear Mr.
H――y. As I have not heard from him for two or three posts, I fear he is
worse. Pray let him know of my sending this; and inform him of my having
been able to go upon the water to-day for several hours, and by land
afterwards. Others can die, but I cannot. Father, thy will be done! What a
God do I serve? Physicians, friends on every side of me. And what is all in
all, the great physician comforting my soul. Thank, O thank him in behalf of
a worthless worm. Tender love to Mrs. K――n, Mr. and Mrs. B――n, Mr.
and Mrs. J――, and all dear friends, who are so kind as to be concerned
for me. You will be very fine when all is painted. Blessed be God, I approve
your conduct, and love your spirit. Lord Jesus, make us all glorious within!
I must drop a line to dear Mr. A―― about Mr. H――, or you should have
more from, my dear old steady friend,

Yours, &c. &c. &c. in Jesus,

 G. W.

LETTER MCCLXXXVI.
To the Reverend Mr. T――.

Greenock, June 4, 1763.

My dear Friend,

A THOUSAND thanks for your kind letters. Jesus is kind. I am better, and
just going on board the Fanny, bound to Rapanach, in Virginia. Yours
to good Lady H――n is taken care of. I hear her daughter died well, and
that her Ladyship is comforted and resigned. Blessed be God! Adieu.
Follow me with your prayers, as being

Ever yours, &c.

G. W.

LETTER MCCLXXXVII.
To the Reverend Mr. G――.

Greenock, June 4, 1763.

S TRANGE! that I should not see one whom I so dearly love. Dear Mr.
S―― will tell you the reasons. I expect to be called every moment.
God bless and reward you and yours. The diploma was sent to Edinburgh
to be signed by Mr. Trail, but hath miscarried. I wrote to Mr. Hamilton to
send it by the Diligence, which is to sail in about six weeks to Boston.
Expecting to be called every moment, I can only hasten to subscribe
myself, reverend and very dear Sir,

Ever yours, &c. &c. in Jesus,

 G. W.

LETTER MCCLXXXVIII.
To Mr. S―― S――.

At Sea, July 15, 1763.

My very dear Friend,

I HOPE that this will find you and yours prospering both in soul and body. It
leaves me looking towards Virginia but only as an harbour in my way to
an infinitely better port, from whence I shall never put out to sea again.
Through mercy I have been surprizingly kept up during the voyage, long
but not tedious. Jesus hath made the ship a Bethel, and I enjoyed that
quietness which I have in vain sought after for some years on shore. Not an
oath to be heard even in the greatest hurry. All hath been harmony and
love. But my breath is short, and I have little hopes, since my late relapse,
of much further public usefulness. A few exertions, like the last struggles of
a dying man, or glimmering flashes of a taper just burning out, is all that
can be expected from me. But blessed be God, the taper will be lighted up
again in heaven. The sun, when setting here, only sets to rise in another
clime. Such is the death of all God’s saints. Why then should we be afraid?
Why should we not rather by faith be looking through the windows of
mortality, and daily crying, “Why are his chariot wheels so long in coming?”
We had need of patience, especially when the evil days of sickness and
declining age come. But we serve a Master who will not forsake his
servants when grey headed. When heart and flesh fail, God, even our God
in Christ, will be our portion and confidence for ever. Does my dear Mr.
S―― repent that he served and worked for Him when young? Is dear Mrs.
S―― sorrowful that he was the God of her youth? Or is Miss now thinking
that she hath lately made a wrong choice? No, no: I will venture to answer
for them all. Let us, therefore, love our Master, and not go from him. Who
knows but our latter end may yet increase? If not in public usefulness,
Lord Jesus, let it be in inward heart-holiness, that we may daily ripen for
the full enjoyment of thyself in heaven! I know who says, Amen; I add
Amen, and Amen! and so subscribe myself, with ten thousand thanks for all
favours, my dear friends,
 Yours, &c. &c. in our Jesus,

G. W.

August 24.

P. S. Since writing the above, we have been exercised by contrary

winds, thunders, lightenings, &c. but out of all the Lord hath brought us,
and we came within the Cape last night. Help me to praise him, O my
friends.
 LETTER MCCLXXXIX.
To Mr. P――ks.

Within Virginia-Cape, August 24, 1763.

My dear Mr. P――ks,

I FULLY purposed to write to you before my embarkation for

America, but sickness prevented. However, I dearly love you, and
often remember you before his throne, who I am persuaded hath
loved and given himself for you. This he hath told you, and assured
you of again and again by his blessed word and Spirit. Be not
therefore faithless, but believing. O that this may find you rejoicing
with that joy which is unspeakable and full of glory. It leaves me
longing for that blissful state, where sorrow and sighing will flee
away. There, there shall we meet, and in spite of all the suggestions
of Satan, and the desperate wickedness of our own deceitful hearts,
ere long join in singing the song of Moses and the Lamb. Faithful is
he that hath promised, who also will do it. Last night, but not till then,
we cast anchor after near a twelve weeks passage. The last six
weeks were very trying to my shattered bark. But Jesus is All in All.
Help, help to praise him. To his infinite and never-failing mercy do I
commend you, as being, for his great name’s sake, my dear Mr.
P――ks,

Yours most affectionately,

G. W.

LETTER MCCXC.
 To all my dear Tabernacle Hearers, that love the Lord
Jesus Christ in Sincerity.

Virginia, September 1, 1763.

Dearly Beloved in the Lord,

T HOUGH absent in body, the Searcher of hearts knows that I

have been present with you in spirit ever since I left London.
Glad, very glad was I to hear from time to time whilst ashore, that the
shout of a king was among you; and it was my continual prayer
whilst at sea, that the glory of the Lord may so fill the Tabernacle,
that all who come to hear the word, may be constrained to say,
“Surely God is in this place.” I doubt not of your wrestling in my
behalf. Certainly it must be in answer to your cryings unto the Lord,
that I have been dealt with so bountifully. For some weeks I was
enabled to preach once a day when in Scotland, and I trust not
without some divine efficacy. But my late disorder kept me silent for
some weeks afterwards, and put me upon thinking sometimes, that
my intended voyage would be retarded, at least for one year longer.
Having obtained a little more bodily strength, I ventured upon the
mighty waters, and thanks, eternal thanks to a never-failing
Redeemer, I have not been laid by an hour through sickness since I
came on board. Every thing hath been providentially ordered,
suitable to my low estate. A large and commodious cabbin, a kind
Captain, and a most orderly and quiet ship’s company, who gladly
attended when I had breath to preach. Scarce an oath have I heard
upon deck, during a twelve weeks voyage; and such a stillness
through the whole ship, both on week days and the Lord’s-day, as
hath from time to time surprized me. Some concern hath appeared,
but of what kind or duration the event alone can discover. The
spiritual bread hath been cast on the waters: who knows but it may
be found after many days. How it shall please my all-bountiful Master
to dispose of me when I get on shore, you shall know hereafter. All
that I can say is, (if I know any thing of my unspeakably deceitful,
and desperately wicked heart) Lord Jesus,
 A life that all things casts behind,

Springs forth obedient to thy call;

A heart, that no desire can move,

But still t’adore, resign, and love,

Give me, my Lord, my life, my all!

You will not forget to persevere in praying for a poor, worthless, but
willing pilgrim, who dearly loves you, and daily rejoices in the
pleasing reflection, that he shall ere long meet you in a better world,
where the inhabitants shall no more say, “I am sick.” Blessed
prospect! Surely on the very mentioning it, you will break forth in
singing,

Rejoice, the Lord is king, &c.

I will not interrupt you. Adieu. The Lord Jesus be with your
spirits. Only when you have done singing, my dear fellow-labourers,
my dear Tabernacle-hearers, forget not to subjoin at least one
petition, that whether absent or present, Jesus may be more and
more precious to,

Your affectionate friend, and willing servant, for his great

name’s sake,

G. W.

LETTER MCCXCI.
To all my dear Tottenham-Court Hearers, that love the Lord
Jesus Christ in Sincerity.

Virginia, September 1, 1763.

 Dearly Beloved in the Lord,

T HOUGH less than the least of all, and unworthy, utterly unworthy
the notice of any, yet I cannot help thinking, but for Christ’s
sake you will be glad to hear of the goodness of the Lord extended
towards me since my departure from London. Surely it was trying, to
leave so many at each end of the town, who, I hope, will be my joy
and crown of rejoicing in the great day. Indeed, after being taken ill of
my old disorder at Edinburgh, and remaining near six weeks silent in
Scotland, I thought of seeing you soon again: but having obtained
help, I embarked, for the eleventh time, in the ship Fanny; and
though we have had a long and trying, yet, blessed be God, it hath
not been an unprofitable voyage. Often, often have I thought of my
dear London friends, when I guessed they were assembled together;
and as often prayed, when I knew they were retired to rest, that he
that keepeth Israel, and neither slumbereth nor sleepeth, would
watch over them, and make their very dreams devout. How I am to
be disposed of when on dry land, is best known to Him whose I am,
and whom I desire to serve in preaching the gospel of his dear Son.
Had I strength equal to my will, I could fly from pole to pole. Though
wearied, and now almost worn out, indeed and indeed I am not
weary of my blessed Master’s service. O love him, love him, for he is
a good Master, and doth not leave us when our strength faileth.
Make him your portion, and he will be your confidence for ever.
According to my present views, if able to do any thing for you,
through his leave I hope to see you again next year. In the mean
while, as long as I have breath to draw, it shall be my heart’s desire
and prayer to God, that the labours of the dear servants of Jesus,
who are called to preach amongst you, may be so blessed and
owned from above, that I may not be missed a single moment. May
they, may you increase with all the increase, till you are all filled with
all the fulness of God. When near his throne, if there be any
consolation in Christ, if any comfort of love, if any fellowship of the
Spirit, if any bowels of mercies, pray that the same blessing may be
conferred, my dear fellow-labourers, my dear Tottenham-Court
hearers, on
 Your most affectionate friend, and ready servant for
Christ’s sake,

G. W.

LETTER MCCXCII.
To Mr. A――.

Virginia, September 7, 1763.

My very dear Mr. A――,

M ANY more letters did I intend to write to you and other dear
friends, had I not been prevented by storms, &c. for some
weeks before our arrival. If enabled, I shall take care to pay them as
I move from place to place. We are now on dry land. Christian
friends, whom I never before heard of, were prepared to receive me:
and I have preached four times. This leaves me in my way to
Philadelphia, still visited with my old disorder, which I now never
expect to drop, till I drop for good and all this body of clay, this body
of sin and death. I suppose you are in like circumstances, as well as
thousands besides, who love the Lord Jesus in sincerity. Well: He
that cometh will come, and will not tarry. Blessed are all they that
wait for him. I hope you are favoured with precious gales of divine
influence. Tender love to all our dear fellow-labourers, and to all our
dear hearers of every denomination, in every place. You will not
forget a poor pilgrim, who, though absent in body is present in spirit.
Hoping to write in a few days to dear Mr. Middleton, &c. and wishing
you and yours all that a blessed never-failing God can give you in
time and eternity, I subscribe myself, my very dear old friend,

Ever yours, &c. in our precious Emmanuel,

G. W.
 LETTER MCCXCIII.
To Mr. W――y.

Philadelphia, September. 29, 1763.

My dear Mr. W――y,

E BENEZER! Hitherto the Lord hath helped! I have been here

above a week; but still an invalid.

Strange, that a harp of thousand strings

Should keep in tune so long!

Poor Wright is taking his American seasoning. He hath the ague and
fever. This prevents his writing. Inform his relations of it. He wants for
nothing. When you write, mention nothing but what relates to the
eternal world. I have no thoughts to throw away on the trifling things
of time. Tender love to all that are travelling to the New-Jerusalem.
There, if no sooner, we shall meet and praise the never-failing
Emmanuel, for whose great name’s sake I subscribe myself,

Yours, &c.

G. W.

LETTER MCCXCIV.
To Mr. R―― K――n.

Philadelphia, October 21, 1763.

 My very dear Mr. K――n,

T HE bearer, Mr. R――d, is a young sober gentleman, intended for

the temple, and will be very glad to see and hear Mr. Romaine,
and other gospel ministers. I hope all are flaming for God, even a
God in Christ. Here are some young bright witnesses rising up in
the church. Perhaps I have already conversed with forty new-
creature ministers of various denominations. Sixteen hopeful
students, I am credibly informed, were converted at New-Jersey
college, last year. What an open door, if I had strength! But—Father,
thy will be done! blessed be His name, I can preach now and then.
Last Tuesday we had a remarkable season among the Lutherans.
Children and grown people were much impressed. Grace! grace! If
possible, I intend returning with Mr. H――m (now here) to Georgia.
You will hear the determination by the next ship, that goes very soon.
I wrote to dear Mr. H――y very lately, by way of Bristol. Tender,
tender love to him, and to all. I have scarce time to beg the
continued interest of all your prayers, in behalf of, my dear steady
old friend,

Yours, &c. in our Jesus,

G. W.

LETTER MCCXCV.
To Mr. D――, &c.

Philadelphia, November 8, 1763.

My very dear Friends,

M AN appoints, God for wise reasons disappoints. All was ready

for my coming by land to you at Bethesda, with Mr. H――m;
but several things concurred to prevent me, and the physicians all
agree, that the only chance I have for growing better, is to stay and
see what the cold weather will do for me. Fain would I say, however
it may cross my will, Father, thy will be done! At present, I make a
shift to preach twice a week. But alas, my strength is perfect
weakness. What a mercy that Jesus is all in all! You will let me hear
from you very particularly, by Captain Bolitha, or any other
opportunity, either to this place or New-York. I want to know the
present state of all your affairs in every respect. Surely the blessed
Emmanuel, who hath brought me thus far, will give us an interview
by and by. That it may be a very happy one here below, and a
prelude to an infinitely more happy and never-ceasing one above, is
the hearty prayer of, my very dear friends,

Yours, &c. &c. in our glorious Head,

G. W.

LETTER MCCXCVI.
To Mr. R―― K――n.

Philadelphia, November 14, 1763.

My dear old Friend,

T HIS comes by one Mr. R――, reputed to be a real christian and

an expert tradesman, but greatly afflicted with a nervous head-
ach. He will be glad of some spiritual acquaintance. Fain would he
have had me under his roof. I wish he may get help, but I think we
have got our life warrant. Mr. Cruttenden I find is released; and a
dear minister of New-York got free on Saturday. I am here yet, left
behind, and now about to make my first excursion to the New-Jersey
college. Twice a week preaching, is my present allowance. Many of
various ranks seem to be brought under real concern. Physicians are
absolutely against my going to Georgia, till I get more strength.
Besides, it is doubtful whether the southern Indians will not break
out, and therefore a little stay in these parts may on that account be
most prudent. Lord Jesus, direct my goings in thy way! Accept my
wonted general salutation; tender love to all. You and yours will not
cease to pray for, my dear steady friend,

Yours, &c. in Jesus,

G. W.

LETTER MCCXCVII.
To Mr. D――n, &c.

Elizabeth-Town, November 26, 1763.

My very dear Friends,

H OW is this? Am I come four thousand miles to winter with you,

and like to be disappointed at last? I fear so; for alas, only by
travelling thus far from Philadelphia in my way to New-York, I am
quite fatigued. But I do not despair yet, if God gives me any
strength. Pray hard, and who knows what a God may do? Dear Mr.
H――m will best acquaint you with northern particulars. He leaves
me this morning, but I hope to see him at New-York the beginning of
the week, and to write more. O that I may come with him! Abba,
Father, all things are possible with thee! Adieu! My dear friend is
going. Cease not to pray for, and write to,

Yours, &c. &c. in Jesus,

G. W.
 LETTER MCCXCVIII.
New-York, December 1, 1763.

My dear Sir,

H OW thankful should I be to the adorable Jesus, and to all that

love me for his great name’s sake, for the blessed contents of
your last, dated September 10. Praise the Lord, O my soul, and all
that is within me praise his holy name! May this be only an earnest of
good things to come, both in England and Wales. Ere now, I
suppose dear Mr. Davis is crying Gogunniant in London. We are
essaying to echo it back from America. Some very good impressions
have been made in Philadelphia, and we had four sweet seasons at
New-Jersey college, and two at Elizabeth-Town, in my way hither.
Some said they resembled old times. My spirits grow better. But
thrice a week is as often as I can preach. To-day I begin here, and
have thoughts of returning with Mr. H――m to Georgia, but am
fearful of relapsing by such a fatiguing passage or journey. The Lord
will direct. Mr. Cruttenden is got above these infirmities; God be
praised that he went off so comfortably! may our expiring hour be
like his! Surprized am I indeed to find that you have a little one
coming into this world which others are leaving. Lord Jesus, spare
root and branch, for thy own glory, and thy people’s good! Lord
Jesus, convert us all more and more, and make us all like little
children! Tender, tender love to all that love him in sincerity. I would
write to many more, but company, low state of health, and travelling,
render more frequent writing impracticable to, my dear steady friend,

Yours, theirs, &c. &c. in our Jesus,

G. W.

New-York, December 4.

S INCE writing the above, blessed be God, I have preached.

Persons of all denominations seem to be athirst. Grace! grace!
Desire dear Mr. H――y to look into the Universal History of Arts and
Sciences, volume the second, page 436, for an account of
Methodism, by a papist. God bless you all. Amen and Amen. I am
just now told that the ship is going. Several other opportunities of
writing will soon offer, which, God willing, shall be embraced by, my
dear steady friend,

Ever yours, &c. in Jesus,

G. W.

LETTER MCCXCIX.
To Mr. D――n, &c.

New-York, December 7, 1763.

My very dear Friends,

W HAT a mortification do you think it must be to me, to part thus

from, and not to accompany my dear Mr. H――m to
Bethesda? Thus it was near twenty years ago, and yet I came,
though he left me so ill at New-England. Assure yourselves, I shall
come as soon as possible. In the mean while, I have desired Mr.
H――m to assist in supervising and settling the accompts, and to
give his advice in respect to the house, plantation, &c. &c. I beg you
will be so good as to let me have an inventory of every individual
thing, the names and number of the negroes, and what you think is
necessary to be done every way. I would only observe in general,
that I would have the family lessened as much as may be, and all
things contracted into as small a compass as possible. And now
once more adieu, though I trust but for a short season. My heart is
too full to enlarge. I have not got the account of the children taken in
since the first institution; it is left I believe in New-England. I purpose
going thither now from the southward. But it will be better to go to
heaven. Come, Lord Jesus, come quickly! Dear Mr. H――m will
inform you of all particulars concerning the gospel ministrations of,
my very dear friends,

Yours, ever yours, &c. &c. in Christ,

G. W.

LETTER MCCC.
To Mr. H――y.

New-York, December 8, 1763.

Dear Sir,

B LESSED be God, I am enabled to preach thrice a week. But

such a flocking of all ranks, I never before saw at New-York. A
great number have been to see me, and several come to me in the
evening, as it should seem, to hear something of the kingdom of
God. My stay here is undetermined. Perhaps it may be till
Christmas. Many thanks are due to my London friends, for their kind
assistance, from time to time, in carrying on outward matters, and
particularly to those who were so ready to assist in compleating the
tabernacle job in such an honourable way. All with you will continue
to pray for me. I would write more, but amidst such a throng of
company and bodily weakness, it is indeed impracticable. I now
repeatedly send all my tender love; and still praying that all may be
filled with all the fulness of God, I beg leave to subscribe myself,

Yours, &c. in Jesus,

G. W.
 LETTER MCCCI.
To Mr. S―― S――.

New-York, December 16, 1763.

My very dear Friend,

I SEE by what you have done lately for the tabernacle, that you do
not forget absent friends. I think you and yours are not forgotten
by them, neither I believe are forgotten by the Friend of all. He
remembers us, though he is advanced to so great a kingdom;
remembers us in our low estate, and remembers that we are but
dust. What a blessing this to worthless, ill and hell-deserving me!
What a mercy, to meet with such a friend in the latter stages of our
road! Surely he is altogether lovely. Having loved his own, he loves
them to the end; witness his yet continuing to own the feeble labours
of an almost worn out pilgrim. Every day the thirst for hearing the
word increases, and the better sort come home to hear more of it. I
must now go soon to New-England. Cold weather and a warm heart
suit my tottering tabernacle best. The ship is going. God bless you
and yours! I hope that all related, and all who are near and dear to
you, are alive for God,—a God,—a God in Christ; in whose great
name, I beg leave to subscribe myself, my very dear friend,

Yours, &c. &c.

G. W.

LETTER MCCCII.
To the Reverend Mr. G――.

New-York, Deuteronomy 18, 1763.

 Reverend and very dear Sir,

B LESSED be God, I am better in health than when I wrote last.

Preaching thrice a week agrees pretty well with me this cold
season of the year. I am apt to believe my disorder will be periodical.
It was so with Mr. Postwick, who is now with God. Our turn must
come by and by. Who would have thought Mr. Robert Scot would
have went off so soon? Lord, what is man? O to be always ready! O
for thousands to go forth to alarm a drowsy world! New-Jersey
college is a blessed nursery; one of the purest perhaps in the
universe. The worthy President and three tutors, are all bent upon
making the students both saints and scholars. I was lately there for a
week. The Redeemer vouchsafed to own the word preached. Some
said it was like old times. Prejudices in this place have most
strangely subsided. The better sort flock as eagerly as the common
people, and are fond of coming for private gospel conversation. This
is all of grace. O for an humble and thankful heart! Perhaps I may
soon go to Boston. I know you will pray that the glorious Emmanuel
may accompany me in all my removes. That this may be the happy
lot of your whole self, and of all dear enquiring friends, is the hearty
prayer of, reverend and very dear Sir,

Yours, theirs, &c. &c. in Jesus,

G. W.

P. S. I wrote to Mr. Niven last week.

LETTER MCCCIII.
To Mr. D――n, &c.

New-York, January 12, 1764.

My very dear Friends,

C APTAIN Bolitho is returned, and not one line from Bethesda!
Surely you were not informed of his sailing, or you expected to
see me with Mr. H――m. That which lets will surely by and by be
taken out of the way. Blessed be God, the cold braces me up a little.
I am enabled to preach twice or thrice a week. Congregations
continue very large, and I trust saving impressions are made upon
many. Some students also in Philadelphia and New Jersey colleges,
I hear are much awakened. O for a blessed gale of divine influences
when we meet at Bethesda! From thence, or Charles-Town, I
purpose to embark for England. But future things belong to Him, who
(whatever may be our thoughts) always orders all things well. To his
never-failing guidance and most tender mercy do I commit you all, as
being, for his great name’s sake, my very dear friends,

Yours, &c. &c.

G. W.

LETTER MCCCIV.
To Mr. R―― K――n.

Boston, March 3, 1764.

My very dear Friend,

A S I find by letters from my wife and Mr. T―― C――, dated in

October and November, and by another from Mr. D――t, dated
in December, that my friends had heard from me more than once, I
was in hopes of receiving a few lines from you by the last New-York
packet. But I suppose you thought I was gone to the southward.
Providence shut up my way: I believe for wise reasons. The inclosed
will let you see how matters went at New-York. Since leaving that
place, a sweet influence hath attended the word at Easthampton,
Bridgehampton, and South-hold upon Long-Island, at Shelter-Island
also, and at New-London, Norwich, and ♦ Providence on the main
land. At Boston I have been received with the usual warmth of
affection. Twice have we seen the Redeemer’s stately steps in the
great congregation. But as the small-pox is likely to take an universal
spread through the town, I purpose making my country tour, and
then return to Boston in my way to the southward. Invitations come
so thick and fast from every quarter, that I know not what to do. I
cannot boast of acquiring much additional bodily strength, any
otherwise than as the cool season of the year helps to keep me up.
Twice a week is as often as I can with comfort ascend my throne.
The Redeemer vouchsafes to speak for himself there, and private
conversation is greatly blessed. Thus the taper keeps burning a little
longer: when extinguished on earth, it will be removed where it shall
burn with uninterrupted lustre in the kingdom of heaven. Till I hear
from you, and see what is determined concerning Bethesda, I cannot
think of undertaking a long voyage. Sometimes I fear my weakness
will never allow me to go on ship-board any more. But I will wait. I
will endeavour to watch and pray, and doubt not but I shall hear a
voice behind me saying, “This is the way, walk thou in it.” In the
mean while, I rejoice to find that dear Mr. Davis is come to his winter
quarters, and do earnestly pray night and day, that he and all my
dear fellow-labourers and hearers may increase with all the increase
of God. Perhaps they may pray me over once more. Whenever the
way is clear, I am ready to say, “Lord Jesus, lo I come.” Tender,
most tender love awaits you all. I must not enlarge, lest my affections
should overpower this feeble frame. In heaven it will be otherwise.
My very dear Sir, farewel. I must away to preach at Charles-Town, a
neighbouring town to Boston. Hoping ere long to join with you all in
praising God for evermore, I beg leave to subscribe myself,

Yours, &c. &c. in our glorious Head,

G. W.

♦ “Provividence” replaced with “Providence”