Bioinformatics Bioinformatics

762 Pages·2007·12.08 MB·English

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Includes
CD-ROM
Introduction to Bioinformatics
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Introduction
to Bioinformatics
A Theoretical and Practical Approach
Edited by
Stephen A. Krawetz, PhD
Wayne State University School of Medicine,
Detroit, MI
and
David D. Womble, PhD
Wayne State University School of Medicine,
Detroit, MI
Humana Press
Totowa, New Jersey
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© 2003 Humana Press Inc.
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Library of Congress Cataloging in Publication Data
Introduction to bioinformatics : a theoretical and practical approach / edited by Stephen
A. Krawetz and David D. Womble.
p. ; cm.
Includes bibliographical references and index.
ISBN 1-58829-064-6 (alk. paper) (HC); 1-58829-241-X (PB); 1-59259-335-6 (e-book)
1. Bioinformatics. I. Krawetz, Stephen A. II. Womble, David D.
[DNLM: 1. Computational Biology--methods. 2. Computer Systems. 3. Databases,
Genetic. 4. Genomics. 5. Sequence Analysis, DNA. 6. Software. QH 506 I646 2002]
QH 507 .I575 2002
570'.285--dc21 2002190207
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Preface
As the sequencing phase of the human and other genome projects nears comple-
tion, we are faced with the task of understanding how the vast strings of Cs, As, Ts,
and Gs encode a being. With the recent advent of microarrays and other high
throughput biologic technologies, we have moved from trying to understand single
molecules and pathways to that of integrative systems. We are only beginning to
grasp the questions we can ask as we are now challenged to understand these large in
silico, in vitro, and in vivo data sets. The new field of Bioinformatics was born of a
series of meetings among “wet-bench” scientists, in the early 1980s, to meet this
challenge. With the recruitment of mathematicians, computer scientists, statisticians,
and astrophysicists to this field, we have now begun to design and implement some
of the basic tools that will enable data integration and multidimensional analyses of
these varied but unified data sets. For those new to Bioinformatics, this cross
pollenization of the Life, Physical, and Theoretical sciences wants for a common
language. With this in mind, Introduction to Bioinformatics: A Theoretical and Prac-
tical Approach was written as an introductory text for the undergraduate, graduate,
or professional.
At once, this text provides the physical scientist, whether mathematician, computer
scientist, statistician or astrophysicist, with a biological framework to understand the
questions a life scientist would pose in the context of the computational issues and
currently available tools. At the same time, it provides the life scientist with a source
for the various computational tools now available, along with an introduction to their
underlying mathematical foundations. As such, this book can be used as a bridge
toward homologation of these fields. By bringing these disciplines together we may
begin our journey toward understanding the nuances of the genetic code.
Introduction to Bioinformatics: A Theoretical and Practical Approach is divided
into four main sections. The first two sections are well suited to the physical scientist
who is new to studying biological systems. They provide the biological vocabulary,
i.e., an overview of the various biological processes that govern an organism and
impact health. The first section, Biochemistry, Cell, and Molecular Biology, describes
basic cellular structure and the biological decoding of the genome. In silico detection
of the promoter elements that modulate genome decoding is also explained. The sec-
ond section, Molecular Genetics, will lead the reader through a discussion of the long
range regulation of genomes, the in silico detection of the elements that impact long
range control, and the molecular genetic basis of disease as a consequence of replica-
tion. Clinical human genetics and the various clinical databases are reviewed, fol-
lowed by a discussion of the various issues within population genetics that can be used
to address the question: “How do we evolve as we respond to our environment?”
The third section, The UNIX Operating System, was written for the life scientist, to
demystify the UNIX operating system that is commonly used to support advanced
computational tools. Along with understanding the installation and management of
UNIX-based software tools, examples of command line sequence analyses are pre-
sented. These chapters should enable the life scientist to become as comfortable in a
command line environment as in the Graphical-User Interface environment.
v
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vi—Preface
The Computer Applications section provides a common area for the physical and
life scientist to meet. The management and analysis of DNA sequencing projects is
presented, along with a review of how DNA can be modeled as a statistical series of
patterns. The latter forms the basis of most protein and nucleic acid sequence analysis
routines. These considerations are followed by a discussion of the various
genome databases, the representation of genomes, and methods for their large scale
analyses. This culminates in addressing the question: “Can I learn about my
sequence from what is known about a similar sequence?” To directly answer this
question a discussion of the various methods of pattern discovery follows, including
basic multiple sequence alignment to identify both functionally and structurally
related components. The accompanying protein visualization chapter outlines how
these tools can aid in predicting structures that often represent homologous segments
from evolutionarily conserved gene families. This final section concludes with a re-
view of how multiple sequence alignment can be used to infer both functional and
structural biological relationships. In closing, the final chapters of the book review
the new field of Transcription Profiling, examining the current state of analysis soft-
ware for systems biology. We conclude our journey with a discussion of the in silico
analysis and prediction of patterns of gene expression that will ultimately guide our
understanding of living systems.
Though the text provides a detailed description and examples, the CD supplement
also contains a complete set of illustrations from each chapter, many of which are
present in color. This provides a visual resource for both the student and the teacher
that should prove invaluable for those of us preparing our next Bioinformatics lecture
or seminar. In addition, several full version and limited trial versions of the programs
that are discussed in the text are included. These encompass a broad spectrum, from
DNA sequencing project management to microarray analysis, offering the reader the
opportunity to easily access some of the software tools that are discussed. It is our
hope that the current and next generation of physical and life scientists will use these
resources as a springboard to help us move forward in the important quest for an inte-
grated understanding of our physical being.
Stephen A. Krawetz
David D. Womble
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Contents
Preface .............................................................................................................v
Contributors ....................................................................................................xi
Part I. Biochemistry, Cell, and Molecular Biology:
A. The Cell
1 •Nucleic Acids and Proteins:
Modern Linguistics for the Genomics and Bioinformatics Era.............5
Bradley C. Hyman
2 •Structure and Function of Cell Organelles ............................................25
Jon Holy
3 •Cell Signaling ........................................................................................55
Daniel A. Rappolee
B. Transcription and Translation
4 • DNA Replication, Repair, and Recombination.....................................75
Linda B. Bloom
5 •Transcription, RNA Processing, and Translation...................................93
Thomas P. Yang and Thomas W. O’Brien
Part II. Molecular Genetics:
A. Genomics
6 •Epigenetic Mechanisms Regulating Gene Expression..........................123
John R. McCarrey
7 • Gene Families and Evolution................................................................141
Ben F. Koop
8 • Repetitive DNA: Detection, Annotation, and Analysis.........................151
Jerzy Jurka
9 •Molecular Genetics of Disease and the Human Genome Project.......169
Paromita Deb-Rinker and Stephen W. Scherer
B. Clinical Human Genetics
10 •Heredity...............................................................................................187
C. A. Rupar
11 •The Clinical Genetics Databases.........................................................199
Peter J. Bridge
12 •Population Genetics............................................................................207
Jill S. Barnholtz-Sloan
Part III. The UNIX Operating System:
A. Basics and Installation
13 • Introduction to UNIX for Biologists.....................................................233
David D. Womble
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viii—Contents
14 • Installation of the Sun Solaris™ Operating Environment.....................247
Bryon Campbell
15 •Sun System Administration..................................................................263
Bryon Campbell
B. Managing Bioinformatics Tools
16 •Installing Bioinformatics Software
in a Server-Based Computing Environment.....................................285
Brian Fristensky
17 •Management of a Server-Based Bioinformatics Resource ...................297
Brian Fristensky
C. Command Line Sequence Analysis
18 •GCG File Management........................................................................309
Sittichoke Saisanit
19 •GCG Sequence Analysis......................................................................315
Sittichoke Saisanit
Part IV. Computer Applications:
A. Management and Analysis of DNA Sequencing Projects
and Sequences
20 •Managing Sequencing Projects in the GAP4 Environment..................327
Rodger Staden, David P. Judge, and James K. Bonfield
21 • OLIGO Primer Analysis Software........................................................345
John D. Offerman and Wojciech Rychlik
22 • Statistical Modeling of DNA Sequences and Patterns.........................357
Gautam B. Singh
23 •Statistical Mining of the Matrix Attachment Regions
in Genomic Sequences ...................................................................375
Gautam B. Singh
24 • Analyzing Sequences
Using the Staden Package and EMBOSS.........................................393
Rodger Staden, David P. Judge, and James K. Bonfield
B. The Genome Database: Analysis and Similarity Searching
25 • Ensembl: An Open-Source Software Tool
for Large-Scale Genome Analysis....................................................413
James W. Stalker and Anthony V. Cox
26 • The PIR for Functional Genomics and Proteomics..............................431
Cathy H. Wu
27 • Sequence Similarity and Database Searching......................................443
David S. Wishart
28 • GCG Database Searching....................................................................463
David J. Heard
C. Identifying Functional and Structural Sequence Elements
29 • Pattern Discovery: Methods and Software...........................................491
^ ^
Brona Brejová, Tomás Vinar, and Ming Li
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Contents—ix
30 •The Role of Transcription Factor Binding Sites in Promoters
and Their In Silico Detection...........................................................523
Thomas Werner
31 • An Introduction to Multiple Sequence Alignment
and Analysis....................................................................................539
Steven M. Thompson
32 • 3D Molecular Visualization with Protein Explorer..............................565
Eric Martz
33 • Multiple Sequence Alignment and Analysis:
The SeqLab Interface: A Practical Guide.........................................587
Steven M. Thompson
D. Analysis of Gene Expression: Microarrays and Other Tools
34 • Overview of the Tools for Microarray Analysis: Transcription
Profiling, DNA Chips, and Differential Display..................................637
Jeffrey A. Kramer
35 • Microarrays: Tools for Gene Expression Analysis.................................665
Sorin Draghici
36 • Knowledge Discovery from the Human Transcriptome.......................693
Kousaku Okubo and Teruyoshi Hishiki
Part V. Appendices:
Appendix 1: CD Contents...........................................................................715
Appendix 2: A Collection of Useful Bioinformatic Tools
and Molecular Tables...............................................................................719
Appendix 3: Simple UNIX Commands........................................................723
Index ............................................................................................................725
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