Applied Bioinformatics

297 Pages·2008·9.28 MB·English

Applied Bioinformatics
P.M. Selzer • R.J. Marhöfer • A. Rohwer
Applied
Bioinformatics
An Introduction
With 69 Figures, 61 in color and 6 Tables
Prof. Paul M. Selzer, Ph.D. Andreas Rohwer, Ph.D.
Intervet Innovation GmbH Intervet Innovation GmbH
BioChemInformatics BioChemInformatics
Zur Propstei Zur Propstei
55270 Schwabenheim 55270 Schwabenheim
Germany Germany
[e-mail] [e-mail]
Richard J. Marhöfer, Ph.D.
Intervet Innovation GmbH
BioChemInformatics
Zur Propstei
55270 Schwabenheim
Germany
[e-mail]
Translators:
PD Frank Seeber, Ph.D. Conor Caffrey, Ph.D.
Dept. Biology/Parasitology Director of Biochemistry and Molecular Parasitology
Philipps University Marburg Sandler Center for Basic Research in Parasitic Diseases
Karl-von-Frisch-Str. 8 Byers Hall N508
35042 Marburg University of California, San Francisco
Germany 1700 4th Street
[e-mail] San Francisco, CA 94158-2330
USA
[e-mail]
ISBN: 978-3-540-72799-6 e-ISBN: 978-3-540-72800-9
Library of Congress Control Number: 2007937094
© 2008 Springer-Verlag Berlin Heidelberg
First published in German under the title: Angewandte Bioinformatik 2004
This work is subject to copyright. All rights are reserved, whether the whole or part of the material
is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation,
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Preface
Though a relatively young discipline, bioinformatics is fi nding
increasing importance in many life science disciplines, includ-
ing biology, biochemistry, medicine, and chemistry. Since its
beginnings in the late 1980s, the success of bioinformatics has
been associated with rapid developments in computer science,
not least in the relevant hardware and software. In addition,
biotechnological advances such as those witnessed in the fi elds
of genome sequencing, microarrays and proteomics have con-
tributed enormously to the bioinformatics boom. Finally, the
simultaneous breakthrough and success of the World-Wide Web
has facilitated the worldwide distribution of and easy access to
bioinformatics tools.
Today, bioinformatics techniques such as the BLAST algo-
rithm, pairwise and multiple sequence comparisons, que-
ries of biological databases, and phylogenetic analyses have
become familiar tools to the natural scientist. Many of the soft-
ware products that were initially unintuitive and cryptic have
matured into relatively simple and user-friendly products being
easily accessible over the Internet. One no longer needs to be a
computer scientist to profi ciently operate bioinformatics tools
with respect to complex scientifi c questions. Nevertheless, what
remains important is an understanding of fundamental bio-
logical principles together with a knowledge of the appropri-
ate bioinformatics tools available and how to access them. Also,
and not least, is the confi dence to apply these tools correctly to
generate meaningful results.
vi Preface
The present book is based on a lecture series of Paul M.
Selzer, professor of biochemistry at the Interfaculty Institute for
Biochemistry, Eberhard-Karls-University, Tübingen, Germany,
and was fi rst published in German in 2004. The book is unique
in that it includes both exercises and their solutions, thereby
making it suitable for the classroom. To access a wider inter-
national audience, the authors have prepared a revised second
edition in English. Each of the three authors has many years
of accumulated expertise in research and development within
the pharmaceutical industry, specifi cally in the area of bioin-
formatics and cheminformatics at Intervet Innovation GmbH,
a worldwide leading animal health company. The aim of this
book is both to introduce the daily application of a variety of
bioinformatics tools and to provide an overview of a complex
fi eld. However, the intent is neither to describe nor even derive
formulae or algorithms, but rather to facilitate rapid and struc-
tured access to applied bioinformatics by interested students
and scientists. Therefore, even though detailed knowledge in
computer programming is not required to understand or apply
this book, profi ciency in operating a PC, its standard software,
and the Internet are prerequisites.
Each of the eight chapters describes important fi elds in
applied bioinformatics and provides both references and WWW
links. Detailed exercises and solutions are meant to encourage
the reader to practice and learn the topic, and become profi -
cient in the relevant software. If possible, the exercises are cho-
sen in such a way as that examples, such as protein or nucleotide
sequences, are interchangeable. This allows the reader to choose
examples that are closer to his/her scientifi c interest based on a
sound understanding of the underlying principles. Direct input
required by the user either through text or by pressing buttons
is indicated in Courier font. Finally, the book concludes with
a detailed glossary of common defi nitions and terminologies
used in applied bioinformatics.
Schwabenheim, June 2007
We thank Intervet Innovation GmbH, Schwabenheim, Germany for its
continuous support in preparing this textbook.
The Circulation of Genetic Information
Genetic information is encoded by a four-letter alphabet, which
in turn is translated into proteins using a 20-letter alphabet.
Proteins fold into three-dimensional structures that perform
essential functions in single-celled or multicellular organisms.
These organisms are under constant selection pressure, which
in turn leads to changes in their genetic information.
Cover picture
The upper left side of the fi gure shows part of a DNA microarray
in which the gene expression patterns of two bacterial strains have
been overlaid. Compared to the reference strain, red spots indicate
overexpression, green spots - lower expression, yellow spots - simi-
lar expression and black spots - a lack of complementary cDNA.
On the right, the three-dimensional molecular structure of a
protein-DNA complex is depicted. The transcription activator Gal4
from Saccharomyces cerevisiae is shown bound to a DNA oligomer
(PDB-ID: 1D66). Gal4 is represented by a ribbon model in which
α-helices and loops are drawn in red and yellow, respectively. The
side chains of the amino acids in the loops are not shown. For the
DNA oligomer, local bending of the molecular surface is color-
coded where darker colors represent increased bending [Brick-
mann J, Exner TE, Keil M, Marhöfer RJ (2000) Molecular graphics
- trends and perspectives. J Mol Mod 6:328-340]. The structure
was produced on a Silicon Graphics Octane 2 workstation using
the software package MOLCAD/Sybyl (Tripos Inc.) [Brickmann J,
Goetze T, Heiden W, Moeckel G, Reiling S, Vollhardt H, Zachmann
CD (1995) Interactive visualization of molecular scenarios with
MOLCAD/Sybyl. In: Bowie JE (Hrsg) Data visualization in molecu-
lar science - tools for insight and innovation. Addison-Wesley Pub-
lishing Company Inc, Reading, Massachusetts, USA, S 83-97].
Contents
1 Computers, Operating Systems and the Internet . . . . 1
1.1 Computers and Operating Systems . . . . . . . . . . . . . 1
1.2 Internet and WWW . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.3 The Physical Connection to the Internet. . . . . . . . . 6
1.4 The Logical Connection to the Internet . . . . . . . . . 8
1.5 Internet Services. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.5.1 E-mail. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
1.5.2 FTP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
1.5.3 World Wide Web. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
1.6 Using UNIX. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
1.7 The History of Bioinformatics . . . . . . . . . . . . . . . . . 23
WWW Links . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
2 The Biological Foundations of Bioinformatics. . . . . . 31
2.1 Nucleic Acids and Proteins . . . . . . . . . . . . . . . . . . . . 31
2.2 Structure of the Nucleic Acids DNA and RNA. . . . 31
2.3 The Storage of Genetic Information . . . . . . . . . . . . 33
2.4 The Structure of Proteins . . . . . . . . . . . . . . . . . . . . . 36
2.4.1 Primary Structure. . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.4.2 Secondary Structure. . . . . . . . . . . . . . . . . . . . . . . . . . 39
2.5 Tertiary and Quaternary Structure . . . . . . . . . . . . . 41
WWW Links . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43