Genomics and Proteomics: Functional and Computational Aspects

246 Pages·2000·6.973 MB·English

by  Suhai S. (ed.)

GENOMICS AND PROTEOMICS
Functional and Computational Aspects
guoxingzhong and huangzhiman
www.dnathink.org
2003.3.5
GENOMICS AND
PROTEOMICS
Functional and Computational Aspects
Editedby
Sándor Suhai
Deutsches Krebsforschungszentrum
Heidelberg, Germany
KLUWER ACADEMIC PUBLISHERS
New York, Boston, Dordrecht, London, Moscow
eBook ISBN: 0-306-46823-9
Print ISBN: 0-306-46312-1
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PREFACE
Genome research will certainly be one of the most important and exciting scien-
tificdisciplines of the 21st century. Deciphering the structure of the human genome, as
wellasthatof severalmodel organisms,is the keytoourunderstandinghowgenesfunc-
tioninhealth anddisease.Withthecombined developmentof innovativetools,resources,
scientificknow-how, and an overall functional genomic strategy, the origins of human
andother organisms’geneticdiseasescan betraced. Scientificresearch groupsanddevel-
opmentaldepartmentsof severalmajor pharmaceuticaland biotechnologicalcompanies
are using new, innovative strategiesto unravel how genes function, elucidating the gene
protein product, understanding how genes interact with others-both in health and in
the disease state.
Presently, the impact of the applications of genome research on our society in
medicine, agriculture and nutrition will be comparable only to that of communication
technologies. In fact, computational methods, including networking, have been playing
a substantialrole even in genomics and proteomics from the beginning. Wecan observe,
however, a fundamental change of the paradigm in life sciences these days: research
focused until now mostly on the study of single processes related to a fewgenes or gene
products, but due to technical developments of the last years we can now potentially
identifyand analyzeall genes and geneproducts of an organism and clarify their role in
the network of life processes.This breakthrough in life sciencesis gaining speed world-
wide and its impact on biology is comparable only to that ofmicrochips on information
technology.
Themain purpose of the International Symposium on Genomics and Proteomics:
Functional and Computational Aspects, held October 4–7, 1998 at the Deutsches
Krebsforschungszentrum (DKFZ) in Heidelberg, was to give an overview of the present
state of the unique relationship between bioinformatics and experimental genome
research. The five main sessions, under the headings: expression analysis; functional
gene identification; functional aspects of higher order DNA-structure; from protein
sequenceto structure and function; and genetic and medical aspects of genomics, com-
prised both computational work and experimental studies to synergetically unify both
approaches.
The content of this volume was presented mostly as plenary lectures. The confer-
..
ence was held at the same time as the Annual Meeting of the Gesellschaft fur Genetik
(GfG). It is a great pleasure to thank Professor Harald zur Hausen and the coworkers
ofDKFZ fortheir help and hospitality extended to the lecturers andparticipants during
the meeting.We would also liketo thank the European Commission and the companies
BASF AG, BASF-LYNX Bioscience AG, Bayer AG, BIOMEVA GmbH, Boehringer
v
vi Preface
Mannheim GmbH, Hoffmann-La Roche Ltd., Knoll AG, Merck KGaA, and Schering
AG for the funding of the symposium. The organizers, Annemarie Poustka, Hermann
Bujard, and Sándor Suhai, profited greatly from the help of the scientificcommittee,
ClausBartram,Jörg Hoheisel, FotisKafatos, Jörg Langowski,Peter Lichter,JensReich,
Manfred Schwab,Peter Seeburg,and Martin Vingron. Furthermore, theeditor isdeeply
indebted to Anke Retzmann and Michaela Knapp-Mohammady for their help in orga-
nizing the meeting and preparing this volume.
Sá'ndor Suhai
CONTENTS
1. ... and Counting: DNA-Microarrays ........................... 1
Jörg D. Hoheisel
2. Obtaining and Evaluating Gene Expression Profiles with cDNA
Microarrays .............................................. 5
Michael Bittner, Yidong Chen, Sally A. Amundson, Javed Khan,
Albert J. Fornace Jr., Edward R. Dougherty, Paul S. Meltzer,
and Jeffrey M. Frent
3. Large Scale Expression Screening Identifies MolecularPathways and
Predicts Gene Function ................................... 27
Nicolas Pollet, Volker Gawantka, Hajo Delius, and Christof Niehrs
4. The Glean Machine: What Can We Learn from DNA Sequence
Polymorphisms? .......................................... 37
Daniel L. Hartl, E. Fidelma Boyd, Carlos D. Bustamante,
and Stanley A. Sawyer
5. Automatic Assembly and Editing of Genomic Data .................. 51
B. Chevreux, T. Pfisterer, and S. Suhai
6. QUEST: An Iterated Sequence Databank Search Method ............... 67
William R. Taylor and Nigel P. Brown
7. A n Essay on Individual Sequence Variatio nin Expressed Sequence Tags
(ESTs) ......................................................... 83
Jens Reich, David Brett, and Jens Hanke
8. Sequence Similarity Based Gene Prediction ............................. 95
Roderic Guigó, Moisés Burset, Pankaj Agarwal, Josep E Abril,
Randall F. Smith and James W. Fickett
9. Functional Proteomics ............................................. 107
Joachim Klose
vii
viii Contents
10. The Genome As a Flexible Polymer Chain: Recent Results from
Simulations and Experiments .................................... 121
Jörg Langowski, Carsten Mehring, Markus Hammermann,
Konstantin Klenin, Christian Münkel, Katalin Tóth, and
Gero Wedemann
1 1. Analysis of Chromosome Territory Architecture in the Human Cell
Nucleus: Overview of Data from a Collaborative Study ........... 133
H. Bornfleth, C. Cremer, T. Cremer, S. Dietzel, P. Edelmann, R. Eils,
W.Jäger,D. Kienle,G. Kreth,P. Lichter, G. Little, C. Münkel,
J. Langowski, I. Solovei, E. H. K. Stelzer, and D. Zink
12. From Sequence to Structure and Function: Modelling and Simulation of
Light-Activated Membrane Proteins .................................. 141
Jerome Baudry, Serge Crouzy, Benoit Roux, and Jeremy C. Smith
13. SHOX Homeobox Gene and Turner Syndrome .......................... 149
E. Rao and G. A. Rappold
14. A Feature-Based Approach to Discrimination and Prediction of
Protein Folding ................................................ 157
Boris Mirkin and Otto Ritter
15. Linking Structural Biology with Genome Research: The Berlin “Protein
Structure Factory” Initiative ....................................... 179
Udo Heinemann, Juergen Frevert, Klaus-Peter Hofmann, Gerd Illing,
Hartmut Oschkinat, Wolfram Saenger, and Rolf Zettl
16. G Protein-coupled Receptors, or the Power of Data ..................... 191
Florence Horn, Mustapha Mokrane, Johnathon Weare,
and Gerrit Vriend
17. Distributed Application Management in Bioinformatics .................. 215
M. Senger, P. Ernst, and K.-H. Glatting
18. Is Human Genetics Becoming Dangerous to Society? .................... 231
Charles J. Epstein
Contributors ............................................................ 243
Index ................................................................... 249
1
... AND COUNTING
DNA-Microarrays
Jörg D. Hoheisel*
Functional Genome Analysis
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 506
D-69 120 Heidelberg
Germany
In recent years, emphasis in genome research has moved away from the more
descriptive presentation of the rather static sequence fundaments of an organism toward
the evaluation of the dynamic processes taking place within a living cell on the level of
nucleic acids (and beyond). This adds another dimension of complexity, since the entire
organism has to be re-analysed very many times over with probes generated under dif-
ferent environmental conditions or taken from different (tissue) parts. The observed scale
of fluctuation is somewhat surprising although this is not news as such. The genomic
approaches only bring home this message more clearly and convincingly, because it is
reflected in the puzzling composition of the information obtained. Toward a compre-
hensive understanding, rather elaborate and fast methods are therefore essential and
accurate numbers need to be determined. The last issue is critical, since already subtle
variations can precipitate enormous consequences, especially in regulative processes.
Many presentations at the recent Symposium on Genomics and Proteomics dealt with
methodologies capable to perform this sort of analyses, at least in principle, and high-
lighted the perspectives and challenges ahead.
The term “DNA-microarray” stands for the currently most prominent and promis-
ing type of technology in this respect. By simultaneously analysing the hybridisation
behaviour of probe molecules at very many different sequences, it combines simplicity
*
Tel.:[phone], Fax: -424682. e-mail: [e-mail]
Genomics and Proteomics, edited by Sándor Suhai.
Kluwer Academic / Plenum Publishers, New York, 2000. 1
2 J.D.Hoheisel
of the assaywith the high throughput required for genomic approaches. A simple look
at the numbers of relevant publications (Figure 1)published during the last few years
illustrates both the increased awareness of the array-based approaches and the actual
start of data production by such means (for review see Nature Biotechnol. 17, 1999),
although a considerable number of relevant publications is missing because of search-
intrinsic restrictions to only certain types of manuscripts andjournals. Also, there are
currently indeed still more reviews and forecasts on the subject than reports on actual
data, yet this is bound tochangevery soon.
The potential range of microarray applications isaswide as isthe field of lifesci-
encesandcommerce.Thus, there isnot a singleone technique for all applications-nor
will there ever be one-but a rather wide spectrum of array types, adapted to the par-
ticular needs. Rather than decrease, this variety will increase with the number of appli-
cations (andcompaniesgettinginvolved)at least for sometime,sincecertain techniques
are well suited for one kind of analysis while less fitting another. Also, there are many
newareasofapplicationout thereeithernotyetbeingworked ator, mostlikely,noteven
thought of today, in a development similar to PCR, when from a single basic principle
very many derivatives evolved. One field, for example, yet virtually unexplored by
microarray techniques is the analysis of the information encoded in the DNA structure
rather than sequence. It has been demonstrated that not only functional information is
geneticallyencoded that way but, in addition, that even short term memory effectsare
possible (e.g., Pohl, 1987).Another example is the determination of the methylation
statusof DNA, important for both structureand function (Olek et al., 1996).
As with many scientific developments during their initial phases, the microarray
techniques arestillfullof pitfalls andproblems.Ithasbeenshownthat mutationalanaly-
sesof thep53-genecanbecarriedoutathigher accuracythan bysequencing, thecurrent
gold standard (Ahrendt et al., 1999), but this does not hold true for many other
Figure 1. Number of hits when searching Medline for manuscripts dealing with applications of DNA-arrays,
microarraysandDNA-chips. Thevaluefor 1999isanextrapolationbasedonthenumberpublishedintheperiod
January to March and probably an underestimate of the eventual total.