MB&B 452a / 752a2
Fall 2000 (Current Page 
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BIOINFORMATICS
SECTION
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MB&B 452a / 752a2 Fall 2000 (Current Page BIOINFORMATICS |
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Intro., Sequences, Web resources, Databases, Surveys, Datamining, Structures, Simulation, Summary, all-in-one, 1999 "Demographics", Projects
Bioinformatics describes the computational analysis of gene sequences, protein structures, and expression datasets on a large scale. Specific topics include sequence alignment, biological database design, geometric analysis of protein structure, and macromolecular simulation.
Meeting from 1:00-2:15 PM on Mondays and Wednesday, in Bass 305.
MB&B Department, Bass
building, Yale University, New Haven, CT
06520
Mark Gerstein
Bass 432A, Phone 203 432-6105, e-mail Mark.Gerstein@yale.edu
Office hours right after class
Handouts and readings with Joann Delvecchio <joann.delvecchio@yale.edu>
J W Gibbs 309C, 203 432-5566.
The bioinformatics module will follow a very similar progression to the course offered last fall.
(See, in particular, http://bioinfo.mbb.yale.edu/course/classes.)Also, see other related on-line lectures.
If you're really motivated, take a look at http://bioinfo.mbb.yale.edu/jobs.
If you want to use the overheads in your own course, feel free, as long
as you give proper attribution.
(A number of the overheads were derived from related courses at Stanford and Yale and
are so acknowledged.)
Most of the reading material is copyright and can NOT be freely distributed.
It should not be accessible outside of Yale.
Required reading is marked below by purple brackets. For instance,
[REQUIRED 6 (iii)]
means sixth required reading due for third bioinformatics section (during week of 6 November).The following directories contain some optional reading material:
http://bioinfo.mbb.yale.edu/mbb452a/reading
http://bioinfo.mbb.yale.edu/course/private-xxxx
http://bioinfo.mbb.yale.edu/e-printThe directories are password protected. Contact the TAs for the password. Some of the material in these directories is copyrighted and should NOT be distributed outside of the course.
2 short ones in class, probably for a third of the class. SIMPLE multiple choice questions that you should be able to answer from the lectures plus the main readings.
11.13 - First quiz will cover Introduction and Sequences material.
12.6 - Second quiz will cover the rest of the material in the bioinformatics section.
From previous year. See overall "course demographics" based on survey plus first quiz.
[REQUIRED 1 (i)] Nicholas M Luscombe, Dov Greenbaum & Mark Gerstein (2001). "What is bioinformatics? An introduction and overview," IMIA 2001 Yearbook (in press)
** http://bioinfo.mbb.yale.edu/e-print/whatis-imia
( Draft of an overview. Please send comments on this to Mark.Gerstein@yale.edu .)
Basic Alignment via Dynamic Programming
Suboptimal Alignment
Gap Penalties
Similarity (PAM) Matrices
Multiple Alignment
Profiles, Motifs, HMMs
Local Alignment
Probabilistic Scoring Schemes
Rapid Similarity Search: Fasta
Rapid Similarity Search: Blast
Practical Suggestions on Sequence Searching
Transmembrane helix predictions
Secondary Structure Prediction: Basic GOR
Secondary Structure Prediction: Other Methods
Assessing Secondary Structure Prediction
Features of Genomic DNA Sequence
[REQUIRED 2 (i)] Needleman, S. B. and Wunsch, C. D. (1971). "A general method applicable to the search for similarities in the amino acid sequence of two proteins." J. Mol. Biol. 48: 443-453.
(The original paper. Still pretty easy to read. Will be used in class.)D J States & M S Boguski, "Similarity and Homology," Chapter 3 from Gribskov, M. and Devereux, J. (1992). Sequence Analysis Primer. New York, Oxford University Press.
(Focus on dynamic programming section of this chapter.)
[REQUIRED 3 (ii)] Altschul,
S. F., Boguski, M. S., Gish, W. and Wootton, J. C. (1994). Issues in searching
molecular sequence databases. Nature Genetics. 6(2): 119-29.
(Most important. A short overall review.)
Alschul et al. (1998). "Gapped BLAST and PSI-BLAST: a new generation of protein
database search programs," Nucleic Acids Res 1997 Sep 1;25(17):3389-402
** http://bioinfo.mbb.yale.edu/course/private-xxxx/altschul-nar-blast2.pdf
Pearson, W. R. (1996). Effective Protein Sequence Comparison. Meth. Enz.
266: 227-259.
(Understand how the FASTA e-value is derived.)
[REQUIRED 5 (iii)] Eddy, S. R. (1996). "Hidden Markov models," Curr. Opin. Struc. Biol. 6, 361-365.
Higgins, D. G., Thompson, J. D. & Gibson, T. J. (1996). "Using CLUSTAL for multiple sequence alignments," Methods Enzymol 266, 383-402.
Garnier, J., Gibrat, J. F. & Robson, B. (1996). "GOR method for predicting protein secondary structure from amino acid sequence," Methods Enzymol 266, 540-53.
[REQUIRED 6 (iii)] King, R. D. & Sternberg, M. J. E. (1996). "Identification and application of the concepts important for accurate and reliable protein secondary structure prediction," Prot. Sci. 5, 2298-2310.
Smith, T. F. and Waterman, M. S. (1981). "Identification of common molecular subsequences." J. Mol. Biol. 147: 195-197
(The original paper on local alignment. Not quite as easy to read, but introduces this important concept.)Frishman D, and Argos P. (1997) "The Future of Protein Secondary Structure Prediction Accuracy," Folding & Design 2:159-62.
(Controversial idea: secondary structure prediction to 80%?)
** http://bioinfo.mbb.yale.edu/mbb452a/reading/frishman-fad-acc-secstr.pdfM Gerstein (1998). "Measurement of the Effectiveness of Transitive Sequence Comparison, through a Third ‘Intermediate’ Sequence," Bioinformatics 14: 707-14.
** http://bioinfo.mbb.yale.edu/e-print/transcmp-bioinfo-reprint.pdf
Structuring Information in Tables
Keys and Joins
Normalization
Complex RDB encoding
Indexes and Optimization
Forms and Reports
Parts Lists: homologs, motifs, orthologs, folds
Fold Library
Overall Sequence-structure Relationships, Annotation Transfer
Parts in Genomes, shared & common folds
Genome Trees
Extent of Fold Assignment: the Bias Problem
Bulk Structure Prediction
The Genomic vs. Single-molecule Perspective
Understanding Biases in Sampling
Relationship to experiment: LIMS, target selection Function Classification
Cross-tabulation, folds and functions
Clustering & Trees
Analysis of Expression Data
Clustering
Bayesian Analysis
Analysis of Other Whole Genome Datasets
[REQUIRED 7 (iv)] M Gerstein (2000). "Integrative database analysis in structural genomics," Nature Structural Biology 7: 960-963.
** http://www.nature.com/cgi-taf/DynaPage.taf?file=/nsb/journal/v7/n11s/full/nsb1100_960.html&filetype=pdf
(Other related articles are available from http://www.nature.com/nsb/structural_genomics.)[REQUIRED 8 (iv)] Korth & Silberschatz, Database System Concepts [amazon]
(CS book on databases; Read pages 1 to 65 [sections 1.0 to mid-3.2] and pages 97 to 108 [part of section 4.1]. Some of the information on SQL is available from the on-line link below.)
** http://bioinfo.mbb.yale.edu/course/private-xxxx/sqltut.htm[REQUIRED 9 (v)] M Gerstein & R Jansen (2000). "The current excitement in bioinformatics, analysis of whole-genome expression data: How does it relate to protein structure and function?" Current Opinion in Structural Biology 2000, 10:574–584.
** http://bioinfo.mbb.yale.edu/e-print/expclust-cosb/text.pdf[REQUIRED 10 (v)] Eisen MB, Spellman PT, Brown PO, & Botstein D (1998). "Cluster analysis and display of genome-wide expression patterns," Proc Natl Acad Sci U S A 1998 95: 14863-8
** http://www.pnas.org/cgi/content/full/95/25/14863
Genome Expression on the World Wide Web, Short review by R Young at MIT on Gene Chips, TIG 15:202-204
** http://bioinfo.mbb.yale.edu/mbb452a/reading/young-tigs-chips.pdfJ Lin & M Gerstein (2000). "Whole-genome trees based on the occurrence of folds and orthologs: implications for comparing genomes on different levels," Genome Res. 10: 808-1
** http://bioinfo.mbb.yale.edu/e-print/genome-tree-genomeres/text.pdfS Teichmann, C Chothia & M Gerstein (1999). "Advances in Structural Genomics," Curr. Opin. Struc. Biol. 9: 390-399.
** http://bioinfo.mbb.yale.edu/e-print/strucgenom-cosb/text-sg.pdfM Gerstein & W Krebs (1998). "A Database of Macromolecular Movements," Nuc. Acid. Res. 26:4280-4290.
** http://bioinfo.mbb.yale.edu/e-print/molmovdb-nar-reprint.pdfFred Tekaia, Antonio Lazcano & Bernard Dujon (1999). "The Genomic Tree as Revealed from Whole Proteome Comparisons," Genome Res. 9:550-557
** http://bioinfo.mbb.yale.edu/mbb452a/reading/dujon-genomeres-proteometree.pdfH Hegyi & M Gerstein (1999). "The Relationship between Protein Structure and Function: a Comprehensive Survey with Application to the Yeast Genome," J Mol. Biol. 228: 147-164.
** http://bioinfo.mbb.yale.edu/e-print/foldfunc-jmb/text-ff.pdfM Gerstein & H Hegyi (1998). "Comparing Microbial Genomes in terms of Protein Structure: Surveys of a Finite Parts List," FEMS Microbiology Reviews 22: 277-304.
** http://bioinfo.mbb.yale.edu/e-print/surveys-fems-preprint.pdfM Gerstein (1998). "Patterns of Protein-Fold Usage in Eight Microbial Genomes: A Comprehensive Structural Census," Proteins 33: 518-534.
** http:// bioinfo.mbb.yale.edu/course/private-xxxx/proteins_33_518.pdf
(This is an example of the application of large-scale, database-style calculations.)Tomb, J.-F., White, O., Kerlavage, A. R., Clayton, R. A., Sutton, G. G., Fleischmann, R. D., Ketchum, K. A., Klenk, H. P., Gill, S., Dougherty, B. A., Nelson, K., Quackenbush, J., Zhou, L., Kirkness, E. F., Peterson, S., Loftus, B., Richardson, D., Dodson, R., Khalak, H. G., Glodek, A., McKenney, K., Fitzegerald, L. M., Lee, N., Adams, M. D., Hickey, E. K., Berg, D. E., Gocayne, J. D., Utterback, T. R., Peterson, J. D., Kelley, J. M., Cotton, M. D., Weidman, J. M., Fujii, C., Bowman, C., Watthey, L., Wallin, E., Hayes, W. S., Borodovsky, M., Karp, P. D., Smith, H. O., Fraser, C. M. & Venter, J. C. (1997). "The complete genome sequence of the gastric pathogen Helicobacter pylori," Nature 388, 539-547.
** http://bioinfo.mbb.yale.edu/course/private-xxxx/nature-hpylori.pdf
** http://bioinfo.mbb.yale.edu/course/private-xxxx/nature-sum-hpylori.html
** http://www.nature.com/Nature2/serve?SID=&CAT=NatGen&PG=pylori/pylori1.html
(This research article describes one of the recent genome sequences.)Cavalli-Sforza, L. & Edwards, S. (1967). "Phylogenetic analysis: models and estimation procedures," Evolution 21, 550-570.
M Gerstein (1998). "How Representative are the Known Structures of the Proteins in a Complete Genome? A Comprehensive Structural Census," Folding & Design 3: 497-512.
** http://bioinfo.mbb.yale.edu/e-print/pdb-v-gen-folddes/fad-3-497-reprint.pdfFitch, W. M. (1971). "Toward defining the course of evolution: minimum change for a specific topology," Syst. Zool. 20, 406-416.
Swofford et al. (1994). "Phylogeny reconstruction," In Molecular Systematics (2nd ed.), Sinauer Press.
(This book chapter is a good reference thought not a neccessary reading.)
Structures & Simulation
What Structures Look Like?
RMS Superposition
Structural Alignment by Iterated Dynamic Programming
Scoring Structural Similarity
Protein Geometry
Calculation of Surface Area
Calculation of Volume
Standard Volumes and Radii
Packing
Basic Forces: Electrostatics
VDW Forces
Bonds as Springs
Energy Minimization
Monte Carlo
Molecular Dynamics
Energy and Entropy
Parameter Sets
Number Density
Poisson-Boltzman Equation
Lattice Models and Simplification
[REQUIRED 11 (vi)] Holm, L. and Sander, C. (1993). Protein Structure Comparison by Alignment of Distance Matrices. J. Mol. Biol. 233: 123-128.
(A different method of structural alignment, which differs more from sequence alignment.)[REQUIRED 12 (vi)] M Gerstein & M Levitt (1998). "Simulating Water and the Molecules of Life," Scientific American 279: 100-105.
** http://bioinfo.mbb.yale.edu/geometry/sciam
M Gerstein & M Levitt (1998). "Comprehensive Assessment of Automatic Structural Alignment against a Manual Standard, the Scop Classification of Proteins," Protein Science 7: 445-456.
** http://bioinfo.mbb.yale.edu/~mbg/preprint/ss-prsci.pdf
(Understand the method, not results, in this paper OR in Gerstein & Levitt (1996), below)M Gerstein & F M Richards, "Protein Geometry: Volumes, Areas, and Distances," (2000) chapter 22 of volume F of the International Tables for Crystallography ("Molecular Geometry and Features" in "Macromolecular Ccrystallography")
** http://bioinfo.mbb.yale.edu/e-print/geom-inttab/geom-inttab.pdfJ Tsai, R Taylor, C Chothia & M Gerstein (1999). "The Packing Density in Proteins: Standard Radii and Volumes," J. Mol. Biol. 290: 253-266.
** http://bioinfo.mbb.yale.edu/e-print/std-vols-jmb/std-vols-jmb.pdfTaylor, W. R. & Orengo, C. A. (1989). Protein Structure Alignment. J. Mol. Biol. 208, 1-22.
Kuntz, I. D. (1992). Structure-Based Strategies for Drug Design and Discovery. Science 257, 1078-1082.
(Docking. See link below for more information.)
** http://www.cmpharm.ucsf.edu/kuntzRichards, F. M. (1977). Areas, Volumes, Packing, and Protein Structure. Ann. Rev. Biophys. Bioeng. 6, 151-76.
** http://bioinfo.mbb.yale.edu/course/private-xxxx/richards-annrev-areas.pdfRichards, F. M. (1974). The Interpretation of Protein Structures: Total Volume, Group Volume Distributions and Packing Density. J. Mol. Biol. 82, 1-14.
(Original Application of Voronoi Method to Proteins. See Int. Tabl. document above for more details on method.)Pattabiraman, N., Ward, K.B. and Fleming, P.J. (1995) Occluded Molecular Surface: Analysis of Protein Packing, Journal of Molecular Recognition, 8:334-344
** http://bioinfo.mbb.yale.edu/course/private-xxxx/fleming-os.pdf
http://csbmet.csb.yale.edu/userguides/datamanip/os/os_descrip.html -- OSJoan Pontius, Jean Richelle, Shoshana J. Wodak (1996). Deviations from Standard Atomic Volumes as a Quality Measure for Protein Crystal Structures. Journal of Molecular Biology 264: 121-136.
** http://bioinfo.mbb.yale.edu/mbb452a/reading/wodak-jmb-volume.pdf
Barry Cipra (1998). “Packing Challenge Mastered At Last,” Science 281: 1267
** http://www.sciencemag.org/cgi/content/full/281/5381/1267
Simon Singh (1998). “Mathematics ‘Proves’ What the Grocer Always Knew,” New York Times (August 25).
** http://bioinfo.mbb.yale.edu/mbb452a/reading/nyt-sci-packproof.txtMcCammon, J. A. & Harvey, S. C. (1987). Dynamics of Proteins and Nucleic Acids. Cambridge UP.
Honig, B. & Nicholls, A. (1995). Classical electrostatics in biology and chemistry. Science 268, 1144-9.
Information on Liquid Simulation Methods (excerpted from a thesis, 1992)
Levitt, M. (1983). Protein folding by restrained energy minimization and molecular dynamics. J Mol Biol 170, 723-64.
Allen, M. P. & Tildesley, D. J. (1987). Computer Simulation of Liquids. Claredon Press, Oxford. (A good reference.)
Karplus, M. & McCammon, J. A. (1986). The dynamics of proteins. Sci. Am. 254, 42-51. (A good reference.)
Duan, Y. & Kollman, P. A. (1998). Pathways to a protein folding intermediate observed in a 1-microsecond simulation in aqueous solution Science 282, 740-4.
** http://bioinfo.mbb.yale.edu/course/private-xxx/kollman-science-longsim.pdf
** http://www.sciencemag.org/cgi/content/abstract/282/5389/740Sharp, K. (1999). Electrostatic Interactions in Proteins. In International Tables for Crystallography, International Union of Crystallography, Chester, UK.
Dill, K. A., Bromberg, S., Yue, K., Fiebig, K. M., Yee, D. P., Thomas, P. D. & Chan, H. S. (1995). Principles of protein folding--a perspective from simple exact models. Protein Sci 4, 561-602.
Franks, F. (1983). Water. The Royal Society of Chemistry, London. Pages 35-56.
Extra material
"Fathering life and other feats," Economist, 2 February 1999
(About synethetized M. genitalium)
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
"The Gutenberg Internet," Wall Street Jounal, June 11, 1999
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
"The hot new job in agriculture is bioinformatics," Work Week, Wall
Street Jounal, August 17, 1999, A1
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
Antonio Regalado (1999), "Mining the Genome," MIT TechReview, Sept/Oct. issue.
** http://www.techreview.com/articles/oct99/regalado.htm
** http://bioinfo.mbb.yale.edu/mbb452a/reading/regalado-techrev-bioinfo.txt
Charles C. Mann, "Biotech Goes Wild," TechReview, July/August
** http://www.techreview.com/articles/july99/mann.htm
DAVID STIPP, "GENE CHIP BREAKTHROUGH, FORTUNE, 03/31/1997
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
Economist, 6/28/99, "Science & Technology: Drowning in data"
** http://www.economist.com/editorial/freeforall/current/st2340.html
** http://bioinfo.mbb.yale.edu/mbb452a/reading/economist-bioinfo.txt
GEORGE JOHNSON, "Searching for the Essence of the World Wide Web,"
April 11, 1999
** http://www.nytimes.com/library/review/041199internet-ecosystem-review.html
HENRY FOUNTAIN, "Hiding Secret Messages Within Human Code," New
York Times, June 22, 1999, F5
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
J L Weldon. "A Career in Data Modeling," Byte, June 1997
(Practical hands-on discussion of data modeling in commercial context, many
of the same issues apply in bioinformatics.)
** http://www.byte.com/art/9706/sec7/art3.htm
J L Weldon. "Data Warehouse Building Blocks," Byte, January 1997
** http://www.byte.com/art/9701/sec7/art1.htm
J L Weldon. "Warehouse Cornerstones," Byte, January 1997
(Other, less relevant articles, on the some of the practical hardware issues
in database design.)
** http://www.byte.com/art/9701/sec7/art2.htm
J L Weldon. "RDBMSes Get a Make-Over," Byte, April 1997
(Practical discussion of what an object database is.)
** http://www.byte.com/art/9704/sec7/art7.htm
Johnson, G. (1997). "Proteins Outthink Computers in Giving Shape to Life,"
New York Times. March 25, 1997, C1.
** http://bioinfo.mbb.yale.edu/course/private-xxxx/nyt-casp2.html
Johnson, G. (1997). "Proteins Outthink Computers in Giving Shape to Life,"
New York Times. March 25, 1997, C1.
** http://bioinfo.mbb.yale.edu/course/private-xxxx/nyt-casp2.html
L Hunter (ed), AI and Molecular Biology, AAAI Press (A new intro. text)
** http://www.aaai.org/Press/Books/Hunter/hunter-contents.html
L. Fisher (1999). "Surfing the Human Genome; Data Bases of Genetic Code Are Moving to the Web," New York Times. 09/20/99, C1
Langreth, R. (1997). "Scientists Unlock Sequence Of Ulcer Bacterium's Genes,"
Wall Street Journal. 7 August.
** http://bioinfo.mbb.yale.edu/course/private-xxxx/wsj-hpylori.txt
Lisa Belkin, "Splice Einstein and Sammy Glick. Add a Little Magellan,"
New York Times Magazine, 08/23/98, Page 26 (Article on J C Venter)
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
M Gerstein (1999). "E-publishing on the Web: Promises, Pitfalls, and Payoffs
for Bioinformatics," Bioinformatics 15: 429-431.
** http://bioinfo.mbb.yale.edu/e-print/epub-ed-bioinfo
MARLISE SIMONS, "Team of Scientists to Prepare a Rolodex of Life on Earth,"
New York Times, July 27, 1999, F2
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
N Wade, "Who'll Sequence Human Genome First? It's Up to Phred," New
York Times, March 23, 1999, F2
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
NICHOLAS WADE, "Cambridge Lab Keeps Britain Ahead in Genome Stakes,"
New York Times, October 6, 1998
** http://www.nytimes.com/library/national/science/100698sci-sanger.html
NICHOLAS WADE, "Gains Are Reported in Decoding Genome," New York
Times, May 22, 1999, A4
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
PAMELA LICALZI O'CONNELL "Beyond Geography: Mapping Unknown of Cyberspace,"
New York Times, September 30, 1999
** http://www.nytimes.com/library/tech/99/09/circuits/articles/30maps.html
** http://graphics.nytimes.com/library/tech/99/09/circuits/articles/30maps.2.jpg
Pollack, A. (1998). Drug Testers Turn to'Virtual Patients' as Guinea Pigs.
New York Times, Nov. 10
** http://www.nytimes.com/library/tech/98/11/biztech/articles/10health-virtual.html
** http://bioinfo.mbb.yale.edu/course/private-xxx/pollack-nytimes-bioinfo.html
Primer on Molecular Genetics from the DOE
** http://www.bis.med.jhmi.edu/Dan/DOE/intro.html
ROBERT LANGRETH, "CuraGen's Finds 55,000 Variations Of Genes, Auguring
Tailored Drugs," Wall Street Jounal, August 16, 1999
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
Steven Vogel, "Academically Correct Biological Science", American Scientist,
November-December 1998
** http://www.amsci.org/amsci/issues/macroscope/macroscope98-11.html
Tanouye, E. & Langreth, R. (1998). "SmithKline-Glaxo Deal Driven By the
Hunt for Human Genes," Wall Street Journal. February 2.
** http://bioinfo.mbb.yale.edu/course/private-xxxx/wsj-drug-merge.txt
Wade, N. (1997). "Now Playing at a Nearby Lab : 'Revenge of the Fly People,'"
New York Times. 05/20/97, C1.
** http://bioinfo.mbb.yale.edu/course/private-xxxx/nyt-flybase.txt
Wade, N. (1997). "Scientists Map Ulcer Bacterium's Genetic Code," New York
Times. August 7.
** http://bioinfo.mbb.yale.edu/course/private-xxxx/nyt-hpylori.html
Wade, N. (1997). "Thinking Small Paying Off Big In Gene Quest," New York
Times. 02/03/97, A1.
** http://bioinfo.mbb.yale.edu/course/private-xxxx/nyt-pathogens-genomes.txt
WILLIAM K. STEVENS, "Rearranging the Branches on a New Tree of Life,"
August 31, 1999, F1
** http://bioinfo.mbb.yale.edu/mbb452a/reading/mailbox-archive.mbx
The DNA-mouse image is adapted from the GCB-98 homepage. What's wrong with the adaptation?
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