Problems and Perspectives in Computational Molecular Biology

Cornell University
Fall 2001

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(1) Using graphical models and genomic expression data to statistically validate models of genetic regulatory networks. abstract (2) Supervised harvesting of expression trees. abstract

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Previous presentations (+ presentation files)

Time and Place

1 credit, S/U only.
Prerequisites:� Permission of instructor.
The seminar is required from students of the Computational Molecular Biology Program.

Instructors

Links

• Introduction
• Books on Bioinformatics and Computational Biology
• Journal webpages
• Recommended background reading
• Suggested papers
  • Sequence Analysis
  • Structure Analysis
  • Micro Array Analysis
  • Co-evolution and Protein-protein Interactions

• Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W. & Lipman, D.J. (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucl. Acids Res. 25, 3389-3402. abstract
• Kann M, Qian B, Goldstein RA. (2000). Optimization of a new score function for the detection of remote homologs. Proteins 41, 498-503. abstract
• Andreas Prlic, Francisco S. Domingues, and Manfred J. Sippl. (2000). Structure-derived substitution matrices for alignment of distantly related sequences. Protein Eng. 13, 545-550. abstract
• Rost B. (1999). Twilight zone of protein sequence alignments. Protein Eng. 12, 85-94. abstract
• Hein J, Wiuf C, Knudsen B, Moller MB, Wibling G. (2000). Statistical alignment: computational properties, homology testing and goodness-of-fit. J Mol Biol. 302, 265-79. abstract
• Yu L, White JV, Smith TF. (1998). A homology identification method that combines protein sequence and structure information. Protein Sci 7, 2499-510. abstract
• Inge Jonassen, Ingvar Eidhammer, Svenn H. Grindhaug, William R. Taylor. Searching the Protein Structure Databank with Weak Sequence Patterns and Structural Constraints. (2000). J. Mol. Biol. 599-619. abstract
• Gouzy, J., Corpet, F. & Kahn, D. (1999). Whole genome protein domain analysis using a new method for domain clustering. Comput Chem 23, 333-340. abstract

Multiple alignments, Profiles

• Lee, C., Grasso, C. & Sharlow, M. (2001). Multiple Sequence Alignment Using Partial Order Graphs. Bioinformatics. abstract, paper, figures
• Notredame C, Higgins DG, Heringa J. (2000). T-Coffee: A Novel Method for Fast and Accurate Multiple Sequence Alignment. J Mol Biol. 302, 205-17. abstract
• Notredame, C., Holm, L. & Higgins, D. G. (1998). COFFEE: an objective function for multiple sequence alignments. Bioinformatics 14, 407-422. abstract
• Taylor WR. (1998). Dynamic sequence databank searching with templates and multiple alignment. J Mol Biol. 280, 375-406. abstract

Hidden markov models

• Krogh, A., Brown, M., Mian, I. S., Sjolander, K. & Haussler, D. (1994). Hidden Markov models in computational biology: Application to protein modeling. J. Mol. Biol. 235, 1501-1531. abstract
• Karplus, K., Barrett, C. & Hughey, R. (1998). Hidden markov models for detecting remote protein homologies. Bioinformatics 14:10, 846-856. abstract

Alternative representations, sequence-function relationships

• Casari, G., Sander, C. & Valencia, A. (1995). A method to predict functional residues in proteins. Nat. Struct. Biol. 2, 171-178. abstract
• Solis AD, Rackovsky S. (2000). Optimized representations and maximal information in proteins. Proteins 38, 149-164. abstract
• Hanke, J., Beckmann, G., Bork, P. & Reich, J. G. (1996). Self-organizing hierarchic networks for pattern recognition in protein sequence. Protein Sci. 5, 72-82. abstract
• Agrafiotis, D. K. (1997). A new method for analyzing protein sequence relationships based on Sammon maps. Protein Sci. 6, 287-293. abstract
• Hannenhalli, S. S. & Russell, R. B. (2000). Analysis and prediction of functional sub-types from protein sequence alignments. J Mol Biol. 303, 61-76. abstract

• Holm, L. & Sander, C. (1997). Dali/FSSP classification of three-dimensional protein folds. Nucl. Acids Res. 25, 231-234. abstract
• Shindyalov, I. N. \& Bourne, P. E. (1998). Protein structure alignment by incremental combinatorial extension (CE) of the optimal path. Protein Eng. 11, 739-747. abstract
• Levitt, M & Gerstein, M. (1998). A Unified Statistical Framework for Sequence Comparison and Structure Comparison. Proc. Natl. Acad. Sci. USA 95, 5913-5920. abstract
• Nussinov R, Wolfson HJ. (1991). Efficient detection of three-dimensional structural motifs in biological macromolecules by computer vision techniques. Proc Natl Acad Sci USA. 88, 10495-10499. abstract
• Godzik A, Skolnick J. (1994). Flexible algorithm for direct multiple alignment of protein structures and sequences. Comput Appl Biosci. 10, 587-596.abstract
• Hadley, C. & Jones, D. T. (1999). A systematic comparison of protein structure classifications: SCOP, CATH and FSSP. Structure Fold Des. 7, 1099-1112. abstract
• Jongsun Jung and Byungkook Lee. (2000). Protein structure alignment using environmental profiles. Protein Eng. 13, 535-543. abstract

Automatic detection of domains

• Jones, S., Stewart, M., Michie, A., Swindells, M. B., Orengo, C. & Thornton, J. M. (1998). Domain assignment for protein structures using a consensus approach: characterization and analysis. Protein Sci. 7, 233-242. abstract
• Taylor, W. R. (1999). Protein structural domain identification. Protein Eng. 12, 203-216. abstract
• Xu, Y., Xu, D. & Gabow, H. N. (2000). Protein domain decomposition using a graph-theoretic approach. Bioinformatics 16, 1091-1104. abstract
• Holm, L. & Sander, C. (1994). Parser for protein folding units. Proteins 19, 256-268. abstract
• Kael F. Fischer, Susan Marqusee. (2000). A Rapid Test for Identification of Autonomous Folding Units in Proteins. J Mol Biol. 302, 701-12. abstract
• Jonassen I, Eidhammer I, Taylor WR. (1999). Discovery of local packing motifs in protein structures. Proteins 34, 206-19. abstract
• Sowdhamini R, Blundell TL. (1995). An automatic method involving cluster analysis of secondary structures for the identification of domains in proteins. Protein Sci 4, 506-520. abstract
• Turcotte M, Muggleton SH, Sternberg MJ. (2001). Automated discovery of structural signatures of protein fold and function. J Mol Biol 306, 591-605. abstract

Fold recognition, Threading, Structure prediction

• Lemer, C. M., Rooman, M. J. & Wodak, S. J. (1995). Protein structure prediction by threading methods: evaluation of current techniques. Proteins 23, 337-355. abstract
• Mirny, L. A. & Shakhnovich, E. I. (1998). Protein structure prediction by threading. Why it works and why it does not. J. Mol. Biol. 283, 507-526. abstract
• Rost, B., Schneider, R. & Sander, C. (1997). Protein fold recognition by prediction-based threading. J. Mol. Biol. 270, 471-480. abstract
• Bryant, S. H. (1996). Evaluation of threading specificity and accuracy. Proteins 26, 172-185. abstract
• Jones, D. T. (1999). GenTHREADER: an efficient and reliable protein fold recognition method for genomic sequences. J. Mol. Biol. 287, 797-815. abstract
• Karplus, K., Barrett, C., Cline, M., Diekhans, M., Grate, L. & Hughey, R. (1999). Predicting protein structure using only sequence information. Proteins 37, 121-125. abstract
• Jaroszewski, L., Rychlewski, L., Zhang, B. & Godzik, A. (1998). Fold prediction by a hierarchy of sequence, threading, and modeling methods. (1998). Protein Sci 7, 1431-1440. abstract
• Olmea, O., Rost, B. & Valencia, A. (1999). Effective use of sequence correlation and conservation in fold recognition. J Mol Biol. 293, 1221-1239. abstract
• Schmidler, S. C., Liu, J. S. & Brutlag, D. L. (2000). Bayesian segmentation of protein secondary structure. J Comput Biol. 7, 233-248. abstract
• Bienkowska JR, Yu L, Zarakhovich S, Rogers RG Jr, Smith TF. (2000). Protein fold recognition by total alignment probability. Proteins 40, 451-62. abstract
• Rykunov DS, Lobanov MY, Finkelstein AV. (2000). Search for the most stable folds of protein chains: III. Improvement in fold recognition by averaging over homologous sequences and 3D structures. Proteins. 40, 494-501. abstract
• Kunin V, Chan B, Sitbon E, Lithwick G, Pietrokovski S. (2001). Consistency analysis of similarity between multiple alignments: prediction of protein function and fold structure from analysis of local sequence motifs.J Mol Biol 307, 939-949. abstract

Structural/evolutionary profiles

• Bystroff, C. \& Baker, D. (1998). Prediction of local structure in proteins using a library of sequence-structure motifs. J. Mol. Biol. 281, 565-577. abstract
• Kasuya, A. & Thornton, J. M. (1999). Three-dimensional structure analysis of PROSITE patterns. J. Mol. Biol. 286, 1673-1691.abstract
• Kelley, L. A., MacCallum, R. M. & Sternberg, M. J. (2000). Enhanced genome annotation using structural profiles in the program 3D-PSSM. J. Mol. Biol. 299, 499-520. abstract
• Pellegrini M, Marcotte EM, Thompson MJ, Eisenberg D, Yeates TO. (1999). Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc Natl Acad Sci USA. 96, 4285-8. abstract
• Marcotte EM, Pellegrini M, Ng HL, Rice DW, Yeates TO, Eisenberg D. (1999). Detecting protein function and protein-protein interactions from genome sequences. Science 285, 751-3. abstract
• Marcotte EM, Pellegrini M, Thompson MJ, Yeates TO, Eisenberg D. (1999).A combined algorithm for genome-wide prediction of protein function. Nature 402, 83-6. abstract
• Marcotte EM, Xenarios I, van Der Bliek AM, Eisenberg D. (2000). Localizing proteins in the cell from their phylogenetic profiles. Proc Natl Acad Sci USA 97, 12115-20. abstract

Overview

Introduction to Microarray Technology

• A Concise Guide to cDNA Microarray Analysis. Hegde P, Qi R, Abernathy R, Gay C, Dharap S, Gaspard R, Earle-Hughes J, Snesrud E, Lee NH, and Quackenbush J Biotechniques (2000), 29(3):548-562. abstract
• Expression profiling using cDNA microarrays. Duggan DJ, Bittner M, Chen Y, Meltzer P, Trent JM Science 1999 Jan 1;283(5398):83-7. abstract, paper

Normalization

• Development of a prostate cDNA microarray and statistical gene expression analysis package. Carlisle AJ, Prabhu VV, Elkahloun A, Hudson J, Trent JM, Linehan WM, Williams ED, Emmert-Buck MR, Liotta LA, Munson PJ, Krizman DB Mol Carcinog 2000 May;28(1):12-22. abstract, paper
• Normalization for cDNA Microarray Data. Y. H. Yang, S. Dudoit, P. Luu and T. P. Speed. UC Berkeley Tech Report December 2000. paper

Imaging and normalization

• Ratio-based decisions and the quantitative analysis of cDNA micro-array images. Chen Y, Dougherty E, Bittner M. Journal of Biomedical Optics 2:364 (1997). paper
• Comparison of methods for image analysis on cDNA microarray data. Y.H. Yang, M. J. Buckley, S. Dudoit and T.P.Speed UC Berkeley Tech Report November 2000. paper

Replication

• Importance of replication in microarray gene expression studies: Statistical methods and evidence from repetitive cDNA hybridizations. Lee ML, Kuo FC, Whitmore GA, Sklar J. Proc Natl Acad Sci USA 2000 Aug 29;97(18):9834-9839. abstract, paper
• Development of a prostate cDNA microarray and statistical gene expression analysis package. Carlisle AJ, Prabhu VV, Elkahloun A, Hudson J, Trent JM, Linehan WM, Williams ED, Emmert-Buck MR, Liotta LA, Munson PJ, Krizman DB Mol Carcinog 2000 May;28(1):12-22. abstract, paper
• Design and Analysis of Gene Expression Microarray Experiments. Kerr K, Churchill, G. paper1, paper2

Clustering

• Cluster analysis and display of genome-wide expression patterns. M.B. Eisen, P.T. Spellman, P.O. Brown, David Botstein PNAS Vol. 95, Issue 25, 14863-14868, December 8, 1998 abstract, paper
• The transcriptional program in the response of human fibroblasts to serum. Iyer VR, Eisen MB, Ross DT, Schuler G, Moore T, Lee JCF, Trent JM, Staudt LM, Hudson J Jr, Boguski MS, Lashkari D, Shalon D, Botstein D, Brown PO Science 1999 Jan 1;283(5398):83-7. abstract, paper
• Gene shaving' as a method for identifying distinct sets of genes with similar expression patterns. T Hastie, R Tibshirani, M B Eisen, A Alizadeh, R Levy, L Staudt, W C Chan, D Botstein, P Brown Genome Biology 1(2):research0003.1-0003.21. abstract, paper

Singular value decomposition, pca's, classification

• Singular value decomposition for genome-wide expression data processing and modeling. Alter, O., P. Brown, and D. Botstein PNAS 97 (18), 10101-10106, 2000. abstract, paper
• Flexible discriminant analysis by optimal scoring. Hastie, T., Tibshirani, R. & Buja, A. Journal of the American Statistical Association (1994) 89: 1255-1270.
• Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Staudt LM, et al. Nature 2000 Feb 3;403(6769):503-11. abstract, paper

Large-scale analysis

• Derisi, J. L., Iyer, V. R. & Brown, P. O. (1997). Exploring the metabolic and genetic control of gene expression on a genomic scale. Science 278, 680-686. abstract
• Hastie T, Tibshirani R, Botstein D, Brown P. (2001). Supervised harvesting of expression trees. Genome Biol. 2. abstract
• Hartemink AJ, Gifford DK, Jaakkola TS, Young RA. (2001). Using graphical models and genomic expression data to statistically validate models of genetic regulatory networks. Pac Symp Biocomput. 422-33. abstract

• Thorne, J. L., N. Goldman and D. T. Jones. (1998). Assessing the impact of secondary structure and solvent accessibility on protein evolution. Genetics 149, 445-458. abstract
• David D. Pollock, William R. Taylor, Nick Goldman. (1999). Coevolving Protein Residues: Maximum Likelihood Identification and Relationship to Structure. Journal of Molecular Biology 287, 187-198. abstract
• Pazos, F., Helmer-Citterich, M., Ausiello, G. \& Valencia, A. (1997). Correlated mutations contain information about protein-protein interaction. J. Mol. Biol. 271, 511-523. abstract
• Goh CS, Bogan AA, Joachimiak M, Walther D, Cohen FE. (2000). Co-evolution of Proteins with their Interaction Partners. J Mol Biol. 299, 283-93. abstract
• Enright AJ, Iliopoulos I, Kyrpides NC, Ouzounis CA. (1999). Protein interaction maps for complete genomes based on gene fusion events. Nature 402, 86-90. abstract
• Gallet X, Charloteaux B, Thomas A, Brasseur R. (2000). A fast method to predict protein interaction sites from sequences. J Mol Biol. 302, 917-26. abstract
• Schwikowski B, Uetz P, Fields S. (2000). A network of protein-protein interactions in yeast. Nat Biotechnol. 18, 1257-61. abstract
• Park J, Lappe M, Teichmann SA. (2001). Mapping protein family interactions: intramolecular and intermolecular protein family interaction repertoires in the PDB and yeast. J Mol Biol. 307, 929-38. abstract