| Part 1: Using DNA Sequence to Explain Mechanism |
| 1 |
Course Introduction |
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| 2 |
Pairwise Alignment |
 Durbin, Richard, Sean R. Eddy, Anders Krogh, and Graeme Mitchison. Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids. Cambridge, UK: Cambridge University Press, 1999. ISBN: 9780521629713. |
| 3 |
Finding Regulatory Sequences in DNA: Motif Discovery |
Hughes, J. D., P. W. Estep, S. Tavazoie, and G. M. Church. "Computational identification of cis-regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae." Journal of Molecular Biology 296, no. 5 (March 10, 2000): 1205-14. |
| 4 |
Finding Regulatory Sequences in DNA: Motif Discovery (cont.) |
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| Part 2: Observing the Mechanism of Transcriptional Regulation |
| 5 |
Microarray Technology |
Microarray Core Facility - Laboratory Services
Pan, Qun, et al. "Revealing Global Regulatory Features of Mammalian Alternative Splicing Using a Quantitative Microarray Platform." Molecular Cell 16, no. 6 (December 22, 2004): 929-941.
Zhang, Wen, et al. "The Functional Landscape of Mouse Gene Expression." Journal of Biology 3, no. 5 (2004): 21.
Lee, Tong Ihn, et al. "Transcriptional Regulatory Networks in Saccharomyces cerevisiae." Science 298, no. 5594 (October 25, 2002): 799-804. |
| 6 |
Expression Arrays, Normalization, and Error Models |
Yang, Yee Hwa, et al. "Normalization for cDNA Microarray Data: A Robust Composite Method for Addressing Single and Multiple Slide Systematic Variation." Nucleic Acid Research 30, no. 4 (2002).
Newton, M. A., et al. "On Differential Variability of Expression Ratios: Improving Statistical Inference about Gene Expression Changes from Microarray Data." Journal of Computational Biology 8, no. 1 (2001): 37-52. |
| 7 |
Expression Profiles, Clustering, and Latent Processes |
Eisen, M. B., et al. "Cluster Analysis and Display of Genome-wide Expression Patterns." PNAS 95, no. 25 (December 8, 1998): 14863-8.
Liao, J. C., et al. "Network Component Analysis: Reconstruction of Regulatory Signals in Biological Systems." PNAS 100, no. 26 (December 23, 2003): 15522-7.
Dueck, and Frey. "Probabilistic Sparse Matrix Factorization." Technical Report, University of Toronto, 2004. (PDF) |
| 8 |
Computational Functional Genomics |
Introduction to SVD |
| 9 |
Stem Cells and Transcriptional Regulation |
Dor, Y., J. Brown, O. Martinez, and D. A. Melton. "Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation." Nature 429, no. 6987 (2004): 41-6. |
| 10 |
Part One: An Example of Clustering Expression Data
Part Two: Computational Functional Genomics (cont.) |
Alizadeh, A. A., et al. "Distinct Types of Diffuse Large B-cell Lymphoma Identified by Gene Expression Profiling." Nature 403, no. 6769 (February 3, 2000): 503-11.
Ramalho-Santos, M., et al. ""Stemness": Transcriptional Profiling of Embryonic and Adult Stem Cells." Science 298, no. 5593 (October 18, 2002): 597-600.
Ivanova, N. B., et al. "A Stem Cell Molecular Signature." Science 298, 5593 (October 18, 2002): 601-4.
Fortunel, et al. "Comment on "'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature"." Science 302, no. 5644 (2003): 393.
Evsikov, et al. "Comment on "'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature"." Science 302, no. 5644 (2003): 393.
Ivanova, N. B., et al. "Response to comments on "'Stemness': transcriptional profiling of embryonic and adult stem cells" and "a stem cell molecular signature"." Science 302 no. 5644 (2003): 393.
Vogel, G. "'Stemness' Genes Still Elusive." Science 302, no. 5644 (October 17, 2003): 371. |
| 11 |
Project Group Meetings |
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| 12 |
Project Group Initial Presentations |
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| 13 |
Computational Discovery of Regulatory Networks |
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| 14 |
RNA Silencing |
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| Part 3: Building Predictive Network Models of Transcriptional Regulation |
| 15 |
Computational Functional Genomics (cont.) |
Heckerman, David. "A Tutorial on Learning with Bayesian Networks." Microsoft Technical Report MSR-TR-95-06, 1996.
Hartemink, Alex. "Principled Computational Methods for the Validation and Discovery of Genetic Regulatory Networks." MIT Ph.D. Thesis (2001). (PDF - 9.0 MB) |
| 16 |
Human Regulatory Networks |
Cooper, G. F., and E. Herskovits. "A Bayesian Method for the Induction of Probabilistic Networks from Data." KSL-91-02 (Knowledge Systems Laboratory, Stanford University), November 1993. |
| 17 |
Protein Networks |
Li, S., et al. "A Map of the Interactome Network of the Metazoan C. elegans." Science 303, no. 5657 (January 23, 2004): 540-3.
Giot, L., et al. "A Protein Interaction Map of Drosophila melanogaster." Science 302, no. 5651 (December 5, 2003): 1727-36.
Gavin, A. C., et al. "Functional organization of the yeast proteome by systematic analysis of protein complexes." Nature 415, no. 6868 (2002): 141-7.
Ho, Y., et al. "Systematic Identification of Protein Complexes in Sacchormyces cerevisiae by Mass Spectrometry." Nature 415, no. 6868 (January 10, 2002): 180-3.
Tong, A. H., et al. "Global mapping of the yeast genetic interaction network." Science 303, no. 5659 (2004): 808-13.
Phizicky, E., P. I. Bastiaens, H. Zhu, M. Snyder, and S. Fields. "Protein Analysis on a Proteomic Scale." Nature 422, no. 6928 (March 13, 2003): 208-15.
von Mering, C., et al. "Comparative Assessment of Large-scale Data Sets of Protein-protein Interactions." Nature 417, no. 6887 (May 23, 2002): 399-403. |
| 18 |
Causal Models |
Heckerman, David. "A Tutorial on Learning with Bayesian Networks." Microsoft Technical Report MSR-TR-95-06, 1996.
Yeang, C. H., et al. "Physical Network Models." Journal of Computational Biology 11, no. 2-3 (2004): 243-263. |
| 19 |
Causal Bayesian Networks, Active Learning |
Segal, E., et al. "Module Networks: Identifying Regulatory Modules and their Condition Specific Regulators from Gene Expression Data." Nature Genetics 34, no. 2 (2003): 166-76.
McCuine S., C. Workman, T. Jaakkola, T. Ideker, C-H. Yeang, H. Mak. "Validation and refinement of gene-regulatory pathways on a network of physical interactions." Genome Biology 6, no. 7 (2005): R62.
Oliver, S. G., et al. "Functional genomic hypothesis generation and experimentation by a robot scientist." Nature 427 (2004): 247 - 252. |
| 20 |
From Biological Data to Biological Insight |
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| 21 |
Modeling Transcriptional Regulation |
Segal, E., et al. "Module Networks: Identifying Regulatory Modules and their Condition Specific Regulators from Gene Expression Data." Nature Genetics 34, no. 2 (2003): 166-76.
Said, M., A. Oppenheim, and D. Lauffenburger. "Modeling Cellular Signal Processing Using Interacting Markov Chains." In Proceedings of the International Conference on Acoustics, Speech, Signal Processing, 2003. |
| 22 |
Dynamics |
Arkin, Ross, and McAdams. "Stochastic Kinetic Analysis of Developmental Pathway Bifurcation in Phage Lambda-Infected Escherichia coli Cells." Genetics 149 (August 1998): 1633-1648.
Gilman, Arkin. "Genetic 'Code': Representations and Dynamic Models of Genetic Components and Networks." Annu. Rev. Genomics Hum. Genet. 3 (2002): 341-69.
McAdams, Arkin. "It's A Noisy Business!: Gene Regulation at the Nanomolar Scale." Trends in Genetics 15 (1999): 65-69.
———. "Simulation of Genetic Circuits." Annu. Rev. Biophys. Biomol. Struct. 27 (1998): 199-224.
Gillespie. "Exact Stochastic Simulation of Coupled Chemical Reactions." Journal of Physical Chemistry 81, no. 25 (1977): 2340-2361. |