This is an archived course. A more recent version may be available at ocw.mit.edu.

Advanced Search

    Readings

    The assigned readings are from primary literature. You are responsible for understanding the essential ideas, results and methods used in Papers 1 and 2 for each session, which may require reading the optional supplementary information or background reference material.

    Tips on Reading Papers and Leading a Discussion about a Paper (PDF)

    SES # TOPICS READINGS
    1

    Course organization/introduction

    Genomics and protein function

    Paper 1

    Marcotte, E. M., M. Pellegrini, H. Ng, D. W. Rice, T. O. Yeates, and D. Eisenberg. "Detecting Protein Function and Protein-Protein Interactions from Genome Sequences." Science 285 (1999): 751-53.

    Paper 2

    Pellegrini, M., E. M. Marcotte, M. J. Thompson, D. Eisenberg, and T. O. Yeates. "Assigning Protein Functions by Comparative Genome Analysis: Protein Phylogenetic Profiles." Proc Natl Acad Sci 96 (1999): 4285-88.
    2 Genomics and RNA function

    Paper 1

    Lim, L. P., N. C. Lau, P. Garett-Engele, A. Grimson, J. M. Schelter, J. Castle, D. P. Bartel, P. S. Linsley, and J. M. Johnson. "Microarray Analysis Shows that Some microRNAs Downregulate Large Numbers of Target mRNAs." Nature 433 (2005): 769-73.

    Paper 2

    Ule, J., G. Stefani, A. Mele, M. Ruggiu, X. Wang, B. Taneri, T. Gaasterland, B. J. Blencowe, and R. B. Darnell. "An RNA Map Predicting Nova-dependent Splicing Regulation." Nature 444 (2006): 580-6.

    Optional

    Du, T., and P. D. Zamore. "microPrimer: The Biogenesis and Function of microRNA." Development 132 (2005): 4645-52.

    Matlin, A. J., F. Clark, and C. W. Smith. "Understanding Alternative Splicing: Towards a Cellular Code." Nat Rev Mol Cell Biol 6 (2005): 386-98.
    3 Signal transduction

    Paper 1

    MacDonald, M. L., J. Lamerdin, S. Owens, B. H. Keon, G. K. Bilter, Z. Shang, Z. Huang, H. Yu, J. Dias, T. Minami, S. W. Michnick, and J. K. Westwick. "Identifying Off-target Effects and Hidden Phenotypes of Drugs in Human Cells." Nat Chem Biol 2 (2006): 329-37.

    Paper 2

    Irish, J. M., R. Hovland, P. O. Krutzik, O. D. Perez, O. Bruserud, B. T. Gjertsen, and G. P. Nolan. "Single Cell Profiling of Potentiated Phospho-Protein Networks in Cancer Cells." Cell 118 (2004): 217-28.

    Optional

    Cram, L. S. "Flow Cytometry, An Overview." Methods in Cell Science 24 (2002): 1-9.
    4 Genetics of gene regulation

    Paper 1

    Brem, R. B., G. Yvert, R. Clinton, and L. Kruglyak. "Genetic Dissection of Transcriptional Regulation in Budding Yeast." Science 296 (2002): 752-5.

    Paper 2

    Johnson, D. S., Q. Zhou, K. Yagi, N. Satoh, W. Wong, and A. Sidow. "de Novo Discovery of a Tissue-specific Gene Regulatory Module in a Chordate." Genome Research 15 (2005): 1315-24.

    Optional

    Zhou, Q., and W. H. Wong. "CisModule: de Novo Discovery of Cis-regulatory Modules by Hierarchical Mixture Modeling." PNAS 101 (2004): 12114-9.
    5 Statistical approaches

    Paper 1

    Storey, J. D., and R. Tibshirani. "Statistical Significance for Genomewide Studies." PNAS 100 (2003): 9440-5.

    Paper 2

    Bailey, T. L., and C. Elkan. "Unsupervised Learning of Multiple Motifs in Biopolymers Using Expectation Maximization." Machine Learning 21 (1995): 51-80.

    Optional

    Woolf, Peter, Christopher Burge, Amy Keating, and Michael Yaffe. "Statistics and Probability Primer for Computational Biologists." MIT. BE.490/7.91 Spring 2004. (PDF - 6.5 MB) (PDF - 6.9 MB)
    6 Gene expression and medicine

    Paper 1

    Hughes, T. R., M. J. Marton, A. R. Jones, C. J. Roberts, R. Stoughton, C. D. Armour, and H. A. Bennett, et al. "Functional Discovery via a Compendium of Expression Profiles." Cell 102 (2000): 109-26.

    Paper 2

    Alizadeh, A. A., M. B. Eisen, R. E. Davis, C. Ma, I. S. Lossos, A. Rosenwald, and J. C. Boldrick, et al. "Distinct Types of Diffuse Large B-cell Lymphoma Identified by Gene Expression Profiling." Nature 403 (2000): 503-11.

    Optional

    Amazon logo Benjamini, Eli, Richard Coico, and Geoffrey Sunshine. Immunology: A Short Course. 5th ed. Hoboken, NJ: Wiley, 2003. Chapters 1, 7, and 17. ISBN: 9780471226895.
    7 Kinetics in biology

    Paper 1

    Hopfield, J. J. "Kinetic Proofreading: A New Mechanism for Reducing Errors in Biosynthetic Processes Requiring High Specificity." Proc Nat Acad Sci 71 (1974): 4135-9.

    Paper 2

    Rodnina, M. V., and W. Wintermeyer. "Ribosome Fidelity: tRNA Discrimination, Proofreading and Induced Fit." Trends in Biochemical Sciences 26 (2001): 124-30.
    8 Protein structure and function

    Paper 1

    Wiedemann, R., P. Boisguerin, R. Leben, D. Leitner, G. Krause, K. Mielling, R. Volkmer-Engert, and H. Oschkinat. "Quantification of PDZ Domain Specificity, Prediction of Ligand Affinity and Rational Design of Super-binding Peptides." J Mol Biol 343 (2004): 703-18.

    Paper 2

    Stiffler, M. A., J. R. Chen, V. P. Grantcharova, Y. Lei, D. Fuchs, J. E. Allen, L. A. Zaslavskaia, and G. MacBeath. "PDZ Domain Binding Selectivity is Optimized Across the Mouse Proteome." Science 317 (2007): 364-9.

    Optional

    Stiffler, M. A., V. P. Grantcharova, M. Sevecka, and G. MacBeath. "Uncovering Quantitative Protein Interaction Networks for Mouse PDZ Domains Using Protein Microarrays." J Am Chem Soc 128 (2006): 5913-22.
    9 Devices and detection

    Paper 1

    McBeath, R., D. M. Pirone, C. M. Nelson, K. Bhadriraju, and C. S. Chen. "Cell Shape, Cytoskeletal Tension, and rhoA Regulate Stem Cell Lineage Commitment." Dev Cell 6 (2004): 483-95.

    Paper 2

    Warren, L., D. Bryder, I. L. Weissman, and S. R. Quake. "Transcription Factor Profiling in Individual Hematopoietic Progenitors by Digital RT-PCR." PNAS 103 (2006): 17801-12.

    Optional

    Thorsen, T., S. J. Maerkl, and S. R. Quake. "Microfluidic Large-scale Integration." Science 298 (2002): 580-4.

    Weissman, I. L. "Stem Cells: Units of Development, Units of Regeneration, and Units in Evolution." Cell 100 (2000): 157-68.

    Stem Cells: Scientific Progress and Future Research Directions. Department of Health and Human Services. June 2001.

    Xia, Y., and G. M. Whitesides. "Soft Lithography." Angewandte Chemie - International Edition in English 27 (1998): 550-75.
    10 Synthetic biology

    Paper 1

    Elowitz, M. B., and S. Leibler. "A Synthetic Oscillatory Network of Transcriptional Regulators." Nature 403 (2000): 335-8.

    Paper 2

    Win, M. N., and C. D. Smolke. "A Modular and Extensible RNA-based Gene-regulatory Platform for Engineering Cellular Function." PNAS 104 (2007): 14283-14288.

    Optional

    Barkai, N., and S. Leibler. "Circadian Clocks Limited by Noise." Nature 403 (2000): 267-8.

    Mandal, M., and R. R. Breaker. "Gene Regulation by Riboswitches." Nat Rev Mol Cell Biol 5 (2004): 451-63.
    11 Randomness in biology

    Paper 1

    Arkin, A., J. Ross, and H. H. McAdams. "Stochastic Kinetic Analysis of Developmental Pathway Bifurcation in Phage Lambda-infected Escherichia Coli Cells." Genetics 149 (1998): 1633-48.

    Paper 2

    Newman, J. R. S., S. Ghaemmaghami, J. Ihmels, D. K. Breslow, M. Noble, J. L. DeRisi, and J. S. Weissman. "Single-cell Proteomic Analysis of S. Cerevisiae Reveals the Architecture of Biological Noise." Nature 441 (2006): 840-6.

    Optional

    The Origin and Consequences of Noise in Biochemical Systems (PDF) (Courtesy of Alexander van Oudenaarden and Mukund Thattai. Used with permission.)

    Raser, J. M., and E. K. O'Shea. "Noise in Gene Expression: Origins, Consequences, and Control." Science 309 (2005): 2010-2013.
    12 Gene networks

    Paper 1

    Shen-Orr, S. S., R. Milo, S. Mangan, and U Alon. "Network Motifs in the Transcriptional Regulation Network of Escherichia Coli." Nature Genet 31 (2002): 64-8.

    Paper 2

    Johnson, D. S., A. Mortazavi, R. M. Myers, and B. Wold. "Genome-wide Mapping of in vivo Protein-DNA Interactions." Science 316 (2007): 1497-1502.

    Optional

    Davidson, E. H., D. R. McClay, and L. Hood. "Regulatory Gene Networks and the Properties of Developmental Process." PNAS 100 (2003): 1475-80.

    Pennisi, E. "A New Window on How Genomes Work." Science 316 (2007): 1120-1.

    Schoenherr, C. J., and D. J. Anderson. "The Neuron-restrictive Silencer Factor (NRSF): A Coordinate Repressor of Multiple Neuron-specific Genes." Science 267 (1995): 1360-3.
    13 Computational and systems biology

    Paper 1

    Kitano, H. "Systems Biology: A Brief Overview." Science 295 (2002): 1662-4.

    Paper 2

    Kirschner, M. W. "The Meaning of Systems Biology." Cell 121 (2005): 503-4.

    Paper 3

    Liu, E. T. "Systems Biology, Integrative Biology, Predictive Biology." Cell 121 (2005): 505-6.

    Paper 4

    Bork, P. "Towards Cellular Systems in 4d." Cell 121 (2005): 507-9.

    Paper 5

    Aderem, A. "Systems Biology: Its Practice and Challenges." Cell 121 (2005): 511-513.

    Paper 6

    Kremling, A., and J. Saez-Rodriguez. "Systems Biology - An Engineering Perspective." J of Biotechnology 129 (2007): 329-351.