7.89J | Fall 2010 | Graduate

Topics in Computational and Systems Biology

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)

Background reading on probability and statistics (PDF - 5.2MB)

(Courtesy of Woolf, P., C. Burge, A. Keating, and M. Yaffe. Used with permission.)

Readings

WEEK # 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 Function of nucleic acid binding factors

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

Johnson, D. S., et al. “Genome-Wide Mapping of in Vivo Protein-DNA Interactions.” Science 316 (2007): 1497-1502.

Optional

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

Metzker, M. “Sequencing Technologies—the Next Generation.” Nature Reviews Genetics 11 (2010): 31-46.

3 Gene expression & medicine

Paper 1

Hughes, T. R., et al. “Functional Discovery via a Compendium of Expression Profiles.” Cell 102 (2000): 109-126.

Paper 2

Alizadeh, A., et al. “Distinct Types of Diffuse Large B-cell Lymphoma Identified by Gene Expression Profiling.” Nature 403 (2000): 503-11.

Optional

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

(The first chapter gives a basic overview of immunology; chapter 7, p. 91 talks about B lymphocytes; and chapter 17, pp. 249-255, talks about lymphomas.)

4 Evolutionary dynamics

Paper 1

Hegreness, M., N. Shoresh, D. Hartl, and R. Kishony. “An Equivalence Principle for the Incorporation of Favorable Mutations in Asexual Populations.” Science 311 (2006): 1615-17.

Paper 2

Weinrich, D. M., N. F. Delaney, M. A. DePristo, and D. L. Hartl. “Darwinian Evolution Can Follow Only Very Few Mutational Paths to Fitter Proteins.” Science 312 (2006): 111-114.

Optional

Poelwijk, F. J., D. J. Kiviet, D. M. Weinreich, and S. J. Tans. “Empirical Fitness Landscapes Reveal Accessible Evolutionary Paths.” Nature 445 (2007): 383-6.

5 Proofreading in biology

Paper 1

Hopfield, J. J. “Kinetic Proofreading: A New Mechanism for Reducing Errors in Biosynthetic Processes Requiring High Specificity.” PNAS 71 (1974): 4135-4139.

Paper 2

Drummond, A., J. D. Bloom, C. Adami, C. O. Wilke, and F. H. Arnold. “Why Highly Expressed Proteins Evolve Slowly.” PNAS 102 (2005): 14338-43.

Optional

Zaher, H. S., and R. Green. “Fidelity at the Molecular Level: Lessons from Protein Synthesis.” Cell 136 (2009): 746-62.

6 Sequencing & translation

Paper 1

Ingolia, N. T., S. Ghaemmaghami, J. R. S. Newman, and J. S. Weissman. “Genome-wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling.” Science 324 (2009): 218-223.

Optional

Hinnebusch, A. G. “Translational Regulation of Yeast GCN4.” The Journal of Biological Chemistry 272 (1997): 21661-4.

Metzker, M. L. “Sequencing Technologies - the Next Generation.” Nature Reviews Genetics 11 (2010): 31-46.

7 Network motifs in biology

Paper 1

Shen-Orr, S. S., R. Milo, S. Mangan, and U. Alon. “Network Motifs in the Transcriptional Regulation Network of Escherichia Coli.” Nature Genetics 31 (2002): 64-68.

Paper 2

Ma, W., A. Trusina, H. El-Samad, W. A. Lim, and C. Tang. “Defining Network Topologies that Can Achieve Biochemical Adaptation.” Cell 138 (2009): 760-73.

Optional

Alon, U. “Network Motifs: Theory and Experimental Approaches.” Nature Publishing Group 8 (2007): 450-461.

8 Pathway modeling

Paper 1

McAdams, H. H., and L. Shapiro. “Circuit Simulation of Genetic Networks.” Science 269 (1995): 650-6.

Paper 2

Gutenkunst, R. N., J. J. Waterfall, F. P. Casey, K. S. Brown, C. R. Myers, and J. P. Sethna. “Universally Sloppy Parameter Sensitivities in Systems Biology Models.” PLoS Computational Biology 3, e189 (2007): 1871-8.

9 Variability between cells

Paper 1

Suel, G. M., R. P. Kulkarni, J. Dworkin, J. Garcia-Ojalvo, and M. B. Elowitz. “Tunability and Noise Dependence in Differentiation.” Science 315 (2007): 1716-19.

Paper 2

Spencer, S. L., S. Gaudet, J. G. Albeck, J. M. Burke, and P. K. Sorger. “Non-Genetic Origins of Cell-to-Cell Variability in TRAIL-Induced Apoptosis.” Nature 459 (2009): 428-33.

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

Tabor, J., H. M. Salis, Z. Booth Simpson, A. A. Chevalier, A. Levskaya, E. M. Marcotte, C. A. Voigt, and A. D. Ellington. “A Synthetic Edge Detection Program.” Cell 137 (2009): 1272-81.

Optional

Purnick, E. M., and R. Weiss. “The Second Wave of Synthetic Biology: From Modules to Systems.” Nature Reviews Molecular Cell Biology 10 (2009): 410-22.

11 Metagenomics

Paper 1

Tringe, S. G., C. von Mering, A. Kobayashi, A. A. Salamov, K. Chen, H. W. Chang, M. Podar, J. M. Short, E. J. Mathur, J. C. Detter, P. Bork, P. Hugenholtz, and E. M. Rubin. “Comparative Metagenomics of Microbial Communities.” Science 308 (2005): 554-7.

Paper 2

Andersson, A. F., and J. F. Banfield. “Virus Population Dynamics and Acquired Virus Resistance in Natural Microbial Communities.” Science 320 (2008): 1047-50.

Optional

Barrangou, R., C. Fremaux, H. Deveau, M. Richards, P. Boyaval, S. Moineau, D. A. Romero, and P. Horvath. “CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes.” Science 315 (2007): 1709-12.

12 Signal transduction

Paper 1

Bhattacharrya, R. P., A. Remenyi, M. C. Good, C. J. Bashor, A. M. Falick, and W. A. Lim. “The Ste5 Scaffold Allosterically Modulates Signaling Output of the Yeast Mating Pathway.” Science 311 (2005): 822-6.

Paper 2

Malleshaiah, M. K., V. Shahrezaei, P. S. Swain, and S. W. Michnick. “The Scaffold Protein Ste5 Directly Controls a Switch-Like Mating Decision in Yeast.” Nature 465 (2010): 101-105.