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.