### Reading Assignments for Fall 2009

#### Reading Assignment 16 (due Wednesday December 9)

Read "A Molecular Model for Intercellular Synchronization in the Mammalian Circadian Clock" T-L To, MA Henson, ED Herzog, and FJ Doyle III,*Biophys. J.*, 2007 (which has been uploaded on Moodle). Answer these questions.

#### "Reading" Assignment 15 (due Mon December 7)

- In class, we determined i and j for which dyi/dpj has the smallest value (at the last time step). What are the i and j for which dyi/dpj has the largest value? Identify the state and parameter by name as well as by index.
- What is vsP (i.e. which process does it describe)? Which state is the most affected by a perturbation to vsP?
- What is k1? Which state is the most affected by a perturbation to k1?

#### Reading Assignment 14 (due Friday December 4)

Read "Modeling the mammalian circadian clock: Sensitivity analysis and multiplicity of oscillatory mechanisms" J-C Leloup and A Goldbeter,*J. theor. Biol.*, 2004 (which has been uploaded on Moodle). Answer these questions.

#### Reading Assignment 13 (due Wednesday Dec 2)

Using the code from Monday's lecture, re-run the sensitivity analysis for times of 0:0.1:25, 0:0.1:100, and 0:0.1:400. How are the results different? How are they the same? Why does the total runtime affect the result? To which parameter is the system most sensitive? Does this make sense? To which parameter is the system the least sensitive? Does this make sense?Turn in a short write-up. No need to turn in code.

#### Reading Assignment 12 (due Monday November 23)

Read "Robustness properties of circadian clock architectures" J Stelling, ED Gilles, and FJ Doyle III,*PNAS*, 2004 (which has been uploaded on Moodle). Answer these questions.

#### "Reading" Assignment 11 (due Friday November 13)

Run the genetic algorithm (with the default settings) multiple times and plot the results, i.e. run the code from the last cell of`run_lec24.m`with the lines

`
disp(['Lowest cost from this run is ', num2str(cost)]);
cost_fcn(params,true);
`

`GA`. Describe your results. How different are they from run to run? How are the amplitudes of the states different? How are the costs different? (Hint: to make it easier to perform this analysis, it may be helpful to add code to the cost function's plotting section to limit the display to two days and to include a legend).

To add the new plotting code to the cost function, cut and paste the following two lines just below the `plot` call in `gol95CostFunction`:

`
xlim([0 48]);
legend({'M','P0','P1','P2','PN'});
`

What can you conclude about the model from your results (i.e. what properties of the model are parameter-dependent and which ones are structure/equation-dependent?)? What can you conclude about the cost function (is there anything missing from the cost function?)?

#### Reading Assignment 10 (due Wednesday November 11)

Read the Wikipedia articles on genetic algorithms and Holland's Schema Theorem. Answer these questions.#### Reading Assignment 9 (due Monday November 9)

Read "Parameter Estimation in Biochemical Pathways: A Comparison of Global Optimization Methods" CG Moles, P Mendes, and JR Banga,*Genome Research*, 2003 (which has been uploaded on Moodle). Answer these questions.

#### Reading Assignment 8 (due Friday November 6)

Read "Modelling genetic networks with noisy and varied experimental data: the circadian clock in Arabidopsis thaliana" JCW Locke, AJ Millar, and MS Turner,*Journal of Theoretical Biology*, 2005 (which has been uploaded on Moodle). Answer these questions.

#### "Reading" Assignment 7 (due Wednesday November 4)

- Download Stephanie's initial implementation of the steepest descent method started in class today.
- Run the method to minimize the vdpCircadianError starting from an initial condition of mu=10, MAX_ITER=100, near_zero=1e-3, fd_pcnt=0.01, and step_pcnt=0.01. What is the result? Does it make sense?
- Rerun the method, but this time use step_pcnt=0.1. What is the result? Does it make sense? Use the output (from the "disp" statement in the optimizer) to guide you.

#### "Reading" Assignment 6 (due Monday November 2)

- Using the code from lecture today, write additional code to generate a figure that plots the period of a van der Pol oscillator against its mu value. In other words, choose a range of mu values to cover. Simulate the van der Pol oscillator for each value and compute its period. Then, plot them with mu on the x-axis and period on the y-axis.
- Ask me a question about some aspect of the code that you do not fully understand or explain a feature of the code that you think is particularly neat.
- I wish the code would run faster. Why?

#### Reading Assignment 5 (due Friday October 9)

Read "Toward a detailed computational model for the mammalian circadian clock" by J-C Leloup and A Goldbeter,*Proceedings of the National Academy of Science (PNAS)*, 2003 (which has been uploaded on Moodle). Answer these questions.

#### Reading Assignment 4 (due Wednesday October 7)

Read "Modeling Feedback Loops of the Mammalian Circadian Oscillator" by S Becker-Weimann, J Wolf, H Herzel, and A Kramer,*Biophysical Journal*, 2004 (which has been uploaded on Moodle). Answer these questions.

#### Reading Assignment 3 (due Wednesday September 23)

Read Chapter 2 sections 2.1 through 2.3.4 (inclusive) and section 2.4 (but not 2.4.1). Answer these questions.#### Reading Assignment 2 (due Monday September 14)

Read "Modeling transcriptional regulatory networks" by H Bolouri and EH Davidson,*BioEsssays*, 2002 (which has been uploaded on Moodle). Answer these questions.

#### Reading Assignment 1 (due Friday September 11)

The reading assignment involves a list of questions to answer about the articles and chapter section listed below. I suggest you read the questions before embarking on your article-reading adventure. The questions indicate what I consider to be the most relevant points made in the articles. When answering the questions, you may be as high- or low-tech as you wish, but please turn in your reponses via email or in person by the beginning of class on Friday.- The Universal Features of Cells on Earth -- a section in Ch. 1 of
*Molecular Biology of the Cell*, ed. B Alberts, 4/e, 2002 (note: there is a new edition of the book, but this is the one freely available on the web) - Systems Biology: A Brief Overview by H Kitano,
*Science*, 2002. (PDF on Moodle) - Computational systems biology by H Kitano,
*Nature*, 2002. (PDF on Moodle) - Can a biologist fix a radio: or what I learned while studying apoptosis by Yuri Lazebnik,
*Cancer Cell*, 2002. (PDF on Moodle)

Further Reading

- More detailed descriptions of transcription and translation can be found in the Alberts book.
- Apoptosis is also known as "programmed cell death". If you are interested learning more about apoptosis see this section in the Alberts book