ECE 6960
Modeling and Analysis of Biological Networks

Course description

With the sequencing of the human genome and the genomes of other organisms, we now have a list of the parts that make up these biological systems. Through the use of microarrays and other new technologies, we are also beginning to get data on the functions of individual genes and how genes interact with each other to perform complex biological functions. In the functional genomic era, we will begin to take this vast amount of data, and try to reason about how these genetic systems work. To accomplish this, a systems biology perspective will need to be taken in which models and new, efficient analysis techniques will need to be developed to reason about these genetic networks. Engineers have had vast experience in modeling and analyzing electronic circuits and systems. It is not difficult to develop a view of a genetic network as a electronic circuit. Such a view was taken by McAdams and Shapiro in their seminal paper in Science in 1995 with encouraging results. Therefore, as in the sequencing of the human genome, collaborations between engineers and systems biologists will be essential to the success of functional genomics. In this new course, we will be reading papers on recent approaches to the modeling and analysis of biological networks. The goal of this course is to be useful to both engineers and computer scientists who wish to learn about biological problems to which their models can be applied and to biologists and bioengineers who would like to learn about models and analysis techniques that can be used to study their systems of interest.

Instructor

Instructor: Dr. Chris Myers.

Prerequisites

Students must have either taken a course(s) in genetics, cell biology, molecular biology, or biochemistry (examples include Biol 2020, 2030, 3510, 5011, 5110, 5255, 5265), or you must have taken a course(s) in formal modeling (examples include ECE 5750/6750, CS 5100, CS 5350, CS 6110).

Textbooks

A Genetic Switch by Mark Ptashne published by Cell and BSP.

Course Requirements

The grading for this course will be broken into two parts: course participation and final project. The grade for course participation will be dependent upon attendence, participation in discussion of required readings, leading of discussions for optional readings, homework assignments, and possibly quizes. In the final project, students must select a modeling methodology and a sample biological system and attempt to model and analyze this system using this methodology.

Meeting Times

Class	3:30pm - 4:30pm	Tuesdays	Dr. Myers	MEB 1208
Class	3:20pm - 4:50pm	Thursdays	Dr. Myers	MEB 1208
Office Hours	2pm - 3pm	TTh	Dr. Myers	MEB 4112

Tentative Syllabus

All information here is tentative.

Week 1: Introduction
- Download the Fall 2003 Guidelines Here
- Read the following science primer
- Lecture 1
- Please read these week 1 reports
Week 2: Phage Lambda
- Read Chapters 1 through 3 of A Genetic Switch (required).
- Read Chapter 4 of A Genetic Switch (optional).
- Lecture 2
Week 3: Systems Biology
- Read de Jong (required).
- Read Baldi and Hatfield, DNA Microarrays and Gene Expression, Chapter 8 Systems Biology, handed out in class (required).
- Read D'haeseleer (optional).
- Read Hasty (optional).
- Read Arkin (optional).
- Read Arkin 2 (optional).
- Read Endy (optional).
- Read Fitch (optional).
- Read Smolen et. al, Modeling transcriptional control in gene networks: methods, recent results, and future directions, 2000 B. Math. Biol., 62:247-292, find in libraryec (optional).
- Read Bower and Bolouri, eds. 2001. Computational Modeling fo Genetic and Biochemical Networks, MIT Press, Cambridge, MA (optional).
- Lecture 3
- Please read these week2 reports
Weeks 4 and 5: Chemical Master Equation
- Readings:
  - Gillespie, Markov Processes, Section 5.3.B, handed out in class (required).
  - Excerpt from Gillespie's 1977 paper (required).
  - Ackers (required).
  - Arkin (required).
  - Srivastav (required).
  - Goss (optional).
  - McAdams (optional).
  - Gibson I (optional).
  - Gibson II (optional).
  - Morton I (optional).
  - Morton II (optional).
  - Kastner (optional).
  - Shea/Ackers 1985 paper (optional).
- Tools:
- Lecture 4
- Lecture 5
- Please read these week 3 reports
- Please read these week 4 reports
Weeks 6 and 7: Differential Equations
- Readings:
  - Tyson and Othmer (pages 1-13 required, rest optional).
  - Gouze (required).
  - DeJong et. al. (required).
  - Turing (required).
- Tools:
  - DBsolve (paper)
  - Gepasi (paper)
  - Jarnac (paper)
  - Genomic Object Net (paper)
  - E-Cell (paper)
- Models:
- Lecture 6
- Lecture 7
- Please read these week 5 reports
Weeks 8 and 9: Circuit Networks
- Readings:
  - McAdams and Shapiro (required).
  - Arkin (required).
  - Thieffry and Thomas, to be handed out in class (required).
  - Myers et. al, to be emailed to class (required).
  - Kauffman, see DeJong's paper for references (optional).
  - Thomas, R. 1991, Regulatory networks seen as asynchronous automata: A logical description. J. Theor. Biol. 153, 1-23 (optional).
  - Huang (optional).
  - Wuensche (optional).
  - Szallasi (optional).
  - Regev (optional).
  - Noda (optional).
  - Maki (optional).
  - Liang (optional).
  - Ideker (optional).
  - Akutsu (optional).
  - Mendoza (optional).
  - Shmulevich (optional).
- Lecture 8
- Lecture 9 (gzip'ed postscript)
- Please read these week 8 reports
Week 10: Bayesian Networks
- Readings:
  - Friedman (required).
  - Ong 1 (optional).
  - Ong 2 (optional).
  - Imoto (optional).
  - Murphy (optional).
  - Pe'er (optional).
  - Tamada (optional).
  - Perrin (optional).
- Lecture 10 (gzip'ed postscript)
Week 11: Miscellaneous Learning Methods
- Readings:
  - Zupan (required).
  - Danks (optional).
  - Mjolsness (optional).
  - Bay (optional).
  - Chrisman (optional).
  - Reiser (optional).
  - Dhaeseleer (optional).
  - Read both Vance and Torralba (optional).
- Lecture 11
Week 12: Directed Graphs and Pathway Databases
- Readings and links:
  - BioCyc Karp (required).
  - aMAZE (optional).
  - KEGG Kaneshia (optional).
  - GeNet Samsonova (optional).
  - GeneNet Ananko (optional).
  - CSNDB Takai-Igarashi (optional).
  - RegulonDB Salgado (optional).
  - MIPS Mewes (optional).
- Lecture 12 (gzip'ed postscript)
Week 13: Flux Balance Analysis
- Readings:
  - Covert (required).
  - Mahadevan (optional).
  - Ramakrishna (optional).
  - Edwards (optional).
  - Schilling (optional).
  - Segre (optional).
- Links:
  - Palsson's Genetic Circuits Research Group
- Lecture 13 (gzip'ed postscript)
Week 14: Engineered Gene Circuits
- Readings:
  - Hasty I (required).
  - Hasty II (optional).
- Lecture 14
Week 15: Project Presentations
- Literature surveys
- Project proposals

ECE 6960 Modeling and Analysis of Biological Networks