CS/BIOL 8802
Networks in Systems Biology
Mondays 12-2 EST L1125
Instructors:
Constantine Dovrolis, KACB 3346: dovrolis@cc.gatech.edu
Todd Streelman, EST 2244: todd.streelman@biology.gatech.edu
Course URL:
http://www.cc.gatech.edu/~dovrolis/BioNets
This course development effort was supported by the NSF award 0831848 ("Towards a Theory of Network Evolution")
Understanding complexity is a central goal of science. Complex networks govern connection speed on the Internet, air traffic and highway control patterns, the flow of energy and species composition in ecological communities, and the relationships of proteins in human hearts and brains. To get a handle on complexity, engineers have begun to collaborate with biologists to study how evolution has "engineered" complex biological designs (i.e., organisms). The upshot of this research includes a catalogue of design principles for complex systems (e.g., diversity, robustness, modularity, evolvability) and unexpected consequences for the relationship between form and function. It has been suggested that complexity is an emergent property of these design principles and that highly complex systems are qualitatively different from simple ones. Are there in fact general rules that biological systems (genes, cells, communities) follow? If so, what are they? These are the sorts of questions we will attempt to answer in this course.
First two weeks:
(classes on August 18 and August 25)
Slides from Network Science overview on August 25
The instructors will cover important concepts in systems biology and network theory. These lectures will be designed to familiarize everyone with the basics. It is important that students read as much of the following literature as possible.
Literature for first two weeks:
Biological Networks: The Tinkerer as an Engineer
U. Alon
Science 26 September 2003: Vol. 301. no. 5641, pp. 1866 - 1867.
Reverse Engineering of Biological Complexity
Marie E. Csete, John C. Doyle
Science 295 (5560): 1664-1669
Network biology: understanding the cell's functional organization
Barabasi AL, Oltvai ZN.
Nat Rev Genet. 2004 Feb;5(2):101-13.
Network thinking in ecology and evolution
Stephen R. Proulx, Daniel E.L. Promislow and Patrick C. Phillips
Trends in Ecology & Evolution, Volume 20, Issue 6, June 2005, Pages 345-353
Exploring Complex Networks
Steven Strogatz
NATURE | VOL 410 | 8 MARCH 2001
Statistical mechanics of complex networks
Reka Albert and Albert-Laszlo Barabasi
Rev. Mod. Phys. 74, 47 - 97 (2002)
Complex networks: Structure and dynamics
S. Boccalettia, V. Latorab, Y. Morenod, M. Chavezf and D.-U. Hwanga
Physics Reports, Volume 424, Issues 4-5, February 2006, Pages 175-308
The Structure and Function of Complex Networks
M. E. J. Newman
SIREV Volume 45 Issue 2, Pages 167-256.
Revisiting scale-free networks
Evelyn Fox Keller
BioEssays, Volume 27 Issue 10, Pages 1060 - 1068.
Next 10 classes
(Sep 8,15,22,29, Oct 6,20,27,Nov 3,10,17. Note: Sep 1 & Oct 13 are holidays)
Students will form 10 teams of 2-4 students by the end of the second class. These teams will work together in two tasks: First, to prepare and present in class one of the syllabus topics, and second, to define and execute a research project. Each student team should be as interdisciplinary as possible. Ideally, each team should include at least one student with Biology background and one student with CS (or Engineering) background.
Each of the 10 teams will present a syllabus topic. We will adopt the following process:
SECTION-I: NETWORK TYPOLOGY
September 8: Networks of Gene Expression
Network motifs in the transcriptional regulation network of Escherichia coli.
Shai S. Shen-Orr, Ron Milo, Shmoolik Mangan, Uri Alon
Nature Genetics 31, 64 - 68 (2002).
A Gene-Coexpression Network for Global Discovery of Conserved Genetic Modules.
Joshua M. Stuart, Eran Segal, Daphne Koller, Stuart K. Kim
Science 10 October 2003: Vol. 302. no. 5643, pp. 249 - 255
Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells.
L . Boyer et al.
Cell, Volume 122, Issue 6, Pages 947 - 956.
Transcriptional Regulatory Networks in Saccharomyces cerevisiae
Tong Ihn Lee, et al.
Science 25 October 2002: Vol. 298. no. 5594, pp. 799 - 804.
Global similarity and local divergence in human and mouse gene co-expression networks.
Tsaparas P, Marino-Ramirez L, Bodenreider O, Koonin EV, Jordan IK.
BMC Evol Biol 2006, 6:70.
A gene expression map for Caenorhabditis elegans.
Kim SK, Lund J, Kiraly M, Duke K, Jiang M, Stuart J, Eizinger A, Wylie BN, Davidson GS
Science 2001, 293:2087-2092.
Natural selection governs local, but not global, evolutionary gene coexpression networks in Caenorahbditis elegans.
Jordan, I.K., L.S. Katz, D.R. Denver and J.T. Streelman. 2008.
Manuscript.
September 15: Protein Interaction Networks
Lethality and centrality in protein networks
H. Jeong, S. P. Mason, A.-L. Barabasi, Z. N. Oltvai
Nature 411, 41 - 42 (2001)
The protein-protein interaction map of Helicobacter pylori
Jean-Christophe Rain et al.
Nature 409, 211 - 215 (2001)
Global protein function prediction from protein-protein interaction networks
Alexei Vazquez, Alessandro Flammini, Amos Maritan, Alessandro Vespignani
Nature Biotechnology 21, 697 - 700 (2003)
Modeling of Protein Interaction Networks
Alexei Vzqueza, Alessandro Flamminia, Amos Maritana,b, Alessandro Vespignani
Complexus 2003;1:38-44 (DOI: 10.1159/000067642)
Specificity and Stability in Topology of Protein Networks
Sergei Maslov, Kim Sneppen
Science 3 May 2002: Vol. 296. no. 5569, pp. 910 - 913
Functional and topological characterization of protein interaction networks
S-H Yook, Z-N Oltvai, A-L Barabasi
PROTEOMICS - Clinical Applications, Vol 4 Issue 4, Pages 928 - 942.
A model of large-scale proteome evolution
Ricard V. Sole, Romualdo Pastor-Satorras, Eric Smith, Thomas B. Kepler
Advances in Complex Systems 5, 43 (2002).
Herpesviral protein networks and their interaction with the human proteome.
Peter Uetz et al.
Science 311: 239 - 242.
September 22: Metabolic networks
The large-scale organization of metabolic networks
H. Jeong, B. Tombor, R. Albert, Z. N. Oltvai, A.-L. Barabasi
Nature 407, 651 - 654 (2000).
Global organization of metabolic fluxes in the bacterium Escherichia coli
E. Almaas, B. Kovcs, T. Vicsek, Z. N. Oltvai, A.-L. Barabasi
Nature 427, 839 - 843 (2004).
The Small World inside Large Metabolic Networks
A. Wagner and D. A. Fell
Proc Biological Sciences, Vol. 268, No. 1478 (Sep. 7, 2001), pp. 1803-1810.
The connectivity structure, giant strong component and centrality of metabolic networks
Hong-Wu Ma and An-Ping Zeng
Bioinformatics Vol. 19 no. 11 2003 Pages 1423-1430.
The metabolic world of Escherichia coli is NOT small
Arita, Masanori
Proceedings of the National Academy of Science, vol. 101, Issue 6, p.1543-1547.
September 29: Developmental Networks
Systematic mapping of genetic interactions in C. elegans identifies common modifiers of diverse signaling pathways
Lehner B et al.
Nature Genetics 38:896-903, 2006.
A genomic regulatory network for development
Davidson EH et al.
Science 295:1669-1678, 2002.
Gene regulatory networks and the evolution of animal body plans
Davidson EH and DH Erwin
Science 311:796-800, 2006.
The segment polarity network is a robust developmental module
von Dassow G, Meir E, Munro EM and GM Odell
406:188-192, 2000.
Global regulatory logic for specification of an embryonic cell lineage
Oliveri et al.
PNAS 105: 5955-5962, 2008.
October 6: Ecological Networks
Interaction strength combinations and the overfishing of a marine food web
Bascompte J, Melian CJ, Sala E
PNAS 102:5443-5447, 2005.
Foraging adaptation and the relationship between food-web complexity and stability
Kondoh M
Science 299:1388-1391, 2003
Ecological networks and their fragility
Montoya JM, Pimm SL and RV Sole
Nature 442:259-264, 2006
Two degrees of separation in complex food webs
R. J. Williams, E. L. Berlowdagger, J. A. Dunne, A-L. Barabasi, N.D. Martinez
PNAS | October 1, 2002 | vol. 99 | no. 20 | 12913-12916
Food-web structure and network theory: The role of connectance and size
Jennifer A. Dunne, Richard J. Williams, and Neo D. Martinez
PNAS | October 1, 2002 | vol. 99 | no. 20 | 12917-12922
Universal scaling relations in food webs
Garlaschelli D, Caldarelli G, Pietronero L.
Nature. 2003 May 8;423(6936):165-8.
October 20: Networks from other disciplines
Superfamilies of Evolved and Designed Networks
Ron Milo, Shalev Itzkovitz, Nadav Kashtan, et al.
Science 5 March 2004, Vol. 303. no. 5663, pp. 1538 - 1542.
Organization, development and function of complex brain networks
Olaf Spornsa, Dante R. Chialvob, Marcus Kaiserc and Claus C. Hilgetagc
Trends in Cognitive Sciences, Vol 8, Issue 9, September 2004, Pages 418-425.
Scaling phenomena in the Internet: Critically examining criticality
W. Willinger, R.Govindan, S.Jamin , V.Paxson, S. Shenker
PNAS | February 19, 2002 | vol. 99 | Suppl. 1 | 2573-2580.
Graph structure in the Web
Andrei Broder, Ravi Kumar, et al.
Computer Networks, Vol. 33, Issues 1-6, June 2000, Pages 309-320.
The web of human sexual contacts
F. Liljeros, C. R. Edling, L.A. Nunes Amaral, H. E. Stanley & Y. Berg
Nature 411, 907-908 (21 June 2001).
SECTION-II: NETWORK PROPERTIES
October 27: Robustness
Biological robustness
Hiroaki Kitano
Nature Reviews Genetics, 2004
Robustness in bacterial chemotaxis
Alon, U | Surette, MG | Barkai, N | Leibler, S*
Nature. Vol. 397, no. 6715, pp. 168-171. 14 Jan 1999.
Robustness of the BMP morphogen gradient in Drosophila embryonic patterning.
Eldar A, Dorfman R, Weiss D, Ashe H, Shilo BZ, Barkai N.
Nature. 2002 Sep 19;419(6904):261-2.
The yeast cell-cycle network is robustly designed
Fangting Li, Tao Long, Ying Lu, Qi Ouyang, and Chao Tang
PNAS | April 6, 2004 | vol. 101 | no. 14 | 4781-4786.
Genetic complexity, robustness and genetic interactions in digital organisms
Lenski RE et al.
Nature 400:661-664, 1999.
November 3: Modularity
From molecular to modular cell biology
Hartwell, Leland H.; Hopfield, John J.; Leibler, Stanislas; Murray, Andrew W.
Nature, Volume 402, Issue 6761, pp. (1999).
Hierarchical Organization of Modularity in Metabolic Networks
E. Ravasz, A. L. Somera, D. A. Mongru, Z. N. Oltvai, A.-L. Barabasi
Science 30 August 2002, Vol. 297. no. 5586, pp. 1551 - 1555.
Protein complexes and functional modules in molecular networks
Victor Spirin, and Leonid A. Mirny
PNAS | October 14, 2003 | vol. 100 | no. 21 | 12123-12128.
Modular organization of cellular networks
Rives AW, Galitski T.
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1128-33.
November 10: Evolvability
Evolvability is a selectable trait
David J. Earl, and Michael W. Deem
PNAS | August 10, 2004 | vol. 101 | no. 32 | 11531-11536.
The evolutionary origin of complex features
Richard E. Lenski, Charles Ofria, Robert T. Pennock and Christoph Adami
Nature 423, 139-144 (8 May 2003).
Balancing Robustness and Evolvability
Richard E. Lenski, Jeffrey E. Barrick, Charles Ofria
PLoS Biol 4(12): e428
Evolvability and hierarchy in rewired bacterial gene networks
Mark Isalan et al.
Nature 452, 840-845 (17 April 2008).
November 17: Dynamical properties
Just-in-time transcription program in metabolic pathways
A.Zaslaver et al.
Nature Genetics 36, 486 - 491 (2004)
Large extinctions in an evolutionary model: The role of innovation and keystone species
S.Jain and S.Krishna
Proc Natl Acad Sci USA. 2002 February 19; 99(4): 2055 - 2060.
The role of computation in complex regulatory networks
P.Fernandez and R.V.Sole
Book chapter in Power Laws, Scale-Free Networks and Genome Biology, Springer 2006.
Function constrains network architecture and dynamics: A case study on the yeast cell cycle Boolean network
K-Y.Lau, S.Ganguli and C.Tang
Physical Review E 75, 051907 (2007)
Random Boolean network models and the yeast transcriptional network
S.Kauffman, C.Peterson, B.Samuelsson and C.Troein
Proc Natl Acad Sci USA, 2003 December 1, 100(25), 14796-14799
The regulatory network of E.coli metabolism as a Boolean dynamical system exhibits both homeostasis and flexibility of response
A.Samal and S.Jain
BMC Systems Biology, 2(21), 2008
SECTION-III: Student research projects
During the semester, each student team will carry out a research project. During the last two classes (Nov 24 and Dec 1), groups will report on their findings/conclusions. Each presentation will last approximately 25-30 minutes. The presentations will probably take place in the early evening hours (5-8pm?).
Group projects might entail (i) reproduction/simulation of some computational results from a paper discussed during class, (ii) synthesis of the literature in a very specific area and a written "research agenda" for that area, (iii) discovery and "proof of concept" of new ways to use existing biological datasets, and/or (iv) conceptual or theoretical design of new experiments with existing datasets.
Project milestones:
PREREQUISITES:
Because this is a highly cross-disciplinary course, it is unlikely that any student will have all the required background. It is thus imperative that students from different disciplines work together in mixed reading and discussion groups. It is also important that students have a strong research aptitude, not being afraid to study well beyond the "comfort zone" of their academic background.
GRADING:
Topic presentation: 35%
Research project: 35%
Class participation and lecture reviews: 30%
In each of the previous three categories, you will receive one of the following grades: Outstanding (125%), Excellent (100%), Very Good (75%), Good (50%) or Poor (0%). To get an A in the course, you will need to have a weighted average of more than 80%.