Course Evaluation Form

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Course Evaluation Form

• About The Course
• -Go more slowly ()
• More lectures ()
• Problem Sets, Class Projects () -Software
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• About The Instructor
• -Accessible out of class (Office Hours, Thursdays
  2pm-5pm)
• Course Discussion

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Networks in Biology
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Todays Lecture - The Cell as a Complex
System -Types of Molecular Networks -Some Results
on the Structure of Molecular Networks(Hierarchic
al Structure, Date and Party Hubs)- Disease
Networks - Impacts of Social Networks in Biology
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http//multimedia.mcb.harvard.edu/media.html
Inner Life of the Cell
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Bio-Map
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METABOLISM
Bio-chemical reactions
Citrate Cycle
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Boehring-Mennheim
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Metab-movie
Nodes chemicals (substrates) Links bio-chemical
reactions
Metabolic Network
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Meta-P(k)
Metabolic network
Archaea
Bacteria
Eukaryotes
Organisms from all three domains of life are
scale-free networks!
H. Jeong, B. Tombor, R. Albert, Z.N. Oltvai, and
A.L. Barabasi, Nature, 407 651 (2000)
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Modular vs. Scale-free Topology
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Global network properties
A.-L. B. and Z.N. Oltvai, Nat. Rev. Gen.(2004)
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Hierarchical Networks
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Scaling of the clustering coefficient C(k)
The metabolism forms a hierachical network.
Ravasz, Somera, Mongru, Oltvai, A-L. B, Science
297, 1551 (2002).
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Characterizing the links
Metabolism Flux Balance Analysis
(Palsson) Metabolic flux for each reaction
Edwards, J. S. Palsson, B. O, PNAS 97, 5528
(2000). Edwards, J. S., Ibarra, R. U. Palsson,
B. O. Nat Biotechnol 19, 125 (2001). Ibarra, R.
U., Edwards, J. S. Palsson, B. O. Nature 420,
186 (2002).
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Global flux organization in the E. coli metabolic
network
E. Almaas, B. Kovács, T. Vicsek, Z. N. Oltvai,
A.-L. B. Nature, 2004.
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Bio-Map
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Prot P(k)
Topology of the protein network
Nodes proteins Links
physical interactions (binding)
H. Jeong, S.P. Mason, A.-L. Barabasi, Z.N.
Oltvai, Nature 411, 41-42 (2001)
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Origin of the scale-free topology Gene
Duplication
Proteins with more interactions are more likely
to get a new link ?(k)k (preferential
attachment).
Wagner (2001) Vazquez et al. 2003 Sole et al.
2001 Rzhetsky Gomez (2001) Qian et al.
(2001) Bhan et al. (2002).
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Prot- robustness
Yeast protein network - lethality and topological
position -
Highly connected proteins are more essential
(lethal)...
H. Jeong, S.P. Mason, A.-L. Barabasi, Z.N.
Oltvai, Nature 411, 41-42 (2001)
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Protein Network Dynamics
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Disease NetworksGenotypic Association Between
Diseases
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Disease Network
Goh et al. PNAS 2007
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Mental Diseases
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P53 P(k)
p53 network (mammals)
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Lethal Genes
Disease Genes
Goh et al. PNAS 2007
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Schematic functional organization
Functional Periphery

• Tissue-specific expression
• Low degree
• Low coexpression
• Low lethality

Functional Core

• Expressed in most tissues (housekeeping)
• High degree
• High coexpression
• Lethal

Lack of disease genes
Enrichment of disease genes
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Phenotypic Association Between Diseases
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Disease 1
Disease 2
Affect Same Individuals Significantly more than
Random
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Study Population
13039018 patients 32341348 records
(hospitalizations)
ICD-9 code Disease Name Prevalence
401.9 Unspecified essential hypertension 4163381
414.0 Coronary Atherosclerosis 2679957
428 Congestive Heart Failure 2343516
496 Chronic Airway Obstruction 1878976
427.31 Atrial Fibrillation 1806969
276.5 Volume Depletion Disorder 1533833
276.8 Hypokalemia 1448586
250 Diabetes Mellitus w/o mention of complication 1303342
486 Pneumonia, organism unspecified 1212287
411.1 Intermediate Coronary Syndrome 1137913
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Building a Net
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P1
P2
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Word of Caution
Underestimates overlap of Common Phenotypes
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Overestimate overlap of Rare Phenotypes
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1 Harley JB. Nature Genetics 39(9) 1053 (2007) 2
Scott LJ et al, Science 316 1341 (2007)
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Building a Net
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P1
P2
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Word of Caution
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Positive Associations
Diseases appear are more likely to be correlated
than anti-correlated
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Visualizing the Network
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http//hudine.neu.edu