introduction to biological...
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UC Davis, May 18th 2006
Introduction to
Biological Networks
Eivind Almaas Microbial Systems Division
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Biological network examples!
• Gene-regulation • Protein interaction • Metabolism • Cell signaling • Cytoskeleton
• …
• Neural network • Lymphatic node system • Circulatory system
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protein-gene interactions
protein-protein interactions
PROTEOME
GENOME
METABOLISM
Bio-chemical reactions
Citrate Cycle
Cellular networks:!
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Protein Interaction Networks (PIN)
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Protein interactions: Yeast two-hybrid method!
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P. Uetz et. al. Nature 403, 601 (2000) H. Jeong et. al. Nature 411, 41 (2001)
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C. Elegans Drosophila M.
Giot et al, Science 302, 1727 (2003) Li et al, Science 303, 540 (2003)
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PINs are scale-free…
Protein interaction networks are scale-free.
• is this because of preferential attachment?
• another mechanism?
• how can we determine the cause?
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Comparison of proteins through evolution
Eisenberg E, Levanon EY, Phys. Rev. Lett. 2003.
Use Protein-Protein BLAST (Basic Local Alignment Search Tool) -check each yeast protein against whole organism dataset -identify significant matches (if any)
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Preferential Attachment!!
k vs. Δk : linear increase in the # of links
Eisenberg E, Levanon EY, Phys. Rev. Lett. 2003.
S. Cerevisiae PIN: proteins classified into 4 age groups
tkk
tk i
ii
Δ
ΔΠ∝
∂
∂ ~)( For given Δt: Δk ∝ Π(k)
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SF topology from: duplication & diversification
Wagner (2001); Vazquez et al. 2003; Sole et al. 2001; Rzhetsky & Gomez (2001); Qian et al. (2001); Bhan et al. (2002).
Proteins with more interactions are more likely to get a new link: Π(k)~k
preferential attachment
Copying DNA: when mistake (gene duplication) happens
Effect on network:
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How can we dissect the PIN?
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Network motifs!
Definition: A motif is a recurrent network module
Examples:
• Can think of networks as constructed by combining these “basic” building blocks
• Do these motifs have special properties?
R. Milo, S. Shen-Orr, S. Itzkovitz, N. Kashtan, D. Chklovskii, U. Alon “Network Motifs: Simple Building Blocks of Complex Networks”, Science 2002
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PIN motifs and evolution!
S. Wuchty, Z.N. Oltvai,!A.-L.Barabasi, 2003.!
Protein BLAST against: A. thaliana C. elegans D. melanogaster M. musculus H. sapiens
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Network peeling!
Core decomposition method: • the k-core consists of all nodes with degree >= k. • recursively remove nodes with degree < k.
S. Wuchty and E. Almaas, Proteomics 5, 444 (2005).
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S. Wuchty and E. Almaas, Proteomics 5, 444 (2005).
Local vs. global centrality
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Metabolic Networks
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Metabolic Networks:
H. Jeong, B. Tombor, R. Albert, Z.N. Oltvai, and A.L. Barabasi, Nature 407, 651 (2000).
100+ organisms, all domains of life are scale-free
networks.
Archaea Bacteria Eukaryotes
Nodes: chemicals (substrates)!
Links: chem. reaction !