lecture16斯坦福大学-计算生物学-课程ppt

What are signal pathways?
Protein-Protein Interactions
Signals from the exterior of a cell are mediated to the inside of that cell by protein-protein interactions of the signaling molecules.
Improves our understanding of diseases and provides the basis for new therapeutic approaches.
Major Challenge of Post-genomic biology: Understanding the complex networks that give rise to biological form and function.
Wprod(E) = Πwe Assumption: Edge scores reflect independent confidence values. All contained edges are true biological interactions.
Dijkstra’s algorithm
Computational inference methods are a valuable tool.
Bow-Tie Structure of networks in other contexts
BowTie Builder
multiple source and target proteins - scenario in BowTieBuilder.
Methods to investigate PPIs
Methods such as yeast two-hybrid screening can be used to detect novel protein-protein interactions.
Large scale experimental data on interactions is often modelled by graph theoretic methods.
Applied if source and target sets both contain only one node.
Runtime complexity : O((|E|+|V|)log|V|),
|V| gives the number of proteins
|E| the number of PPIs.
The distance matrix D|S|*|T| is constructed by determining maximal scoring paths between the nodes in S and T.
Finds the most probable pathway – core proteins favored.
Objective Function
For any given pathway, the overall confidence is calculated by multiplying the individual confidence values of the utilized edges:
Two or more proteins bind together often to carry out their biological function.
Important for the majority of biological functions.
PPI - Why do we care?
(Jochen Supper , Lucía Spangenberg , Hannes Planatscher , Andreas Dräger , Adrian Schröder and Andreas Zell)
Many complex signaling pathways yet to be derived.
Multiple source and target proteins – Greedy approach employed.
BowTieBuilder initializes signaling pathway P by including the source S and target T nodes and flagging these nodes as ‘not visited’.
Detecting significant network structures
SERENE KOSARAJU
Signal pathways
What are they? Why do we care about them? What techniques are used to infer these pathways? Pros and cons of these methods
PPIs - crucial to the assembly of protein machinery and the formation of protein signaling cascades.
Great potential to improve the understanding of cellular machinery and to assist in deciphering protein function.
Database Collections
DIP(the database of interacting proteins)
BioGRID and STRING(Search Tool for the
Retrieval of Interacting Genes/Proteins).
Hale Waihona Puke Paper 1-BowTieBuilder:modeling signal transduction pathways