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Networks: what? what for? how? https://mia.toulouse.inra.fr/NETBIO - PowerPoint PPT Presentation

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Networks: what? what for? how? https://mia.toulouse.inra.fr/NETBIO Julien Chiquet, tienne Delannoy, Marie-Laure Martin-Magniette, Franoise Monger, Guillem Rigaill & Nathalie Villa-Vialaneix Formation LIPM, Toulouse - April 27th 2017

  1. Networks: what? what for? how? https://mia.toulouse.inra.fr/NETBIO Julien Chiquet, Étienne Delannoy, Marie-Laure Martin-Magniette, Françoise Monéger, Guillem Rigaill & Nathalie Villa-Vialaneix Formation LIPM, Toulouse - April 27th 2017 JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 1 / 38

  2. Outline 1 What are networks/graphs? 2 What are networks useful for in biology? Visualization Simple analyses based on network topology More advanced analyses based on network topology Biological interaction models 3 How to build networks? JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 2 / 38

  3. What are networks/graphs? Outline 1 What are networks/graphs? 2 What are networks useful for in biology? Visualization Simple analyses based on network topology More advanced analyses based on network topology Biological interaction models 3 How to build networks? JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 3 / 38

  4. What are networks/graphs? What is a graph? graphe Mathematical object used to model relational data between entities . JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 4 / 38

  5. What are networks/graphs? What is a graph? graphe Mathematical object used to model relational data between entities . The entities are called nodes or vertices nœuds/sommets JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 4 / 38

  6. What are networks/graphs? What is a graph? graphe Mathematical object used to model relational data between entities . A relation between two entities is modeled by an edge arête JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 4 / 38

  7. What are networks/graphs? Graphs are a way to represent biological knowledge Nodes can be... genes, mRNAs, proteins, small RNAs, hormones, metabolites, species, populations, individuals, ... JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 5 / 38

  8. What are networks/graphs? Graphs are a way to represent biological knowledge Nodes can be... genes, mRNAs, proteins, small RNAs, hormones, metabolites, species, populations, individuals, ... Additional information can be attached to these nodes (GO term, protein family, functional motifs, cis-regulatory motifs, ...) JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 5 / 38

  9. What are networks/graphs? Graphs are a way to represent biological knowledge Nodes can be... genes, mRNAs, proteins, small RNAs, hormones, metabolites, species, populations, individuals, ... Additional information can be attached to these nodes (GO term, protein family, functional motifs, cis-regulatory motifs, ...) Relations can be... • molecular regulation (transcriptional regulation, phosphorylation, acetylation, ...) • molecular interaction (protein-protein, protein-siRNA, ...) • enzymatic reactions • genetic interactions (when gene A is mutated, gene B expression is up-regulated) • co-localisation (genomic, sub-cellular, cellular, ...) • co-occurence (when two entities are systematically found together) JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 5 / 38

  10. What are networks/graphs? Example of a molecular network with molecular regulation Nodes are genes Relations are transcriptional regulations [de Leon and Davidson, 2006] JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 6 / 38

  11. What are networks/graphs? Example of a molecular network with physical interactions Nodes are proteins Relations are physical interactions (Y2H) [Vernoux et al., 2011] made from data in [ Arabidopsis Interactome Mapping Consortium, 2011] JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 7 / 38

  12. What are networks/graphs? Example of a metabolic network Nodes are metabolites Relations are enzymatic reactions Image taken from Project “Trypanosome” (F. Bringaud - iMET team, RMSB, Bordeaux) JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 8 / 38

  13. What are networks/graphs? Example of an ecologic network Nodes are species Relations are trophic links [The QUINTESSENCE Consortium, 2016] JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 9 / 38

  14. What are networks/graphs? Example of a molecular network with heterogeneous information Nodes • shapes represent the nature of the entities • colors indicate tissue localisation Edges are direct molecular relations of different types • reliability: bold, dashed, normal lines • inhibition or activation: T-line or arrow [La Rota et al., 2011] JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 10 / 38

  15. What are networks/graphs? What is a model? Model : simplified representation of reality JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 11 / 38

  16. What are networks/graphs? What is a model? Model : simplified representation of reality Biological model simplified representation of a biological process JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 11 / 38

  17. What are networks/graphs? What is a model? Model : simplified representation of reality Biological model simplified representation of a biological process Mathematical model • simplified description of a system using mathematical concepts • in particular, statistical models represent the data-generating process JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 11 / 38

  18. What are networks/graphs? What is a model? Model : simplified representation of reality Biological model simplified representation of a biological process Mathematical model • simplified description of a system using mathematical concepts • in particular, statistical models represent the data-generating process biological interaction model = biological network + mathematical model JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 11 / 38

  19. What are networks useful for in biology? Outline 1 What are networks/graphs? 2 What are networks useful for in biology? Visualization Simple analyses based on network topology More advanced analyses based on network topology Biological interaction models 3 How to build networks? JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 12 / 38

  20. What are networks useful for in biology? Visualization Outline 1 What are networks/graphs? 2 What are networks useful for in biology? Visualization Simple analyses based on network topology More advanced analyses based on network topology Biological interaction models 3 How to build networks? JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 13 / 38

  21. What are networks useful for in biology? Visualization Advantages and drawbacks of network visualization Visualization helps understand the network macro-structure and provides an intuitive understanding of the network. JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 14 / 38

  22. What are networks useful for in biology? Visualization Advantages and drawbacks of network visualization Visualization helps understand the network macro-structure and provides an intuitive understanding of the network. But all network visualizations are subjective and can mislead the person looking at it if not careful. [Shen-Orr et al., 2002] Escherichia coli transcriptional regulation network JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 14 / 38

  23. What are networks useful for in biology? Visualization How to represent networks? Many different algorithms that often produce solutions that are not unique (integrate some randomness) Most popular: force directed placement algorithms • Fruchterman & Reingold [Fruchterman and Reingold, 1991] • Kamada & Kawaï [Kamada and Kawai, 1989] Such algorithms are computationally extensive and hard to use with large networks (more than a few thousands nodes) Another useful layout • attribute circle layout (quick but can be hard to read) JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 15 / 38

  24. What are networks useful for in biology? Visualization Network visualization software (not only for biological networks) • NetworkX (python library, not really interactive but produces javascript) https://networkx.github.io • igraph (python and R libraries, not really interactive) http://igraph.org • Tulip (interactive) http://tulip.labri.fr • Cytoscape (interactive) http://cytoscape.org • Gephi (interactive) gephi.org • ... JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 16 / 38

  25. What are networks useful for in biology? Simple analyses based on network topology Outline 1 What are networks/graphs? 2 What are networks useful for in biology? Visualization Simple analyses based on network topology More advanced analyses based on network topology Biological interaction models 3 How to build networks? JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 17 / 38

  26. What are networks useful for in biology? Simple analyses based on network topology What is network topology? Network topology • study of the network global and local structure • produces numerical summaries ⇒ biological interpretation Credits: S.M.H. Oloomi, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=35247515 (network) and AJC1, CC BY-NC-SA 2.0, https://www.flickr.com/photos/ajc1/4830932578 (biology) JCEDMLM 2 FMGRNV 2 NETBIO (27/04/2017) Networks 18 / 38

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