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Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Signaling pathways analysis Modeling KEGG Subpathways Normalization Method Marta R. Hidalgo Computing the signal Functional annotation Further analysis Exercises Systems Genomics Lab, CIPF September 30th, GDA 2015 Outline Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Signaling Pathways Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Signaling pathways Marta R. Hidalgo Signaling pathways Databases Pathway methods Signal transduction Cellular mechanism which allows the cell to respond to different stimuli by means of biochemical reactions Signaling pathways Cascades of protein activations and inhibitions Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Databases Signaling pathways analysis Marta R. Hidalgo I KEGG Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Databases Signaling pathways analysis Marta R. Hidalgo I KEGG I Reactome Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Databases Signaling pathways analysis Marta R. Hidalgo I KEGG I Reactome I Others: WikiPathways,... Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Pathway methods Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess I SPIA Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Pathway methods Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess I SPIA I PARADIGM Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Pathway methods Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess I SPIA I PARADIGM I Pathifier Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Pathway methods Signaling pathways analysis Marta R. Hidalgo Signaling pathways Score per pathway Databases Pathway methods Preprocess I SPIA I PARADIGM I Pathifier Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Pathway methods Signaling pathways analysis Marta R. Hidalgo Signaling pathways Score per pathway Databases Pathway methods Preprocess I SPIA I PARADIGM I Pathifier Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises I SubSPIA Pathway methods Signaling pathways analysis Marta R. Hidalgo Signaling pathways Score per pathway Databases Pathway methods Preprocess I SPIA I PARADIGM I Pathifier Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises I I SubSPIA Pathiways Pathway methods Signaling pathways analysis Marta R. Hidalgo Signaling pathways Score per pathway Databases Pathway methods Preprocess I SPIA I PARADIGM I Pathifier Modeling KEGG Subpathways Normalization Method Score per subpathway I I SubSPIA Pathiways Computing the signal Functional annotation Further analysis Exercises Pathway methods Signaling pathways analysis Marta R. Hidalgo Signaling pathways Score per pathway Databases Pathway methods Preprocess I SPIA I PARADIGM I Pathifier Modeling KEGG Subpathways Normalization Method Score per subpathway I I SubSPIA Pathiways I I I Probabilistic approach Only Microarray data Only processed KEGG pathways Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Method Computing the signal Functional annotation Further analysis Exercises Method Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization I Independent from gene expression technology Method Computing the signal Functional annotation Further analysis Exercises Method Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization I I Independent from gene expression technology Independent from pathway database Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Method Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization I I Independent from gene expression technology Independent from pathway database I SIF + attributes file Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Method Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization I I Independent from gene expression technology Independent from pathway database I I SIF + attributes file Module to process KEGG pathways Method Computing the signal Functional annotation Further analysis Exercises Workflow Signaling pathways analysis Marta R. Hidalgo Signaling pathways Input I SIF file + attributes I Expression matrix Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Workflow Marta R. Hidalgo Signaling pathways Input Output I SIF file + attributes I Pathways matrix I Expression matrix I Functions matrix Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Preprocess Method Computing the signal Functional annotation Further analysis Exercises Modeling KEGG pathways Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Modeling KEGG pathways Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Modeling KEGG pathways Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Modeling KEGG pathways Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Only activations/inhibitions allowed Method Computing the signal Functional annotation Further analysis Exercises Modeling KEGG pathways Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Only activations/inhibitions allowed I Relation edges: Simplified to activation/inhibition Method Computing the signal Functional annotation Further analysis Exercises Modeling KEGG pathways Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Only activations/inhibitions allowed I Relation edges: Simplified to activation/inhibition I Association edges: The net is modeled to include the information Method Computing the signal Functional annotation Further analysis Exercises Modeling KEGG pathways Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Plain nodes Complex nodes Include one node, many genes Include different nodes Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Modeling KEGG pathways Marta R. Hidalgo Signaling pathways Databases Pathway methods Plain nodes Complex nodes Include one node, many genes Include different nodes I Binding/association Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Modeling KEGG pathways Marta R. Hidalgo Signaling pathways Databases Pathway methods Plain nodes Complex nodes Include one node, many genes Include different nodes I Binding/association I Group Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Modeling the graph Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Effector subpathways Signaling pathways analysis Marta R. Hidalgo Effector proteins Last genes of the network, responsibles for performing the corresponding molecular function Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Effector subpathways Signaling pathways analysis Marta R. Hidalgo Effector subpathway Subgraph of the pathway including any node in a path ending in an effector protein Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Effector subpathways Signaling pathways analysis Marta R. Hidalgo Effector subpathway Subgraph of the pathway including any node in a path ending in an effector protein Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Decomposed subpathways Signaling pathways analysis Marta R. Hidalgo Single subpathway Subgraph of the pathway including only one input and one output node Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Decomposed subpathways Signaling pathways analysis Marta R. Hidalgo Single subpathway Subgraph of the pathway including only one input and one output node Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Decomposed subpathways Signaling pathways analysis Marta R. Hidalgo Single subpathway Subgraph of the pathway including only one input and one output node Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Decomposed subpathways Signaling pathways analysis Marta R. Hidalgo Single subpathway Subgraph of the pathway including only one input and one output node Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Decomposed subpathways Signaling pathways analysis Marta R. Hidalgo Single subpathway Subgraph of the pathway including only one input and one output node Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Decomposed subpathways Signaling pathways analysis Marta R. Hidalgo Single subpathway Subgraph of the pathway including only one input and one output node Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Normalization Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Normalization Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess The expression matrix is normalized to [0,1] Modeling KEGG Subpathways Normalization Method Options Computing the signal Functional annotation Further analysis Exercises I By quantiles: a quantiles normalization is performed I By gene: the normalization is performed by rows I Percentil: normalize taking the percentil Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Method Computing the signal Functional annotation Further analysis Exercises Method Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Method Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Node values Signaling pathways analysis Marta R. Hidalgo Signaling pathways I Plain nodes: Percentil 90 of the genes included I Complex nodes: Compute value of each node, take percentil 10 Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Signal value through a node Marta R. Hidalgo For node n Sn = vn · (1 − Signaling pathways Y (1 − si )) · si ∈A Y Databases Pathway methods (1 − sj ) sj ∈I Preprocess Modeling KEGG Subpathways Normalization Method Sn : Signal value through n A: Activation edges vn : Node value I : Inhibition edges Computing the signal Functional annotation Further analysis Exercises Computing the signal Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Computing the signal Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Computing the signal Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signal values Signaling pathways analysis Marta R. Hidalgo Signaling pathways I Input signal 1 in any input node Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signal values Signaling pathways analysis Marta R. Hidalgo Signaling pathways I Input signal 1 in any input node I Compute the signal through each node iteratively Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signal values Signaling pathways analysis Marta R. Hidalgo Signaling pathways I Input signal 1 in any input node I Compute the signal through each node iteratively I Loops can be processed Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signal values Signaling pathways analysis Marta R. Hidalgo Signaling pathways I Input signal 1 in any input node I Compute the signal through each node iteratively I Loops can be processed I Subpathway signal: last node signal Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Functional annotation Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Functional annotation Signaling pathways analysis Marta R. Hidalgo Signaling pathways Subpathway function ∼ Effector protein function Databases Pathway methods Preprocess I KEGG annotation I Uniprot keywords I GO annotation Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Further analysis Signaling pathways analysis Marta R. Hidalgo I Heatmap Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Further analysis Signaling pathways analysis Marta R. Hidalgo I Heatmap I PCA Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Further analysis Signaling pathways analysis Marta R. Hidalgo I Heatmap I PCA I Compare groups: Wilcoxon Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Further analysis Signaling pathways analysis Marta R. Hidalgo I Heatmap I PCA I Compare groups: Wilcoxon Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Method Computing the signal Functional annotation Further analysis Exercises Signaling pathways analysis Marta R. Hidalgo Signaling pathways Databases Pathway methods Preprocess Modeling KEGG Subpathways Normalization Exercises Method Computing the signal Functional annotation Further analysis Exercises
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