Merging Curated and in silico Interaction Data in Network Analysis

without prior knowledge Overview Curated Networks Problem in silico Outlook without prior knowledge

Introduction

Integration across Studies By group By platform 4 Integration across Studies

Integration by Normalization

Integration by Ranking Gene Exp1 Exp2 Rank SIL 2.3 COL 3.2 CEAC NOV 2.2 3.0 NID 2.1 2.7 … PROM TUBA1 1.6 1.5 FEL 1.4 Gene Exp1 Exp2 SIL 2.3 COL 3.2 NOV 2.2 CEAC 3.0 2.1 NID 2.7 PROM TUBA1 1.6 1.5 FEL 1.4 Integration by Ranking

Using Gene Set Enrichment Analysis

Overlap of significant genes Gene fold change in list A B C D Gene 2 1.3 1.5 Gene 17 2.2 2 0.4 Gene 22 -1.9 -5 Gene 3 0.5 -2.4 -0.5 -2 List B List C Gene 3 List D Overlap of significant genes

Overlap of significant gene function List B List C Regulation of B-cell mediated immunity Gene 3 List D Overlap of significant gene function

Overlap of significant genes Gene fold change in list A B C D Gene 2 1.3 1.5 Gene 17 2.2 2 0.4 Gene 22 -1.9 -5 Gene 3 0.5 -2.4 -0.5 -2 Gene 3 Gene 17 Gene 2 Gene 22 Overlap of significant genes

Example gene sets Function: Gene Ontology, KEGG Pathways, ... Localization: X-Chromosome Regulation: Targets of FOXP3 ...

Genomica: defining gene sets

Gene sets to experiments

Enriched gene sets

Enriched gene sets

Grouping to modules 16

Defining conditions 17

Modules to conditions 18

Integration via Networks

Leishmania

Filtering (by integration) Analysis Workflow Up/down-regulated genes, proteinsSignificance analysisFunctional annotation Trem Lipids Unfolded Protein Response Oxidative Stress Arginin Iron Filtering (by integration)

Intersection Proteins Pathway Intersection Proteins Genes Functional Selection 22

Protein Interactions: Intersection

Finding ‘Fringe’ Proteins Intersection Proteins Finding ‘Fringe’ Proteins 24

Intersection Proteins Fringe Proteins Intersection Proteins Trem and other pathways Trem (other) Trem ‘Fringe’ Non-Trem

Unfolded Protein Response Trem Iron Arginin Lipids Oxidative Stress Unfolded Protein Response Repeat for all Categories

Unfolded Protein Response Trem Iron Arginin Lipids Oxidative Stress Unfolded Protein Response Add Fringe Interactions

Interactions Captured Intersection Intersection & Fringe Fringe (within pathway) Fringe & Fringe (different pathways) 28

Combined Representation Trem Arg Iron Oxidative Stress Lipids Unfolded Protein Response Combined Representation

Add Expression Time Series 0/3/6/12/24h after infection Identify active Subnetworks

Oxidative Stress and Lipid Pathway Lipids Oxidative Stress and Lipid Pathway

Experimental validation Oxidative Stress Response linked to alternative Lipid Pathway