1: Hematological system development and Function. 2: Cellular movement. 3: Immune cell trafficking. 4: Cell-to- cell signaling and interaction. 5: Inflammatory response. 6: Small molecular chemistry. 7: Lipid metabolism. 8: Molecular transport. 9: Tissue development Suppl. Figure 1

A B C Intrinsic Prothrombin Activation Pathway Coagulation System HIF1α Signaling Type II Diabetes Mellitus Signaling p70S6K Signaling Extrinsic Prothrombin Activation Pathway p38 MAPK Signaling Intrinsic Prothrombin Activation Pathway Coagulation System HIF1α Signaling Type II Diabetes Mellitus Signaling p70S6K Signaling Extrinsic Prothrombin Activation Pathway p38 MAPK Signaling Intrinsic Prothrombin Activation Pathway Coagulation System Extrinsic Prothrombin Activation Pathway p38 MAPK Signaling Type II Diabetes Mellitus Signaling HIF1α Signaling HMGB1 Signaling log(p-value) log(p-value) log(p-value) Threshold Suppl. Figure 2

Clathrin-mediated Endocytosis Signaling Production of Nitric Oxide and Reactive Oxygen Species in Macrophages TREM1 Signaling Crosstalk between Dendritic Cells and Natural Killer Cells IL-12 Signaling and Production in Macrophages Role of cytokines in Mediating Communication between Immune Cells Caveolar-mediated Endocytosis Signaling Communication between Innate and Adaptive Immune Cells MSP-RON Signaling Pathway IL-10 signaling P38 MAPK Signaling Role of Pattern Recognition Receptors in Recognition of Bacteria and Virus IL-6 signaling Role of Pattern Recognition Receptors in Recognition of Bacteria and Virus TREM1 Signaling MSP-RON Signaling Pathway Crosstalk between Dendritic Cells and Natural Killer Cells Communication between Innate and Adaptive Immune Cells IL-12 Signaling and Production in Macrophages Role of cytokines in Mediating Communication between Immune Cells T Helper Cell Differentiation MIF-mediated Glucocorticoid Regulation Production of Nitric Oxide and Reactive Oxygen Species in Macrophages MIF Regulation of Innate Immunity IL-10 signaling IL-6 signaling Role of Pattern Recognition Receptors in Recognition of Bacteria and Virus TREM1 Signaling MSP-RON Signaling Pathway Crosstalk between Dendritic Cells and Nature Killer Cells Communication between Innate and Adaptive Immune Cells Dendritic Cell Maturation IL-12 Signaling and Production in Macrophages Role of cytokines in Mediating Communication between Immune Cells T Helper Cell Differentiation IL-10 signaling IL-6 signaling Airway Inflammation in Asthma Toll-like Signaling log(p-value) log(p-value) log(p-value) Threshold ABC Suppl. Figure 3

A B C Regulation of Cytokine Production in Macrophages and T Helper Cells by IL-17A and IL 17-F TREM1 Signaling Regulation of Cytokine Production in Intestinal Epithelial Cell by IL-17A and IL 17-F Acute Phase Response Signaling Dendritic Cell Maturation IL-12 Signaling and Production in Macrophages Role of cytokines in Mediating Communication between Immune Cells T Helper Cell Differentiation Airway Pathology in Chronic Obstructive Pulmonary Disease IL-10 signaling IL-6 signaling Role of IL-17F in Allergic Inflammatory Airway Disease Regulation of Cytokine Production in Macrophages and T Helper Cells by IL-17A and IL 17-F TREM1 Signaling Regulation of Cytokine Production in Intestinal Epithelial Cell by IL-17A and IL 17-F Acute Phase Response Signaling IL-12 Signaling and Production in Macrophages IL—17A in Arthritis Role of cytokines in Mediating Communication between Immune Cells T Helper Cell Differentiation Airway Pathology in Chronic Obstructive Pulmonary Disease IL-10 signaling IL-6 signaling Role of IL-17F in Allergic Inflammatory Airway Disease Acute Phase Response Signaling Regulation of Cytokine Production in Macrophages and T Helper Cells by IL-17A and IL 17-F TREM1 Signaling Regulation of Cytokine Production in Intestinal Epithelial Cell by IL-17A and IL 17-F IL-12 Signaling and Production in Macrophages Chemokine Signaling Role of cytokines in Mediating Communication between Immune Cells IL-10 signaling P38 MAPK Signaling IL-17A Signaling in Gastric Cells IL-6 signaling Role of IL-17F in Allergic Inflammatory Airway Disease log(p-value) log(p-value) log(p-value) Threshold Suppl. Figure 4