Network Catalog

Each curated network is backed by a BEL script. Below are options to summarize the networks' contents, explore them with an in-browser navigator, or run analyses with data sets such as differential gene expression data. Upload more networks here.

Exported from Bel-c 15.bel 2.0.4 by Exported fromBel-C
27 nodes | 125 edges | 3 citations | Public

Exported from Bel-c 10.bel 2.0.4 by Exported fromBel-C
26 nodes | 115 edges | 2 citations | Public

Exported from Bel-c1.bel 2.0.4 by Exported fromBel-C
2 nodes | 1 edge | 1 citation | Public

Exported from Bel-c.bel 2.0.4 by Exported fromBel-C
43 nodes | 218 edges | 1 citation | Public

Progress and Developments in Tau Aggregation Inhibitors for Alzheimer Disease 0.1.0 by Charles Tapley Hoyt
23 nodes | 23 edges | 1 citation | Public

A small assortment of academic articles describing quantitatively described interactions between the MAPT (Tau) protein and small molecules

30232325.bel 2.0.4 by Debolina Roy
43 nodes | 150 edges | 1 citation | Public

30232325(2).bel 2.0.1 by Debolina Roy
0 nodes | 0 edges | 0 citations | Public

30232325(1).bel 2.0.1 by Debolina Roy
0 nodes | 0 edges | 0 citations | Public

20392114 2.0.8 by Aparna
3 nodes | 4 edges | 1 citation | Public

Project1 2.0.2 by Aparna
0 nodes | 0 edges | 0 citations | Public

test 2 1.1.13 by Priya S
0 nodes | 0 edges | 0 citations | Public

BEL Training sentences edited 1.1.8 by Aparna Mohan
31 nodes | 44 edges | 5 citations | Public

test 1 1.1.8 by Priya S
0 nodes | 0 edges | 0 citations | Public

test pr 1.1.6 by Priya S
23 nodes | 26 edges | 4 citations | Public

DR 1 1.1.1 by Deolina Roy
23 nodes | 23 edges | 5 citations | Public

AB Test2 1.1.1 by ABISH K
38 nodes | 51 edges | 5 citations | Public

Test1 1.1.1 by Thrishna K G
26 nodes | 33 edges | 4 citations | Public

AB Test1 1.1.1 by ABISH K
37 nodes | 46 edges | 5 citations | Public

Colorectal Cancer Model 2.0.6 by Miguel A. Ibarra-Arellano, et. al
1655 nodes | 4989 edges | 490 citations | Public

CRC combined 1.1 by Miguel A. Ibarra Arellano
1361 nodes | 3680 edges | 390 citations | Public

CRC combined.bel 1.0 by Miguel A. Ibarra Arellano
523 nodes | 1604 edges | 172 citations | Public

colorectal cancer Knowledge Assembly - Drugs 1.0.1 by Miguel A. Ibarra-Arellano
122 nodes | 254 edges | 39 citations | Public

colorectal cancer Knowledge Assembly with drug associations.

Colorectal Cancer Knowledge Assembly - Drugs Pathways 1.0.0 by Miguel A. Ibarra-Arellano
74 nodes | 117 edges | 22 citations | Public

Colorectal Cancer Knowledge Assembly with drug associations and Pathways.

mTor-2.0-Rn 2.0 by Causal Biological Networks Database
39 nodes | 76 edges | 39 citations | Public

The mTor network depicts the causal mechanisms involved in the canonical mTor signaling pathway, including AMPK, TSC1/2, RHEB, and RPS6KB1. Elements of this pathway are important for mediating the proliferative processes seen following lung injury.

Xenobiotic Metabolism Response-2.0-Rn 2.0 by Causal Biological Networks Database
91 nodes | 206 edges | 121 citations | Public

The Xenobiotic Metabolism Response depicts the causal mechanisms that are involved in xenobiotic metabolism response, including the various environmental stressors and signaling components that regulate AHR and cytochrome p450 enzymes.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eIdentify additional lung-relevant phase II (GST) and phase III (SLC) mechanisms that study protein/activity relationships as opposed to gene expression. Expand phase I regulation beyond AHR to include other transcription factors relevant for airway epithelia such as CAR, LXR and PXR. Reviewed during Jamboree2014

Wound Healing-2.0-Rn 2.0 by Causal Biological Networks Database
148 nodes | 368 edges | 203 citations | Public

The Wound Healing network describes the causal mechanisms involved in the wound healing response in pulmonary tissue following exposure to cigarette smoke. This includes processes related to cell migration as a result of MMP degradation of matrix components and progenitor cell differentiation mediated by NOTCH1, SOX2, KRT14 and CTNNB1.

Wnt-2.0-Rn 2.0 by Causal Biological Networks Database
80 nodes | 177 edges | 85 citations | Public

The Wnt Signaling network depicts the causal mechanisms that regulate aspects of Wnt signaling primarily in the context of heightened cell proliferation observed following lung injury. The network includes multiple pathways leading to the degradation of beta-catenin as it relates to Wnt signaling.

Treg Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
50 nodes | 118 edges | 75 citations | Public

The Treg Signaling network depicts the causal mechanisms that are activated in CD4+ Foxp3+ regulatory T-cells following T-cell receptor (TCR) ligation. Expanding on these processes, the network highlights the chemokines secreted by macrophages and dendritic cells, as well as the cognate T-cell receptors, involved in mediating T-cell recruitment to compromised lung tissue during COPD development.

Tissue Damage-2.0-Rn 2.0 by Causal Biological Networks Database
68 nodes | 209 edges | 141 citations | Public

The Tissue Damage network depicts the causal mechanisms leading to the secretion of damage-associated molecular patterns (DAMPs) and pathogen associated molecular patterns (PAMPs) following tissue injury. The network includes pathways related to the detection of DAMPs, which serve to perpetuate heightened immune responses to noninfectious tissue insult.

Th17 Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
65 nodes | 118 edges | 73 citations | Public

The Th17 Signaling network depicts the causal mechanisms that are activated in IL-17-producing T helper (Th17) cells following T-cell receptor (TCR) ligation. Expanding on these processes, the network highlights the chemokines secreted by macrophages and dendritic cells, as well as the cognate T-cell receptors, involved in mediating T-cell recruitment to compromised lung tissue during COPD development.

Th1-Th2 Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
108 nodes | 253 edges | 134 citations | Public

The Th1/Th2 Signaling network depicts the causal mechanisms that are activated in T helper 1 (Th1) cells following engagement with macrophages including pathways related to the STAT4 and T-bet transcription factors leading to Th1-specific differentiation as well as the causal mechanisms that are activated in T helper 2 (Th2) cells following engagement primarily with B-cells including pathways related to the STAT6 and GATA transcription factors leading to Th2-specific differentiation. The network also encompasses the chemokine pathways involved in mediating T-cell recruitment to compromised lung tissue during COPD development and Th1-produced cytokines that activate cytotoxic T-cells, natural killer cells and macrophages and Th2-produced cytokines that activate B cells, eosinophils and suppress macrophage activation.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eLung memory CD4+ T cell signaling and T-helper cell interaction with other immune cells including T-helper and B cell CD40L-CD40 interaction and NK and Tc activation by Th cells. Reviewed during Jamboree2014. Reviewed during Jamboree2015

Senescence-2.0-Rn 2.0 by Causal Biological Networks Database
200 nodes | 349 edges | 195 citations | Public

The Mechanisms of Cellular Senescence network depicts the causal mechanisms that are involved in induction of senescence in non-transformed cells in response to a variety of external stimuli (including replicative senescence, stress-induced senescence, and oncogene-induced senescence). The network includes components that participate in intercellular signaling such as growth factors, chemokines, cytokines and proteases, which ultimately lead to manifestation of the senescence-associated secretory phenotype (SASP). \nReviewed during Jamboree2015

Response to DNA Damage-2.0-Rn 2.0 by Causal Biological Networks Database
224 nodes | 522 edges | 256 citations | Public

The Response to DNA Damage network depicts the causal mechanisms that are involved in multiple DNA damage response pathways. This includes those components that regulate TP53, TP63, and TP73 activities, the impact of G1/S and G2/M transitions of the cell cycle downstream of DNA damage, and DNA repair processes following single-strand and double-strand DNA damage. The network describes inhibition of DNA repair by various exogenous compounds, as well as components that function in nucleotide excision repair such as the XP proteins.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eInterplay of components medaiting the processes of non-homologous end-joining (NHEJ) and homologous recombination (HR). Reviewed during Jamboree2014

PGE2-2.0-Rn 2.0 by Causal Biological Networks Database
51 nodes | 145 edges | 102 citations | Public

The PGE2 network depicts the pathways exerting regulatory control of PGE2 in the context of cellular proliferation. The network includes cAMP-mediated activation of PKA-, Epac/Rap1- and Tiam1/Vav2-dependent pathways of Rac1 activation.

Oxidative Stress-2.0-Rn 2.0 by Causal Biological Networks Database
277 nodes | 777 edges | 400 citations | Public

The Oxidative Stress network depicts pathways regulating cellular responses to oxidative stress, which includes intracellular free radical management, cellular responses to endogenous/exogenous oxidants and anti-oxidants and the glutathione metabolism. The network details transcriptional regulation of AP-1, NF-kB, and Nrf2 complexes as they relate to management of oxidative stress. Reviewed during Jamboree2014. Reviewed during Jamboree2015

Osmotic Stress-2.0-Rn 2.0 by Causal Biological Networks Database
60 nodes | 107 edges | 77 citations | Public

The Osmotic Stress network depicts the causal mechanisms that regulate osmotic stress including NFAT5, aquaporins, and CFTR pathways downstream of the hyperosmotic response.

Nuclear Receptors-2.0-Rn 2.0 by Causal Biological Networks Database
31 nodes | 59 edges | 42 citations | Public

The Nuclear Receptors network depicts the causal mechanisms in the nuclear receptor signaling pathway that leads to cell proliferation and cell cycle progression as indicated by the core elements (cyclin-dependent kinases, E2F family members, cyclins, and CDKN1A). \nReviewed during Jamboree2014

Notch-2.0-Rn 2.0 by Causal Biological Networks Database
48 nodes | 111 edges | 48 citations | Public

The Notch network depicts the causal mechanisms that regulate Notch signaling, which controls lung cell proliferation and differentiation through DLK1 (an upstream initiator of the Notch signaling pathway) and JAG1/2 (ligands for the Notch receptors).

Neutrophil Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
186 nodes | 629 edges | 357 citations | Public

The Neutrophil Signaling network depicts the causal mechanisms that lead to various cellular functions in neutrophils, such as polarization, extravasation, respiratory burst, response to stimuli, and chemotaxis, in response to upstream signals such as CSF3, TNF, IL8, CXCL12, F2, and FPR1. \nReviewed during Jamboree2014\nReviewed during Jamboree2015

Necroptosis-2.0-Rn 2.0 by Causal Biological Networks Database
56 nodes | 199 edges | 108 citations | Public

The Necroptosis network describes the causal mechanisms involved in the activation of the Fas receptor and TNFR1 receptor, leading to RIPK/ROS (reactive oxygen species) signaling and the subsequent induction of necroptosis as a result of exposure to environmental insults. The network includes the array of proinflammatory mediators released from necrotic cells that may contribute to COPD development. \Reviewed during Jamboree2015

NK Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
48 nodes | 77 edges | 47 citations | Public

The NK Signaling network depicts the causal mechanisms involved in NK cell activation and the induction of target cell cytolysis in response to upstream signals, including interleukins, TGFB1, IFNs and ITGB2.

NFE2L2 Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
84 nodes | 149 edges | 59 citations | Public

The NFE2L2 Signaling network depicts the causal mechanisms that are involved in transcriptional activation of NFE2L2 (central mediator of the cellular oxidative stress response), its interaction with MAF proteins, and its downstream target genes such as ATF4, GCLC, NQO1, and PRDX1.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eInteraction of NFE2L2 with MAF proteins. Reviewed during Jamboree2014

Megakaryocyte Differentiation-2.0-Rn 2.0 by Causal Biological Networks Database
113 nodes | 321 edges | 195 citations | Public

The Megakaryocyte Differentiation network depicts the causal mechanisms involved in megakaryocyte differentiation in response to upstream signals (e.g. IL11, CXCL12, and THPO).

Mast cell activation-2.0-Rn 2.0 by Causal Biological Networks Database
46 nodes | 93 edges | 67 citations | Public

The Mast Cell Activation network depicts the causal mechanisms that occur in mast cells following exposure to antigen and IgE/Fc receptor ligation and stimulation with IL4 and KITLG. The network also includes elements involved in the resulting downstream signal transduction (e.g. Lyn, MEK and MAPK1, and LTC4) that lead to mast cell activation and subsequent release of several cytokines and other factors such as histamine and prostaglandin D2.

Mapk-2.0-Rn 2.0 by Causal Biological Networks Database
38 nodes | 68 edges | 44 citations | Public

The Mapk network depicts the causal mechanisms that regulate different families of MAPK signaling (p38, JNK, ERK, MAP2K) in the context of cell proliferation.

Macrophage Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
174 nodes | 526 edges | 376 citations | Public

The Macrophage Signaling describes the causal mechanisms in pathways related to the recruitment of macrophages to sites of tissue injury, differentiation of macrophages from hematopoietic progenitors and macrophage activation in response to environmental cues. The network also includes cell surface receptors and signaling pathways involved in macrophage efferocytosis, a process known to be largely inhibited during COPD development.\nReviewed during Jamboree2014\nReviewed during Jamboree2015

Jak Stat-2.0-Rn 2.0 by Causal Biological Networks Database
48 nodes | 144 edges | 95 citations | Public

The Jak Stat network depicts the causal mechanisms involved in canonical Jak Stat signaling leading to cell proliferation and components of cell cycle machinery (e.g. cyclins, CDKN1B).

Immune Regulation of Tissue Repair-2.0-Rn 2.0 by Causal Biological Networks Database
132 nodes | 645 edges | 460 citations | Public

The Immune Regulation of Tissue Repair network depicts the causal mechanisms involved in the immune cell regulation of tissue repair, including the activation of macrophages, dendritic cells, neutrophils and monocytes.

Hypoxic Stress-2.0-Rn 2.0 by Causal Biological Networks Database
111 nodes | 262 edges | 144 citations | Public

The Hypoxic Stress network depicts the causal mechanisms that regulate hypoxic stress including activation of HIF1A and its targets, control of transcription, protein synthesis, and crosstalk with oxidative stress, ER stress, and osmotic stress response pathways.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eExpand ER stress-relevant pathways. \nReviewed during Jamboree2014

Hox-2.0-Rn 2.0 by Causal Biological Networks Database
27 nodes | 30 edges | 18 citations | Public

The Hox network describes the causal mechanisms in the Hox signaling pathway that leads to cell proliferation as well as downstream targets of the HOX family members such as CDKN1A, CDKN1B, CDKN1C, ITGAV, and ITGB3.

Hedgehog-2.0-Rn 2.0 by Causal Biological Networks Database
37 nodes | 60 edges | 27 citations | Public

The Hedgehog network depicts causal mechanisms that are involved in Hedgehog signaling, which regulates cell proliferation and branching morphogenesis in the developing mammalian lung. These processes may contribute to heightened proliferative activity following exposure to environmental insults.

Growth Factor-2.0-Rn 2.0 by Causal Biological Networks Database
219 nodes | 569 edges | 278 citations | Public

The Growth Factor network depicts the causal mechanisms of common extracellular growth factors involved in regulating lung cell proliferation, namely EGF, TGF-beta, VEGF, and FGF family members. The EGF family members EGF and TGF-alpha play critical roles in regulating the proliferation of airway epithelial cells through EGF receptor activation. FGF7 and FGF10, largely through activation of FGFR2 signaling, stimulate lung epithelial cell proliferation as well as regulate branching morphogenesis in the developing lung. VEGF, a key regulator of normal angiogenesis that is also involved in regulating proliferation of human fetal airway epithelial cells, was also included in the network. \nReviewed during Jamboree2014

Fibrosis-2.0-Rn 2.0 by Causal Biological Networks Database
146 nodes | 510 edges | 308 citations | Public

The Fibrosis network depicts causal mechanisms that describe fibrosis and epithelial-to-mesenchymal cell transition (EMT) in lung tissue repair, including distinct characteristics of lung fibrosis such as TGFB1, collagen and MMPs. The network also contains signaling components of the Wnt, Hedgehog, and EGFR pathways that promote fibrosis and EMT.

Epithelial Mucus Hypersecretion-2.0-Rn 2.0 by Causal Biological Networks Database
128 nodes | 432 edges | 269 citations | Public

The Epithelial Mucus Hypersecretion network depicts the causal mechanisms that lead to increased expression of MUC5AC and mucus hypersecretion in pulmonary epithelial cells in response to pro-inflammatory signals (e.g. IL13, CCL2, and TNF) and environmental insults. The network also includes COPD-specific signaling components such as various mucins and mucocilliary clearance processes.

Epithelial Innate Immune Activation-2.0-Rn 2.0 by Causal Biological Networks Database
135 nodes | 574 edges | 386 citations | Public

The Epithelial Innate Immune Activation network depicts causal mechanisms involved in aspects of the innate immune system that are initially activated in pulmonary epithelium in response to cigarette smoke exposure, and remain in a state of constitutive activation during COPD development. These processes include Toll-like receptor activation and respective pathways leading to subsequent proinflammatory cytokine production by lung epithelial cells.

Epigenetics-2.0-Rn 2.0 by Causal Biological Networks Database
67 nodes | 127 edges | 47 citations | Public

The Epigenetics network describes epigenetic changes reported to be associated with COPD, as well as epigenetic modulators reported to be affected by COPD or smoking including the histone deacetylase (HDAC) family and DNA methyltransferase (DMT) family member DNMT1, as well as connections from these epigenetic mediators to the core cell cycle components (e.g. CCND1, CDKN2A). Reviewed during Jamboree2015

Endothelial Innate Immune Activation-2.0-Rn 2.0 by Causal Biological Networks Database
133 nodes | 416 edges | 276 citations | Public

The Endothelial Innate Immune Activation network depicts the causal mechanisms that describe acute response of healthy pulmonary endothelium to pro-inflammatory stimuli. These response mechanisms include production of the inflammatory chemokines, adhesion molecules and other mediators during endothelial cells activation leading to lung microvascular endothelial cells dysfunction. The network also includes causal mechanisms associated with angiogenic regulation by immune cells, including drivers of VEGF secretion and other related signaling pathways that crosstalk between the immune system and angiogenesis.

Endoplasmic Reticulum Stress-2.0-Rn 2.0 by Causal Biological Networks Database
83 nodes | 155 edges | 77 citations | Public

The Endoplasmic Reticulum Stress network depicts the causal mechanisms that regulate endoplasmic reticulum stress including the unfolded protein response and the pathways downstream of the three key stress mediators: PERK (EIF2AK3), ATF6, and IRE1alpha (ERN1). The pro-apoptotic arm of the ER stress response was excluded from this network, but included in the Apoptosis network where the context is more relevant.

ECM Degradation-2.0-Rn 2.0 by Causal Biological Networks Database
52 nodes | 147 edges | 63 citations | Public

The ECM Degradation network depicts the causal mechanisms involved in the key events leading to degradation of the extracellular matrix (ECM) in the context of COPD, including the release of proteases (e.g. MMPs and neutrophil elastase) from inflammatory cells, which degrade ECM components such as collagens, laminins and elastins. ECM degradation results in destruction of the alveolar walls, contributing to emphysema and COPD.

Dendritic Cell Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
140 nodes | 338 edges | 238 citations | Public

The Dendritic Cell Signaling network depicts the causal mechanisms in key cytokine pathways leading to the activation of dendritic cells and their migration to both the lung tissue and lymph nodes. Chemokines and surface receptors expressed by dendritic cells that serve to promote T-cell migration and subsequent differentiation in the lung during COPD are included in the network. Reviewed during Jamboree2014

Cytotoxic T-cell Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
44 nodes | 50 edges | 36 citations | Public

The Cytotoxic T-cell Signaling network depicts the causal mechanisms that are activated in CD8+ cytotoxic T-cells following T-cell receptor (TCR) ligation. Expanding on these processes, the network highlights the chemokines secreted by macrophages and dendritic cells, as well as the cognate T-cell receptors, involved in mediating T-cell recruitment to compromised lung tissue during COPD development.

Clock-2.0-Rn 2.0 by Causal Biological Networks Database
67 nodes | 108 edges | 26 citations | Public

The Clock network depicts the causal mechanisms that regulate circadian clock signaling leading to cell proliferation. The network focuses on downstream targets of the CLOCK:ARNTL transcriptional complex such as NR1D1, CRY1, PERs, and BHLHs.

Cell Interaction-2.0-Rn 2.0 by Causal Biological Networks Database
92 nodes | 125 edges | 44 citations | Public

The Cell Interaction network describes the causal mechanisms involved in the signal transduction pathways leading to cell proliferation that originate from the interactions between common cell adhesion molecules (including ITGB1 complexes with ITGA1-3 chains) and extracellular matrix components (specifically collagen, fibronectin, and laminin).

Cell Cycle-2.0-Rn 2.0 by Causal Biological Networks Database
153 nodes | 320 edges | 172 citations | Public

The Cell Cycle network depicts the causal mechanisms that regulate cell cycle including canonical elements of the core machinery regulating entry and exit from the mammalian cell cycle, such as cyclins, cyclin-dependent kinases and members of the E2F family. Reviewed during Jamboree2014

Calcium-2.0-Rn 2.0 by Causal Biological Networks Database
31 nodes | 54 edges | 37 citations | Public

The Calcium network depicts the causal mechanisms that regulate calcium signaling in the context of cell proliferation. The network describes increases in calcineurin complex activity as a result of Wnt-mediated calcium signaling and VEGF signaling, which leads to the induction of NFATC1 transcriptional activity and subsequent cell proliferation. \nReviewed during Jamboree2015

B-cell Signaling-2.0-Rn 2.0 by Causal Biological Networks Database
51 nodes | 109 edges | 86 citations | Public

The B-cell Signaling network depicts the causal mechanisms linking the repertoire of surface receptors expressed on B-cells to a variety of causal downstream signaling pathways leading to B-cell activation and differentiation. The network includes key components involved in the class switching process frequently observed during COPD development, which may contribute to the generation of an autoimmune component underlying disease progression.

Autophagy-2.0-Rn 2.0 by Causal Biological Networks Database
135 nodes | 282 edges | 129 citations | Public

The Autophagy network depicts the causal mechanisms involved in the induction of autophagy following pulmonary tissue damage as a result of exposure to environmental insults. This includes the regulation of mTOR in the context of autophagy, ATG signaling that leads to autophagic vacuole formation, and regulation of protein translation via S6K and AMPK.

Apoptosis-2.0-Rn 2.0 by Causal Biological Networks Database
224 nodes | 821 edges | 494 citations | Public

The Apoptosis network describes causal mechanisms in several different signaling pathways that are involved in the induction of apoptosis in response to environmental cues. The pathways include ER stress signaling, particularly the PERK-eIF2alpha-ATF4-CHOP pathway, MAPK components that regulate the pro-apoptotic proteins (Bad,Bax, Bim) via PI3K/AKT and JNK pathways, NFkB signaling which induces downstream expressions of anti-apoptotic proteins, PKC-mediated apoptosis, and activation of TNFR1 and Fas receptor leading to downstream signaling of caspase-8. The network also characterizes the transcriptional role of TP53 in apoptosis through the presence of its downstream anti-apoptotic and pro-apoptotic targets. \nReviewed during Jamboree2014

Angiogenesis-2.0-Rn 2.0 by Causal Biological Networks Database
173 nodes | 481 edges | 289 citations | Public

The Angiogenesis network depicts the causal mechanisms that lead to the angiogenic processes of migration, proliferation and vascular permeability downstream of growth factor signaling (PDGF, TGF, IGF, FGF, VEGF, and angiopoietin), as well as key angiogenic processes of sprouting and tubulogenesis including the DLL4-NOTCH pathway. The model also contains causal mechanisms involved in the regulation of HIF1A transcriptional activity leading to angiogenesis.

mTor-2.0-Mm 2.0 by Causal Biological Networks Database
39 nodes | 76 edges | 39 citations | Public

The mTor network depicts the causal mechanisms involved in the canonical mTor signaling pathway, including AMPK, TSC1/2, RHEB, and RPS6KB1. Elements of this pathway are important for mediating the proliferative processes seen following lung injury.

Xenobiotic Metabolism Response-2.0-Mm 2.0 by Causal Biological Networks Database
92 nodes | 206 edges | 121 citations | Public

The Xenobiotic Metabolism Response depicts the causal mechanisms that are involved in xenobiotic metabolism response, including the various environmental stressors and signaling components that regulate AHR and cytochrome p450 enzymes.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eIdentify additional lung-relevant phase II (GST) and phase III (SLC) mechanisms that study protein/activity relationships as opposed to gene expression. Expand phase I regulation beyond AHR to include other transcription factors relevant for airway epithelia such as CAR, LXR and PXR. Reviewed during Jamboree2014

Wound Healing-2.0-Mm 2.0 by Causal Biological Networks Database
147 nodes | 368 edges | 203 citations | Public

The Wound Healing network describes the causal mechanisms involved in the wound healing response in pulmonary tissue following exposure to cigarette smoke. This includes processes related to cell migration as a result of MMP degradation of matrix components and progenitor cell differentiation mediated by NOTCH1, SOX2, KRT14 and CTNNB1.

Wnt-2.0-Mm 2.0 by Causal Biological Networks Database
80 nodes | 177 edges | 85 citations | Public

The Wnt Signaling network depicts the causal mechanisms that regulate aspects of Wnt signaling primarily in the context of heightened cell proliferation observed following lung injury. The network includes multiple pathways leading to the degradation of beta-catenin as it relates to Wnt signaling.

Treg Signaling-2.0-Mm 2.0 by Causal Biological Networks Database
50 nodes | 118 edges | 75 citations | Public

The Treg Signaling network depicts the causal mechanisms that are activated in CD4+ Foxp3+ regulatory T-cells following T-cell receptor (TCR) ligation. Expanding on these processes, the network highlights the chemokines secreted by macrophages and dendritic cells, as well as the cognate T-cell receptors, involved in mediating T-cell recruitment to compromised lung tissue during COPD development.

Tissue Damage-2.0-Mm 2.0 by Causal Biological Networks Database
68 nodes | 209 edges | 141 citations | Public

The Tissue Damage network depicts the causal mechanisms leading to the secretion of damage-associated molecular patterns (DAMPs) and pathogen associated molecular patterns (PAMPs) following tissue injury. The network includes pathways related to the detection of DAMPs, which serve to perpetuate heightened immune responses to noninfectious tissue insult.

Th17 Signaling-2.0-Mm 2.0 by Causal Biological Networks Database
65 nodes | 118 edges | 73 citations | Public

The Th17 Signaling network depicts the causal mechanisms that are activated in IL-17-producing T helper (Th17) cells following T-cell receptor (TCR) ligation. Expanding on these processes, the network highlights the chemokines secreted by macrophages and dendritic cells, as well as the cognate T-cell receptors, involved in mediating T-cell recruitment to compromised lung tissue during COPD development.

Th1-Th2 Signaling-2.0-Mm 2.0 by Causal Biological Networks Database
108 nodes | 253 edges | 134 citations | Public

The Th1/Th2 Signaling network depicts the causal mechanisms that are activated in T helper 1 (Th1) cells following engagement with macrophages including pathways related to the STAT4 and T-bet transcription factors leading to Th1-specific differentiation as well as the causal mechanisms that are activated in T helper 2 (Th2) cells following engagement primarily with B-cells including pathways related to the STAT6 and GATA transcription factors leading to Th2-specific differentiation. The network also encompasses the chemokine pathways involved in mediating T-cell recruitment to compromised lung tissue during COPD development and Th1-produced cytokines that activate cytotoxic T-cells, natural killer cells and macrophages and Th2-produced cytokines that activate B cells, eosinophils and suppress macrophage activation.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eLung memory CD4+ T cell signaling and T-helper cell interaction with other immune cells including T-helper and B cell CD40L-CD40 interaction and NK and Tc activation by Th cells. Reviewed during Jamboree2014. Reviewed during Jamboree2015

Senescence-2.0-Mm 2.0 by Causal Biological Networks Database
200 nodes | 349 edges | 195 citations | Public

The Mechanisms of Cellular Senescence network depicts the causal mechanisms that are involved in induction of senescence in non-transformed cells in response to a variety of external stimuli (including replicative senescence, stress-induced senescence, and oncogene-induced senescence). The network includes components that participate in intercellular signaling such as growth factors, chemokines, cytokines and proteases, which ultimately lead to manifestation of the senescence-associated secretory phenotype (SASP). \nReviewed during Jamboree2015

Response to DNA Damage-2.0-Mm 2.0 by Causal Biological Networks Database
224 nodes | 522 edges | 256 citations | Public

The Response to DNA Damage network depicts the causal mechanisms that are involved in multiple DNA damage response pathways. This includes those components that regulate TP53, TP63, and TP73 activities, the impact of G1/S and G2/M transitions of the cell cycle downstream of DNA damage, and DNA repair processes following single-strand and double-strand DNA damage. The network describes inhibition of DNA repair by various exogenous compounds, as well as components that function in nucleotide excision repair such as the XP proteins.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eInterplay of components medaiting the processes of non-homologous end-joining (NHEJ) and homologous recombination (HR). Reviewed during Jamboree2014

PGE2-2.0-Mm 2.0 by Causal Biological Networks Database
51 nodes | 145 edges | 102 citations | Public

The PGE2 network depicts the pathways exerting regulatory control of PGE2 in the context of cellular proliferation. The network includes cAMP-mediated activation of PKA-, Epac/Rap1- and Tiam1/Vav2-dependent pathways of Rac1 activation.

Oxidative Stress-2.0-Mm 2.0 by Causal Biological Networks Database
277 nodes | 777 edges | 400 citations | Public

The Oxidative Stress network depicts pathways regulating cellular responses to oxidative stress, which includes intracellular free radical management, cellular responses to endogenous/exogenous oxidants and anti-oxidants and the glutathione metabolism. The network details transcriptional regulation of AP-1, NF-kB, and Nrf2 complexes as they relate to management of oxidative stress. Reviewed during Jamboree2014. Reviewed during Jamboree2015

Osmotic Stress-2.0-Mm 2.0 by Causal Biological Networks Database
59 nodes | 107 edges | 77 citations | Public

The Osmotic Stress network depicts the causal mechanisms that regulate osmotic stress including NFAT5, aquaporins, and CFTR pathways downstream of the hyperosmotic response.

Nuclear Receptors-2.0-Mm 2.0 by Causal Biological Networks Database
31 nodes | 59 edges | 42 citations | Public

The Nuclear Receptors network depicts the causal mechanisms in the nuclear receptor signaling pathway that leads to cell proliferation and cell cycle progression as indicated by the core elements (cyclin-dependent kinases, E2F family members, cyclins, and CDKN1A). \nReviewed during Jamboree2014

Notch-2.0-Mm 2.0 by Causal Biological Networks Database
48 nodes | 111 edges | 48 citations | Public

The Notch network depicts the causal mechanisms that regulate Notch signaling, which controls lung cell proliferation and differentiation through DLK1 (an upstream initiator of the Notch signaling pathway) and JAG1/2 (ligands for the Notch receptors).

Neutrophil Signaling-2.0-Mm 2.0 by Causal Biological Networks Database
187 nodes | 631 edges | 358 citations | Public

The Neutrophil Signaling network depicts the causal mechanisms that lead to various cellular functions in neutrophils, such as polarization, extravasation, respiratory burst, response to stimuli, and chemotaxis, in response to upstream signals such as CSF3, TNF, IL8, CXCL12, F2, and FPR1. \nReviewed during Jamboree2014\nReviewed during Jamboree2015

Necroptosis-2.0-Mm 2.0 by Causal Biological Networks Database
55 nodes | 199 edges | 108 citations | Public

The Necroptosis network describes the causal mechanisms involved in the activation of the Fas receptor and TNFR1 receptor, leading to RIPK/ROS (reactive oxygen species) signaling and the subsequent induction of necroptosis as a result of exposure to environmental insults. The network includes the array of proinflammatory mediators released from necrotic cells that may contribute to COPD development. \Reviewed during Jamboree2015

NK Signaling-2.0-Mm 2.0 by Causal Biological Networks Database
48 nodes | 77 edges | 47 citations | Public

The NK Signaling network depicts the causal mechanisms involved in NK cell activation and the induction of target cell cytolysis in response to upstream signals, including interleukins, TGFB1, IFNs and ITGB2.

NFE2L2 Signaling-2.0-Mm 2.0 by Causal Biological Networks Database
83 nodes | 149 edges | 59 citations | Public

The NFE2L2 Signaling network depicts the causal mechanisms that are involved in transcriptional activation of NFE2L2 (central mediator of the cellular oxidative stress response), its interaction with MAF proteins, and its downstream target genes such as ATF4, GCLC, NQO1, and PRDX1.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eInteraction of NFE2L2 with MAF proteins. Reviewed during Jamboree2014

Megakaryocyte Differentiation-2.0-Mm 2.0 by Causal Biological Networks Database
113 nodes | 321 edges | 195 citations | Public

The Megakaryocyte Differentiation network depicts the causal mechanisms involved in megakaryocyte differentiation in response to upstream signals (e.g. IL11, CXCL12, and THPO).

Mast cell activation-2.0-Mm 2.0 by Causal Biological Networks Database
46 nodes | 93 edges | 67 citations | Public

The Mast Cell Activation network depicts the causal mechanisms that occur in mast cells following exposure to antigen and IgE/Fc receptor ligation and stimulation with IL4 and KITLG. The network also includes elements involved in the resulting downstream signal transduction (e.g. Lyn, MEK and MAPK1, and LTC4) that lead to mast cell activation and subsequent release of several cytokines and other factors such as histamine and prostaglandin D2.

Mapk-2.0-Mm 2.0 by Causal Biological Networks Database
38 nodes | 68 edges | 44 citations | Public

The Mapk network depicts the causal mechanisms that regulate different families of MAPK signaling (p38, JNK, ERK, MAP2K) in the context of cell proliferation.

Macrophage Signaling-2.0-Mm 2.0 by Causal Biological Networks Database
174 nodes | 526 edges | 376 citations | Public

The Macrophage Signaling describes the causal mechanisms in pathways related to the recruitment of macrophages to sites of tissue injury, differentiation of macrophages from hematopoietic progenitors and macrophage activation in response to environmental cues. The network also includes cell surface receptors and signaling pathways involved in macrophage efferocytosis, a process known to be largely inhibited during COPD development.\nReviewed during Jamboree2014\nReviewed during Jamboree2015

Jak Stat-2.0-Mm 2.0 by Causal Biological Networks Database
48 nodes | 144 edges | 95 citations | Public

The Jak Stat network depicts the causal mechanisms involved in canonical Jak Stat signaling leading to cell proliferation and components of cell cycle machinery (e.g. cyclins, CDKN1B).

Immune Regulation of Tissue Repair-2.0-Mm 2.0 by Causal Biological Networks Database
132 nodes | 645 edges | 460 citations | Public

The Immune Regulation of Tissue Repair network depicts the causal mechanisms involved in the immune cell regulation of tissue repair, including the activation of macrophages, dendritic cells, neutrophils and monocytes.

Hypoxic Stress-2.0-Mm 2.0 by Causal Biological Networks Database
111 nodes | 262 edges | 144 citations | Public

The Hypoxic Stress network depicts the causal mechanisms that regulate hypoxic stress including activation of HIF1A and its targets, control of transcription, protein synthesis, and crosstalk with oxidative stress, ER stress, and osmotic stress response pathways.\u003c/p\u003e\n\u003ch2\u003eJamboree Review Focus\u003c/h2\u003e\n\u003cp\u003eExpand ER stress-relevant pathways. \nReviewed during Jamboree2014

Hox-2.0-Mm 2.0 by Causal Biological Networks Database
27 nodes | 30 edges | 18 citations | Public

The Hox network describes the causal mechanisms in the Hox signaling pathway that leads to cell proliferation as well as downstream targets of the HOX family members such as CDKN1A, CDKN1B, CDKN1C, ITGAV, and ITGB3.

Hedgehog-2.0-Mm 2.0 by Causal Biological Networks Database
37 nodes | 60 edges | 27 citations | Public

The Hedgehog network depicts causal mechanisms that are involved in Hedgehog signaling, which regulates cell proliferation and branching morphogenesis in the developing mammalian lung. These processes may contribute to heightened proliferative activity following exposure to environmental insults.

Growth Factor-2.0-Mm 2.0 by Causal Biological Networks Database
219 nodes | 569 edges | 278 citations | Public

The Growth Factor network depicts the causal mechanisms of common extracellular growth factors involved in regulating lung cell proliferation, namely EGF, TGF-beta, VEGF, and FGF family members. The EGF family members EGF and TGF-alpha play critical roles in regulating the proliferation of airway epithelial cells through EGF receptor activation. FGF7 and FGF10, largely through activation of FGFR2 signaling, stimulate lung epithelial cell proliferation as well as regulate branching morphogenesis in the developing lung. VEGF, a key regulator of normal angiogenesis that is also involved in regulating proliferation of human fetal airway epithelial cells, was also included in the network. \nReviewed during Jamboree2014

Fibrosis-2.0-Mm 2.0 by Causal Biological Networks Database
146 nodes | 510 edges | 308 citations | Public

The Fibrosis network depicts causal mechanisms that describe fibrosis and epithelial-to-mesenchymal cell transition (EMT) in lung tissue repair, including distinct characteristics of lung fibrosis such as TGFB1, collagen and MMPs. The network also contains signaling components of the Wnt, Hedgehog, and EGFR pathways that promote fibrosis and EMT.

Epithelial Mucus Hypersecretion-2.0-Mm 2.0 by Causal Biological Networks Database
128 nodes | 432 edges | 269 citations | Public

The Epithelial Mucus Hypersecretion network depicts the causal mechanisms that lead to increased expression of MUC5AC and mucus hypersecretion in pulmonary epithelial cells in response to pro-inflammatory signals (e.g. IL13, CCL2, and TNF) and environmental insults. The network also includes COPD-specific signaling components such as various mucins and mucocilliary clearance processes.

Epithelial Innate Immune Activation-2.0-Mm 2.0 by Causal Biological Networks Database
135 nodes | 574 edges | 386 citations | Public

The Epithelial Innate Immune Activation network depicts causal mechanisms involved in aspects of the innate immune system that are initially activated in pulmonary epithelium in response to cigarette smoke exposure, and remain in a state of constitutive activation during COPD development. These processes include Toll-like receptor activation and respective pathways leading to subsequent proinflammatory cytokine production by lung epithelial cells.

Epigenetics-2.0-Mm 2.0 by Causal Biological Networks Database
67 nodes | 127 edges | 47 citations | Public

The Epigenetics network describes epigenetic changes reported to be associated with COPD, as well as epigenetic modulators reported to be affected by COPD or smoking including the histone deacetylase (HDAC) family and DNA methyltransferase (DMT) family member DNMT1, as well as connections from these epigenetic mediators to the core cell cycle components (e.g. CCND1, CDKN2A). Reviewed during Jamboree2015

Endothelial Innate Immune Activation-2.0-Mm 2.0 by Causal Biological Networks Database
133 nodes | 416 edges | 276 citations | Public

The Endothelial Innate Immune Activation network depicts the causal mechanisms that describe acute response of healthy pulmonary endothelium to pro-inflammatory stimuli. These response mechanisms include production of the inflammatory chemokines, adhesion molecules and other mediators during endothelial cells activation leading to lung microvascular endothelial cells dysfunction. The network also includes causal mechanisms associated with angiogenic regulation by immune cells, including drivers of VEGF secretion and other related signaling pathways that crosstalk between the immune system and angiogenesis.

Endoplasmic Reticulum Stress-2.0-Mm 2.0 by Causal Biological Networks Database
83 nodes | 155 edges | 77 citations | Public

The Endoplasmic Reticulum Stress network depicts the causal mechanisms that regulate endoplasmic reticulum stress including the unfolded protein response and the pathways downstream of the three key stress mediators: PERK (EIF2AK3), ATF6, and IRE1alpha (ERN1). The pro-apoptotic arm of the ER stress response was excluded from this network, but included in the Apoptosis network where the context is more relevant.

ECM Degradation-2.0-Mm 2.0 by Causal Biological Networks Database
52 nodes | 147 edges | 63 citations | Public

The ECM Degradation network depicts the causal mechanisms involved in the key events leading to degradation of the extracellular matrix (ECM) in the context of COPD, including the release of proteases (e.g. MMPs and neutrophil elastase) from inflammatory cells, which degrade ECM components such as collagens, laminins and elastins. ECM degradation results in destruction of the alveolar walls, contributing to emphysema and COPD.

Dendritic Cell Signaling-2.0-Mm 2.0 by Causal Biological Networks Database
141 nodes | 339 edges | 239 citations | Public

The Dendritic Cell Signaling network depicts the causal mechanisms in key cytokine pathways leading to the activation of dendritic cells and their migration to both the lung tissue and lymph nodes. Chemokines and surface receptors expressed by dendritic cells that serve to promote T-cell migration and subsequent differentiation in the lung during COPD are included in the network. Reviewed during Jamboree2014

Cytotoxic T-cell Signaling-2.0-Mm 2.0 by Causal Biological Networks Database
44 nodes | 50 edges | 36 citations | Public

The Cytotoxic T-cell Signaling network depicts the causal mechanisms that are activated in CD8+ cytotoxic T-cells following T-cell receptor (TCR) ligation. Expanding on these processes, the network highlights the chemokines secreted by macrophages and dendritic cells, as well as the cognate T-cell receptors, involved in mediating T-cell recruitment to compromised lung tissue during COPD development.

Clock-2.0-Mm 2.0 by Causal Biological Networks Database
67 nodes | 108 edges | 26 citations | Public

The Clock network depicts the causal mechanisms that regulate circadian clock signaling leading to cell proliferation. The network focuses on downstream targets of the CLOCK:ARNTL transcriptional complex such as NR1D1, CRY1, PERs, and BHLHs.

Cell Interaction-2.0-Mm 2.0 by Causal Biological Networks Database
92 nodes | 125 edges | 44 citations | Public

The Cell Interaction network describes the causal mechanisms involved in the signal transduction pathways leading to cell proliferation that originate from the interactions between common cell adhesion molecules (including ITGB1 complexes with ITGA1-3 chains) and extracellular matrix components (specifically collagen, fibronectin, and laminin).

Cell Cycle-2.0-Mm 2.0 by Causal Biological Networks Database
153 nodes | 320 edges | 172 citations | Public

The Cell Cycle network depicts the causal mechanisms that regulate cell cycle including canonical elements of the core machinery regulating entry and exit from the mammalian cell cycle, such as cyclins, cyclin-dependent kinases and members of the E2F family. Reviewed during Jamboree2014