BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000001018?filename=Bakshi2020%20properdin%20model.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000001018?filename=Bakshi2020%20properdin%20model.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000001018?filename=Bakshi2020%20properdin%20model.cpsprimaryOK200Emilia ChenManually curatedordinary differential equation modelL2V4https://www.ebi.ac.uk/biomodels/BIOMD000000101832062771falseBioModelsSBMLModelsBakshi2020 Properdin model of alternative pathway of complement system2020MODEL2107200004Bakshi S, Cunningham F, Nichols EM, Biedzka-Sarek M, Neisen J, Petit-Frere S, Bessant C, Bansal L, Peletier LA, Zamuner S, van der Graaf PHBakshi S32062771,
The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP.. 2, 82.
1 Division of Systems Biomedicine and Pharmacology, LACDR, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands. suruchi.bakshi@certara.com.
2 Certara QSP, 4818 SJ, Breda, The Netherlands. suruchi.bakshi@certara.com.
3 Cytokine, Chemokine and Complement DPU, Immunoinflammation TA Unit, GSK, Stevenage, UK.
4 Computational and Modelling Sciences, Platform Technology Sciences, GSK, Collegeville, Pennsylvania, USA.
5 Mathematical Institute, Leiden University, P.O. Box 9512, 2300 RA, Leiden, The Netherlands.
6 Clinical Pharmacology, Modelling and Simulation, GSK, Stevenage, UK.
7 Division of Systems Biomedicine and Pharmacology, LACDR, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
8 Certara QSP, Canterbury, CT2 7FG, UK.emiliachen1@gmail.comUniversity of CambridgeBIOMD0000001018The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP.Mathematical Modelling of Alternative Pathway of Complement System.Bakshi Suruchi S, Cunningham Fraser F, Nichols Eva-Maria EM, Biedzka-Sarek Marta M, Neisen Jessica J, Petit-Frere Sebastien S, Bessant Christina C, Bansal Loveleena L, Peletier Lambertus A LA, Zamuner Stefano S, van der Graaf Piet H PHorgan system, BFD, Complement Factor P, anatomical systems, Factor P, Complement, body system., PFC, Pfc, PFD, system, connected anatomical system, Complement factor P, PROPERDIN, BCFGother disease, constant, Effects, nonspecific immune response, disorders, number, Longterm Effect, innate immunity, function, medical condition, body system, presence, Migrant Workers, Long Term, Concept, period, count in organism, Role Concept, diseases, Roles, Migrant, responsivity, Long Term Effects, Diseases, Role, Nomad, Concepts, disease or disorder, condition, system, diseases and disorders, Workers, connected anatomical system, Effect, regulation., Migrants and Transients, activation, reactivity, human disease, anatomical systems, absence, Migrant Worker, Longterm, absent from organism, Transients, uniform, Nonmigrant, Nonmigrants, Long-Term, Worker, Transient, Longterm Effects, organ system, non-neoplastic, Squatter, disease, Nomads, transient structure, Role Concepts, Pathologies, Squatters, disorder, Homo sapiens disease, Migrants, Long-Term Effect, regulation, response, quantitative, time, Long-Term Effects, presence or absence in organismNip40-1, DER/faint little ball, VAN, Van, HB-6, DCT1, other disease, D-Egf, BELLRINGER, Effects, C-erb, gdf3-a, nonspecific immune response, Elp-B1, der, number, Elp-1, mor1, ABIN, PNY, EK2-6, body system, presence, Migrant Workers, Long Term, DOI, van, period, l(3)04276, Publication, diseases, Roles, responsivity, c-erbB, EGFr, Concepts, disease or disorder, torpedo/Egfr, system, diseases and disorders, TOP, Egf-r, CG1977, d-egf-r, Effect, Virion-associated nuclear shuttling protein, doi, reactivity, mVAN, EGF-R, human disease, anatomical systems, vgr2, Migrant Worker, BLR, PENNYWISE, Longterm, absent from organism, Transients, uniform, Nonmigrant, top, Nonmigrants, dre1, Torpedo/DER, ABIN1, Long-Term, Worker, Transient, Nramp2, flb, top/flb, non-neoplastic, Squatter, Abstract, l(2)57EFa, transient structure, Nef, Role Concepts, Pathologies, Squatters, disorder, D-EGFR, Homo sapiens disease, l(2)57Ea, Long-Term Effect, Viewpoint, Editorial Comment, T7H20_80, Long-Term Effects, l(3)dre1, REPLUMLESS, HIV-1 Nef-interacting protein, DER1, Elp-B1RB1, constant, ABIN-1, DMT1, AU018810, Elp, l(2)09261, dEGFR1, DEgfr, T7H20.80, disorders, Longterm Effect, innate immunity, function, medical condition, derriere, CG10079, mk, Commentary, Concept, EVA1, BLH9, torpedo/egfr, count in organism, LSN, Role Concept, DmelCG10079, hVAN, Migrant, Long Term Effects, Diseases, Role, Nomad, EVA, condition, BEL1-LIKE HOMEODOMAIN 9, Workers, connected anatomical system, DmelCG32315, DER/top, Naf1, NAF1, regulation., CG32315, Migrants and Transients, activation, LARSON, egfr, A20-binding inhibitor of NF-kappa-B activation 1, absence, VAAMANA, HD-33, El, top/DER, Dlt, DER/EGFR, EGFR, EGfr, EgfR, Nef-associated factor 1, dEgfr, DER flb, Torpedo/Egfr, Longterm Effects, Degfr, organ system, disease, Egf, EFG-R, nip40-1, vgr-2, DEGFR, Nomads, l(2)57DEFa, l(2)05351, Manuscripts, Der, DER, dEGFR, Migrants, regulation, DmHD-33, response, quantitative, l(3)62Ba, time, DER/torpedo, presence or absence in organismorgan system, system, anatomical systems, connected anatomical system, body system.falseBakshi2020 - Properdin model of alternative pathway of complement system
This model is based on the publication:
"Mathematical Modelling of Alternative Pathway of Complement System".
Suruchi Bakshi, Fraser Cunningham, Eva-Maria Nichols, Marta Biedzka-Sarek, Jessica Neisen, Sebastien Petit-Frere, Christina Bessant, Loveleena Bansal, Lambertus A Peletier, Stefano Zamuner, Piet H van der Graaf
DOI: 10.1007/s11538-020-00708-z
Comment:
Correction to the original manuscript is accessible here
Model schematics in Figure 3 and parameter d4 were corrected.
Abstract:
The complement system (CS) is an integral part of innate immunity and can be activated via three different pathways. The alternative pathway (AP) has a central role in the function of the CS. The AP of complement system is implicated in several human disease pathologies. In the absence of triggers, the AP exists in a time-invariant resting state (physiological steady state). It is capable of rapid, potent and transient activation response upon challenge with a trigger. Previous models of AP have focused on the activation response. In order to understand the molecular machinery necessary for AP activation and regulation -of a physiological steady state, we built parsimonious AP models using experimentally supported kinetic parameters. The models further allowed us to test quantitative roles played by negative and positive regulators of the pathway in order to test hypotheses regarding their mechanisms of action, thus providing more insight into the complex regulation of AP.
2022-01-202021-07-202021-07-20BIOMD0000001018SBO:0000393SBO:0000179SBO:0000376SBO:0000181SBO:0000169SBO:0000180SBO:0000665PR:000004900PR:000019178PR:000005374PR:000019308PR:000005378PR:000005384PR:000005376PR:00000538732062771C17123MODEL2107200004BIOMD0000001018PW:0000505PATO:0000608PATO:0000610PATO:0002355GO:0045087GO:0030451GO:0045958GO:0005488GO:0002020GO:00459579606BTO:000013100044860024874