Becker2010_EpoR_CoreModel

This is the core model described in the article:
Covering a Broad Dynamic Range: Information Processing at the Erythropoietin Receptor

Verena Becker, Marcel Schilling, Julie Bachmann, Ute Baumann, Andreas Raue, Thomas Maiwald, Jens Timmer and Ursula Klingmüller; Science
Published Online May 20, 2010; DOI: 10.1126/science.1184913
PMID: 20488988

Abstract:
Cell surface receptors convert extracellular cues into receptor activation, thereby triggering intracellular signaling networks and controlling cellular decisions. A major unresolved issue is the identification of receptor properties that critically determine processing of ligand-encoded information. We show by mathematical modeling of quantitative data and experimental validation that rapid ligand depletion and replenishment of cell surface receptor are characteristic features of the erythropoietin (Epo) receptor (EpoR). The amount of Epo-EpoR complexes and EpoR activation integrated over time corresponds linearly to ligand input, covering a broad range of ligand concentrations. This relation solely depends on EpoR turnover independent of ligand binding, suggesting an essential role of large intracellular receptor pools. These receptor properties enable the system to cope with basal and acute demand in the hematopoietic system.
SBML model exported from PottersWheel.
% PottersWheel model definition file

function m = BeckerSchilling2010_EpoR_CoreModel()

m = pwGetEmptyModel();

%% Meta information

m.ID = 'BeckerSchilling2010_EpoR_CoreModel';
m.name = 'BeckerSchilling2010_EpoR_CoreModel';
m.description = 'BeckerSchilling2010_EpoR_CoreModel';
m.authors = {'Verena Becker',' Marcel Schilling'};
m.dates = {'2010'};
m.type = 'PW-2-0-42';

%% X: Dynamic variables
% m = pwAddX(m, ID, startValue, type, minValue, maxValue, unit, compartment, name, description, typeOfStartValue)

m = pwAddX(m, 'EpoR' , 516, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'Epo' , 2030.19, 'global', 1890, 2310, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'Epo_EpoR' , 0, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'Epo_EpoRi', 0, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'dEpoi' , 0, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'dEpoe' , 0, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');

%% R: Reactions
% m = pwAddR(m, reactants, products, modifiers, type, options, rateSignature, parameters, description, ID, name, fast, compartments, parameterTrunks, designerPropsR, stoichiometry, reversible)

m = pwAddR(m, { }, {'EpoR' }, { }, 'C' , [] , 'k1*k2', {'kt','Bmax'}, [], 'reaction0001');
m = pwAddR(m, {'EpoR' }, { }, { }, 'MA', [] , [] , {'kt' }, [], 'reaction0002');
m = pwAddR(m, {'Epo','EpoR'}, {'Epo_EpoR' }, { }, 'MA', [] , [] , {'kon' }, [], 'reaction0003');
m = pwAddR(m, {'Epo_EpoR' }, {'Epo','EpoR'}, { }, 'MA', [] , [] , {'koff' }, [], 'reaction0004');
m = pwAddR(m, {'Epo_EpoR' }, {'Epo_EpoRi' }, { }, 'MA', [] , [] , {'ke' }, [], 'reaction0005');
m = pwAddR(m, {'Epo_EpoRi' }, {'Epo','EpoR'}, { }, 'MA', [] , [] , {'kex' }, [], 'reaction0006');
m = pwAddR(m, {'Epo_EpoRi' }, {'dEpoi' }, { }, 'MA', [] , [] , {'kdi' }, [], 'reaction0007');
m = pwAddR(m, {'Epo_EpoRi' }, {'dEpoe' }, { }, 'MA', [] , [] , {'kde' }, [], 'reaction0008');

%% C: Compartments
% m = pwAddC(m, ID, size, outside, spatialDimensions, name, unit, constant)

m = pwAddC(m, 'cell', 1);

%% K: Dynamical parameters
% m = pwAddK(m, ID, value, type, minValue, maxValue, unit, name, description)

m = pwAddK(m, 'kt' , 0.0329366 , 'global', 1e-007, 1000);
m = pwAddK(m, 'Bmax', 516 , 'fix' , 492 , 540 );
m = pwAddK(m, 'kon' , 0.00010496, 'global', 1e-007, 1000);
m = pwAddK(m, 'koff', 0.0172135 , 'global', 1e-007, 1000);
m = pwAddK(m, 'ke' , 0.0748267 , 'global', 1e-007, 1000);
m = pwAddK(m, 'kex' , 0.00993805, 'global', 1e-007, 1000);
m = pwAddK(m, 'kdi' , 0.00317871, 'global', 1e-007, 1000);
m = pwAddK(m, 'kde' , 0.0164042 , 'global', 1e-007, 1000);

%% Default sampling time points
m.t = 0:3:99;

%% Y: Observables
% m = pwAddY(m, rhs, ID, scalingParameter, errorModel, noiseType, unit, name, description, alternativeIDs, designerProps)

m = pwAddY(m, 'Epo + dEpoe' , 'Epo_extracellular_obs');
m = pwAddY(m, 'Epo_EpoR' , 'Epo_cellsurface_obs' );
m = pwAddY(m, 'Epo_EpoRi + dEpoi', 'Epo_intracellular_obs');

%% S: Scaling parameters
% m = pwAddS(m, ID, value, type, minValue, maxValue, unit, name, description)

m = pwAddS(m, 'scale_Epo_extracellular_obs', 1, 'fix', 0, 100);
m = pwAddS(m, 'scale_Epo_cellsurface_obs' , 1, 'fix', 0, 100);
m = pwAddS(m, 'scale_Epo_intracellular_obs', 1, 'fix', 0, 100);

%% Designer properties (do not modify)
m.designerPropsM = [1 1 1 0 0 0 400 250 600 400 1 1 1 0 0 0 0];
This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2010 The BioModels.net Team.
For more information see the terms of use
.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

本数据集对应发表于《科学》（Science）期刊的文章核心模型：覆盖宽广动态范围：促红细胞生成素受体的信息处理过程

作者：Verena Becker、Marcel Schilling、Julie Bachmann、Ute Baumann、Andreas Raue、Thomas Maiwald、Jens Timmer及Ursula Klingmüller；发表于2010年5月20日在线版；DOI：10.1126/science.1184913；PMID：20488988

摘要：细胞表面受体可将胞外信号转换为受体激活状态，进而触发胞内信号网络并调控细胞命运决策。目前尚未解决的关键科学问题之一，是如何鉴定可决定性调控配体编码信息处理过程的受体特性。本文通过对定量数据的数学建模与实验验证，证明配体快速耗竭与细胞表面受体补充循环是促红细胞生成素（Erythropoietin, Epo）受体（EpoR）的典型特征。随时间积分得到的Epo-EpoR复合物总量与EpoR激活程度，与配体输入量呈线性相关，可覆盖极宽范围的配体浓度。该关联关系仅依赖于不依赖配体结合的EpoR周转过程，提示胞内大型受体库发挥了关键作用。上述受体特性使得该系统可满足造血系统的基础与急性需求。

本SBML模型由PottersWheel工具导出。
% PottersWheel模型定义文件
function m = BeckerSchilling2010_EpoR_CoreModel()

m = pwGetEmptyModel();

%% 元信息
m.ID = 'BeckerSchilling2010_EpoR_CoreModel';
m.name = 'BeckerSchilling2010_EpoR_CoreModel';
m.description = 'BeckerSchilling2010_EpoR_CoreModel';
m.authors = {'Verena Becker',' Marcel Schilling'};
m.dates = {'2010'};
m.type = 'PW-2-0-42';

%% X: 动态变量
% m = pwAddX(m, 标识符, 初始值, 类型, 最小值, 最大值, 单位, 区室, 名称, 描述, 起始值类型)
m = pwAddX(m, 'EpoR' , 516, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'Epo' , 2030.19, 'global', 1890, 2310, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'Epo_EpoR' , 0, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'Epo_EpoRi', 0, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'dEpoi' , 0, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');
m = pwAddX(m, 'dEpoe' , 0, 'fix' , 0, 10000, [], 'cell', [] , [] , [] , [] , 'protein.generic');

%% R: 反应
% m = pwAddR(m, 反应物, 产物, 修饰因子, 类型, 选项, 速率特征, 参数, 描述, 标识符, 名称, 快速反应, 区室, 参数Trunks, 设计器属性, 化学计量比, 可逆性)
m = pwAddR(m, { }, {'EpoR' }, { }, 'C' , [] , 'k1*k2', {'kt','Bmax'}, [], 'reaction0001');
m = pwAddR(m, {'EpoR' }, { }, { }, 'MA', [] , [] , {'kt' }, [], 'reaction0002');
m = pwAddR(m, {'Epo','EpoR'}, {'Epo_EpoR' }, { }, 'MA', [] , [] , {'kon' }, [], 'reaction0003');
m = pwAddR(m, {'Epo_EpoR' }, {'Epo','EpoR'}, { }, 'MA', [] , [] , {'koff' }, [], 'reaction0004');
m = pwAddR(m, {'Epo_EpoR' }, {'Epo_EpoRi' }, { }, 'MA', [] , [] , {'ke' }, [], 'reaction0005');
m = pwAddR(m, {'Epo_EpoRi' }, {'Epo','EpoR'}, { }, 'MA', [] , [] , {'kex' }, [], 'reaction0006');
m = pwAddR(m, {'Epo_EpoRi' }, {'dEpoi' }, { }, 'MA', [] , [] , {'kdi' }, [], 'reaction0007');
m = pwAddR(m, {'Epo_EpoRi' }, {'dEpoe' }, { }, 'MA', [] , [] , {'kde' }, [], 'reaction0008');

%% C: 区室
% m = pwAddC(m, 标识符, 体积, 外部, 空间维度, 名称, 单位, 恒定)
m = pwAddC(m, 'cell', 1);

%% K: 动力学参数
% m = pwAddK(m, 标识符, 值, 类型, 最小值, 最大值, 单位, 名称, 描述)
m = pwAddK(m, 'kt' , 0.0329366 , 'global', 1e-007, 1000);
m = pwAddK(m, 'Bmax', 516 , 'fix' , 492 , 540 );
m = pwAddK(m, 'kon' , 0.00010496, 'global', 1e-007, 1000);
m = pwAddK(m, 'koff', 0.0172135 , 'global', 1e-007, 1000);
m = pwAddK(m, 'ke' , 0.0748267 , 'global', 1e-007, 1000);
m = pwAddK(m, 'kex' , 0.00993805, 'global', 1e-007, 1000);
m = pwAddK(m, 'kdi' , 0.00317871, 'global', 1e-007, 1000);
m = pwAddK(m, 'kde' , 0.0164042 , 'global', 1e-007, 1000);

%% 默认采样时间点
m.t = 0:3:99;

%% Y: 可观测变量
% m = pwAddY(m, 右式, 标识符, 缩放参数, 误差模型, 噪声类型, 单位, 名称, 描述, 替代标识符, 设计器属性)
m = pwAddY(m, 'Epo + dEpoe' , 'Epo_extracellular_obs');
m = pwAddY(m, 'Epo_EpoR' , 'Epo_cellsurface_obs' );
m = pwAddY(m, 'Epo_EpoRi + dEpoi', 'Epo_intracellular_obs');

%% S: 缩放参数
% m = pwAddS(m, 标识符, 值, 类型, 最小值, 最大值, 单位, 名称, 描述)
m = pwAddS(m, 'scale_Epo_extracellular_obs', 1, 'fix', 0, 100);
m = pwAddS(m, 'scale_Epo_cellsurface_obs' , 1, 'fix', 0, 100);
m = pwAddS(m, 'scale_Epo_intracellular_obs', 1, 'fix', 0, 100);

%% 设计器属性（请勿修改）
m.designerPropsM = [1 1 1 0 0 0 400 250 600 400 1 1 1 0 0 0 0];

本模型源自BioModels数据库：一款经过注释的已发表量化动力学模型数据库。版权所有©2005-2010 The BioModels.net Team。
更多信息请参阅使用条款。
如需引用BioModels数据库，请使用：Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92。