BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000989?filename=MODEL1712050001.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000989?filename=SMAD2_dose_kinetics.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000989?filename=MODEL1712050001.omexhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000989?filename=MODEL1712050001.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000989?filename=MODEL1712050001.cpsprimaryOK200uddipan sarmaManually curatedordinary differential equation modelL2V4https://www.ebi.ac.uk/biomodels/BIOMD000000098929371237falseBioModelsSBMLModelsMultiomicsStrasen2018 TGFb SMAD Signalling Dose dependent dynamics upon TGFb stimulation2018MODEL1712050001Strasen J, Sarma U, Jentsch M, Bohn S, Sheng C, Horbelt D, Knaus P, Legewie S, Loewer AStrasen J29371237,
The cytokine TGFb provides important information during embryonic development, adult tissue homeostasis, and regeneration. Alterations in the cellular response to TGFb are involved in severe human diseases. To understand how cells encode the extracellular input and transmit its information to elicit appropriate responses, we acquired quantitative time-resolved measurements of pathway activation at the single-cell level. We established dynamic time warping to quantitatively compare signaling dynamics of thousands of individual cells and described heterogeneous single-cell responses by mathematical modeling. Our combined experimental and theoretical study revealed that the response to a given dose of TGFb is determined cell specifically by the levels of defined signaling proteins. This heterogeneity in signaling protein expression leads to decomposition of cells into classes with qualitatively distinct signaling dynamics and phenotypic outcome. Negative feedback regulators promote heterogeneous signaling, as a SMAD7 knock-out specifically affected the signal duration in a subpopulation of cells. Taken together, we propose a quantitative framework that allows predicting and testing sources of cellular signaling heterogeneity.. 1, 14.
Berlin Institute for Medical Systems Biology, Max Delbrueck Center in the Helmholtz Association, Berlin, Germany.udi.tgfb.2015@gmail.comBIOMD0000000989The cytokine TGFβ provides important information during embryonic development, adult tissue homeostasis, and regeneration. Alterations in the cellular response to TGFβ are involved in severe human diseases. To understand how cells encode the extracellular input and transmit its information to elicit appropriate responses, we acquired quantitative time-resolved measurements of pathway activation at the single-cell level. We established dynamic time warping to quantitatively compare signaling dynamics of thousands of individual cells and described heterogeneous single-cell responses by mathematical modeling. Our combined experimental and theoretical study revealed that the response to a given dose of TGFβ is determined cell specifically by the levels of defined signaling proteins. This heterogeneity in signaling protein expression leads to decomposition of cells into classes with qualitatively distinct signaling dynamics and phenotypic outcome. Negative feedback regulators promote heterogeneous signaling, as a SMAD7 knock-out specifically affected the signal duration in a subpopulation of cells. Taken together, we propose a quantitative framework that allows predicting and testing sources of cellular signaling heterogeneity.Cell-specific responses to the cytokine TGFβ are determined by variability in protein levels.Strasen Jette J, Sarma Uddipan U, Jentsch Marcel M, Bohn Stefan S, Sheng Caibin C, Horbelt Daniel D, Knaus Petra P, Legewie Stefan S, Loewer Alexander ATgfb-1, ced, biological signaling, TGFB, tgf-beta, TGF-beta5, b2b1000Clo, 9830146M04, tgfb, DPD1, lap, Ltbp-1, TGF-beta1, signalling, TGFbeta, tgfbeta, CED, Tgfb, signalling process, TGFbeta1, signaling process, TGFbeta., 9430031G15Rik, tgfb5, dpd1, LAP, single organism signalingUVO Gene Mutation, ERBB2 Gene Amplification Negative, H. pylori Positive, CDH1 Wild-Type, Cytogenetically Normal, CEK Gene Mutation Negative, BCC7 Gene Mutation Negative, Post-implantation, ESTRB Negative, ECT1 Gene Rearrangement Negative, ERBB2 Amplification, Positive Charge, dmTAF[[II]]230, TRT Promoter Mutation Negative, GNA11 Gene Mutation Negative, Normal Tissue, RET/PTC Rearrangement, Hepatitis C Virus RNA Positive, p53 Mutation, PGR Positive, Met Proto-Oncogene (Hepatocyte Growth Factor Receptor) Gene Amplification Negative, responsivity, Accepted, HOW, node-negative, Importance Rating Score 0, BRAF Wildtype, H. pylori Negative, Hepatitis B Virus Core Antibody Negative, Methylated MGMT Promoter, ERA Positive, No rearrangement detected, HER2/neu Gene Mutation Negative, Involvement, G Protein Subunit Alpha q Gene Mutation, cel, IDH Gene Mutation, CD324 Gene Mutation, ESR Negative, FGFBR Gene Mutation Negative, Hepatitis B Virus Core Antibody Positive, c-KIT Positive, KGFR Gene Mutation Negative, PDCD1L1 Negative, N, result, Flavoprotein Subunit of Complex II Positive, Tissue, stru, B7H1 Positive, BEK Gene Mutation, l(3)S053606, MET Amplification Negative, node-positive, Cadherin 1 Gene Mutation, ESTRB Positive, HER2 Non-Amplified, XH2 Gene Mutation, PGR Negative, ATRX Mutation Negative, XNP Gene Mutation Negative, Catenin Beta 1 Gene Mutation, ER Beta Positive, Taken, FMS-Like Tyrosine Kinase 2 Gene Rearrangement Negative, PAX8 Gene Rearrangement Negative, Homo sapiens disease, Telomerase Reverse Transcriptase Gene Promoter Mutation, FGFR1 Rearrangement Negative, Combined, Methylated MGMT Gene Promoter, dTAF[[II]]230, TP53 Gene Mutation Negative, Human Immunodeficiency Virus Positive, Anti-HBc Negative, KGFR Gene Rearrangement, c-erbB2 Gene Amplification, Serum CA 19-9 Normal, TP53 Mutation Negative, Longterm Effect, B-RAF Gene Rearrangement, Endogenous, Anti-HBc Positive, BRAF wt, Normal skin, Normalcy, Hepatitis B Virus Surface Antibody Positive, not genetically inherited, Estrogen Receptor Alpha Positive, 1p/19q Co-deletion Negative, Human Immunodeficiency Virus Negative, TMEM16A Negative, SDHIP Positive, CTNNB1 Wildtype, Normal Cell, Cellular, FGFR-2 Gene Rearrangement, FLT2 Gene Mutation, FGFR-1 Gene Rearrangement, LCAM Gene Mutation Negative, Flavoprotein Subunit of Complex II Negative, RET Gene Rearrangement, Ret Proto-Oncogene Rearrangement Negative, activation, FGFR3 Wild-Type, NRAS Gene Mutation, ECAD Gene Mutation, Androgen Receptor Negative, EST2 Promoter Mutation, B7-H Negative, Present, ESR Positive, PDCD1L1 Positive, c-KIT Negative, p16INK4a Negative, v-Ets Erythroblastosis Virus E26 Oncogene Like Gene Rearrangement Negative, Positive EBV Serum Test, IDH Gene Family Mutation, Taf250, ATRX Gene Mutation Negative, Info, Unmethylated O-6-Methylguanine-DNA Methyltransferase Gene Promoter, Cells, EBV Negative, N-RAS Gene Mutation, HER2/Neu Amplification, Regeneration, TRP53 Gene Mutation Negative, KRAS Gene Mutation, B7H1 Negative, Feedbacks, Expression of PD-L1, Embryonic Programmings, Hepatitis B Core Antibody Negative, SDHF Positive, Nuclear Receptor Subfamily 3 Group A Member 2 Positive, heterogeneity., BRCA1-Associated Protein 1 Gene Mutation, CDHE Gene Mutation, HER-2 Gene Mutation Negative, B-RAF1 Gene Rearrangement Negative, number, Alpha Thalassemia/Mental Retardation Syndrome X-Linked Gene Mutation Negative, {Cells}, Anti-HBc Antibody Negative, Succinate Dehydrogenase [Ubiquinone] Iron-Sulfur Subunit, Hepatitis B Virus Surface Antigen Positive, Affected, Prenidation Embryo Development, period, CRCS3, SDHF Negative, BRCA1 Associated Protein 1 Gene Mutation Negative, K-SAM Gene Mutation Negative, Gene Products, Nuclear Receptor Subfamily 3 Group A Member 2 Negative, N-SAM Gene Rearrangement Negative, NRAS Wildtype, G Protein Subunit Alpha 11 Gene Mutation, CD333 Gene Mutation Negative, Expression Negative, KRAS Wildtype, GNA11 Wild-Type, ETV Rearrangement Negative, ESR1 Negative, B7-H Positive, c-MET Gene Amplification Negative, Cadherin-Associated Protein, B-RAF1 Gene Mutation Negative, dTAF[[II]]250, Pathologic Process Resolution, MGMT Gene Methylation, Longterm, cell, Hepatitis B Core Antibody Positive, Tissues, FGFR1 Gene Mutation Negative, FGFR-2 Gene Mutation Negative, CDH1 Mutation Negative, FGFR-2 Gene Rearrangement Negative, SDHA Negative, Population, outcome, KRAS2 Gene Mutation Negative, BEK Gene Rearrangement, dTAF250, RET Rearrangement, Alpha 11 Gene Mutation Negative, CELLULAR, RAD54 Homolog Gene Mutation, Mathematical, Estrogen Receptor Alpha Negative, ETV Family Rearrangement Negative, FLT2 Gene Mutation Negative, Keratinocyte Growth Factor Receptor Gene Rearrangement Negative, ERBB2 wt, p53 Gene Mutation Negative, HBsAg Negative, HER-2 Gene Amplification, NORMAL, Positive EBV Test, Cellularity Grade, SINGLE, Hepatitis B Virus Surface Antibody Negative, Q Polypeptide Gene Mutation Negative, Fibroblast Growth Factor Receptor 1 Gene Rearrangement Negative, ETS Transcription Factor ERG Gene Rearrangement Negative, PR Positive, Harvey Rat Sarcoma Viral Oncogene Homolog Gene Mutation Negative, Hepatitis B Surface Protein Antigen Positive, disorders, SDHIP Negative, Post-implantation Embryo Development, Preimplantation, Estrogen Receptor Positive, Madh7, FGFR2 Wild-Type, l(3)S090417, Negative Number, dTAF230, B-RAF1 Gene Rearrangement, Beta Catenin Gene Mutation Negative, del(10q23)/PTEN Gene Locus Deletion Negative, Cytokine, ATRX, CTNNB1 Gene Mutation Negative, BRAF Gene Rearrangement, affected, Long Term Effects, condition, TP53 wt, FLG Gene Mutation, PAX8 Rearrangement, Alpha-11 Gene Mutation Negative, Androgen Receptor Positive, HGFR Gene Amplification, ESR1 Positive, Hepatitis B Surface Protein Antigen Negative, NEGATIVE, Postimplantation Embryo Development, MET Gene Amplification, c-MET Gene Amplification, Paired Domain Gene 8 Gene Rearrangement Negative, Taf[[II]]250, ER-Alpha Positive, Single Person, BEK Gene Mutation Negative, Methylated MGMT, Unmethylated MGMT Promoter, ERG Rearrangement, HBsAg Positive, TERT Gene Promoter Mutation, ERBB2 Wildtype, No, extracellular, Ret Proto-Oncogene Rearrangement, signalling process, Lack of Expression of PD-L1, Catenin Beta 1 Gene Mutation Negative, IDH Mutation, 1p/19q Co-deletion, SDHA Positive, Q Polypeptide Gene Mutation, quantitative, Succinate Dehydrogenase [Ubiquinone] Flavoprotein Subunit, Estrogen Receptor 2 Positive, Anti-Hepatitis B Core Antibody Negative, XNP Gene Mutation, O-6-Methylguanine-DNA Methyltransferase Gene Promoter Methylation, LFS1 Gene Mutation Negative, ER Positive, Normal Male External Genitalia, BAP1 Wildtype, Telomerase Reverse Transcriptase Gene Promoter Mutation Negative, v-Ets Erythroblastosis Virus E26 Oncogene Like Gene Rearrangement, Human Herpesvirus-4 Negative, protein expression, HRAS1 Gene Mutation, G-ALPHA-q Gene Mutation, BAP1 Gene Mutation, Embryo Development, Cell Type, Population Group, ESR2 Negative, v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 Gene Mutation, ORAOV2 Negative, l(3)j5D5, TP53, Abnormal, gene expression, ATRX Wildtype, BRAF Mutation Negative, 24B, Group, MADH7, human disease, ESR-Beta Negative, Estrogen Receptor Beta Positive, CD274 Negative, DOG1 Positive, Keratinocyte Growth Factor Receptor Gene Mutation Negative, BAP1 wt, ETV Family Gene Rearrangement, Ets Variant Family Rearrangement, FLT2 Gene Rearrangement, hSMAD7, PAX8 Rearrangement Negative, l(3)j5B5, Rearrangement identified, How Often Felt Normal, FGFR3 Gene Rearrangement, Chromatin Remodeler Gene Mutation Negative, FGFR-1 Gene Rearrangement Negative, ECT1 Gene Mutation, Estrogen Receptor 1 Positive, Fibroblast Growth Factor Receptor 2 Gene Mutation, Erb-B2 Receptor Tyrosine Kinase Gene Mutation Negative, IDH Family Mutation, CD333 Gene Rearrangement, Normal, Mothers against decapentaplegic homolog 8, None detected, BAP1 Wild-Type, ER-Alpha Negative, Long-Term Effects, MADH8, None Detected, ATRX Gene Mutation, SDHB Loss, ERG Gene Rearrangement, Ha-ras Gene Mutation Negative, GNA-11 Gene Mutation Negative, GNAQ Wildtype, HBsAb Negative, FGFR-1 Gene Mutation Negative, Negative, Importance 0, HER2 Gene Mutation, TAFII-250, TAF250/230, FLT-2 Gene Mutation Negative, BRAF Wild Type, Gene Expression, Ets Variant Gene Family Rearrangement Negative, TAFII250, Defined, ESRA Negative, FGFR3 Rearrangement Negative, Involved, Hepatitis B Surface Antibody Positive, KAL2 Gene Mutation Negative, SZ1, ESTRR Negative, HIV Positive, Fibroblast Growth Factor Receptor 2 Gene Mutation Negative, HIV positive, 1p/19q Codeletion, FGFR2 Mutation Negative, POSITIVE, p16INK4 Negative, Guanine Nucleotide Binding Protein (G Protein), Yes, Modeling, HHV-4 Negative, SDH2 Positive, HRAS Gene Mutation Negative, Heterogeneity, E-Cadherin Gene Mutation Negative, ERBB2 Gene Mutation, estrogen receptor negative, CG17603, TAF[[II]], 1p/19q Intact, HER2 Wildtype, disease, FLT-2 Gene Rearrangement Negative, Expressed, ER-Beta Positive, HRAS Gene Mutation, Tumor Protein p53 Gene Mutation Negative, Unmethylated MGMT Gene Promoter, Harvey Rat Sarcoma Viral Oncogene Homolog Gene Mutation, Postimplantation, time, PR Negative, Resolved License, BRAF Rearrangement, Normal Chest Appearance, Important, CDH1 Gene Mutation, KAL2 Gene Rearrangement Negative, experimental, tissue, Math, P62, GAQ Gene Mutation Negative, Importance, Negative Finding, v-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog Negative, Anti-HBs Positive, dTAFII250, c-erbB2 Gene Activation, Development, Established, JKT4 Gene Mutation Negative, Cellularity Measurement, FGFR1 Wildtype, Degree, Neuroblastoma RAS Viral Oncogene Homolog Gene Mutation Negative, Definition, OGD Gene Mutation Negative, dmTAF1, Fp Positive, Fibroblast Growth Factor Receptor 1 Gene Rearrangement, Genetic heterogeneity, OGD Gene Mutation, SDHB Deficient, Anti-HBcAb Positive, Hep C RNA Positive, Anti-Hepatitis B Virus Surface Antibody Negative, c-K-ras Gene Mutation Negative, CD274 Antigen Positive, Epithelial Gene Mutation, Knock-out, TAF250, MET Proto-Oncogene, Mitochondrial Negative, Postnidation, reactivity, study, methods, Given, NR3A1 Negative, HHV4 Negative, NRAS Wild-Type, Promotion, experimental section, SWS Gene Mutation, TAOS2 Positive, GNA11 Wildtype, Normal Gait, G-ALPHA-q Gene Mutation Negative, PDL1 Negative, MAD homolog 7, MAD homolog 8, Methylguanine-DNA Methyltransferase Gene Promoter Methylation, FGFR1 Gene Rearrangement Negative, CD331 Gene Mutation Negative, p16(INK4a) Negative, Neuroblastoma RAS Viral Oncogene Homolog Gene Mutation, H-ras Gene Mutation, ETV Gene Rearrangement, Erg-3 Gene Rearrangement Negative, heterogeneity, CD332 Gene Rearrangement, Physiologic Resolution, Ets Variant Gene Family Rearrangement, Normal Abdomen on Visual Inspection, disorder, N-RAS Gene Mutation Negative, HER2 Gene Amplification, Long-Term Effect, TAF, CTNNB Gene Mutation, progesterone receptor positive, RASH1 Gene Mutation, KGFR Gene Rearrangement Negative, CD332 Gene Rearrangement Negative, TAF[[II]]250, Succinate Dehydrogenase Complex Flavoprotein Subunit A Negative, FLG Gene Rearrangement Negative, Anti-Hepatitis B Virus Core Antibody Positive, Beta Gene Mutation Negative, clone 2.39, FGFR3 Gene Mutation Negative, Input, Promoting, l(3)84Ab, FGFR1 Mutation Negative, medical condition, Normal Precordial Palpation Finding, Anti-HBs Antibody Negative, count in organism, NR3A2 Positive, p230, MGMT Gene Promoter Methylation, GNA11 wt, TMEM16A Positive, Catenin Beta-1 Gene Mutation, MGMT Methylation, AR Positive, who, Resolution, Anoctamin-1 Negative, ER Beta Negative, TAF[[II]]230, FMS-Like Tyrosine Kinase 2 Gene Mutation, UVO Gene Mutation Negative, HIV Positivity, Mast/Stem Cell Growth Factor Receptor Kit Positive, ERBB2 Mutation Negative, Normality, FGFR3 wt, Succinate Dehydrogenase Complex Iron Sulfur Subunit B Negative, Embryogenesis, FGFR-2 Gene Mutation, KIT Negative, ERA Negative, OGD Gene Rearrangement Negative, B-RAF Gene Mutation Negative, CTNNB1 wt, Calcium-Dependent Adhesion Protein, Absent, Protein Gene Products, SDH1 Negative, NEU Gene Amplification Negative, DmelCG17603, GTPase Gene Mutation Negative, CD324 Gene Mutation Negative, B7 Homolog 1 Negative, Only, qkr[93F], IDH wt Allele, HBs Antigen Positive, CD274 Molecule Positive, BAP1 Gene Mutation Negative, Single, presence or absence in organism, TAF1, GTPase Gene Mutation, Postnidation Embryo, Anti-HBsAb Positive, Beta Gene Mutation, SMAD family member 7, CDKN2A-p16(INK4a) Negative, Cyclin-Dependent Kinase 4 Inhibitor A Negative, Hepatitis B Surface Antigen Negative, Progesterone Receptor Positive, sci, FGFBR Gene Rearrangement, GNAQ Gene Mutation Negative, CDH1 Wildtype, Story, Long Term, UCHL2 Gene Mutation Negative, Compared, Nuclear Receptor Subfamily 3 Group A Member 1 Negative, GNAQ Mutation Negative, Progesterone Receptor Negative, FGFR-3 Gene Mutation Negative, H-ras Gene Mutation Negative, Normal Appearance of the Extremities, population, C-HA-RAS1 Gene Mutation Negative, How, Nuclear Receptor Subfamily 3 Group A Member 1 Positive, CDKN2A-p16 Negative, Erg-3 Gene Rearrangement, CD332 Gene Mutation, adult, Ha-ras Gene Mutation, v-raf Murine Sarcoma Viral Oncogene Homolog B1 Gene Rearrangement Negative, average, EXPRESSED, Theory, HRas Proto-Oncogene, Loss of Expression, BFGFR Gene Rearrangement Negative, TFIID TAF250, TRT Promoter Mutation, HBcAb Negative, GAQ Gene Mutation, Met Proto-Oncogene (Hepatocyte Growth Factor Receptor) Gene Amplification, Comparison, proteins, Isocitrate Dehydrogenase (NADP+) Gene Family Wildtype, Cytogenetic Abnormalities Absent, FGFR1 Gene Rearrangement, IP Negative, Normality-Based Dosing Unit, PD-L1+, Normal Capillary Refill Time, NEU Gene Mutation, v-raf Murine Sarcoma Viral Oncogene Homolog B1 Gene Rearrangement, Anti-HBsAb Negative, FGFR3 Gene Mutation, SDHB Positive, K-RAS Mutation, Receptor Tyrosine Kinase Gene Amplification Negative, CD331 Gene Rearrangement, Catenin Beta-1 Gene Mutation Negative, C-HA-RAS1 Gene Mutation, MET Amplification, ZNF-HX Gene Mutation, Negative Charge, HBs Antigen Negative, single organism signaling, ERBB2 Gene Amplification, Beta Catenin Gene Mutation, FGFR-3 Gene Rearrangement Negative, ER Alpha Negative, ERB Negative, ERBB2 Wild-Type, FGFR1 wt, CDH1 Gene Mutation Negative, TAF200, Resolution of Pathologic Process, Alpha 11 Gene Mutation, GNA11 Mutation Negative, CD331 Gene Mutation, ERB Positive, CD117 Negative, Cadherin, JKT4 Gene Rearrangement, Helicobacter pylori Negative, Arc-1 Gene Mutation Negative, CMC1 Gene Mutation, P53 Gene Mutation, Mathematics, Epstein Barr Virus Negative, EST2 Promoter Mutation Negative, HGFR Gene Amplification Negative, Guanine Nucleotide-Binding Protein, PAX8 Gene Rearrangement, HRAS Mutation Negative, v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 Gene Amplification Negative, NR3A1 Positive, Keratinocyte Growth Factor Receptor Gene Rearrangement, HER2 Amplification, Beta-Catenin Gene Mutation Negative, ATRX wt, human, experimental procedures, CD333 Gene Mutation, Positive Epstein-Barr Virus Test, Anti-Hepatitis B Virus Core Antibody Negative, HBs Negative, TERT Promoter Mutation Negative, ERG Gene Rearrangement Negative, GNAQ wt, CDHE Gene Mutation Negative, FGFBR Gene Mutation, CTNNB Gene Mutation Negative, TCS1 Promoter Mutation, MET Gene Amplification Negative, KRAS Gene Mutation Negative, Pathology Resolution, BRAF Gene Mutation Negative, TAF230, BFGFR Gene Mutation, Epstein-Barr Virus Negative, c-Met Amplification Negative, HER2 Gene Mutation Negative, G Protein Subunit Alpha q Gene Mutation Negative, Not Expressed, Effects, HCV RNA Positive, Determine, Negative Estrogen Receptor, HER2 wt, Theoretical, ER+, ER-, Receptor Tyrosine Kinase Gene Amplification, FGFR1 Gene Mutation, Cellularity, p55 Gene Rearrangement, FLG Gene Rearrangement, SMAD 7, CMC1 Gene Mutation Negative, PDCD1LG1 Positive, FGFBR Gene Rearrangement Negative, Li-Fraumeni Syndrome Gene Mutation Negative, disease or disorder, IDH Family Gene Mutation Negative, NRAS Gene Mutation Negative, Negative Lymph Node, Normalities, ETV Rearrangement, androgen receptor positive, Normal Skin, HBs Positive, Positive Number, FGFR3 Mutation Negative, Postnidation Embryo Development, JKT4 Gene Rearrangement Negative, positive test result, v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Gene Mutation, ZNF-HX Gene Mutation Negative, GA11 Gene Mutation Negative, Pre-implantation, Ets Variant Family Rearrangement Negative, Paired Box Gene 8 Gene Rearrangement Negative, Long-Term, GNAQ Gene Mutation, man, PDCD1LG1 Negative, Solution, PD-L1 Positive, NEU Gene Mutation Negative, CTNNB1 Gene Mutation, FGFR2 Gene Rearrangement, del10q23/Phosphatase and Tensin Homolog Gene Locus Negative, ANO1 Positive, CTNNB1 Wild-Type, Resolve, RAD54 Gene Mutation, NEG, ER-Beta Negative, Expression, BRCA1-Associated Protein 1 Gene Mutation Negative, Programmed Cell Death 1 Ligand 1 Negative, BFGFR Gene Mutation Negative, TCS1 Promoter Mutation Negative, HER2/neu Gene Amplification Negative, CD117 Positive, FGFR2 Gene Mutation, Helicobacter pylori Positive, Epithelial Gene Mutation Negative, FGFR3 Wildtype, ESRB Positive, Result, Proteins, Post implantation Embryo Development, BG:DS00004.13, qkr, CTNNB1 Mutation Negative, Hepatocyte Growth Factor Receptor Gene Amplification Negative, Cell, Positive Finding, TERT Gene Promoter Mutation Negative, GNA11 Gene Mutation, KH93F, KRAS Wild-Type, TAF[[II]]250/230, ATRX Wild-Type, CD333 Gene Rearrangement Negative, KIT Proto-Oncogene Tyrosine Protein Kinase Negative, Hepatocyte Growth Factor Receptor Gene Amplification, ESRB Negative, B-RAF Gene Rearrangement Negative, Embryonic, RET Rearrangement Negative, Regenerations, BRAF Rearrangement Negative, IDH Mutation Negative, Erb-B2 Receptor Tyrosine Kinase Gene Amplification Negative, HBcAb Positive, p16 Negative, Information, PD-L1 Negative, HER2 Gene Amplification Negative, Tumor Protein p53 Gene Mutation, Fibroblast Growth Factor Receptor 1 Gene Mutation Negative, IP Positive, Hepatitis B Surface Antigen Positive, Normal Appearance of Extremities, Normal Capillary Refill, RAD54L Gene Mutation Negative, Longterm Effects, signalling, N-RAS Mutation, FLT-2 Gene Mutation, Gene Proteins, ETS Transcription Factor ERG Gene Rearrangement, Fibroblast Growth Factor Receptor 3 Gene Rearrangement Negative, IDP Gene Mutation Negative, NRAS Mutation Negative, CDH1 wt, ETV Family Gene Rearrangement Negative, CEK Gene Mutation, Cell Types, ANO1 Negative, Solitary, FGFR1 Wild-Type, p16-INK4 Negative, Alpha-11 Gene Mutation, Chromatin Remodeler Gene Mutation, Alone, CEK Gene Rearrangement Negative, Fibroblast Growth Factor Receptor 1 Gene Mutation, Pre-implantation Embryo Development, SWS Gene Mutation Negative, adult stage, G Protein Subunit Alpha 11 Gene Mutation Negative, Hepatitis C Viral RNA Positive, ER Negative, FLT-2 Gene Rearrangement, JKT4 Gene Mutation, AR+, Pre implantation Embryo Development, KRAS Mutation, Embryonic Programming, BRAF Gene Rearrangement Negative, ESR-Beta Positive, Fibroblast Growth Factor Receptor 2 Gene Rearrangement, FGFR-3 Gene Rearrangement, diseases, FLG Gene Mutation Negative, diseases and disorders, HRAS Wild-Type, KGFR Gene Mutation, Human Herpesvirus 4 Negative, Effect, BAP1 Mutation Negative, estrogen receptor positive, CD332 Gene Mutation Negative, No mutation detected, Protein Expression, Determination, p55 Gene Rearrangement Negative, Cyclin-Dependent Kinase Inhibitor 2A Negative, CD331 Gene Rearrangement Negative, Alpha Thalassemia/Mental Retardation Syndrome X-Linked Gene Mutation, CG10293, Preimplantation Embryo Development, c-Met Gene Amplification, Mothers against DPP homolog 8, PR+, FMS-Like Tyrosine Kinase 2 Gene Rearrangement, PR-, TP53 Wildtype, Mothers against DPP homolog 7, signaling process, FGFR2 Gene Rearrangement Negative, Anti-Hepatitis B Core Antibody Positive, Estrogen Receptor 2 Negative, FGFR2 Gene Mutation Negative, B7 Homolog 1 Positive, Beta 1 (88kD) Gene Mutation, Positive, Outcome, CD274 Molecule Negative, Importance Score 0, SDH2 Negative, v-Ha-ras Harvey Rat Sarcoma Viral Oncogene Homolog Gene Mutation Negative, Normal Thoracic Appearance, negative test result, 0904/17, FMS-Like Tyrosine Kinase 2 Gene Mutation Negative, Estrogen Receptor 1 Negative, Determined, Anti-HBs Antibody Positive, XH2 Gene Mutation Negative, TP53 Gene Mutation, Paired Box 8 Gene Rearrangement Negative, Hepatitis B Surface Antibody Negative, Normal Reference Range, 1p/19q co-deletion, KIT Proto-Oncogene Tyrosine Protein Kinase Positive, v-Ha-ras Harvey Rat Sarcoma Viral Oncogene Homolog Gene Mutation, Positive Estrogen Receptor, NR3A2 Negative, HBsAb Positive, K-SAM Gene Mutation, Succinate Dehydrogenase Complex Flavoprotein Subunit A Positive, HRAS wt, Diseases, NOS, Estrogen Receptor Negative, Succinate Dehydrogenase Complex Iron Sulfur Subunit B Positive, Adults, KRAS2 Gene Mutation, Normal Immune Presence, ETV Gene Rearrangement Negative, IDH Gene Family Wildtype, HER-2 Gene Amplification Negative, adults, Paired Domain Gene 8 Gene Rearrangement, ERBB2 Gene Mutation Negative, RASH1 Gene Mutation Negative, IDH Gene Mutation Negative, Isocitrate Dehydrogenase Gene Family Wild Type, GNAQ Wild-Type, 10q23/PTEN Locus Deletion Negative, Programmed Cell Death 1 Ligand 1 Positive, ESR2 Positive, BEK Gene Rearrangement Negative, Hepatitis C RNA Positive, Type 1, Positive Laboratory Test Result, Paired Box 8 Gene Rearrangement, ECAD Gene Mutation Negative, LCAM Gene Mutation, Health, Endogenous Regeneration, transmit, SR3-5, DOG1 Negative, E-Cadherin Gene Mutation, v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog Gene Mutation Negative, Knockout, FGFR2 Wildtype, anon-EST:Liang-2.39, Hepatitis B Virus Surface Antigen Negative, Subpopulation, Arc-1 Gene Mutation, N-SAM Gene Mutation, N-SAM Gene Rearrangement, CD274 Positive, other disease, d230, biological signaling, human being, LOST, v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 Gene Mutation Negative, Definable, KRAS-2 Gene Mutation, Give, PDL1 Positive, IDH Family Wildtype, Gene, KIT Positive, Anti-HBc Antibody Positive, Compare, TERT Promoter Mutation, ECT1 Gene Mutation Negative, EfW1, presence, KAL2 Gene Mutation, ECT1 Gene Rearrangement, Anti-HBcAb Negative, FGFR2 wt, Anoctamin-1 Positive, FGFR-3 Gene Mutation, Taf230, FLT2 Gene Rearrangement Negative, CD274 Antigen Negative, Embryonic Developments, HRAS Wildtype, Anti-Hepatitis B Virus Surface Antibody Positive, Fp Negative, Negative Test Result, Anti-HBs Negative, Animal, Level, HIV test positive, FGFR3 Gene Rearrangement Negative, N-SAM Gene Mutation Negative, Erb-B2 Receptor Tyrosine Kinase Gene Mutation, BFGFR Gene Rearrangement, Taf200, SDHB Deficiency, tissue maintenance, l(3)s2612, 1p/19q Codeletion Negative, Fibroblast Growth Factor Receptor 3 Gene Mutation, Cadherin 1, Mast/Stem Cell Growth Factor Receptor Kit Negative, E-Cadherin (Epithelial) Gene Mutation, HER2/neu Gene Mutation, Taf1p, BRCA1 Associated Protein 1 Gene Mutation, v-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog Positive, Positive Surgical Margin, RAD54 Gene Mutation Negative, non-neoplastic, Cellularity Index, Positive Lymph Node, Percent Cellularity, TISSUE, Promote, DmelCG10293, C-H-RAS Gene Mutation, OGD Gene Rearrangement, KAL2 Gene Rearrangement, SDH1 Positive, ER Alpha Positive, Cadherin 1 Gene Mutation Negative, Smad7, UCHL2 Gene Mutation, v-raf Murine Sarcoma Viral Oncogene Homolog B1 Gene Mutation Negative, RAD54L Gene Mutation, AR Negative, GNA-11 Gene Mutation, RET Gene Rearrangement Negative, HIV Negative, CEK Gene Rearrangement, NRAS wt, KRAS-2 Gene Mutation Negative, del(1p/19q) Negative, FGFR2 Rearrangement Negative, ERBB2 Non-Amplified, Fibroblast Growth Factor Receptor 3 Gene Mutation Negative, Resolved, Loss of Chromosomes 1p/19q, ESTRR Positive, K-SAM Gene Rearrangement, KRAS wt, Testing, TP2 Promoter Mutation Negative, IDH Wild Type, del(1p/19q), Normal Point of Maximum Impulse, HER2 Wild-Type, Fibroblast Growth Factor Receptor 3 Gene Rearrangement, Protein, TFIID, Fibroblast Growth Factor Receptor 2 Gene Rearrangement Negative, ESRA Positive, ERG Rearrangement Negative, K-SAM Gene Rearrangement Negative, ERBB2 Mutation, Embryo, progesterone receptor negative, ETV Family Rearrangement, Beta-Catenin Gene Mutation, GA11 Gene Mutation, distinct, MGMT Gene Promoter Methylation Negative, Paired Box Gene 8 Gene Rearrangement, TP2 Promoter Mutation, ORAOV2 Positive, TAF[II]250, Who/How, Unit of Concentration, RET/PTC Rearrangement Negative, Unmethylated Methylguanine-DNA Methyltransferase Gene Promoter, No abnormality detected, Floor, BAP1 Mutation, c-K-ras Gene Mutation, Data Transmission, Estrogen Receptor Beta Negative, SDHB Negative, FGFR-1 Gene Mutation, response, Mitochondrial Positive, Positive Margins, TAOS2 NegativeTgfb-1, Manuscripts., tgfbeta, ced, CED, Ligand, Tgfb, TGFB, tgf-beta, TGFbeta1, ligand, TGF-beta5, 9430031G15Rik, tgfb5, dpd1, b2b1000Clo, 9830146M04, tgfb, DPD1, lap, LAP, Ltbp-1, TGF-beta1, TGFbetaTaf[[II]]250, Taf200, dTAF[[II]]230, TAF[[II]]250, d230, dTAF[[II]]250, TAF[[II]]230, Determined, TFIID TAF250, cel, Determination, cell, TAF200, l(3)84Ab, dTAFII250, Taf1p, TAF[II]250, BG:DS00004.13, TAFII-250, Determine, CG17603, TAF250/230, TAF[[II]], EfW1, Cell, dTAF230, Specified, dTAF250, dmTAF[[II]]230, protein levels., TAFII250, DmelCG17603, Cytokine, Taf250, dmTAF1, SR3-5, Taf230, Specific, p230, TAF[[II]]250/230, TFIID, variability of a physical quality, TAF, TAF230, TAF250, TAF1falseStrasen2018 - TGFb SMAD Signalling - Dose dependent dynamics upon TGFb stimulation
This model simulates TGFb dose dependent kinetics of The SMADs. TGFb ligand dose applied are 1pM, 2.5pM, 5pM, 25pM, and 100pM as explained in the manuscript.
2021-02-172021-02-172017-12-05BIOMD00000009890000274SBO:0000179SBO:0000216SBO:0000180SBO:0000330SBO:0000393SBO:0000297SBO:0000665TEDDY_0000034PR:00003707029371237C45329C13226C13197C13376C154407C20139C40702MODEL1712050001BIOMD0000000989GO:0001881GO:0070208SBO:0000180GO:0070207GO:0006606GO:0006611GO:0009299GO:0006397GO:0038105GO:0007179GO:0070021GO:0016197GO:0070206GO:0032801GO:0034394GO:0007181GO:0048227GO:19901269606BTO:0001211P36897P01137P37173Q15796Q13485O15105