Merge branch 'main' of https://github.com/sys-bio/temp-biomodels

sys-bio · Jun 4, 2024 · 63d91f4 · 63d91f4
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diff --git a/final/BIOMD0000001013/metadata.rdf b/final/BIOMD0000001013/metadata.rdf
@@ -9,46 +9,59 @@
   <rdf:Description rdf:about="http://omex-library.org/BIOMD0000001013.omex">
     <bqmodel:isDescribedBy rdf:resource="local:00001"/>
     <ns1:keyword xmlns:ns1="http://prismstandard.org/namespaces/basic/2.0/">Biomodels</ns1:keyword>
-    <ns2:title xmlns:ns2="http://purl.org/dc/elements/1.1/">Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept</ns2:title>
-    <ns3:thumbnail xmlns:ns3="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 3a - CAR-T cells.png"/>
+    <ns2:description xmlns:ns2="http://purl.org/dc/elements/1.1/">&lt;body xmlns="http://www.w3.org/1999/xhtml"&gt;
+  &lt;pre&gt;This model of the use of chimeric antigen receptor (CAR)-T cell therapy in the treatment of solid tumours is described in the article:
+&amp;quot;Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept&amp;quot;
+Odelaisy León-Triana, Antonio Pérez-Martínez, Manuel Ramírez-Orellana and Víctor M. Pérez-García
+Cancers 2021, 13, 703.; doi: 10.3390/cancers13040703
+
+Comment:
+This is the first mathematical model, derived from equations 1 and 2, used in the paper.
+Reproduction of Fig. 5a was achieved by setting alpha_1 = 0.04, different to the value quoted in the article caption for Fig. 5.
+
+Abstract:
+Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial success against B-cell malignancies, which has led to a growing scientific and clinical interest in extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immunosuppressive tumour microenvironment, which is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, taking into account their immunosuppressive capacity. Using the mathematical model, we show that the use of large numbers of CAR-T cells targetting the solid tumour antigens could overcome the immunosuppressive potential of cancer. To achieve such high levels of CAR-T cells we propose, and study computationally, the manufacture and injection of CAR-T cells targetting two antigens: CD19 and a tumour-associated antigen. We study in silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive production of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its immune suppression capabilities. This strategy could benefit from the combination with PD-1 inhibitors and low tumour loads. Our computational results provide theoretical support for the treatment of different types of solid tumours using T cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD-1 drugs after completion of classical cytoreductive treatments.&lt;/pre&gt;
+&lt;/body&gt;</ns2:description>
+    <ns3:title xmlns:ns3="http://purl.org/dc/elements/1.1/">Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept</ns3:title>
     <ns4:thumbnail xmlns:ns4="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 3a - tumour cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 3a - CAR-T cells.png"/>
     <ns5:thumbnail xmlns:ns5="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 3b - CAR-T cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 3a - tumour cells.png"/>
     <ns6:thumbnail xmlns:ns6="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 3b - tumour cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 3b - CAR-T cells.png"/>
     <ns7:thumbnail xmlns:ns7="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4a - CAR-T cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 3b - tumour cells.png"/>
     <ns8:thumbnail xmlns:ns8="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4a - tumour cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4a - CAR-T cells.png"/>
     <ns9:thumbnail xmlns:ns9="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4b - CAR-T cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4a - tumour cells.png"/>
     <ns10:thumbnail xmlns:ns10="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4b - tumour cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4b - CAR-T cells.png"/>
     <ns11:thumbnail xmlns:ns11="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4c - CAR-T cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4b - tumour cells.png"/>
     <ns12:thumbnail xmlns:ns12="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4c - tumour cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4c - CAR-T cells.png"/>
     <ns13:thumbnail xmlns:ns13="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 1a.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Fig 4c - tumour cells.png"/>
     <ns14:thumbnail xmlns:ns14="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 1b.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 1a.png"/>
     <ns15:thumbnail xmlns:ns15="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 1c.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 1b.png"/>
     <ns16:thumbnail xmlns:ns16="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 1d.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 1c.png"/>
     <ns17:thumbnail xmlns:ns17="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 5a - CAR T-cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 1d.png"/>
     <ns18:thumbnail xmlns:ns18="http://www.collex.org/schema#"
-       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 5a - tumour cells.png"/>
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 5a - CAR T-cells.png"/>
     <ns19:thumbnail xmlns:ns19="http://www.collex.org/schema#"
+       rdf:resource="http://omex-library.org/BIOMD0000001013.omex/Leon-Triana2021 Fig 5a - tumour cells.png"/>
+    <ns20:thumbnail xmlns:ns20="http://www.collex.org/schema#"
        rdf:resource="http://omex-library.org/BIOMD0000001013.omex/curation_image.png"/>
   </rdf:Description>
   <rdf:Description rdf:about="local:00001">
-    <ns20:identifier xmlns:ns20="http://purl.org/dc/elements/1.1/"
+    <ns21:identifier xmlns:ns21="http://purl.org/dc/elements/1.1/"
        rdf:resource="http://identifiers.org/doi/10.3390/cancers13040703"/>
-    <ns21:label xmlns:ns21="http://www.w3.org/2000/01/rdf-schema#">Odelaisy León-Triana, Antonio Pérez-Martínez, Manuel Ramírez-Orellana &amp; Víctor M. Pérez-García. Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept. Cancers 13, 4 (2021).</ns21:label>
+    <ns22:label xmlns:ns22="http://www.w3.org/2000/01/rdf-schema#">Odelaisy León-Triana, Antonio Pérez-Martínez, Manuel Ramírez-Orellana &amp; Víctor M. Pérez-García. Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept. Cancers 13, 4 (2021).</ns22:label>
   </rdf:Description>
 </rdf:RDF>
 
diff --git a/final/BIOMD0000001027/metadata.rdf b/final/BIOMD0000001027/metadata.rdf
@@ -9,14 +9,46 @@
   <rdf:Description rdf:about="http://omex-library.org/BIOMD0000001027.omex">
     <bqmodel:isDescribedBy rdf:resource="local:00001"/>
     <ns1:keyword xmlns:ns1="http://prismstandard.org/namespaces/basic/2.0/">Biomodels</ns1:keyword>
-    <ns2:title xmlns:ns2="http://purl.org/dc/elements/1.1/">Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues</ns2:title>
-    <ns3:thumbnail xmlns:ns3="http://www.collex.org/schema#"
+    <ns2:description xmlns:ns2="http://purl.org/dc/elements/1.1/">&lt;body xmlns="http://www.w3.org/1999/xhtml"&gt;
+  &lt;p&gt;This model is supplementary material of publication &amp;quot;Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues&amp;quot;
+by Darta Maija Zake, Linda Zaharenko, Janis Kurlovics, Vitalijs Komasilovs, Janis Klovins and Egils Stalidzans.
+
+The model is pre-set for simulation of a single peroral dose.
+
+This is a whole-body model representing the pharmacokinetics of metformin in the mouse body. The model is in the form of ordinary differential equations and describes metformin concentration in 20 compartments. 
+
+The model consists of 20 compartments (“Compartments” in COPASI model) describing various tissues or tissue sub-compartments and body fluids of metformin action (venous and arterial plasma, intestine, kidney, heart, fat, muscle, brain, lungs, stomach, liver, portal vein, remainder urine and feces). Body weight and the weight of all compartments is expressed as a volume in mL and for the calculations it is assumed that 1mL = 1g. The volumes of most compartments are calculated as a fraction of the body weight/volume, and the fractions are determined from literature data, the volumes of the stomach lumen and intestine lumen are fixed and do not change depending on the body weight.  Similarly, the volume of external urine and feces is set to 1mL, but those are “volumeless” compartments as they are only necessary for the calculation of metformin amount, not concentration. 
+
+
+The model consists of 20 species (“Species” in COPASI model) that correspond to the metformin concentrations in the 20 compartments. The initial concentrations for all the species are 0 nmol/mL as metformin is not produced in the body and can only be detected after dose administration. 
+
+
+The model consists of 33 reactions – they describe the transport processes of metformin in the body. The reactions include local parameters that are involved only in that particular reaction and global parameters – parameters that are used in multiple reactions or are calculated depending on another parameter e.g. scale-up coefficients. 
+
+
+The model consists of 52 global quantities – parameters involved in multiple reactions or necessary for another parameter calculation:
+
+1.Parameters describing metformin dose – either in peroral (Metformin Dose in Lumen in mg) or intravenous (Metformin Dose in Plasma in mg). 
+
+2.Parameter describing mice physiology – body weight (in mL), cardiac output, blood flow to different compartments described as Q”compartment_name” (for example Qliver describes blood flow to the liver compartment). Qgfr refers to the glomerular filtration rate. 
+
+3.Tissue:plasma partition coefficients (Ktp) that are necessary for the scale-up to humans.
+
+4.Parameters involved in the calculation of metformin amount in mg, these parameters are named mg”Compartment_name” (for example mgLiver describes the metformin amount in mg in the liver tissues). 
+
+
+The time points of dose release are defined as “events” in COPASI and can be changed as necessary. 
+
+Time course simulations can be accessed through the section “Time Course” in this section the time duration and intervals can be changed. When time-course simulations are run three plots are created – Metformin amount in the 20 compartments, metformin concentrations in the compartments and reaction fluxes of all the reactions (see “Output Specifications” -&amp;gt; “Plots” to activate or deactivate plots).&lt;/p&gt;
+&lt;/body&gt;</ns2:description>
+    <ns3:title xmlns:ns3="http://purl.org/dc/elements/1.1/">Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues</ns3:title>
+    <ns4:thumbnail xmlns:ns4="http://www.collex.org/schema#"
        rdf:resource="http://omex-library.org/BIOMD0000001027.omex/curation_image.png"/>
   </rdf:Description>
   <rdf:Description rdf:about="local:00001">
-    <ns4:identifier xmlns:ns4="http://purl.org/dc/elements/1.1/"
+    <ns5:identifier xmlns:ns5="http://purl.org/dc/elements/1.1/"
        rdf:resource="http://identifiers.org/doi/10.1371/journal.pone.0249594"/>
-    <ns5:label xmlns:ns5="http://www.w3.org/2000/01/rdf-schema#">Darta Maija Zake, Janis Kurlovics, Linda Zaharenko, Vitalijs Komasilovs, Janis Klovins &amp; Egils Stalidzans. Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues. PLOS ONE 16, 4 (2021).</ns5:label>
+    <ns6:label xmlns:ns6="http://www.w3.org/2000/01/rdf-schema#">Darta Maija Zake, Janis Kurlovics, Linda Zaharenko, Vitalijs Komasilovs, Janis Klovins &amp; Egils Stalidzans. Physiologically based metformin pharmacokinetics model of mice and scale-up to humans for the estimation of concentrations in various tissues. PLOS ONE 16, 4 (2021).</ns6:label>
   </rdf:Description>
 </rdf:RDF>