scikit-complexity 0.2.0__py3-none-any.whl

skcomplex/models/biology/oncology/_suppressed_tumour.py

@@ -0,0 +1,338 @@
+"""Tumour, dendritic cells, proliferating and active T cells, IL-2, IL-10, and TGF-beta."""
+
+# Author: Georgios Douzas <gdouzas@icloud.com>
+# License: MIT
+
+from typing import Annotated
+
+from sage.all__sagemath_symbolics import oo
+from sage.sets.real_set import RealSet
+
+from ....core.elements import Element
+from ....specs import ParameterSpec, StateSpec, VisualSpec
+
+
+class SuppressedTumourElement(Element):
+    """Tumour, dendritic cells, proliferating and active T cells, IL-2, IL-10, and TGF-beta.
+
+    The equations are those of Padmanabhan et al. (4.22) to (4.33). The tumour grows by the smooth minimum
+    `A / ((1 / r1)^p + (A^(1 - n) / r2)^p)^(1/p)` of exponential and power growth and is killed through its fraction
+    `A* = A / (1 + (A^(1 - q) / g3)^p)^(1/p)` accessible to the cytotoxic T cells `E`, at the rate
+    `a1 A* E / (E + A* / g1 + ER / g2) / (1 + C3 / C3_50)`. Antigen matures unlicensed dendritic cells, which helper
+    memory cells license, and dendritic cells recruit the memory pools `EMC`, `EMH`, and `EMR` into proliferating
+    cytotoxic, helper, and regulatory cells, which IL-2 matures. IL-10 and TGF-beta, from regulatory and tumour cells,
+    suppress maturation, IL-2 production, and killing, and TGF-beta converts helper into regulatory cells.
+
+    The element holds the states and parameters and has no laws of its own: the interactions of
+    `tumour_immune_suppression` read its parameters.
+
+    Args:
+        label:
+            The label of the tumour site.
+
+        visual:
+            How the element is drawn, or `None` for `default_visual_`.
+
+        A:
+            The initial tumour cells.
+
+        EUD:
+            The initial unlicensed dendritic cells.
+
+        ED:
+            The initial licensed dendritic cells.
+
+        EPC:
+            The initial proliferating cytotoxic T cells.
+
+        E:
+            The initial active cytotoxic T cells.
+
+        EPH:
+            The initial proliferating helper T cells.
+
+        EH:
+            The initial active helper T cells.
+
+        EPR:
+            The initial proliferating regulatory T cells.
+
+        ER:
+            The initial active regulatory T cells.
+
+        C1:
+            The initial IL-2 concentration.
+
+        C2:
+            The initial IL-10 concentration.
+
+        C3:
+            The initial TGF-beta concentration.
+
+        r1:
+            The exponential growth rate of the tumour.
+
+        r2:
+            The power growth coefficient of the tumour.
+
+        n:
+            The exponent of the power growth.
+
+        p:
+            The smoothness of the transitions.
+
+        q:
+            The exponent of the accessible fraction of a large tumour.
+
+        a1:
+            The maximal kill rate of tumour cells.
+
+        g1:
+            The ratio of tumour to cytotoxic cells at half kill.
+
+        g2:
+            The ratio of regulatory to cytotoxic cells at half kill.
+
+        g3:
+            The size scale of the accessible fraction.
+
+        C3_50:
+            The TGF-beta at half kill.
+
+        alpha_a:
+            The antigenicity of the tumour.
+
+        C2_50:
+            The IL-10 at half dendritic maturation.
+
+        ER_50:
+            The regulatory cells at half dendritic maturation.
+
+        lambda_a:
+            The licensing rate of dendritic cells.
+
+        d1:
+            The death rate of unlicensed dendritic cells.
+
+        d2:
+            The death rate of licensed dendritic cells.
+
+        a2:
+            The recruitment rate of proliferating cytotoxic cells.
+
+        g4:
+            The steepness of the recruitment by dendritic cells.
+
+        d3:
+            The death rate of proliferating cytotoxic cells.
+
+        a3:
+            The maturation rate of cytotoxic cells.
+
+        EC1_50:
+            The IL-2 at half maturation.
+
+        EC3_50:
+            The TGF-beta at half maturation.
+
+        d4:
+            The death rate of active cytotoxic cells.
+
+        a4:
+            The recruitment rate of proliferating helper cells.
+
+        d5:
+            The death rate of proliferating helper cells.
+
+        a5:
+            The maturation rate of helper cells.
+
+        a6:
+            The conversion rate of helper into regulatory cells.
+
+        g5:
+            The TGF-beta at half conversion.
+
+        d6:
+            The death rate of active helper cells.
+
+        a7:
+            The recruitment rate of proliferating regulatory cells.
+
+        d7:
+            The death rate of proliferating regulatory cells.
+
+        a8:
+            The maturation rate of regulatory cells.
+
+        d8:
+            The death rate of active regulatory cells.
+
+        a9:
+            The IL-2 production by helper cells.
+
+        CC2_50:
+            The IL-10 at half suppression of IL-2.
+
+        CC3_50:
+            The TGF-beta at half suppression of IL-2.
+
+        tau1:
+            The lifetime of IL-2.
+
+        r3:
+            The IL-10 production by regulatory cells.
+
+        r4:
+            The IL-10 production by tumour cells.
+
+        tau2:
+            The lifetime of IL-10.
+
+        r5:
+            The TGF-beta production by regulatory cells.
+
+        r6:
+            The TGF-beta production by tumour cells.
+
+        tau3:
+            The lifetime of TGF-beta.
+
+        EMC:
+            The memory cytotoxic T cells.
+
+        EMH:
+            The memory helper T cells.
+
+        EMR:
+            The memory regulatory T cells.
+
+    Examples:
+        >>> from skcomplex.models.biology.oncology import SuppressedTumourElement
+        >>> SuppressedTumourElement('site').lambda_a
+        0.5
+    """
+
+    def __init__(
+        self,
+        label: str,
+        visual: VisualSpec | None = None,
+        *,
+        A: Annotated[float, StateSpec(domain=RealSet.open(0, oo))] = 1.0,
+        EUD: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1e-05,
+        ED: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1e-05,
+        EPC: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1e-05,
+        E: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1e-05,
+        EPH: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1e-05,
+        EH: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1e-05,
+        EPR: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1e-05,
+        ER: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1e-05,
+        C1: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 0.0,
+        C2: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 0.0,
+        C3: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 0.0,
+        r1: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.333,
+        r2: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 333.0,
+        n: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.5,
+        p: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 3.0,
+        q: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 2 / 3,
+        a1: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.9,
+        g1: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 1.2,
+        g2: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 11.0,
+        g3: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 100.0,
+        C3_50: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 3.5,
+        alpha_a: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.0,
+        C2_50: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.4,
+        ER_50: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 20000000.0,
+        lambda_a: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.5,
+        d1: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.14,
+        d2: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.5,
+        a2: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 23.0,
+        g4: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.33,
+        d3: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.2,
+        a3: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 16.0,
+        EC1_50: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.3,
+        EC3_50: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 2.9,
+        d4: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.0,
+        a4: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 9.9,
+        d5: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.2,
+        a5: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.9,
+        a6: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.022,
+        g5: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 1.7,
+        d6: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.1,
+        a7: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 5.1,
+        d7: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.2,
+        a8: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 2.1,
+        d8: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.1,
+        a9: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.7e-05,
+        CC2_50: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.75,
+        CC3_50: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.9,
+        tau1: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.08,
+        r3: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.4e-08,
+        r4: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.3e-10,
+        tau2: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.05,
+        r5: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.8e-08,
+        r6: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.1e-07,
+        tau3: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.07,
+        EMC: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 10000.0,
+        EMH: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 10000.0,
+        EMR: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 10000.0,
+    ) -> None:
+        super().__init__(label, visual=visual)
+        self.A = A
+        self.EUD = EUD
+        self.ED = ED
+        self.EPC = EPC
+        self.E = E
+        self.EPH = EPH
+        self.EH = EH
+        self.EPR = EPR
+        self.ER = ER
+        self.C1 = C1
+        self.C2 = C2
+        self.C3 = C3
+        self.r1 = r1
+        self.r2 = r2
+        self.n = n
+        self.p = p
+        self.q = q
+        self.a1 = a1
+        self.g1 = g1
+        self.g2 = g2
+        self.g3 = g3
+        self.C3_50 = C3_50
+        self.alpha_a = alpha_a
+        self.C2_50 = C2_50
+        self.ER_50 = ER_50
+        self.lambda_a = lambda_a
+        self.d1 = d1
+        self.d2 = d2
+        self.a2 = a2
+        self.g4 = g4
+        self.d3 = d3
+        self.a3 = a3
+        self.EC1_50 = EC1_50
+        self.EC3_50 = EC3_50
+        self.d4 = d4
+        self.a4 = a4
+        self.d5 = d5
+        self.a5 = a5
+        self.a6 = a6
+        self.g5 = g5
+        self.d6 = d6
+        self.a7 = a7
+        self.d7 = d7
+        self.a8 = a8
+        self.d8 = d8
+        self.a9 = a9
+        self.CC2_50 = CC2_50
+        self.CC3_50 = CC3_50
+        self.tau1 = tau1
+        self.r3 = r3
+        self.r4 = r4
+        self.tau2 = tau2
+        self.r5 = r5
+        self.r6 = r6
+        self.tau3 = tau3
+        self.EMC = EMC
+        self.EMH = EMH
+        self.EMR = EMR

skcomplex/models/biology/oncology/_tamoxifen_tumour.py

@@ -0,0 +1,172 @@
+"""Breast tumour in three Gompertzian cell-cycle phases under tamoxifen, its metabolite, and the lymphocytes."""
+
+# Author: Georgios Douzas <gdouzas@icloud.com>
+# License: MIT
+
+from typing import Annotated
+
+from sage.all__sagemath_symbolics import oo
+from sage.sets.real_set import RealSet
+
+from ....core.elements import Element
+from ....specs import ParameterSpec, StateSpec, VisualSpec
+
+
+class TamoxifenTumourElement(Element):
+    """Breast tumour in three Gompertzian cell-cycle phases under tamoxifen, its metabolite, and the lymphocytes.
+
+    The phases follow `dAg/dt = -mg Ag L + 2 mm Am L - a1 Ag (UX + delta1 UH)`, `dAs/dt = -ms As + mg Ag L`, and
+    `dAm/dt = -mm Am L + ms As`, with `L = log(Asat / (Ag + As + Am))`. Tamoxifen passes from the gut `X0` through
+    `X1` to the plasma `X2`, `dX0/dt = -k01 X0 + u(t)`, `dX1/dt = k01 X0 - k12 X1`,
+    `dX2/dt = k12 X1 - (du1 + k23) X2`, and the plasma turns it into 4-hydroxytamoxifen,
+    `dX3/dt = k23 X2 - du2 X3`, with the concentrations `UX = X2 / V` and `UH = X3 / V`. The lymphocytes follow
+    `dE/dt = s - d1 E - a2 E (UX + delta2 UH)`, and tamoxifen enters the gut at the constant rate `u`.
+
+    The element holds the states and parameters and has no laws of its own: the interactions of
+    `tamoxifen_cell_cycle` read its parameters.
+
+    Args:
+        label:
+            The label of the tumour.
+
+        visual:
+            How the element is drawn, or `None` for `default_visual_`.
+
+        Ag:
+            The initial volume of cells in the growth phase.
+
+        As:
+            The initial volume of cells in the synthesis phase.
+
+        Am:
+            The initial volume of cells in mitosis.
+
+        X0:
+            The initial tamoxifen in the gut.
+
+        X1:
+            The initial tamoxifen in the second compartment.
+
+        X2:
+            The initial tamoxifen in the plasma.
+
+        X3:
+            The initial 4-hydroxytamoxifen.
+
+        E:
+            The initial circulating lymphocytes, in millions.
+
+        mg:
+            The transit rate out of the growth phase.
+
+        ms:
+            The transit rate out of the synthesis phase.
+
+        mm:
+            The transit rate out of mitosis.
+
+        Asat:
+            The volume at which growth saturates.
+
+        a1:
+            The kill rate of the tumour per unit of drug.
+
+        a2:
+            The kill rate of the lymphocytes per unit of drug.
+
+        delta1:
+            The tumour kill of the metabolite relative to tamoxifen.
+
+        delta2:
+            The lymphocyte kill of the metabolite relative to tamoxifen.
+
+        k01:
+            The transfer rate from the gut.
+
+        k12:
+            The transfer rate to the plasma.
+
+        k23:
+            The rate at which the plasma metabolizes tamoxifen.
+
+        du1:
+            The elimination rate of tamoxifen.
+
+        du2:
+            The elimination rate of the metabolite.
+
+        V:
+            The volume of distribution.
+
+        s:
+            The influx of lymphocytes, in millions per unit of time.
+
+        d1:
+            The death rate of lymphocytes.
+
+        u:
+            The infusion rate of tamoxifen.
+
+    Examples:
+        >>> from skcomplex.models.biology.oncology import TamoxifenTumourElement
+        >>> TamoxifenTumourElement('tumour').Asat
+        10000.0
+    """
+
+    def __init__(
+        self,
+        label: str,
+        visual: VisualSpec | None = None,
+        *,
+        Ag: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 900.0,
+        As: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 50.0,
+        Am: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 50.0,
+        X0: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 0.0,
+        X1: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 0.0,
+        X2: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 0.0,
+        X3: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 0.0,
+        E: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 10.0,
+        mg: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.0013,
+        ms: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.039,
+        mm: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.0169,
+        Asat: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 10000.0,
+        a1: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.0062,
+        a2: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.01,
+        delta1: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 25.0,
+        delta2: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 25.0,
+        k01: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.048,
+        k12: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.993,
+        k23: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 35.932,
+        du1: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.145,
+        du2: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 39.525,
+        V: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 8.592,
+        s: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.121,
+        d1: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.012,
+        u: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 12.5,
+    ) -> None:
+        super().__init__(label, visual=visual)
+        self.Ag = Ag
+        self.As = As
+        self.Am = Am
+        self.X0 = X0
+        self.X1 = X1
+        self.X2 = X2
+        self.X3 = X3
+        self.E = E
+        self.mg = mg
+        self.ms = ms
+        self.mm = mm
+        self.Asat = Asat
+        self.a1 = a1
+        self.a2 = a2
+        self.delta1 = delta1
+        self.delta2 = delta2
+        self.k01 = k01
+        self.k12 = k12
+        self.k23 = k23
+        self.du1 = du1
+        self.du2 = du2
+        self.V = V
+        self.s = s
+        self.d1 = d1
+        self.u = u

skcomplex/models/biology/oncology/_tcr_gene_therapy.py

@@ -0,0 +1,98 @@
+"""Effector cells and tumour cells under a gene therapy that makes the T cells express a tumour receptor."""
+
+# Author: Georgios Douzas <gdouzas@icloud.com>
+# License: MIT
+
+from typing import Annotated
+
+from sage.all__sagemath_symbolics import oo
+from sage.sets.real_set import RealSet
+
+from ....core.elements import Element
+from ....specs import ParameterSpec, StateSpec, VisualSpec
+
+
+class TcrGeneTherapyElement(Element):
+    """Effector cells and tumour cells under a gene therapy that makes the T cells express a tumour receptor.
+
+    The effector cells follow `dE/dt = s + alpha A - d1 E + r1 E / (E + g1)` and the tumour cells
+    `dA/dt = r2 A (1 - b A) - a E A / (A + g2)`, a predator-prey model of the immune attack.
+
+    The element holds the states and parameters and has no laws of its own: the interactions of `tcr_gene_therapy` read
+    its parameters.
+
+    Args:
+        label:
+            The label of the tumour site.
+
+        visual:
+            How the element is drawn, or `None` for `default_visual_`.
+
+        E:
+            The initial number of effector cells.
+
+        A:
+            The initial number of tumour cells.
+
+        s:
+            The influx rate of effector cells.
+
+        alpha:
+            The antigenicity of the tumour.
+
+        d1:
+            The death rate of effector cells.
+
+        r1:
+            The proliferation rate of effector cells.
+
+        g1:
+            The half-saturation constant of the proliferation of effector cells.
+
+        r2:
+            The growth rate of tumour cells.
+
+        b:
+            The reciprocal carrying capacity of tumour cells.
+
+        a:
+            The kill rate that the therapy gives the effector cells.
+
+        g2:
+            The half-saturation constant of the kill.
+
+    Examples:
+        >>> from skcomplex.models.biology.oncology import TcrGeneTherapyElement
+        >>> TcrGeneTherapyElement('site').r2
+        0.18
+    """
+
+    def __init__(
+        self,
+        label: str,
+        visual: VisualSpec | None = None,
+        *,
+        E: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1000.0,
+        A: Annotated[float, StateSpec(domain=RealSet.closed_open(0, oo))] = 1000.0,
+        s: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.0,
+        alpha: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.05,
+        d1: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.03,
+        r1: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.1245,
+        g1: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 0.001,
+        r2: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.18,
+        b: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1e-09,
+        a: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 1.0,
+        g2: Annotated[float, ParameterSpec(domain=RealSet.open(0, oo))] = 100000.0,
+    ) -> None:
+        super().__init__(label, visual=visual)
+        self.E = E
+        self.A = A
+        self.s = s
+        self.alpha = alpha
+        self.d1 = d1
+        self.r1 = r1
+        self.g1 = g1
+        self.r2 = r2
+        self.b = b
+        self.a = a
+        self.g2 = g2

skcomplex/models/biology/oncology/_therapy_switch.py

@@ -0,0 +1,86 @@
+"""Define therapy switches, crossings that set a therapy on or off when a signal of the tumour crosses a threshold."""
+
+# Author: Georgios Douzas <gdouzas@icloud.com>
+# License: MIT
+
+from collections.abc import Callable
+from types import SimpleNamespace
+from typing import Annotated
+
+from sage.all__sagemath_symbolics import Expression, oo
+from sage.sets.real_set import RealSet
+
+from ....core.interactions import CrossingInteraction
+from ....specs import ParameterSpec, RoleSpec
+
+
+class TherapySwitchInteraction(CrossingInteraction):
+    """Switch that sets the therapy state of a tumour to a value when a signal crosses a threshold in a direction.
+
+    A pair of switches, one that sets the therapy to 1 when the signal rises through a high threshold and one that
+    sets it to 0 when the signal falls through a low one, is the relay with hysteresis of intermittent therapy. Every
+    switch is an event labelled by the interaction.
+
+    Args:
+        label:
+            The label of the interaction and of its events.
+
+        target:
+            The path of the tumour.
+
+        signal:
+            A function of the namespace that returns the signal, such as the PSA of the tumour.
+
+        threshold:
+            The value of the signal at the switch.
+
+        value:
+            The value of the therapy state after the switch.
+
+        state:
+            The name of the therapy state.
+
+        direction:
+            The direction of the crossing, 1 for a rising and -1 for a falling signal.
+
+    Raises:
+        ValidationError:
+            The direction is not -1, 0, or 1, or the signal is not a function.
+
+    Examples:
+        >>> from skcomplex.models.biology.oncology import TherapySwitchInteraction
+        >>> switch = TherapySwitchInteraction('on', target='tumour', signal=lambda s: s.target.AD, threshold=15.0)
+        >>> switch.check().threshold
+        15.0
+    """
+
+    def __init__(
+        self,
+        label: str,
+        *,
+        target: Annotated[str, RoleSpec()],
+        signal: Callable[[SimpleNamespace], object],
+        threshold: Annotated[float, ParameterSpec(domain=RealSet.closed_open(0, oo))] = 0.0,
+        value: float = 1.0,
+        state: str = 'u',
+        direction: int = 1,
+    ) -> None:
+        super().__init__(
+            label,
+            target=target,
+            guard=self._get_guard,
+            reset={state: self._get_value},
+            direction=direction,
+        )
+        self.signal = signal
+        self.threshold = threshold
+        self.value = value
+        self.state = state
+
+    def _get_guard(self, s: SimpleNamespace) -> Expression:
+        """Return the signal above the threshold."""
+        return self.signal(s) - s.threshold
+
+    def _get_value(self, s: SimpleNamespace) -> float:
+        """Return the value of the therapy state after the switch."""
+        return self.value