/// <summary>
/// Enriches the target model with the appropriate drugs having a positive effect on the target phenotype
/// </summary>
/// <param name="model">The target model</param>
/// <param name="targetPhenotypes">The target phenotypes</param>
/// <param name="drugsList">The available drugs list</param>
/// <param name="drugNodes">The drug nodes that have been added to the model</param>
/// <param name="drugEdges">The drug edges that have been added to the model</param>
public void AddDrugsToModel(BinaryModel model, List <TargetPhenotype> targetPhenotypes, List <DrugDescription> drugsList, out List <BinaryNode> drugNodes, out List <BinaryEdge> drugEdges)
{
var phenotypes = GetTargetPhenotypes(model, targetPhenotypes);
// Get drugs nodes and edges for each model
drugNodes = new List <BinaryNode>();
drugEdges = new List <BinaryEdge>();
foreach (var phenotype in phenotypes)
{
var clonedModel = model.Clone();
FindDrugs(clonedModel, phenotype.Key.Id, phenotype.Value, drugsList, out List <BinaryNode> intDrugNodes, out List <BinaryEdge> intDrugEdges);
foreach (var drugNode in intDrugNodes)
{
if (!drugNodes.Any(n => n.Id.Equals(drugNode.Id)))
{
drugNodes.Add(drugNode);
}
}
foreach (var drugEdge in intDrugEdges)
{
if (!drugEdges.Any(e => e.Input.Id.Equals(drugEdge.Input.Id) && e.Output.Id.Equals(drugEdge.Output.Id) && e.Type == drugEdge.Type))
{
drugEdges.Add(drugEdge);
}
}
}
}
/// <summary>
/// In a target model, finds the drugs that could have the desired effect on the target node.
/// </summary>
/// <param name="model">The target model</param>
/// <param name="nodeId">The Id of the target node</param>
/// <param name="drugEffect">The desired effect</param>
/// <param name="drugsList">The list of available drugs</param>
/// <param name="drugNodes">The new nodes added for the drugs</param>
/// <param name="drugsEdges">The new edges added for the drugs</param>
public void FindDrugs(BinaryModel model, string nodeId, DrugEffect drugEffect, List <DrugDescription> drugsList, out List <BinaryNode> drugNodes, out List <BinaryEdge> drugsEdges)
{
drugNodes = new List <BinaryNode>();
drugsEdges = new List <BinaryEdge>();
var node = model.GetNode(nodeId);
if (node.State != State.Unset)
{
return;
}
node.State = drugEffect == DrugEffect.Activation ? State.Active : State.Inactive;
var targetDrug = drugsList.FirstOrDefault(d => d.TargetId.Equals(nodeId) && d.Effect == drugEffect);
if (targetDrug != null)
{
var drugNode = new BinaryNode(model, targetDrug.Id);
drugNode.State = State.Active;
drugNodes.Add(drugNode);
var drugEdge = new BinaryEdge(model, string.Concat(targetDrug.Id, node.Id), targetDrug.Effect == DrugEffect.Activation ? EdgeType.Positive : EdgeType.Negative);
drugEdge.Input = drugNode;
drugEdge.Output = node;
drugsEdges.Add(drugEdge);
}
foreach (var edge in model.Edges.Where(e => e.Output == node))
{
var modelClone = model.Clone();
var inputEffect = DrugEffect.Activation;
switch (edge.Type)
{
case EdgeType.Positive:
inputEffect = drugEffect;
break;
case EdgeType.Negative:
inputEffect = drugEffect == DrugEffect.Activation
? DrugEffect.Inhibition
: DrugEffect.Activation;
break;
}
FindDrugs(modelClone, edge.Input.Id, inputEffect, drugsList, out var newDrugNodes, out var newDrugEdges);
drugNodes.AddRange(newDrugNodes);
drugsEdges.AddRange(newDrugEdges);
}
}
/// <summary>
/// Simplifies the input model and extends it with drugs susceptible of having a posiive efect on the target phenotypes.
/// </summary>
/// <param name="model">The binary model to extend</param>
/// <param name="protectedNodes">The nodes that should be protected</param>
/// <param name="targetPhenotypes">The target phenotypes</param>
public void SimplifyAndExtendModelWithDrugs(BinaryModel model, List <string> protectedNodes, List <TargetPhenotype> targetPhenotypes)
{
// Clone the model
var modelClone = model.Clone();
// Set inputs and outputs as protected
_networkSimplifier.ProtectInputsAndOutputs(modelClone);
// Get available drugs list
var drugsList = _drugDatabase.GetAvailableDrugs();
// Set protected nodes based on configuration
_networkSimplifier.ProtectNodes(modelClone, protectedNodes, drugsList, new List <BinaryNode>());
// Remove all intermediary nodes
int removedNodes;
do
{
removedNodes = _networkSimplifier.CleanupNodes(modelClone);
} while (removedNodes != 0);
// Add drugs
AddDrugsToModel(modelClone, targetPhenotypes, drugsList, out var drugNodes, out var drugEdges);
// Add the nodes to the original model
AddEntitiesToModel(model, drugNodes, drugEdges, true);
// Protect other nodes if nescessary
// More than nodes impacted by drugs and mandatory nodes, protect target phenotypes nodes
_networkSimplifier.ProtectNodes(model, protectedNodes, new List <DrugDescription>(), GetTargetPhenotypes(model, targetPhenotypes).Keys.ToList());
// Remove all unnescesary nodes
do
{
removedNodes = _networkSimplifier.CleanupNodes(model);
} while (removedNodes != 0);
}
