private static void PathHelper_CalP(List <Route> allPaths, LocalizationGraph localizationGraph, int xind, int yind, int[] temp, double[] temp_costs, double p, int n)
{
if (xind == 0)
{
var k = temp_costs.Sum() + localizationGraph.NoLocalCost;
//To understand the math, ref to "phosphoRS" papar.
var cp = 1 / (1 - MathNet.Numerics.Distributions.Binomial.CDF(p, n, k) + MathNet.Numerics.Distributions.Binomial.PMF(p, n, (int)k));
var route = GetLocalizedPath(localizationGraph, temp);
route.Score = k;
route.ReversePScore = cp;
allPaths.Add(route);
return;
}
foreach (var pre in localizationGraph.array[xind][yind].AllSources)
{
xind--;
yind = pre;
temp[xind] = yind;
temp_costs[xind] = localizationGraph.array[xind][yind].CurrentCost;
PathHelper_CalP(allPaths, localizationGraph, xind, yind, temp, temp_costs, p, n);
xind++;
}
}
//To understand this funciton, ref to "phosphoRS" papar. It is complicated unless you understand how 'phosphoRS' works.
//In order to calculate localization probability for each glycosite, one need to get all possible modifications combinations; which is all Routes from a Graph.
//The function is to get all routes and calculate the 1/P value for each route which is used to calculate localization probability later.
public static List <Route> GetAllPaths_CalP(LocalizationGraph localizationGraph, double p, int n)
{
List <Route> allPaths = new List <Route>();
int xlength = localizationGraph.array.Length;
int ylength = localizationGraph.array.First().Length;
//temp is a path. check function GetLocalizedPath.
int[] temp = new int[xlength];
double[] temp_cost = new double[xlength];
//A path in graph localization is always the end of the matrix.
temp[xlength - 1] = ylength - 1;
PathHelper_CalP(allPaths, localizationGraph, xlength - 1, ylength - 1, temp, temp_cost, p, n);
return(allPaths);
}
//The original path we get is just an array of AdjNode positions. For example, path = [1, 1, 2, 2] means the best nodes are at array[0][1], array[1][1], array[2][2], array[3][2]
//This function here is to transfer the path into localized Route. Route contains each glycosite with glycanId.
//Basicly, any change from left to right of the path indicates a modification. For example, the path = [1, 1, 2, 2] which means there is a modification at ModPos[0] and ModPos[2]
public static Route GetLocalizedPath(LocalizationGraph localizationGraph, int[] path)
{
Route route = new Route();
if (path.Length == 1)
{
bool onlyOneLocalized = false;
if (localizationGraph.TotalScore > 0)
{
onlyOneLocalized = true;
}
route.AddPos(localizationGraph.ModPos[0], localizationGraph.ChildModBoxes[path[0]].ModIds.First(), onlyOneLocalized);
return(route);
}
//Add first mod. If the childBoxes[path[0]].ModIds.Count == 0, means this is an empty childBox.
//Otherwise childBoxes[path[0]].ModIds.Count == 1 and childBoxes[path[0]].ModIds only contains one ModId.
if (localizationGraph.ChildModBoxes[path[0]].ModIds.Count() != 0)
{
route.AddPos(localizationGraph.ModPos[0], localizationGraph.ChildModBoxes[path[0]].ModIds.First(), localizationGraph.array[0][path[0]].CurrentCost > 0);
}
for (int i = 1; i < path.Length; i++)
{
//If there is a change of the path, get the difference between the two Adjnodes of the array.
if (path[i] != path[i - 1])
{
var left = GetLeft(localizationGraph.array[i][path[i]].ModBox.ModIds, localizationGraph.array[i - 1][path[i - 1]].ModBox.ModIds).First();
var localPeakExist = localizationGraph.array[i - 1][path[i - 1]].CurrentCost > 0 && (localizationGraph.array[i][path[i]].CurrentCost > 0 || i == path.Length - 1);
route.AddPos(localizationGraph.ModPos[i], left, localPeakExist);
}
}
return(route);
}
//The modification problem is turned into a Directed Acyclic Graph. The Graph was build with matrix, and dynamic programming is used.
//The function goes through the AdjNode[][] array from left to right, assign weight to each AdjNode, keep track of the heaviest previous AdjNode.
public static void LocalizeOGlycan(LocalizationGraph localizationGraph, Ms2ScanWithSpecificMass theScan, Tolerance productTolerance, List <Product> products)
{
var boxSatisfyBox = BoxSatisfyBox(localizationGraph.ChildModBoxes);
for (int i = 0; i < localizationGraph.ModPos.Length; i++)
{
//maxLength: the most mods we can have up to current mod pos; minlengtt: the least mods we can have up to current mod pos.
int maxLength = i + 1;
int minlength = localizationGraph.ModBox.ModIds.Length - (localizationGraph.ModPos.Length - 1 - i);
for (int j = 0; j < localizationGraph.ChildModBoxes.Length; j++)
{
if (localizationGraph.ChildModBoxes[j].NumberOfMods <= maxLength && localizationGraph.ChildModBoxes[j].NumberOfMods >= minlength)
{
AdjNode adjNode = new AdjNode(i, j, localizationGraph.ModPos[i], localizationGraph.ChildModBoxes[j]);
double cost = 0;
if (i != localizationGraph.ModPos.Length - 1)
{
var fragments = GlycoPeptides.GetLocalFragment(products, localizationGraph.ModPos, i, localizationGraph.ModBox, localizationGraph.ChildModBoxes[j]);
cost = CalculateCost(theScan, productTolerance, fragments);
}
adjNode.CurrentCost = cost;
//The first line of the graph didnot have Sources.
if (i == 0)
{
//Get cost
adjNode.maxCost = cost;
}
else
{
double maxCost = 0;
for (int prej = 0; prej <= j; prej++)
{
//Check if a previous AdjNode exist and the current AdjNode could link to previous AdjNode.
if (boxSatisfyBox[j][prej] && localizationGraph.array[i - 1][prej] != null)
{
adjNode.AllSources.Add(prej);
var tempCost = cost + localizationGraph.array[i - 1][prej].maxCost;
if (tempCost > maxCost)
{
adjNode.CummulativeSources.Clear();
adjNode.CummulativeSources.Add(prej);
maxCost = tempCost;
}
else if (tempCost == maxCost)
{
adjNode.CummulativeSources.Add(prej);
}
}
}
adjNode.maxCost = maxCost;
}
localizationGraph.array[i][j] = adjNode;
}
}
}
var unlocalFragments = GlycoPeptides.GetUnlocalFragment(products, localizationGraph.ModPos, localizationGraph.ModBox);
var noLocalScore = CalculateCost(theScan, productTolerance, unlocalFragments);
localizationGraph.NoLocalCost = noLocalScore;
localizationGraph.TotalScore = localizationGraph.array[localizationGraph.ModPos.Length - 1][localizationGraph.ChildModBoxes.Length - 1].maxCost + noLocalScore;
}
//Correct Localization Level based on site specific probability. If LocalizationLevel = 1, and there are site probability lower than 0.75, Correct the level to 1b.
public static LocalizationLevel CorrectLocalizationLevel(Dictionary <int, List <Tuple <int, double> > > siteSpeciLocalProb, LocalizationGraph localizationGraph, Route route, List <Tuple <int, int, bool> > localizedGlycan, LocalizationLevel localizationLevel)
{
if (siteSpeciLocalProb == null || localizationLevel != LocalizationLevel.Level1)
{
return(localizationLevel);
}
if (localizationGraph.ModPos.Length == 1 && localizationGraph.TotalScore == 0)
{
return(LocalizationLevel.Level1b);
}
for (int i = 0; i < localizedGlycan.Count; i++)
{
var g = localizedGlycan[i];
if (siteSpeciLocalProb[g.Item1].Where(p => p.Item1 == g.Item2).First().Item2 < 0.75)
{
return(LocalizationLevel.Level1b);
}
if (!route.Mods[i].Item3)
{
return(LocalizationLevel.Level1b);
}
}
return(localizationLevel);
}