public static List <CleavageSite> ReadCleavageSite(string file)
{
string[] lines = FileExtension.ReadList(file);
List <CleavageSite> sites = new List <CleavageSite>();
foreach (string line in lines)
{
var arr = line.Split(',');
if (!arr[2].IsDigit())
{
continue;
}
CleavageSite site = new CleavageSite();
site.MiRNA = arr[0];
site.Gene = arr[1];
site.StartAt = int.Parse(arr[2]);
//int extendLeft = site.StartAt - 1;
//int extendRight = Gene.GetCount(site.Gene) - (site.StartAt - 1 + 21);
//site.Extendability = Math.Min(extendLeft, extendRight);
sites.Add(site);
}
return(sites);
}
public static void ToFasta(string keyFile, string fastaFile)
{
List <CleavageSite> sites = new List <CleavageSite>();
string content = string.Empty;
using (StreamReader sr = new StreamReader(keyFile))
{
content = sr.ReadToEnd();
}
var lines = content.Split(new char[] { '\n' }, StringSplitOptions.RemoveEmptyEntries);
foreach (string line in lines)
{
var arr = line.Split('_');
if (!arr[2].IsDigit())
{
continue;
}
CleavageSite site = new CleavageSite();
site.MiRNA = arr[0];
site.Gene = arr[1];
site.StartAt = int.Parse(arr[2]);
sites.Add(site);
}
using (StreamWriter sr = new StreamWriter(fastaFile))
{
foreach (CleavageSite site in sites)
{
string id = ">" + site.MiRNA + ":[" + site.StartAt.ToString() + "," + site.EndAt.ToString() + "]";
}
}
}
private static void GenerateShapeFile(CleavageSite site, int startAt, int endAt, string fileName)
{
string content = string.Empty;
for (int position = startAt; position < endAt; position++)
{
content += $"{position - startAt + 1} {Reactivity.GetReactivity(site.Gene, position)}\r\n";
}
FileExtension.Save(content, fileName);
}
/// <summary>
/// Generate the cleavage sites and sort it by the extendability
/// </summary>
public static void GenerateCleavegeSites()
{
string[] lines = FileExtension.ReadList(Config.AllCleavegSiteFile);
Console.WriteLine($"Total Cleavage Sites:{lines.Length}");
List <CleavageSite> sites = new List <CleavageSite>();
foreach (string line in lines)
{
var arr = line.Split('_');
if (!arr[2].IsDigit())
{
continue;
}
if (!Config.ValidNames.Contains(arr[1]))
{
continue;
}
CleavageSite site = new CleavageSite();
site.MiRNA = arr[0];
site.Gene = arr[1];
site.StartAt = int.Parse(arr[2]);
int extendLeft = site.StartAt - 1;
int extendRight = Gene.GetCount(site.Gene) - (site.StartAt - 1 + 21);
site.Extendability = Math.Min(extendLeft, extendRight);
sites.Add(site);
}
sites.Sort((a, b) => - a.Extendability.CompareTo(b.Extendability));
//create file
StringBuilder site_content = new StringBuilder();
foreach (var site in sites)
{
site_content.AppendLine(site.ToString());
}
FileExtension.Save(site_content.ToString(), Config.WorkingFolder + "\\cleavage_sites_repeat.csv");
List <CleavageSite> combinedSites = Combine(sites);
//create file
StringBuilder combined_site_content = new StringBuilder();
foreach (var site in combinedSites)
{
combined_site_content.AppendLine(site.ToString());
}
FileExtension.Save(combined_site_content.ToString(), Config.WorkingFolder + "\\cleavage_sites.csv");
}
public static bool HasEfficiency_21(CleavageSite site, DegradomeType dType)
{
var dict = LoadDict(dType);
for (int i = 0; i <= 21; i++)
{
if (dict[site.Gene].ContainsKey(site.StartAt - 1 + i))
{
return(true);
}
}
return(false);
}
public static CleavageSite Parse(string s)
{
CleavageSite site = new CleavageSite();
var arr = s.Split(new char[] { '_', ',' });
site.MiRNA = arr[0];
site.Gene = arr[1];
site.StartAt = int.Parse(arr[2]);
if (arr.Length > 3)
{
site.Extendability = int.Parse(arr[3]);
}
return(site);
}
public static void GenerateCleavageSiteFiles_Yang()
{
List <CleavageSite> sites = new List <CleavageSite>();
string[] lines = FileExtension.ReadList(Config.WorkingFolder + "cleavage_sites.csv");
Console.WriteLine($"Total Cleavage Sites:{lines.Length}");
foreach (string line in lines)
{
var arr = line.Split('_');
CleavageSite site = CleavageSite.Parse(line);
sites.Add(site);
}
Console.WriteLine($"After filtered by clevage efficiency and reactivity:{sites.Count}");
//Generate 4 files filtered by 4 degradome datasets.
foreach (DegradomeType dType in EnumUtil.GetValues <DegradomeType>())
{
StringBuilder site_content_1 = new StringBuilder();
StringBuilder site_content_3 = new StringBuilder();
StringBuilder site_content_4 = new StringBuilder();
foreach (CleavageSite site in sites)
{
//if (site.Extendability < 50)
//{
// break;
//}
float efficiency = Efficiency.GetEfficiency(site, dType);
if (efficiency > 0)
{
site_content_1.AppendLine(site.ToStringWithMiRNANames());
}
else if (Efficiency.HasEfficiency_21(site, dType))
{
site_content_3.AppendLine(site.ToStringWithMiRNANames());
}
else if (Efficiency.HasEfficiency_Gene(site, dType))
{
site_content_4.AppendLine(site.ToStringWithMiRNANames());
}
}
FileExtension.Save(site_content_1.ToString(), Config.WorkingFolder + "\\cleavage_sites_" + dType + "_1.csv");
FileExtension.Save(site_content_3.ToString(), Config.WorkingFolder + "\\cleavage_sites_" + dType + "_3.csv");
FileExtension.Save(site_content_4.ToString(), Config.WorkingFolder + "\\cleavage_sites_" + dType + "_4.csv");
}
}
private static List <CleavageSite> Combine(List <CleavageSite> sites)
{
List <CleavageSite> result = new List <CleavageSite>();
var groups = from site in sites group site by site.Gene + site.StartAt into newGroup select newGroup;
foreach (var group in groups)
{
CleavageSite cs = new CleavageSite();
cs.Extendability = group.First().Extendability;
cs.EndAt = group.First().EndAt;
cs.Gene = group.First().Gene;
cs.StartAt = group.First().StartAt;
cs.MiRNA = string.Join("|", group.ToList().Select(c => c.MiRNA));
result.Add(cs);
}
return(result);
}
public static bool HasEfficiency_Gene(CleavageSite site, DegradomeType dType)
{
var dict = LoadDict(dType);
return(dict[site.Gene].Count > 0);
}
public static float GetEfficiency(CleavageSite site, DegradomeType dType)
{
return(GetEfficiency(site.Gene, site.StartAt - 1 + 10, site.StartAt - 1 + 11, dType));
}
public static void GenerateStructureFiles()
{
if (!Directory.Exists(Config.CsStrucFolder))
{
Directory.CreateDirectory(Config.CsStrucFolder);
}
foreach (DegradomeType dType in EnumUtil.GetValues <DegradomeType>())
{
string degDir = Config.CsStrucFolder + dType.ToString();
if (!Directory.Exists(degDir))
{
Directory.CreateDirectory(degDir);
}
string[] cleavageSiteSList = FileExtension.ReadList($"{Config.WorkingFolder}\\cleavage_site_{dType}.csv");
foreach (int extend in new int[] { 25, 50 })
{
int length = extend * 2 + 21;
//$"{dir}\\{length}
string lengthDir = $"{degDir}\\{length}";
if (!Directory.Exists(lengthDir))
{
Directory.CreateDirectory(lengthDir);
}
List <string> dotBrackets = new List <string>();
for (int i = 0; i < cleavageSiteSList.Length; i++)
{
if (string.IsNullOrWhiteSpace(cleavageSiteSList[i]))
{
continue;
}
CleavageSite site = CleavageSite.Parse(cleavageSiteSList[i]);
//Generate .seq file
int startAt = site.StartAt - 1 - extend;
//Check if the extended cleavage site is available
//(the start and ending points are legal)
if (startAt < 0)
{
Console.WriteLine(startAt);
continue;
}
int endAt = site.StartAt - 1 + extend + 21;
string fullSequence = Gene.GetSequence(site.Gene);
//check if the ending point is reasonable
if (endAt > fullSequence.Length)
{
Console.WriteLine(endAt);
continue;
}
string cleavageSiteSequence = fullSequence.Substring(startAt, endAt - startAt);
string seqFileContent = $">{site.Gene}[{startAt},{endAt}]\r\n{cleavageSiteSequence.Replace("U", "T")}";
FileExtension.Save(seqFileContent, $"{degDir}\\{length}\\{i}.seq");
//generate the .shape file
GenerateShapeFile(site, startAt, endAt, $"{degDir}\\{length}\\{i}.shape");
//generate .db file
//Use ViennaRNA/RNAFold to do that.
//RNAFold--shape = ap2.shape < ap2.seq
string dotBracket = RnaFoldWrapper.Fold($"{degDir}\\{length}\\{i}.shape", $"{degDir}\\{length}\\{i}.seq");
dotBrackets.Add(dotBracket);
//availableCleavageSites.Add(cleavage_site_sList[i]);
}
FileExtension.SaveList($"{Config.CsStrucFolder}\\cs_structure_{length}_{dType}.txt", dotBrackets);
}
}
GenerateRnaStructPlots();
}
public static void GenerateCleavageSiteFiles()
{
List <CleavageSite> sites = new List <CleavageSite>();
string[] lines = FileExtension.ReadList(Config.WorkingFolder + "cleavage_sites.csv");
Console.WriteLine($"Total Cleavage Sites:{lines.Length}");
foreach (string line in lines)
{
var arr = line.Split('_');
CleavageSite site = CleavageSite.Parse(line);
sites.Add(site);
}
Console.WriteLine($"After filtered by cleavage efficiency and reactivity:{sites.Count}");
//Generate 4 files filtered by 4 degradome datasets.
foreach (DegradomeType dType in EnumUtil.GetValues <DegradomeType>())
{
string site_content = string.Empty;
string efficiency_content = string.Empty;
string efficiency_log_content = string.Empty;
string reactivity_content = string.Empty;
string reactivity_25_content = string.Empty;
string reactivity_50_content = string.Empty;
//string reactivity_75_content = string.Empty;
//string reactivity_100_content = string.Empty;
foreach (CleavageSite site in sites)
{
if (site.Extendability < 50)
{
break;
}
//if the cleavage efficiency is zero,
//we can say that this is not a cleavage site.
//filter it out.
float efficiency = Efficiency.GetEfficiency(site, dType);
if (efficiency == 0)
{
continue;
}
site_content += site.ToString() + "\n";
efficiency_content += efficiency.ToString() + "\n";
efficiency_log_content += Math.Log(efficiency).ToString() + "\n";
for (int j = 0; j < 21; j++)
{
reactivity_content += Reactivity.GetReactivity(site.Gene, site.StartAt - 1 + j) + ",";
}
for (int j = 0 - 25; j < 21 + 25; j++)
{
reactivity_25_content += Reactivity.GetReactivity(site.Gene, site.StartAt - 1 + j) + ",";
}
for (int j = 0 - 50; j < 21 + 50; j++)
{
reactivity_50_content += Reactivity.GetReactivity(site.Gene, site.StartAt - 1 + j) + ",";
}
reactivity_content = reactivity_content.TrimEnd(',') + "\n";
reactivity_25_content = reactivity_25_content.TrimEnd(',') + "\n";
reactivity_50_content = reactivity_50_content.TrimEnd(',') + "\n";
}
FileExtension.Save(site_content, Config.WorkingFolder + "\\cleavage_site_" + dType + ".csv");
FileExtension.Save(efficiency_content, Config.WorkingFolder + "\\cs_efficiencies_" + dType + ".csv");
FileExtension.Save(efficiency_log_content, Config.WorkingFolder + "\\cs_efficiencies_log_" + dType + ".csv");
FileExtension.Save(reactivity_content, Config.WorkingFolder + "\\cs_reactivity_" + dType + ".csv");
FileExtension.Save(reactivity_25_content, Config.WorkingFolder + "\\cs_reactivity_" + dType + "_25.csv");
FileExtension.Save(reactivity_50_content, Config.WorkingFolder + "\\cs_reactivity_" + dType + "_50.csv");
//FileExtension.Save(reactivity_75_content, Config.WorkingFoler + "\\cs_reactivity_" + dType + "_75.csv");
//FileExtension.Save(reactivity_100_content, Config.WorkingFoler + "\\cs_reactivity_" + dType + "_100.csv");
}
}
