/// <summary>
/// Pre-optimized Construct constructor.
/// </summary>
/// <param name="fragList">Fragment list.</param>
public Construct(List<Overlap> overlaps, ISequence sequence, DesignerSettings settings)
: base()
{
this.Overlaps = overlaps;
this.Sequence = sequence;
this.Settings = settings;
}
/// <summary>
/// Overlap optimizer constructor.
/// </summary>
/// <param name="construct">A construct to assemble.</param>
public OverlapOptimizer(Construct construct, DesignerSettings settings)
{
this.Construct = construct;
this.Templates = new List<Overlap>();
foreach (Overlap o in this.Construct.Overlaps)
{
this.Templates.Add(new Overlap(o));
}
this.Settings = settings;
this.leaBestAcrossGenerations = new List<double>();
this.IgnorePreoptimizationExceptions = true;
}
/// <summary>
/// Construct constructor.
/// </summary>
/// <param name="fragDict">Fragment Dictionary.</param>
/// <param name="constructionList">Fragment names. Dictionary keys.</param>
public Construct(ObservableCollection<String> constructionList, Dictionary<String, Fragment> fragDict, DesignerSettings settings)
: base()
{
ObservableCollection<String> nameList = new ObservableCollection<String>(constructionList);
for (int i = 0; i < nameList.Count; i++)
{
nameList[i] = nameList[i].Replace(Designer.VectorLabel, "");
}
ObservableCollection<Fragment> fragList = new ObservableCollection<Fragment>();
for (int i = 0; i < nameList.Count; i++)
{
Fragment f = fragDict[nameList[i]];
if (i == 0)
{
f.IsVector = true;
}
fragList.Add(f);
}
Init(fragList, settings);
}
/// <summary>
/// Evaluate the chromosome.
/// </summary>
/// <param name="templates">List of overlap templates.</param>
/// <param name="settings">Designer settings.</param>
/// <returns>Total score of the chromosome.</returns>
public ScoreTotal Evaluate(List<Overlap> templates, DesignerSettings settings, bool ignoreHeterodimers)
{
this.ToOverlaps(templates);
bool accept = true;
foreach (Overlap o in this.Overlaps)
{
if (!o.IsAcceptable(settings.MaxTh, settings.MaxTd, ignoreHeterodimers))
{
accept = false;
break;
}
}
if (accept)
this.Score.Rescore(Overlaps);
else
this.Score = ScoreTotal.Inacceptable;
return this.Score;
}
/// <summary>
/// Construct initialization.
/// </summary>
/// <param name="fragList">Fragment list.</param>
/// <param name="maxOverlapLen">Minimum overlap length.</param>
private void Init(ObservableCollection <Fragment> fragList, DesignerSettings settings)
{
this.Overlaps = new List <Overlap>();
this.Settings = settings;
//forward
String seq5 = "";
String seq3 = "";
String name = "";
List <MiscFeature> featList = new List <MiscFeature>();
for (int i = 0; i < fragList.Count; i++)
{
name += fragList[i].Name;
seq3 = fragList[i].GetString();
int len5 = Math.Min(settings.MaxOverlapLen, seq5.Length);
int len3 = Math.Min(settings.MaxGeneSpecificLen, seq3.Length);
String overlapping = seq5.Substring(seq5.Length - len5, len5);
String geneSpecific = seq3.Substring(0, len3);
String loc = (seq5.Length + 1).ToString() + ".." + (seq5.Length + seq3.Length).ToString();
MiscFeature gene = new MiscFeature(loc);
gene.StandardName = fragList[i].Name;
featList.Add(gene);
seq5 += seq3;
if (i == 0)
{
Overlaps.Add(new Overlap(fragList[i].Name + "_fwd", new Sequence(Alphabets.DNA, geneSpecific)));
}
else
{
Overlaps.Add(new Overlap(fragList[i].Name + "_fwd", new Sequence(Alphabets.DNA, overlapping), new Sequence(Alphabets.DNA, geneSpecific)));
}
}
this.Sequence = new Sequence(Alphabets.DNA, seq5);
//meta
GenBankMetadata meta = new GenBankMetadata();
meta.Locus = new GenBankLocusInfo();
meta.Locus.MoleculeType = MoleculeType.DNA;
meta.Locus.Name = name;
meta.Locus.Date = System.DateTime.Now;
meta.Locus.SequenceLength = seq5.Length;
meta.Comments.Add("designed with mufasa");
meta.Definition = "synthetic construct";
meta.Features = new SequenceFeatures();
meta.Features.All.AddRange(featList);
this.Sequence.Metadata.Add("GenBank", meta);
//reverse
fragList.Add(new Fragment(fragList[0]));
fragList.RemoveAt(0);
seq5 = "";
seq3 = "";
for (int i = fragList.Count - 1; i >= 0; i--)
{
seq5 = fragList[i].GetReverseComplementString();
int len3 = Math.Min(settings.MaxOverlapLen, seq3.Length);
int len5 = Math.Min(settings.MaxGeneSpecificLen, seq5.Length);
String overlapping = seq3.Substring(seq3.Length - len3, len3);
String geneSpecific = seq5.Substring(0, len5);
seq3 += seq5;
if (i == fragList.Count - 1)
{
Overlaps.Add(new Overlap(fragList[i].Name + "_rev", new Sequence(Alphabets.DNA, geneSpecific)));
}
else
{
Overlaps.Add(new Overlap(fragList[i].Name + "_rev", new Sequence(Alphabets.DNA, overlapping), new Sequence(Alphabets.DNA, geneSpecific)));
}
}
TermoOptimizeOverlaps();
}
/// <summary>
/// Construct constructor.
/// </summary>
/// <param name="fragDict">Fragment Dictionary.</param>
/// <param name="nameList">Fragment names. Dictionary keys.</param>
public Construct(ObservableCollection <String> nameList, Dictionary <String, Fragment> fragDict, DesignerSettings settings)
: base()
{
ObservableCollection <Fragment> fragList = new ObservableCollection <Fragment>();
for (int i = 0; i < nameList.Count; i++)
{
Fragment f = fragDict[nameList[i]];
if (i == 0)
{
f.IsVector = true;
}
fragList.Add(f);
}
Init(fragList, settings);
}
/// <summary>
/// Construct constructor.
/// </summary>
/// <param name="fragList">Fragment list.</param>
public Construct(ObservableCollection <Fragment> fragList, DesignerSettings settings)
: base()
{
Init(fragList, settings);
}
/// <summary>
/// Construct constructor.
/// </summary>
/// <param name="fragList">Fragment list.</param>
public Construct(ObservableCollection<Fragment> fragList, DesignerSettings settings)
: base()
{
Init(fragList, settings);
}
/// <summary>
/// Construct initialization.
/// </summary>
/// <param name="fragList">Fragment list.</param>
/// <param name="maxOverlapLen">Minimum overlap length.</param>
private void Init(ObservableCollection<Fragment> fragList, DesignerSettings settings)
{
this.Overlaps = new List<Overlap>();
this.Settings = settings;
Thermodynamics.thal_results results = new Thermodynamics.thal_results();
Thermodynamics.p3_get_thermodynamic_values(Settings.TmThalParamPath, ref results);
String message = new String(results.msg);
message = message.Trim('\0');
if (!String.IsNullOrEmpty(message))
{
throw new TmThalParamException(message);
}
//forward
String seq_5 = "";
String seq_3 = "";
String name = "";
List<MiscFeature> featList = new List<MiscFeature>();
int pairIndex;
int len_5;
int len_3;
for (int i = 0; i < fragList.Count; i++)
{
name += fragList[i].Name;
seq_3 = fragList[i].GetString();
len_5 = Math.Min(settings.MaxLen_5, seq_5.Length);
len_3 = Math.Min(settings.MaxLen_3, seq_3.Length);
String overhang_5 = seq_5.Substring(seq_5.Length - len_5, len_5);
String geneSpecific_3 = seq_3.Substring(0, len_3);
String loc = (seq_5.Length + 1).ToString() + ".." + (seq_5.Length + seq_3.Length).ToString();
MiscFeature gene = new MiscFeature(loc);
gene.StandardName = fragList[i].Name;
featList.Add(gene);
seq_5 += seq_3;
if (i == 0)
{
pairIndex = fragList.Count;
Overlaps.Add(new Overlap(Designer.VectorLabel + fragList[i].Name + "-fwd", new Sequence(Alphabets.AmbiguousDNA, geneSpecific_3), settings.TmThalSettings, pairIndex));
}
else
{
pairIndex = 2 * fragList.Count - i;
Overlaps.Add(new Overlap(fragList[i].Name + "-fwd", new Sequence(Alphabets.AmbiguousDNA, overhang_5), new Sequence(Alphabets.AmbiguousDNA, geneSpecific_3), settings.TmThalSettings, pairIndex));
}
}
this.Sequence = new Sequence(Alphabets.AmbiguousDNA, seq_5);
//meta
GenBankMetadata meta = new GenBankMetadata();
meta.Locus = new GenBankLocusInfo();
meta.Locus.MoleculeType = MoleculeType.DNA;
meta.Locus.Name = name;
meta.Locus.Date = System.DateTime.Now;
meta.Locus.SequenceLength = seq_5.Length;
meta.Comments.Add("designed with mufasa");
meta.Definition = "synthetic construct";
meta.Features = new SequenceFeatures();
meta.Features.All.AddRange(featList);
this.Sequence.Metadata.Add("GenBank", meta);
//reverse
fragList.Add(new Fragment(fragList[0]));
fragList.RemoveAt(0);
seq_5 = "";
seq_3 = "";
for (int i = fragList.Count - 1; i >= 0; i--)
{
seq_5 = fragList[i].GetReverseComplementString();
len_5 = Math.Min(settings.MaxLen_5, seq_3.Length);
len_3 = Math.Min(settings.MaxLen_3, seq_5.Length);
String overhang_5 = seq_3.Substring(seq_3.Length - len_5, len_5);
String geneSpecific_3 = seq_5.Substring(0, len_3);
seq_3 += seq_5;
if (i == fragList.Count - 1)
{
pairIndex = 0;
Overlaps.Add(new Overlap(Designer.VectorLabel + fragList[i].Name + "-rev", new Sequence(Alphabets.AmbiguousDNA, geneSpecific_3), settings.TmThalSettings, pairIndex));
}
else
{
pairIndex = i + 1;
Overlaps.Add(new Overlap(fragList[i].Name + "-rev", new Sequence(Alphabets.AmbiguousDNA, overhang_5), new Sequence(Alphabets.AmbiguousDNA, geneSpecific_3), settings.TmThalSettings, pairIndex));
}
}
for (int i = 0; i < fragList.Count; i++)
{
//Duplex melting temperatures
Overlaps[i].HeterodimerMeltingTemperature = Overlaps[i].GetDuplexTemperature(Overlaps[Overlaps[i].PairIndex]);
}
}
