public Ontology_enrichment_class Analyse_data_instance(Data_class data_input)
{
Data_class data = data_input.Deep_copy();
data.Keep_only_input_rowNames(this.Bg_genes);
int data_length = data.Data_length;
int col_length = data.ColChar.Columns_length;
string[] symbols;
List <Ontology_enrichment_line_class> enrich_list = new List <Ontology_enrichment_line_class>();
Ontology_enrichment_line_class[] add_enrich;
Entry_type_enum entryType;
int timepoint;
string sample_name;
for (int indexCol = 0; indexCol < col_length; indexCol++)
{
entryType = data.ColChar.Columns[indexCol].EntryType;
timepoint = data.ColChar.Columns[indexCol].Timepoint;
sample_name = (string)data.ColChar.Columns[indexCol].SampleName.Clone();
symbols = data.Get_alphabetically_ordered_ncbi_official_symbols__with_non_empty_entries_in_indicated_column(indexCol);
add_enrich = Generate_enrichment_lines_and_calculate_pvalues(symbols, entryType, timepoint, sample_name);
add_enrich = Add_missing_process_information(add_enrich);
add_enrich = Add_upregulated_downregulated_symbol_information(add_enrich, data, indexCol);
enrich_list.AddRange(add_enrich);
}
Ontology_enrichment_line_class[] enrich_array = Add_missing_process_information(enrich_list.ToArray());
Ontology_enrichment_class enrich = new Ontology_enrichment_class();
enrich.Add_other_lines(enrich_array);
return(enrich);
}
private void Write_scp_network_for_results_of_dynamic_enrichment_analsyis(Ontology_enrichment_class dynamic_onto_enrichment_filtered, Ontology_enrichment_class standard_onto_enrichment_filtered)
{
if (Options.Report)
{
Report_class.WriteLine("{0}: Visualize SCP relationships of dynamic enrichment results", typeof(Mbc_enrichment_pipeline_class).Name);
}
string subdirectory = Get_results_subdirectory_for_indicated_ontology(Ontology_type_enum.Molecular_biology_cell);
dynamic_onto_enrichment_filtered.Order_by_complete_sample_pvalue();
standard_onto_enrichment_filtered.Order_by_complete_sample_pvalue();
Leave_out_class leave_out = new Leave_out_class();
leave_out.Generate_by_reading_safed_file();
List <Ontology_enrichment_line_class> sameSample_ontology_enrichment = new List <Ontology_enrichment_line_class>();
int dynamic_onto_enrich_length = dynamic_onto_enrichment_filtered.Enrich.Length;
Ontology_enrichment_line_class enrichment_line;
Leave_out_scp_scp_network_class current_scp_network;
List <string> current_scpNames = new List <string>();
string complete_sampleName;
string[] standard_enriched_scps;
Dictionary <string, Shape_enum> nodeLable_shape_dict = new Dictionary <string, Shape_enum>();
for (int indexE = 0; indexE < dynamic_onto_enrich_length; indexE++)
{
enrichment_line = dynamic_onto_enrichment_filtered.Enrich[indexE];
if ((indexE == 0) || (!enrichment_line.Equal_complete_sample(dynamic_onto_enrichment_filtered.Enrich[indexE - 1])))
{
sameSample_ontology_enrichment.Clear();
}
sameSample_ontology_enrichment.Add(enrichment_line);
if ((indexE == dynamic_onto_enrich_length - 1) || (!enrichment_line.Equal_complete_sample(dynamic_onto_enrichment_filtered.Enrich[indexE + 1])))
{
current_scpNames.Clear();
foreach (Ontology_enrichment_line_class sameSample_enrichment_line in sameSample_ontology_enrichment)
{
current_scpNames.AddRange(sameSample_enrichment_line.Scp_name.Split(Global_class.Scp_delimiter));
}
complete_sampleName = enrichment_line.Complete_sample_name;
current_scp_network = Leave_out_scp_network_for_dynamicEnrichment_visualization.Deep_copy_scp_network();
current_scp_network.Scp_nw.Keep_only_input_nodeNames(current_scpNames.ToArray());
current_scp_network.Add_ancestors_of_missing_levels(this.Mbco_parentChild_nw);
standard_enriched_scps = standard_onto_enrichment_filtered.Get_all_scps_of_completeSample(complete_sampleName);
nodeLable_shape_dict.Clear();
foreach (string standard_enriched_scp in standard_enriched_scps)
{
nodeLable_shape_dict.Add(standard_enriched_scp, Shape_enum.Rectangle);
}
current_scp_network.Scp_nw.Write_yED_nw_in_results_directory_with_nodes_colored_by_level_and_sameLevel_processes_grouped(subdirectory + complete_sampleName + "_dynamicEnrichment_nw", Shape_enum.Diamond, nodeLable_shape_dict);
}
}
}
public Ontology_enrichment_class Calculate_p_values_and_do_multiple_hypothesis_correction(Deg_class deg_input)
{
if (Options.Report)
{
Report_class.Write_major_separation_line();
Report_class.WriteLine("{0}: Calculate p values and perform multiple hypothesis correction for {1}", typeof(Ontology_fisher_exact_class).Name, this.Ontology_association.Ontology);
}
Deg_class deg = deg_input.Deep_copy();
deg.Keep_only_input_genes(this.Background_genes);
this.Ontology_association.Process_gene_associations = this.Ontology_association.Process_gene_associations.OrderBy(l => l.ProcessName).ThenBy(l => l.GeneSymbol).ToArray();
deg.Degs = deg.Degs.OrderBy(l => l.Sequencing_run).ThenBy(l => l.Cell).ThenBy(l => l.Condition1).ThenBy(l => l.Condition2).ToArray();
int degs_length = deg.Degs.Length;
Deg_line_class deg_line;
List <string> inputGenes = new List <string>();
Ontology_enrichment_line_class[] add_enrichment_results;
List <Ontology_enrichment_line_class> enrichment_results = new List <Ontology_enrichment_line_class>();
for (int indexDeg = 0; indexDeg < degs_length; indexDeg++)
{
deg_line = deg.Degs[indexDeg];
if ((indexDeg == 0) ||
(!deg_line.Sequencing_run.Equals(deg.Degs[indexDeg - 1].Sequencing_run)) ||
(!deg_line.Cell.Equals(deg.Degs[indexDeg - 1].Cell)) ||
(!deg_line.Condition1.Equals(deg.Degs[indexDeg - 1].Condition1)) ||
(!deg_line.Condition2.Equals(deg.Degs[indexDeg - 1].Condition2)))
{
inputGenes.Clear();
}
if ((indexDeg != 0) &&
(!deg_line.Sequencing_run.Equals(deg.Degs[indexDeg - 1].Sequencing_run)) &&
(!deg_line.Cell.Equals(deg.Degs[indexDeg - 1].Cell)) &&
(!deg_line.Condition1.Equals(deg.Degs[indexDeg - 1].Condition1)) &&
(!deg_line.Condition2.Equals(deg.Degs[indexDeg - 1].Condition2)) &&
(deg_line.Gene.Equals(deg_line.Gene)))
{
throw new Exception(); //duplicated gene in same condition
}
inputGenes.Add(deg_line.Gene);
if ((indexDeg == degs_length - 1) ||
(!deg_line.Sequencing_run.Equals(deg.Degs[indexDeg + 1].Sequencing_run)) ||
(!deg_line.Cell.Equals(deg.Degs[indexDeg + 1].Cell)) ||
(!deg_line.Condition1.Equals(deg.Degs[indexDeg + 1].Condition1)) ||
(!deg_line.Condition2.Equals(deg.Degs[indexDeg + 1].Condition2)))
{
add_enrichment_results = Calculate_p_values_and_do_mutliple_hypothesis_correcion_for_input_genes(inputGenes.ToArray(), deg_line);
enrichment_results.AddRange(add_enrichment_results);
}
}
Ontology_enrichment_class onto_enrich = new Ontology_enrichment_class();
onto_enrich.Add_to_array(enrichment_results.ToArray());
return(onto_enrich);
}
public Ontology_enrichment_class Deep_copy()
{
Ontology_enrichment_class copy = (Ontology_enrichment_class)this.MemberwiseClone();
Ontology_enrichment_line_class onto_enrich_line;
int enrich_length = this.Enrich.Length;
copy.Enrich = new Ontology_enrichment_line_class[enrich_length];
for (int indexE = 0; indexE < enrich_length; indexE++)
{
onto_enrich_line = this.Enrich[indexE];
copy.Enrich[indexE] = this.Enrich[indexE].Deep_copy();
}
return(copy);
}
public void Analyze_de_instance(Data_class data, string base_file_name)
{
this.Base_file_name = (string)base_file_name.Clone();
Data_class data_sep = Generate_data_instance_with_separated_or_combined_entries(data);
data_sep.Set_all_ncbi_official_gene_symbols_to_upper_case();
Ontology_enrichment_class standard_onto_enrich_standard;
Ontology_enrichment_class standard_onto_enrich_filtered = Do_standard_enrichment_analysis_and_write_results(data_sep, out standard_onto_enrich_standard);
Ontology_enrichment_class dynamic_onto_enrich_filtered = Do_dynamic_enrichment_analysis_for_mbco_and_write(standard_onto_enrich_standard, data_sep);
Write_parent_child_network_for_results_of_standard_enrichment_analysis(standard_onto_enrich_filtered);
Write_scp_network_for_results_of_dynamic_enrichment_analsyis(dynamic_onto_enrich_filtered, standard_onto_enrich_filtered);
Write_legend_for_networks(base_file_name);
}
public Ontology_enrichment_class Do_fisher_exact_test_for_de_instance_filter_and_write_for_individual_ontology(Deg_class deg)
{
int ontologies_length = this.Ontology_fishers.Length;
Ontology_fisher_exact_class fisher;
Ontology_enrichment_class onto_enrich = new Ontology_enrichment_class();
Ontology_enrichment_class onto_enrich_add;
for (int indexO = 0; indexO < ontologies_length; indexO++)
{
fisher = this.Ontology_fishers[indexO];
onto_enrich_add = fisher.Calculate_p_values_and_do_multiple_hypothesis_correction(deg);
onto_enrich.Add_other(onto_enrich_add);
}
return(onto_enrich);
}
private Ontology_enrichment_class Do_standard_enrichment_analysis_and_write_results(Data_class data, out Ontology_enrichment_class onto_enrich)
{
if (Options.Report)
{
Report_class.WriteLine("{0}: Do standard enrichment analysis and write results", typeof(Mbc_enrichment_pipeline_class).Name);
}
onto_enrich = this.MBCO_fisher_standard.Analyse_data_instance(data);
Ontology_type_enum ontology = Ontology_type_enum.Molecular_biology_cell;
string subdirectory = Get_results_subdirectory_for_indicated_ontology(ontology);
onto_enrich.Write(subdirectory, "Standard_enrichment_results.txt");
Ontology_enrichment_class onto_enrich_filtered = onto_enrich.Deep_copy();
onto_enrich_filtered.Keep_enrichment_lines_below_pvalue_cutoff(Options.Maximum_pvalue_for_standardDynamicEnrichment);
onto_enrich_filtered.Keep_top_x_predictions_per_level_for_each_sample(Options.Kept_top_predictions_standardEnrichment_per_level);
onto_enrich_filtered.Write(subdirectory, "Standard_enrichment_results_filtered.txt");
return(onto_enrich_filtered);
}
public void Add_other(Ontology_enrichment_class other_onto_enrich)
{
Add_to_array(other_onto_enrich.Onto_enrich);
}
public void Add_other(Ontology_enrichment_class other)
{
Add_other_lines(other.Enrich);
}
private Ontology_enrichment_class Do_dynamic_enrichment_analysis_for_mbco_and_write(Ontology_enrichment_class mbco_onto_enrich_standard, Data_class data)
{
if (Options.Report)
{
Report_class.WriteLine("{0}: Do dynamic enrichment analysis and write results", typeof(Mbc_enrichment_pipeline_class).Name);
}
string subdirectory = Get_results_subdirectory_for_indicated_ontology(Ontology_type_enum.Molecular_biology_cell);
mbco_onto_enrich_standard.Order_by_complete_sample_pvalue();
int mbco_onto_enrich_length = mbco_onto_enrich_standard.Enrich.Length;
Ontology_enrichment_line_class enrich_line;
MBCO_association_line_class[] new_mbco_association_lines;
MBCO_association_class new_mbco_association;
List <Ontology_enrichment_line_class> current_onto_enrich = new List <Ontology_enrichment_line_class>();
Ontology_fisher_class mbco_fisher_dynamic;
int col_length = data.ColChar.Columns.Length;
Data_class current_data;
Colchar_column_line_class current_column_line;
Ontology_enrichment_class current_dynamic_onto_enrich;
Ontology_enrichment_class complete_dynamic_onto_enrich = new Ontology_enrichment_class();
List <Ontology_enrichment_line_class> dynamic_onto_enrich_list = new List <Ontology_enrichment_line_class>();
int added_standard_results_count = 0;
for (int indexCol = 0; indexCol < col_length; indexCol++)
{
current_data = data.Deep_copy();
current_data.Keep_only_input_columns_and_remove_all_rows_that_are_left_over_with_only_zero_values(indexCol);
current_column_line = current_data.ColChar.Columns[0];
current_onto_enrich.Clear();
for (int indexMbco = 0; indexMbco < mbco_onto_enrich_length; indexMbco++)
{
enrich_line = mbco_onto_enrich_standard.Enrich[indexMbco];
if ((enrich_line.EntryType.Equals(current_column_line.EntryType)) &&
(enrich_line.Timepoint.Equals(current_column_line.Timepoint)) &&
(enrich_line.Sample_name.Equals(current_column_line.SampleName)))
{
current_onto_enrich.Add(enrich_line);
added_standard_results_count++;
}
}
if (current_onto_enrich.Count == 0)
{
throw new Exception();
}
new_mbco_association_lines = Generate_new_mbco_association_lines_by_merging_neighboring_scps(current_onto_enrich.ToArray());
new_mbco_association = new MBCO_association_class();
new_mbco_association.Add_to_array(new_mbco_association_lines);
mbco_fisher_dynamic = new Ontology_fisher_class();
mbco_fisher_dynamic.Generate(new_mbco_association, Ontology_type_enum.Molecular_biology_cell, this.Final_bg_genes);
current_dynamic_onto_enrich = mbco_fisher_dynamic.Analyse_data_instance(current_data);
complete_dynamic_onto_enrich.Add_other(current_dynamic_onto_enrich);
}
if (added_standard_results_count != mbco_onto_enrich_standard.Enrich.Length)
{
throw new Exception();
}
complete_dynamic_onto_enrich.Add_other(mbco_onto_enrich_standard);
complete_dynamic_onto_enrich.Keep_only_enrichment_lines_of_indicated_levels(Options.Scp_levels_for_dynamicEnrichment);
complete_dynamic_onto_enrich.Write(subdirectory, "Dynamic_enrichment_results.txt");
Ontology_enrichment_class complete_dynamic_onto_enrich_filtered = complete_dynamic_onto_enrich.Deep_copy();
complete_dynamic_onto_enrich_filtered.Keep_enrichment_lines_below_pvalue_cutoff(Options.Maximum_pvalue_for_standardDynamicEnrichment);
complete_dynamic_onto_enrich_filtered.Keep_top_x_predictions_per_level_for_each_sample(Options.Kept_top_predictions_dynamicEnrichment_per_level);
complete_dynamic_onto_enrich_filtered.Keep_top_x_predictedSCPs_as_part_of_SCPunit_or_singleSCPs(Options.Kept_singleSCPs_dynamicEnrichment_per_level);
complete_dynamic_onto_enrich_filtered.Write(subdirectory, "Dynamic_enrichment_results_filtered.txt");
return(complete_dynamic_onto_enrich_filtered);
}
private void Write_parent_child_network_for_results_of_standard_enrichment_analysis(Ontology_enrichment_class onto_enrich_mbc_for_nw_visualization)
{
if (Options.Report)
{
Report_class.WriteLine("{0}: Visualize parent child relationships of standard enrichment results", typeof(Mbc_enrichment_pipeline_class).Name);
}
string mbc_results_subdirectory = Get_results_subdirectory_for_indicated_ontology(Ontology_type_enum.Molecular_biology_cell);
int enrich_length = onto_enrich_mbc_for_nw_visualization.Enrich.Length;
Ontology_enrichment_line_class enrich_line;
List <Ontology_enrichment_line_class> sameLevel_enrich_list = new List <Ontology_enrichment_line_class>();
onto_enrich_mbc_for_nw_visualization.Order_by_complete_sample_pvalue();
MBCO_obo_network_class current_obo_mbc;
string complete_sampleName;
for (int indexE = 0; indexE < enrich_length; indexE++)
{
enrich_line = onto_enrich_mbc_for_nw_visualization.Enrich[indexE];
if ((indexE == 0) || (!enrich_line.Complete_sample_name.Equals(onto_enrich_mbc_for_nw_visualization.Enrich[indexE - 1].Complete_sample_name)))
{
sameLevel_enrich_list.Clear();
}
sameLevel_enrich_list.Add(enrich_line);
if ((indexE == enrich_length - 1) || (!enrich_line.Complete_sample_name.Equals(onto_enrich_mbc_for_nw_visualization.Enrich[indexE + 1].Complete_sample_name)))
{
complete_sampleName = enrich_line.Complete_sample_name;
current_obo_mbc = this.Mbco_parentChild_nw.Deep_copy_mbco_obo_nw();
current_obo_mbc.Add_significance_and_remove_unsignificant_nodes_but_keep_all_ancestors(sameLevel_enrich_list.ToArray());
current_obo_mbc.Write_yED_nw_in_results_directory_with_nodes_colored_by_minusLog10Pvalue_without_sameLevel_processes_grouped(mbc_results_subdirectory + complete_sampleName + "_parentChild_nw");
}
}
}
