/// <summary>
/// Author: Andy Tang
/// </summary>
public static PDB_Information GetPDBInfo(Protein_Information protein, Drug_Information drug)
{
PDB_Information PDBInfo = null;
if (protein == null || drug == null)
{
return(PDBInfo);
}
string uniprot_ID = protein.Uniprot_ID;
string drug_PDB_ID = drug.Drug_PDB_ID;
using (DrugProNETEntities context = new DrugProNETEntities())
{
DbSet <PDB_Information> dbSet = context.PDB_Information;
foreach (PDB_Information pdb in dbSet)
{
if (string.Equals(pdb.Uniprot_ID, uniprot_ID, StringComparison.OrdinalIgnoreCase) &&
string.Equals(pdb.Drug_PDB_ID, drug_PDB_ID, StringComparison.OrdinalIgnoreCase))
{
PDBInfo = pdb;
}
}
}
return(PDBInfo);
}
/// <summary>
/// Author: Andy Tang
/// </summary>
protected void Search_Textbox_Changed(object sender, EventArgs e)
{
search_drop_down.Items.Clear();
search_drop_down.Items.Add(DROP_DOWN_PROMPT_MESSAGE);
List <Protein_Information> proteinList = new List <Protein_Information>();
const int minPrefixLength = 3;
if (search_textBox.Text.Length < minPrefixLength)
{
return;
}
Drug_Information drug = EF_Data.GetDrugsQuery(search_textBox.Text).FirstOrDefault();
if (drug != null)
{
List <PDB_Information> pdbInfoList = EF_Data.GetPDBInfoUsingDrug(drug.Drug_PDB_ID);
foreach (PDB_Information pdb in pdbInfoList)
{
Protein_Information protein = EF_Data.GetProteinByUniprotID(pdb.UniProt_ID);
if (protein != null)
{
proteinList.Add(protein);
}
}
}
if (proteinList.Count > 0)
{
List <string> valuesList = new List <string>();
foreach (Protein_Information protein in proteinList)
{
valuesList.Add(protein.UniProt_ID);
valuesList.Add(protein.Protein_Short_Name);
valuesList.Add(protein.Protein_Full_Name);
valuesList.Add(protein.Protein_Alias);
valuesList.Add(protein.NCBI_RefSeq_NP_ID);
valuesList.Add(protein.PhosphoNET_Name);
valuesList.Add(protein.PDB_Protein_Name);
}
valuesList = DataUtilities.FilterDropdownList(valuesList);
foreach (string value in valuesList)
{
search_drop_down.Items.Add(new ListItem(value, value, true));
}
}
else
{
search_drop_down.Items.Clear();
search_drop_down.Items.Add(DROP_DOWN_NO_MATCHES_MESSAGE);
}
}
/// <summary>
/// Author: Andy Tang
/// </summary>
protected void Search_Textbox_Changed(object sender, EventArgs e)
{
search_drop_down.Items.Clear();
search_drop_down.Items.Add(DROP_DOWN_PROMPT_MESSAGE);
List <Drug_Information> drugList = new List <Drug_Information>();
const int minPrefixLength = 3;
if (search_textBox.Text.Length < minPrefixLength)
{
return;
}
Protein_Information protein = EF_Data.GetProteinsInfoQuery(search_textBox.Text).FirstOrDefault();
if (protein != null)
{
List <PDB_Information> pdbInfoList = EF_Data.GetPDBInfoUsingProtein(protein.UniProt_ID);
foreach (PDB_Information pdb in pdbInfoList)
{
Drug_Information drug = EF_Data.GetDrugByDrugPDBID(pdb.Drug_PDB_ID);
if (drug != null)
{
drugList.Add(drug);
}
}
}
if (drugList.Count > 0)
{
List <string> valuesList = new List <string>();
foreach (Drug_Information drug in drugList)
{
valuesList.Add(drug.Other_Drug_Name_Alias);
valuesList.Add(drug.Drug_Common_Name);
valuesList.Add(drug.Drug_Chemical_Name);
valuesList.Add(drug.Compound_CAS_ID);
valuesList.Add(drug.PubChem_CID);
valuesList.Add(drug.ChEMBL_ID);
}
valuesList = DataUtilities.FilterDropdownList(valuesList);
foreach (string value in valuesList)
{
search_drop_down.Items.Add(new ListItem(value, value, true));
}
}
else
{
search_drop_down.Items.Clear();
search_drop_down.Items.Add(DROP_DOWN_NO_MATCHES_MESSAGE);
}
}
/// <summary>
/// Author: Ryan Liang
/// </summary>
public void LoadDrug(Drug_Information drug, SNV_Mutation mutation)
{
ProcessRow(PDB_drug_ID_row, PDB_drug_ID, mutation.Drug_PDB_ID, drug.Drug_PDB_ID_URL);
ProcessRow(drug_name_row, drug_name, drug.Drug_Common_Name);
ProcessRow(pubchem_cid_row, pubchem_cid, drug.PubChem_CID, drug.PubChem_Compound_Link);
ProcessRow(chembl_id_row, chembl_id, drug.ChEMBL_ID, drug.ChEMBL_Link);
ProcessRow(chemspider_id_row, chemspider_id, drug.ChemSpider_ID, drug.ChemSpider_Link);
ProcessRow(drugbank_id_row, drugbank_id, drug.DrugBank_ID, drug.DrugBank_Link);
ProcessRow(drug_information_result_url_row, drug_information_result_url, "Click here for more drug information from DrugProNET",
"DrugInfoResult.aspx?query_string=" + drug.Drug_Name_for_Pull_Down_Menu);
}
protected void Search_Textbox_Changed(object sender, EventArgs e)
{
drug_specification_drop_down.Items.Clear();
drug_specification_drop_down.Items.Add(DROP_DOWN_PROMPT_MESSAGE);
amino_acid_specification_drop_down.Items.Clear();
amino_acid_specification_drop_down.Items.Add(DROP_DOWN_PROMPT_MESSAGE);
const int minPrefixLength = 3;
if (search_textBox.Text.Length < minPrefixLength)
{
return;
}
Protein_Information protein = EF_Data.GetProteinsInfoQuery(search_textBox.Text).FirstOrDefault();
if (protein != null)
{
List <PDB_Information> pdbList = EF_Data.GetPDBInfoUsingProtein(protein.UniProt_ID);
List <Drug_Information> drugList = new List <Drug_Information>();
foreach (PDB_Information pdb in pdbList)
{
Drug_Information drug = EF_Data.GetDrugByDrugPDBID(pdb.Drug_PDB_ID);
if (drug != null)
{
drugList.Add(drug);
}
}
if (drugList.Count > 0)
{
List <string> dropdownValues = new List <string>();
foreach (Drug_Information drug in drugList)
{
dropdownValues.Add(drug.Drug_Name_for_Pull_Down_Menu);
}
dropdownValues = DataUtilities.FilterDropdownList(dropdownValues);
foreach (string dropdownValue in dropdownValues)
{
drug_specification_drop_down.Items.Add(dropdownValue);
}
}
else
{
drug_specification_drop_down.Items.Clear();
drug_specification_drop_down.Items.Add(DROP_DOWN_NO_MATCHES_MESSAGE);
}
}
}
/// <summary>
/// Author: Ryan Liang
/// </summary>
public static Drug_Information GetDrugByDrugPDBID(string query)
{
Drug_Information drug = null;
using (DrugProNETEntities context = new DrugProNETEntities())
{
drug = context.Drug_Information.Where(d =>
d.Drug_PDB_ID.ToLower().Contains(query.ToLower())).FirstOrDefault();
}
return(drug);
}
/// <summary>
/// Author: Ryan Liang
/// </summary>
public static Drug_Information GetDrugUsingDropDownName(string query)
{
Drug_Information drug = null;
using (DrugProNETEntities context = new DrugProNETEntities())
{
drug = context.Drug_Information.Where(d =>
d.Drug_Name_for_Pull_Down_Menu.ToLower().Contains(query.ToLower())).FirstOrDefault();
}
return(drug);
}
/// <summary>
/// Author: Ryan Liang
/// </summary>
private TableRow CreateTableRow(Drug_Information drug, PDB_Interaction interaction, SNV_Mutation mutation)
{
TableRow tableRow = new TableRow();
tableRow.Cells.Add(new TableCell()
{
Text = drug.Drug_Common_Name
});
tableRow.Cells.Add(new TableCell()
{
Text = mutation.PDB_File_ID
});
tableRow.Cells.Add(new TableCell()
{
Text = mutation.Drug_PDB_ID
});
tableRow.Cells.Add(new TableCell()
{
Text = drug.PubChem_CID
});
tableRow.Cells.Add(new TableCell()
{
Text = drug.ChEMBL_ID
});
if (double.TryParse(interaction?.Interaction_Distance_Ratio, out double result))
{
tableRow.Cells.Add(new TableCell()
{
Text = result.ToString("0.0")
});
}
else
{
tableRow.Cells.Add(new TableCell()
{
Text = ""
});
}
string predictedEffiency = FindPredictedEffiency(mutation);
tableRow.Cells.Add(new TableCell()
{
Text = predictedEffiency
});
return(tableRow);
}
/// <summary>
/// Author: Ryan Liang
/// </summary>
public void LoadDrug(Drug_Information drug, PDB_Information PDB_Info)
{
ProcessRow(PDB_drug_ID_row, PDB_drug_ID, drug.Drug_PDB_ID);
ProcessRow(drug_name_row, drug_name, drug.Drug_Common_Name);
ProcessRow(drug_chemical_name, drug_chemical_name, drug.Drug_Chemical_Name);
ProcessRow(drug_alias_row, drug_alias, drug.Other_Drug_Name_Alias);
ProcessRow(drug_formula_row, drug_formula, drug.Drug_Formula);
ProcessRow(drug_mass_da_row, drug_mass_da, drug.Molecular_Mass);
ProcessRow(potency_row, potency, "IC50 (nM):" + PDB_Info.IC50_nM_
+ " (BINDINGDB); Ki (nM): " + PDB_Info.Ki_nM_
+ " (BINDINGDB); Kd(nM): " + PDB_Info.Kd_nM_
+ " (BINDINGDB)");
ProcessRow(drug_information_result_url_row, drug_information_result_url, "Link to further drug information", "DrugInfoResult.aspx?query_string=" + drug.Drug_Name_for_Pull_Down_Menu);
}
/// <summary>
/// Author: Garth Nelson
/// </summary>
protected new void Page_Load(object sender, EventArgs e)
{
base.Page_Load(sender, e);
SNV_ID_Key = Request.QueryString["query_string"];
try
{
string stringAfterPDot = SNV_ID_Key.Substring(SNV_ID_Key.IndexOf("p.") + 2);
string specifiedAAType = new string(stringAfterPDot.TakeWhile(c => char.IsLetter(c)).ToArray());
string specifiedAANumber = new string(stringAfterPDot.Substring(specifiedAAType.Length).TakeWhile(c => char.IsNumber(c)).ToArray());
string specifiedAA = specifiedAAType + "-" + specifiedAANumber;
mutations = EF_Data.GetMutationsBySNVIDKey(SNV_ID_Key);
proteinMutation = EF_Data.GetMutationBySNVIDKey(SNV_ID_Key);
protein = EF_Data.GetProteinByUniprotID(proteinMutation.UniProt_ID);
foreach (SNV_Mutation mutation in mutations)
{
Drug_Information drug = EF_Data.GetDrugByDrugPDBID(mutation.Drug_PDB_ID);
drugs.Add(drug);
PDB_Interaction interaction = EF_Data.GetPDB_Interaction(mutation.UniProt_ID, mutation.Drug_PDB_ID, specifiedAA);
interactions.Add(interaction);
}
Session["drugs"] = drugs;
Session["interactions"] = interactions;
Session["mutations"] = mutations;
Session["SNV_ID_Key"] = SNV_ID_Key;
LoadSNVID(SNV_ID_Key);
LoadTargetGeneID(protein, mutations[0]);
CreateIDofPDILinkedSNVTable(drugs, interactions, mutations);
}
catch (Exception)
{
Page.Master.FindControl("BodyContentPlaceHolder").Visible = false;
ExceptionUtilities.DisplayAlert(this, QUERY_PAGE);
}
}
protected void LoadAminoAcidDropDown(object sender, EventArgs e)
{
amino_acid_specification_drop_down.Items.Clear();
amino_acid_specification_drop_down.Items.Add(DROP_DOWN_PROMPT_MESSAGE);
try
{
if (drug_specification_drop_down.SelectedItem.Value != DROP_DOWN_PROMPT_MESSAGE)
{
Protein_Information protein = EF_Data.GetProtein(search_textBox.Text);
Drug_Information drug = EF_Data.GetDrugUsingDropDownName(drug_specification_drop_down.SelectedItem.Value);
PDB_Information PDB = EF_Data.GetPDBInfo(protein, drug);
List <SNV_Mutation> mutations = EF_Data.GetMutations(protein.UniProt_ID, drug.Drug_PDB_ID, PDB.PDB_File_ID);
if (mutations.Count > 0)
{
List <string> dropdownValues = new List <string>();
foreach (SNV_Mutation mutation in mutations)
{
dropdownValues.Add(mutation.SNV_Key);
}
dropdownValues = DataUtilities.FilterDropdownList(dropdownValues);
foreach (string dropdownValue in dropdownValues)
{
amino_acid_specification_drop_down.Items.Add(dropdownValue);
}
}
else
{
amino_acid_specification_drop_down.Items.Clear();
amino_acid_specification_drop_down.Items.Add(DROP_DOWN_NO_MATCHES_MESSAGE);
}
}
}
catch (Exception)
{
amino_acid_specification_drop_down.Items.Clear();
amino_acid_specification_drop_down.Items.Add(DROP_DOWN_PROMPT_MESSAGE);
}
}
/// <summary>
/// Author: Andy Tang
/// </summary>
public static PDB_Information GetPDBInfo(Protein_Information protein, Drug_Information drug)
{
PDB_Information PDBInfo = null;
if (protein == null || drug == null)
{
return(PDBInfo);
}
using (DrugProNETEntities context = new DrugProNETEntities())
{
PDBInfo = context.PDB_Information.Where(pdb =>
pdb.UniProt_ID.Equals(protein.UniProt_ID, StringComparison.OrdinalIgnoreCase) &&
pdb.Drug_PDB_ID.Equals(drug.Drug_PDB_ID, StringComparison.OrdinalIgnoreCase)
).FirstOrDefault();
}
return(PDBInfo);
}
/// <summary>
/// Author: Andy Tang
/// </summary>
protected new void Page_Load(object sender, EventArgs e)
{
base.Page_Load(sender, e);
string query = Request.QueryString["query_string"];
try
{
drug = EF_Data.GetDrugUsingDropDownName(query);
if (drug != null)
{
LoadData(drug);
}
}
catch (Exception)
{
throw;
}
}
/// <summary>
/// Author: Andy Tang
/// </summary>
private void LoadData(Drug_Information drug)
{
ProcessRow(compound_name_row, compound_name, drug.Drug_Common_Name);
ProcessRow(chemical_name_row, chemical_name, drug.Drug_Chemical_Name);
ProcessRow(compound_alias_row, compound_alias, drug.Other_Drug_Name_Alias);
ProcessRow(compound_inchl_row, compound_inchl_id, drug.Drug_InChl);
ProcessRow(drug_formula_row, drug_formula, drug.Drug_Formula);
ProcessRow(molecular_mass_row, molecular_mass, drug.Molecular_Mass);
ProcessRow(pdb_drug_id_row, pdb_drug_id, drug.Drug_PDB_ID, drug.Drug_PDB_ID_URL);
ProcessRow(compound_cas_id_row, compound_cas_id, drug.Compound_CAS_ID);
ProcessRow(chembl_id_row, chembl_id, drug.ChEMBL_ID, drug.ChEMBL_Link);
ProcessRow(kinase_sarfair_row, kinase_sarfair, drug.ChEMBL_ID, drug.CHEMBL_Kinase_SARFari_Link);
ProcessRow(pubchem_sid_row, pubchem_sid, drug.PubChem_SID, drug.PubChem_Substance_Link);
ProcessRow(pubchem_cid_row, pubchem_cid, drug.PubChem_CID, drug.PubChem_Compound_Link);
ProcessRow(chemspider_sid_row, chemspider_sid, drug.ChemSpider_ID, drug.ChemSpider_Link);
ProcessRow(chebi_id_row, chebi_id, drug.ChEBI_ID, drug.ChEBI_Link);
ProcessRow(bindingdb_id_row, bindingdb_id, drug.BindingDB_ID, drug.BindingDB_Link);
ProcessRow(drugbank_id_row, drugbank_id, drug.DrugBank_ID, drug.DrugBank_Link);
ProcessRow(drug_reg_row, drug_registration, drug.Drug_Registration_Number);
ProcessRow(kegg_drug_id_row, kegg_drug_id, drug.KEGG_Drug_ID, drug.KEGG_Drug_Link);
ProcessRow(therapeautic_target_row, therapeutic_target_id, drug.Therapeutic_Targets_ID, drug.Therapeutic_Targets_Link);
ProcessRow(pharmgkb_id_row, pharmgkb_id, drug.PharmGKB_ID, drug.PharmGKB_Link);
ProcessRow(het_id_row, het_id, drug.HET_ID, drug.HET_Link);
ProcessRow(drug_product_row, drug_product_id, drug.Drug_Product_ID, drug.Drug_Product_ID_Link);
ProcessRow(rxlist_id_row, rxlist_id, drug.RxList_ID, drug.RxList_Link);
ProcessRow(drugs_com_id_row, drugs_com_id, drug.Drugs_com_ID, drug.Drugs_com_Link);
ProcessRow(wikipedia_row, wikipedia, drug.Wikipedia, drug.Wikipedia_Link);
ProcessRow(general_activity_row, general_activity, drug.General_Activity);
ProcessRow(general_targets_row, general_targets, drug.General_Targets);
ProcessRow(commentary_row, commentary, drug.Commentary);
ProcessRow(source_type_row, source_type, drug.Source_Type);
ProcessRow(living1_source_row, living_source1, drug.Living_Source1);
ProcessRow(living2_source_row, living_source2, drug.Living_Source2);
ProcessRow(approved_row, clinically_approved, drug.Clinically_Approved);
ProcessRow(latest_stage_trial_row, latest_stage_trials, drug.Latest_Stage_Trials);
ProcessRow(producer_row, producer, drug.Producer);
ProcessRow(disease_applications_row, disease_applications, drug.Disease_Applications);
ProcessRow(toxic_effects_row, toxic_effects, drug.Toxic_Effects);
ProcessRow(reference1_row, reference_1, drug.Reference_1);
ProcessRow(reference2_row, reference_2, drug.Reference_2);
}
/// <summary>
/// Author: Garth Nelson
/// </summary>
protected new void Page_Load(object sender, EventArgs e)
{
base.Page_Load(sender, e);
try
{
string protein_specification = Request.QueryString["query_string"];
string drug_specification = Request.QueryString["drug_specification"];
string SNV_Key = Request.QueryString["snv_id_key"];
Session["SNV_Key"] = SNV_Key;
Protein_Information protein = EF_Data.GetProtein(protein_specification);
Drug_Information drug = EF_Data.GetDrugUsingDropDownName(drug_specification);
PDB_Information PDB = EF_Data.GetPDBInfo(protein, drug);
string[] SNV_KEYsplit = SNV_Key.Split('-');
// Retrieve second and third elements
string amino_acid_specification = SNV_KEYsplit[1] + "-" + SNV_KEYsplit[2];
PDB_Interaction interaction = EF_Data.GetPDB_Interaction(protein.Uniprot_ID, drug.Drug_PDB_ID, amino_acid_specification);
mutation = EF_Data.GetMutationBySNVKey(SNV_Key);
Session["mutation"] = mutation;
LoadProtein(protein, interaction, mutation);
LoadDrug(drug, mutation);
LoadPDB_Info(PDB);
CreateSNVIdentificationTable(mutation);
}
catch (Exception)
{
Page.Master.FindControl("BodyContentPlaceHolder").Visible = false;
ExceptionUtilities.DisplayAlert(this, QUERY_PAGE);
}
}
/// <summary>
/// Author: Andy Tang, Ryan Liang
/// </summary>
protected new void Page_Load(object sender, EventArgs e)
{
base.Page_Load(sender, e);
if (!IsPostBack)
{
string fromPage = null;
string query_string = null;
try
{
query_string = Request.QueryString["query_string"];
drug_specification = Request.QueryString["drug_specification"];
protein_specification = Request.QueryString["protein_specification"];
if (!string.IsNullOrEmpty(drug_specification))
{
protein_specification = query_string;
fromPage = "protein";
}
else if (!string.IsNullOrEmpty(protein_specification))
{
drug_specification = query_string;
fromPage = "drug";
}
drug = EF_Data.GetDrugsQuery(drug_specification).FirstOrDefault();
protein = EF_Data.GetProteinsInfoQuery(protein_specification).FirstOrDefault();
PDB = EF_Data.GetPDBInfo(protein, drug);
Session["PDB_File_ID"] = PDB.PDB_File_ID;
interaction_distance = double.Parse(Request.QueryString["interaction_distance"]);
protein_chain = bool.Parse(Request.QueryString["protein_chain"]);
protein_atoms = bool.Parse(Request.QueryString["protein_atoms"]);
protein_residues = bool.Parse(Request.QueryString["protein_residues"]);
protein_residue_numbers = bool.Parse(Request.QueryString["protein_residue_numbers"]);
drug_atoms = bool.Parse(Request.QueryString["drug_atoms"]);
Session["interaction_distance"] = interaction_distance;
}
catch (Exception)
{
throw;
}
if (drug == null || protein == null || PDB == null)
{
Page.Master.FindControl("BodyContentPlaceHolder").Visible = false;
if (fromPage != null)
{
ExceptionUtilities.DisplayAlert(this, fromPage.Equals("drug") ? DRUG_QUERY_PAGE : PROTEIN_QUERY_PAGE);
}
else
{
ExceptionUtilities.DisplayAlert(this, DEFAULT_REDIRECT_PAGE);
}
}
else
{
Session["interaction_distance"] = interaction_distance;
Session["protein_chain"] = protein_chain;
Session["protein_atoms"] = protein_atoms;
Session["protein_residues"] = protein_residues;
Session["protein_residue_numbers"] = protein_residue_numbers;
Session["drug_atoms"] = drug_atoms;
LoadProtein(protein);
LoadDrug(drug, PDB);
LoadPDB_Info(PDB);
GetDrugAtomNumberingImage(drug);
CreateInteractionList(PDB, interaction_distance, protein_chain, protein_atoms, protein_residues, protein_residue_numbers, drug_atoms);
CreateInteractionSummary();
ScriptManager.RegisterStartupScript(Page, GetType(), "D_3DViewer", "javascript:loadDrugLigand('" + drug.Drug_PDB_ID + "');", true);
ScriptManager.RegisterStartupScript(Page, GetType(), "PDB_3DViewer", "javascript:loadStage('" + drug.PDB_File_ID + "', '" + drug.Drug_PDB_ID + "');", true);
}
}
}
/// <summary>
/// Author: Ryan Liang
/// </summary>
private void GetDrugAtomNumberingImage(Drug_Information drug)
{
selected_amino_acid_residue_atom_numbering.ImageUrl =
"https://cdn.rcsb.org/images/ligands/" +
drug.Drug_PDB_ID.Substring(0, 1) + "/" + drug.Drug_PDB_ID + "/" + drug.Drug_PDB_ID + "-large.png";
}
