Lead Discovery 5.2. User Guide. Powered by TIBCO Spotfire

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1 User Guide Powered by TIBCO Spotfire Last Modified: July 26, 2013

2 Table of Contents 1. Introduction Loading Data Opening an SDFile Importing a ChemDraw for Excel File Auto Detection of Structure Column and Content Type Exporting Data Exporting Data to an SDFile Details on Export to SDFile Dialog Exporting Data to a ChemDraw for Excel file Details on Export to ChemDraw for Excel Dialog Working with Structures About the Structure Viewer Using the Structure Viewer About the Structure Viewer Toolbar About the Structure Viewer List Content Pane About the Structure Viewer Structure Viewer Pane Configuring Structure Connections Working with ID Lists About ID Lists in the Structure Viewer About Manage Lists in the Structure Viewer About New Lists Dialog Searching Structures Searching for Compounds using Structure Search About the Structure Search Dialog Viewing Structures in Virtual Columns Viewing Structures in Labels or Tooltips Calculation of Chemical Properties Structural Clustering Structure Filtering About the Structure Filter Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 2 of 93

3 9.2. Accessing the Structure Filter About the Structure Filter Toolbar Search Types Performing a Structure Filter Editing a Filter Clearing a Filter Viewing Historical Structure Filters Saving Structure Filters R-Group Decomposition Setting the R-Group Decomposition Threshold Preference Performing an R-Group Decomposition Analysis Structure Alignment Settings Supported Renderers Renderer Settings Glossary Chemical Property Calculations Balaban Index Boiling Point Cluster Count Critical Pressure Critical Temperature Critical Volume Elemental Analysis Exact Mass Formal Charge Gibbs Free Energy Heat of Forma tion Henry s Constant Law Ideal Gas Thermal Capacity m/z Mass Melting Point Mol Formula Mol Formula HTML Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 3 of 93

4 Mol Refractivity Molecular Topological Index Mol Weight Number of HBond Acceptors Number of HBond Donors Number of Rotable Bonds Polar Surface Area Principal Moment Radius Shape Attribute Shape Coefficient Sum of Degrees Sum of Valence Degrees Topological Diameter Total Connectivity Total Valence Connectivity Vapour Pressure Water Solubility Wiener Index Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 4 of 93

5 1. Introduction Lead Discovery powered by TIBCO Spotfire empowers scientific professionals to freely analyze data and create analytic applications and dashboards. It puts scientists in control, which speeds the time to insight while reducing typical technical bottlenecks to understanding data. Layered on top of the core TIBCO Spotfire feature set, Lead Discovery adds chemical intelligence to an analysis. Visualize chemical structures alongside other data in the creation of SAR tables and interactive dashboards. TIBCO Spotfire supports the use of most chemical renderers able to interpret molfile, SMILES or CDX including the PerkinElmer ChemDraw software. This Guide provides a description of the chemical structure display, interpretation and search functionality available in Lead Discovery. With Lead Discovery, you can: Render Chemical Structures (SMILES, Molfile, ChemDraw) alongside text, numbers and dates in TIBCO Spotfire tables. Open an SDFile and view its fields in the table visualization, including the molecular structures. Load chemical structures from a database in molfile, smiles or ChemDraw formats. Export data to an SDFile or ChemDraw for Excel file format, preserving the structure data. Use the Structure Viewer to view chemical structures, and to create, export, and import ID lists. Search on structures in a database using similarity and substructure search. Set a ChemDraw template (.cds) to be used for visualizing structures. Filter the contents of a data table based on structure. Access Structure Filter history the last ten structure filters applied are saved for re-use. Save structure filter definitions with a user defined name. This allows for manipulation on multiple structure filters at once resulting in dynamic toggling between structures in the filter. Highlight the query molecule when using the Structure filter. Perform an R-Group decomposition analysis on the results of a substructure filter. R-Group columns are created as real SMILES columns allowing you to use the text representation in plot axes, legends etc. Export of R-Groups to ChemDraw for Excel Import a ChemDraw for Excel file with specified columns including structure columns. Calculation of Chemical Properties based on a molecular structure Clustering by Chemical Structure linked dendrogram, 2D scatter plot and 3D scatter plot are created. Calculation of Similarity Score based on similarity search Structure Alignment chemical structures in a dataset can be aligned to a user selected structure in the existing dataset or to a scaffold drawn in the structure filter. The following features are supported in the Web Player: Rendering of Chemical Structures in tables and tooltips Export data to an SDFile Export Data to a ChemDraw for Excel file format Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 5 of 93

6 Structure Alignment Copy Structure 2. Loading Data 2.1. Opening an SDFile You can open an SDFile to view in the table visualization. To open an SDFile: 1. Click on Open on the toolbar, or select File > Open from the File menu. 2. Browse to the SDFile you want to open and click Open. An initial visualization using the fields of the SDFile appears. 3. If your initial visualization is not a table, create a new Table visualization. The table containing the fields of the SDFile, including the chemical structures appears. As with any table visualization, you can: Save this analysis to file or library (see the "Saving an Analysis file in the Library" topic of the Spotfire online help). Change the column order, column width, or row height; add, remove, sort, or mark rows (see the "How to Use the Table" topic of the Spotfire online help). Change the table appearance and settings using the Table Properties Dialog. You can export the contents of table visualization to an SDFile or a ChemDraw for Excel file. Note: When an SDFile containing structures is opened, the row height will automatically default to 10. Tip: You can change the default initial visualization to be a table by going to the Document page, and changing the Initial visualization when loading data to Table Importing a ChemDraw for Excel File You can import a ChemDraw for Excel File (*.xlsx), containing structures, to view in the table visualization. Only one Worksheet can be imported at a time. You can select the columns to import including multiple structure columns. Note: Files from ChemDraw for Excel v12 and v13 are supported as well as files exported to ChemDraw for Excel from Lead Discovery. To import a ChemDraw for Excel file: 1. Click on Open on the toolbar, or select File > Open from the File menu. 2. Browse to the ChemDraw for Excel File you want to open and click Open. The ChemDraw for Excel Import dialog opens. From here, you can select the Worksheet to import as well as the specific columns to import. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 6 of 93

7 Note: If the selected file is found to contain standard Excel Worksheets in addition to ChemDraw for Excel Worksheets, you will be prompted if you want to continue to import the ChemDraw for Excel Worksheets. If not, the Worksheets will be imported into Lead Discovery using Spotfire s standard Excel Import functionality. 3. Once the Worksheet and columns to import have been selected, click OK. An initial visualization using the selected columns to import appears. Note: When a ChemDraw for Excel file containing structures is opened, the row height will automatically default to 10. The following table explains the fields displayed in the ChemDraw for Excel Import window, as shown above. Option Description ChemDraw for Excel Worksheet Lists the available Worksheets for the selected file. Only one Worksheet can be imported at a time. Available columns Lists the columns of the data table that are currently not selected for exporting to the ChemDraw for Excel File. Columns to Import Lists the columns of the Worksheet that are currently selected for importing. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 7 of 93

8 Add > Adds the selected column to the list of columns to import. < Remove Removes the selected column from the list of columns to import and returns it to the list of available columns. Remove All Removes all columns from the list of columns to include in the import and returns them to the list of available columns. Move Up Moves the selected items in the Columns to import list up one step. The order of the columns in this list determines the order of the columns in the imported file. Move Down Moves the selected items in the Columns to import list down one step. The order of the columns in this list determines the order of the columns in the imported file Auto Detection of Structure Column and Content Type Structure column(s) and the content type for each structure column are automatically detected when data is imported into Spotfire. If the content type is mistakenly identified, you can change the content type through the Column Properties for a data table. Additionally if a structure column was not identified as such, you can set the content type through the Column Properties. To identify the content type for a column: 1. Select Edit > Column Properties from the Edit menu. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 8 of 93

9 2. Select the column for which you want to specify the content type. If there is more than one table, you may have to choose the table first. 3. Select the Properties tab. Select the Content Type property. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 9 of 93

10 4. Click on the Edit button to open the Edit Property dialog. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 10 of 93

11 . 5. Edit the value to reflect the correct content type. Note: The content type you enter can be an arbitrary string, but it is recommended that you use the MIME types defined for molfiles, CHIME, SMILES and CDX strings as shown in the table below. Structure Format MDL molfile MDL Chime string Daylight SMILEs string Content Type chemical/x-mdl-molfile chemical/x-mdl-chime chemical/x-daylight-smiles ChemDraw Chemical Structure Exchange chemical/x-cdx 6. Click OK to return to the Column Properties dialog. The value field is updated with the content type. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 11 of 93

12 7. Click OK. Note: Chemical structures loaded into Spotfire in ChemDraw s native file format (CDX, CDMXL) are supported for chemical rendering, chemical searching and exporting. This content in data tables will be displayed natively in renderers that support the format (ChemDraw) or converted to MOLfiles or SMILES for renderers that do not offer support. Query molecules will be extracted from renderers that support the format (ChemDraw) and sent unchanged to cartridges that support the format or converted to MOLfiles or SMILES for cartridges that do not. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 12 of 93

13 3. Exporting Data You can export data from Lead Discovery to an SDFile or to a ChemDraw for Excel file. Note: It is possible to include data in a table visualization (or labels and tooltips of some other visualizations) that is not part of the original data table. A virtual column connects to a remote data source and collects data from there. The virtual column is only part of the table visualization and not part of the data table. Exporting of the data table does not include the virtual columns. To export the data contained in the virtual columns, you must export the visualization data for all items Exporting Data to an SDFile To export data from visualization table to an SDFile: 1. Right-click on the table and select Export to SDFile. 2. Select whether to export Visualization data for all items or Data table. Visualization data for all items Exports all items from current visualization table. Data table Exports the data table from current visualization table. 3. If Data table is selected, specify whether to export all rows, marked rows, or filtered rows only: All rows - Exports every row in the data table regardless of filtering. Marked rows - Exports the marked rows of the table only. Filtered rows - Exports the rows remaining after filtering only. 4. Select the Structure column from the drop-down list. If Visualization data for all items is selected, all virtual structure columns will be available for selection here. Comment: The SDFile format supports only one structure per record. You can select any column in the table that contains Molfile or SMILES structures. The first column containing structures displays as the default choice. 5. If Data table is selected, use Add >, < Remove, and Remove All to select the columns to export with the structure. Use Move Up and Move Down to specify the order of columns in the SDFile. 6. Click OK. 7. In the Save As dialog, specify a filename, browse to the location where you want to save the file. 8. Click Save. Tip: You can export data to an SDFile by selecting File > Export > Data from the main menu and choosing Save as type: SDFile (*.sd;*.sdf). However, you will not be able to change the columns to include in the export if you use this method. To export data from the Structure Viewer to an SDFile: 1. Select the IDs you want to export in the List Content pane of the Structure Viewer panel or popover. 2. Right-click on any of the selected IDs and select Export Selection to SDFile. 3. Select the Structure column from the drop-down list. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 13 of 93

14 Comment: The SDFile format supports only one structure per record. You can select any column in the table that contains Molfile or SMILES structures. The first column containing structures is displayed as the default choice. 4. Use Add >, < Remove, and Remove All to select the columns to be exported with the structure. 5. Use Move Up and Move Down to specify the order of columns in the SDFile. 6. Click OK. 7. In the Save As dialog, specify a filename, browse to the location where you want to save the file. 8. Click Save Details on Export to SDFile Dialog To navigate to the Export to SDFile dialog: 1. Right-click on the table and select Export to SDFile. Comment: If the table does not contain any structures, the Export to SDFile menu item will be unavailable. OR 2. Select the IDs you want to export in the List Content pane of the Structure Viewer panel or popover. 3. Right-click on any of the selected IDs and select Export Selection to SDFile. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 14 of 93

15 The following table explains the fields displayed in the Export to SDFile window, as shown above. Option Description Export data from: Note: If you exported data from the Structure Viewer, these options will not be available since you have already selected which rows to export. Visualization data for all items Exports all data from the current visualization. Data Table All rows Marked rows Filtered rows Exports data from current data table. Exports all rows in the selected data table. Exports data for the marked rows only. Exports data for the filtered rows only. Structure column Specify the column in the data table that contains Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 15 of 93

16 molecular structures. Displays the available structure columns. Select the one you wish to export. If no structure column is available in the actual data set (for example, if structures are shown in a virtual column) you will not be able to export the structures using this tool. Note: If Visualization data for all items is selected, all virtual structure columns will be available for selection here. The following options are only available if Export data from Data Table is selected. Available columns Lists the columns of the data table that are currently not selected for exporting to the SDFile. Columns to include in SDFile Lists the columns of the table that are currently selected for exporting to the SDFile. Add > Adds the selected column to the list of columns to include in the SDFile. < Remove Removes the selected column from the list of columns to include in the SDFile and returns it to the list of available columns. Remove All Removes all columns from the list of columns to include in the SDFile and returns them to the list of available columns. Move Up Moves the selected items in the Columns to include in SDFile list up one step. The order of the columns in this list determines the order of the columns in the resulting SDFile. Move Down Moves the selected items in the Columns to include in SDFile list down one step. The order of the columns in Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 16 of 93

17 this list determines the order of the columns in the resulting SDFile Exporting Data to a ChemDraw for Excel file Note: The Export to ChemDraw for Excel menu item is available on all clients, regardless of the presence of ChemDraw for Excel. Lead Discovery does not need ChemDraw for Excel present in order to produce an Excel file that is compatible with ChemDraw for Excel. The user will need the ChemDraw/Excel Add-In to open the file, but not to export it. The file produced by Lead Discovery is saved in Excel s *.xlsx format. The file that can be opened by Excel, regardless of whether it is equipped with the ChemDrawExcel Add-In. However, the chemical structures will only be converted into pictures when the ChemDrawExcel Add-In is present. After successfully opening in Excel, the file, if re-saved, will contain the chemical structure pictures. It will display structure systems in Excel (without ChemDrawExcel Add-In); however, the structures will not be searchable or editable in Excel. Note: Chemical structures loaded into Spotfire in ChemDraw s native file format (CDX) can also be exported to ChemDraw for Excel. Note: The File > Export > Data feature in Spotfire is not the same as the Export to ChemDraw for Excel feature. Any results exported into Excel using the native Spotfire export feature may vary depending on how the structure data was imported into Spotfire. It is recommended that you use the Export to ChemDraw for Excel option. To export data from visualization table to ChemDraw for Excel file: 1. Right-click on the table and select Export to ChemDraw for Excel. 2. Select whether to export Visualization data for all items or Data table. Visualization data for all items Exports all items from current visualization table. Include virtual structure columns if enabled, includes virtual structure columns for export. Data table Exports the data table from current visualization table. 3. If Data table is selected, specify whether to export all rows, marked rows, or filtered rows only: All rows - Exports every row in the data table regardless of filtering. Marked rows - Exports the marked rows of the table only. Filtered rows - Exports the rows remaining after filtering only. 4. Select the Structure column from the drop-down list. If Visualization data for all items is selected, and Include virtual structure columns is enabled, all virtual structure columns will be available for selection here. Comment: The Export to ChemDraw for Excel feature supports the export of one structure column per record. You can select any column in the table that contains Molfile, SMILES, and CDX structures. The first column containing structures displays as the default choice. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 17 of 93

18 5. If Data table is selected, use Add >, < Remove, and Remove All to select the columns to export with the structure. Use Move Up and Move Down to specify the order of columns in the ChemDraw for Excel file. 6. Click OK. 7. In the Save As dialog, specify a filename, browse to the location where you want to save the file. 8. Click Save. Tip: You can export data to a ChemDraw Excel File by selecting File > Export > Data from the main menu and choosing Save as type: ChemDraw for Excel File (*.xlsx). However, you will not be able to change the columns to include in the export if you use this method. To export data from the Structure Viewer to a ChemDraw for Excel File: 1. Select the IDs you want to export in the List Content pane of the Structure Viewer panel or popover. 2. Right-click on any of the selected IDs and select Export Selection to ChemDraw for Excel. 3. Select the Structure column from the drop-down list. Comment: The ChemDraw Excel File format supports only one structure per record. You can select any column in the table that contains Molfile, SMILES, and CDX structures. The first column containing structures displays as the default choice. 4. Use Add >, < Remove, and Remove All to select the columns to be exported with the structure. 5. Use Move Up and Move Down to specify the order of columns in the ChemDraw Excel File. 6. Click OK. 7. In the Save As dialog, specify a filename, browse to the location where you want to save the file. 8. Click Save Details on Export to ChemDraw for Excel Dialog To navigate to the Export to ChemDraw for Excel dialog: 1. Right-click on the table and select Export to ChemDraw for Excel. Comment: If the table does not contain any structures, the Export to ChemDraw for Excel menu item will be unavailable. OR 2. Select the IDs you want to export in the List Content pane of the Structure Viewer panel or popover. 3. Right-click on any of the selected IDs and select Export Selection to ChemDraw for Excel. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 18 of 93

19 Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 19 of 93

20 The following table explains the fields displayed in the Export to ChemDraw Excel File window, as shown above. Option Description Export data from: Note: If you exported data from the Structure Viewer, these options will not be available since you have already selected which rows to export. Visualization data for all items Include virtual structure columns Exports all data from the current visualization Exports all virtual columns containing molecular structures when this checkbox is enabled. Data table All rows Marked rows Filtered rows Exports data from current data table. Exports all rows in the selected data table. Exports data for the marked rows only. Exports data for the filtered rows only. Structure column Specify the column in the data table that contains molecular structures. Displays the available structure columns. Select the one you wish to export. If no structure column is available in the actual data set (for example, if structures are shown in a virtual column) you will not be able to export the structures using this tool. The following options are only available if Export Data from Data table is selected. Available columns Lists the columns of the data table that are currently not selected for exporting to ChemDraw for Excel. Columns to include in Lists the columns of the table that are currently selected Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 20 of 93

21 ChemDraw for Excel for exporting to ChemDraw for Excel. Add > Adds the selected column to the list of columns to include in the ChemDraw Excel File. < Remove Removes the selected column from the list of columns to include in the ChemDraw Excel File and returns it to the list of available columns. Remove All Removes all columns from the list of columns to include in the ChemDraw Excel File and returns them to the list of available columns. Move Up Moves the selected items in the Columns to include in ChemDraw Excel File list up one step. The order of the columns in this list determines the order of the columns in the resulting ChemDraw Excel File. Move Down Moves the selected items in the Columns to include in ChemDraw Excel File list down one step. The order of the columns in this list determines the order of the columns in the resulting ChemDraw Excel File. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 21 of 93

22 4. Working with Structures 4.1. About the Structure Viewer The Structure Viewer is used to: View the structures marked in the visualization or to display structure search results. View, create, import, and export ID lists. The key elements of the Structure Viewer are: Toolbar and lists drop-down List Content pane Structure Viewer pane Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 22 of 93

23 The following table describes the fields in the Structure Viewer window, as shown above. Option Description Toolbar Contains the buttons that allow you to export, import, rename and delete ID lists, and to edit list settings. Lists You can select an existing list in the Lists drop-down. The Structure Viewer maintains a dynamic list called Marked Rows that contains the marked rows in the active visualization. The number of items in each list is displayed within parentheses after the name of the list. List Content pane Structure Viewer pane Displays the list of identifiers for the list selected in the Lists dropdown. The values in this pane are taken from the ID column you selected when opening the Structure Viewer. Displays the chemical structures for the list selected in the Lists drop-down. The structures in this pane are taken from the structure column you selected when opening the Structure Viewer, or from the results of a structure query Using the Structure Viewer To navigate to the Structure Viewer: 1. Open data in Lead Discovery. 2. Click the Structure Viewer button in the toolbar. Comment: You can also select View > Structure Viewer from the menu. The Configure Structure Connection dialog displays. 3. Select the columns in the visualization containing molecular structures and identifiers. 4. Click OK. The Structure Viewer displays. Mark or highlight compounds in a visualization. When there are no marked rows, the structure from the currently highlighted row in the data table is displayed in the Structure Viewer pane of the Structure Viewer, and its identifier is displayed in the List Content pane. When there are marked rows, the structures from the marked rows are displayed in the Structure Viewer pane and their identifiers are displayed in the List Content pane. When you highlight a marked row, its corresponding identifier and structure will be highlighted in the Viewer and List Content panes. Note: The Structure Viewer automatically becomes active when you perform a structure search. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 23 of 93

24 4.3. About the Structure Viewer Toolbar The image below shows the toolbar for the Structure Viewer. The following table explains the icons found on the Structure Viewer toolbar, as shown in the image above. Button / Control Description Imports an ID list file to Structure Viewer. Exports the ID list currently selected in the Lists drop-down to an LST file. Displays the structures with the IDs from the active ID list in separate data table visualizations. Creates a new data table containing the structures and IDs from the current list. If additional data is available, it is included in the new table. Additional data may be drawn from the linked rows in the active data table or from an information link, depending on the source of the list. Opens the Structure Connection dialog where you can re-configure the mapping of ID and structure columns between data tables and Structure Viewer. Opens the Manage Lists dialog where you can change the name and description for previously created lists, as well as delete lists. Displays the name of the selected list followed by the number of items in the list within parentheses. The elements of the selected list are displayed in the List Content and Viewer panes. Use this dropdown to select a different list About the Structure Viewer List Content Pane In the List Content pane of the Structure Viewer, you can view the identifiers of the molecular structures from the ID list currently selected in the Lists drop-down. This can represent: The marked rows in the active data table. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 24 of 93

25 A previously-created or imported ID list. The results of a structure search. The List Content pane displays the identifiers of the rows in the list. The identifiers are taken from the column you selected as the ID column when the Structure Viewer was first opened. If the result of a structure query is shown, the metadata supplied by the information link are used. The right-click pop-up menu of the List Content pane contains a number of options. These options are explained in the table below. Right-click Menu Option Mark Selection in Active Visualization Create New List from Selection Export Selection to SDFile Description Marks the rows with the selected IDs in the active visualization. Creates a new ID list from the IDs selected in the List Content pane. Opens the Export to SDFile dialog where you can export the selected IDs to an SDFile. Export Selection to ChemDraw for Excel Copy IDs Select All Invert Selection Remove IDs from List Manage Lists Opens the Export to ChemDraw for Excel dialog where you can export the selected IDs to a ChemDraw for Excel file. Copies the selected IDs to the clipboard. Selects all IDs in the List Content pane. Inverts the selection in the List Content pane. Removes the selected IDs from the list in the List Content pane. Opens the Manage Lists dialog where you can change the names and descriptions of all previously added lists. You can also remove unwanted lists from Structure Viewer. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 25 of 93

26 4.5. About the Structure Viewer Structure Viewer Pane In the Structure Viewer pane, you can see the structures of either the marked rows of the data table, or of the currently active ID list. This pane also displays the structures of the search results after you run a Structure Search. The right-click context menu of the Structure Viewer pane contains a number of options. These options are explained in the table below: Right-click Menu Option Structure Search Copy Renderer Print Description Displays the Structure Search dialog. Copies information from the Structure Viewer to the Windows clipboard: Structure - Copies the selected structure as a structure which can be edited in the structure renderer. Image - Copies the selected structure as an image. Image with All Visible Structures - Copies the visible contents of the Structure Viewer pane as an image. Use this option to select the default renderer used in the Structure Viewer pane (see Supported Renderers for more information). You can also change the renderer settings in the Renderer Settings dialog. All - When selected, specifies that all structures from the current list will be printed. Visible Structures - When selected, specifies that only those structures from the current list that are visible in the Structure Viewer pane will be printed. Print - Prints the structures according to the print settings Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 26 of 93

27 (All or Visible Structures). Print Preview - Displays the Print Preview window. Show IDs Layout Shows or hides the molecule IDs for the structures displayed in the Structure Viewer pane. Specifies the number of columns to be shown in the Structure Viewer pane Configuring Structure Connections In the Configure Structure Connection dialog, you specify the columns of the table which will be treated by the Structure Viewer as the columns containing structures and IDs. The structure connection can be different for different lists. To navigate to the structure connection dialog: 1. Click on the Structure Viewer button on the toolbar. The Configure Structure Connection dialog displays. Comment: You can also select View > Structure Viewer from the menu. 2. In Structure Viewer, you can also click on the Configure Structure Connection button, to open the dialog again. The following table explains the fields found in the Configure Structure Connection dialog, as shown above. Option ID column Description Select the column from the data table which you want to use as the identifier of the structure. The values from this column will be displayed in the List Contents pane of the Structure Viewer panel. Also, the Structure Viewer will use the IDs from this column for creating, exporting, and importing the ID lists. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 27 of 93

28 Structure Column Select a column that contains structures from those available in the active table visualization. The contents of this column will be rendered in the Structure Viewer pane. Displays the content type for the structure column. This field is read-only. Link Select an information link that contains structures from those available in the drop-down list. The structures from this link display in the Structure Viewer pane. The information links that are available here are configured using Information Designer. See the TIBCO Spotfire Lead Discovery - Installation Manual for more information. 5. Working with ID Lists 5.1. About ID Lists in the Structure Viewer The ID lists in the Structure Viewer let you keep track of groups of compounds. Each time you conduct a structure search, the result is added as a new list in the List Content pane of the Structure Viewer. All the lists that you create are stored locally and appear in the Lists drop-down of the Structure Viewer. The Structure Viewer also maintains a dynamic list called "Marked Rows", which contains the current set of marked rows. To save the results of a structure query or the set of marked rows more permanently, create a new list and convert the list to a data table, or export a list file or an SDFile. To display the Structure Viewer: 1. Select Tools > Structure Viewer, or, click on the Structure Viewer button on the toolbar. Comment: Another way to launch the Structure Viewer is to perform a structure search by right-clicking on a table column containing structures and selecting Structure Search. The Structure Viewer appears and the search results are displayed in the List Content and Structure Viewer panes. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 28 of 93

29 The following table explains the actions you can perform from the Structure Viewer. Action Create a list Change list settings Instruction Do either one of: Perform a search using the Structure Search tool. Select the IDs in the current list, right-click and select Create New List from Selection Click the Manage Lists button,, on the Structure Viewer toolbar. You can also right-click and select Manage Lists from the pop-up menu. In the Manage Lists dialog, you can change the list name and description. In the Structure Connection dialog, reached from the Configure Structure Connection button, you can re-map the ID and structure columns, if necessary. Rename a list Export the list as an LST file Import a list Export selected IDs to an SDFile Export selected IDs to a ChemDraw for Excel file Click the Manage Lists button, on the Structure Viewer toolbar. You can also right-click and select Manage Lists from the pop-up menu. In the Manage Lists dialog, click to select the list you want to rename, then click Rename. Select the list in the Lists drop-down and click the Export button,, on the Structure Viewer toolbar. Click the Import button,, on the Structure Viewer toolbar and select the list file to import in the Open File dialog. Right-click on any of the selected IDs and select Export Selection to SDFile from the pop-up menu to open the Export to SDFile dialog. Right-click on any of the selected IDs and select Export Selection to ChemDraw for Excel from the pop-up menu to open the Export to ChemDraw for Excel dialog. Display structure for a compound ID Create a new data table with the compounds from the current list Click on one or more identifiers in the List Content pane. The Structure Viewer pane will display the structures corresponding to the selected identifiers. Select the list in the Lists drop-down and click the Create Table button,, on the Structure Viewer toolbar. A new data table will be created with the ID, structure, and any related data for the compounds in the list. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 29 of 93

30 Mark compounds from the list Copy a list Select all identifiers in a list Invert the selection in the list Remove identifiers from the list In the list, select the desired identifiers. Right-click and select Mark Selection in Active Visualization. In the list, select the desired identifiers. Right-click and select Copy IDs. Right-click in the List Content pane and select Select All. In the list, select the desired identifiers. Right-click and select Invert Selection. In the list, select the desired identifiers. Right-click and select Remove IDs from List About Manage Lists in the Structure Viewer In the Manage Lists dialog, you can specify the list name and description of all available lists. See an image of the Manage Lists dialog below. To open to the Manage Lists dialog: 1. Click the Manage Lists button,, on the Structure Viewer toolbar or right-click in the List Content pane and select Manage Lists. The following table explains the fields found in the Manage Lists dialog. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 30 of 93

31 Option ID Lists Rename Delete Description Description Lists all currently available ID Lists in Structure Viewer. Click on a list in the ID Lists pane and then click Rename to change the name of the selected list. Click on a list in the ID Lists pane and then click Delete to remove the selected list from the Structure Viewer. Optional. Type a description of the contents of the selected list About New Lists Dialog New lists are automatically created when you perform a structure search. To create a new list from a selection in another list: 1. Ensure that the IDs are selected in the List Contents pane of the Structure Viewer. See Working with ID Lists for more information. 2. Right-click in the List Contents pane and select Create New List from Selection. The New List dialog displays. The following table describes the fields found in the New List dialog, as shown in the image above. Option Name Description Description Type a suitable name for the new list. Optional. Type a description of the contents of the list. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 31 of 93

32 6. Searching Structures 6.1. Searching for Compounds using Structure Search The Structure Search tool allows you to perform substructure and similarity searches. See Details on Structure Search for more information regarding the individual search methods. The search returns a list of identifiers that is displayed in the Structure Viewer. To search for compounds in a structure database: 1. In the Structure Viewer or in a table visualization with structures, click to activate the compound on which you want to base the search. The Structure Search dialog displays. 2. Right-click on the structure and select Structure Search from the pop-up menu. Comment: You can also select Tools > Structure Search from the main menu. 3. Select one of the alternatives under Search for. Comment: You can search for Substructure or Similarity. 4. If the Parameters button becomes available, click on it to edit the parameters available for the selected search method. Comment: If you select Similarity search, you must enter a range of similarity values in the Similarity Search Parameters dialog. Similarity values range from 0 (least similar) to 100 (most similar). 5. If you want to import a structure from a file, click Import Structure. The Open File dialog appears. Select the file you want to import and click Open. The structure from the file will be displayed in the Structure Search dialog. 6. If required, click Edit. If more than one structure editor is available, you can choose which editor to use from a drop-down list. Your selected structure editor is launched. Edit the structure and click the button that returns the structure to Spotfire (in ChemDraw: OK, in Symyx Draw (MDL): Transfer). Please refer to the documentation of your current structure editor for more details. 7. Select an information link in the Search in drop-down. Comment: See Configuring Information Links in the Lead Discovery Installation Guide for more information about how to configure information links. 8. If required, limit the search to the current list of identifiers. Comment: This option is only available when performing the search from the Structure Viewer and when any list except for the Marked Rows list is selected in the Lists drop-down of the Structure Viewer. When you start a structure search from table visualization without activating the Structure Viewer, or, if the Marked Rows list is selected, the Data Source option will be the only one available. 9. Specify the name for the resulting list. 10. Click OK. Structures in the database that match the search criteria are displayed in the Structure Viewer (Viewer pane). A new ID list is added and displayed in the List Content pane. To show the Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 32 of 93

33 search results as a separate data table, select the search results list in the Lists drop-down and click the button on the Structure Viewer toolbar. Note: Using Information Links, configured through the Information Designer, structures can be returned with the query molecule highlighted when performing a chemical substructure search as shown in the following example. This capability is only available with the CSCartridge. Refer to the Lead Discovery Installation Guide for instructions on how to configure these information links About the Structure Search Dialog To open the Structure Search dialog: 1. Select Tools > Structure Search, or right-click on a structure in a table, or the Structure Viewer and select Structure Search from the pop-up menu. The Structure Search dialog appears. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 33 of 93

34 Note: Structures searches can also be performed in Lead Discovery without opening a file first (Tools > Structure Search). The following table explains the fields found in the Structure Search dialog, as shown in the image above. Option Search for Substructure Similarity Parameters Import Structure Edit... Description Performs a search for structures containing the specified substructure. Performs a search for structures similar to the specified master structure. Open the Similarity Search Parameters dialog and specify a range of values between 0 (least similar) and 100 (most similar). Launches the Parameters dialog where you can provide search parameters for similarity search. Launches the Open dialog where you can select a structure file to use in the search. Launches your current structure editor where you can edit the structure before performing the search. The same thing is achieved by double-clicking the structure. If more than one structure editor is available, you can choose which editor to use from a drop-down list. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 34 of 93

35 After editing the structure and sending it back, the Structure Search dialog is updated with the edited structure. Search in Limit search to Name of resulting list Specifies the information link (predefined query) to the data source in which the search will be performed. See chapter 2.4 of the TIBCO Spotfire Lead Discovery - Installation Manual for more information about Configuring Information Links. See Information Links topics in the TIBCO Spotfire online help for general information about information links. Allows you to limit the search to a set of identifiers from the list currently selected in the Lists drop-down. This option is only available when any (not empty) list except for the Marked Rows list is selected. Allows you to give the resulting structure search list a name of your choice Viewing Structures in Virtual Columns In the table visualization, you can view structures from remote data sources using virtual columns. You can connect to a virtual column and collect structure data from the remote data source both when showing structures in table visualization and when structures are shown in the Structure Viewer. To add a virtual column: 1. Right-click on a table visualization and select Properties. 2. Select Virtual Columns and click Add > Structure Column. 3. In the Structure Column Settings dialog, select the key column, for example, the column that contains the IDs of the structures in your visualization. 4. Click Browse. The Open from Library dialog displays. 5. Select the information link that contains the data you want to retrieve in your virtual columns and click Open. Note: Ensure the columns containing the key column data (in our example - structure IDs) and the data you would like to view in the virtual column (for example, molecular structures) are included in the information link. 6. Click OK. The virtual Structure column is displayed in the active table visualization Viewing Structures in Labels or Tooltips You can display structures and other images in the labels or tooltips of visualizations. To show structures from the loaded data in labels: 1. Open the Properties dialog for the visualization. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 35 of 93

36 Comment: This is done by right-clicking on the visualization and selecting Properties from the pop-up menu. 2. Click on the Labels page in the list on the left. The Labels page displays. Note: Not all visualizations support labels. 3. Select the structure column under Label By. Comment: This is possible if the loaded data contains the structure information directly (e.g., if the loaded data is an SDFile). For example, select "Structure <MOLFILE>". If you want to retrieve the structures from an information link instead, see below. 4. Specify whether to Show labels for: All or Marked rows. 5. Ensure that Get content from is set to (Selected column). 6. Ensure that Show as is set to your current structure renderer. For example, Symyx Draw (MDL). 7. If desired, change the Size of the structures using the slider. 8. Click Close. To show structures from an information link in labels: 1. Open the Properties dialog for the visualization. Comment: This is done by right-clicking on the visualization and selecting Properties from the pop-up menu. 2. Click on the Labels page in the list on the left. The Labels page displays. Note: Not all visualizations support labels. 3. Select an identifier column under Label By. Comment: Here you select the identifier column in your data table that will be used to match the identifier in the information link from which structures are to be retrieved. 4. Specify whether to Show labels for: All or Marked rows. 5. Select Get content from: Structure Column. Comment: This specifies that rather than displaying the information from the selected Label by column directly, the selected column will be used as an identifier when retrieving data from an information link. 6. Click on the Settings button next to Get content from. The Structure Column Settings dialog displays. 7. Ensure that the correct Key column is selected, and click Browse. The Open from Library dialog displays. 8. Click to select the information link containing your structures and click Open. Note: Ensure columns containing the key column data (in our example - structure IDs) and the data you would like to view in the virtual column (for example, molecular structures) are included in the information link. 9. Click OK. 10. Ensure that Show as is set to your current structure renderer. For example, Symyx Draw (MDL). 11. Click Close. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 36 of 93

37 To show structures from the loaded data in tooltips: Most visualizations can display images from a binary image column, a shape file, or chemical structures in tooltips. 1. Open the Properties dialog for the visualization. Comment: This is done by right-clicking on the visualization and selecting Properties from the pop-up menu. 2. Click on the Tooltip page in the list on the left. The Tooltip page displays. 3. Click on Add. The Add Tooltip Value dialog displays. 4. Select the structure Column of interest. 5. Type a Name to display. Comment: This is the text shown together with the expression value in the tooltip, and also will be shown in the list of available tooltip values. 6. Ensure that Get content from is set to (Selected column). Comment: Make sure that Show as is set to your current structure renderer. 7. If desired, change the Size of the tooltip image by moving the slider, 8. Clear the Include value name in tooltip check box if you only want to display the image in the tooltip and not the name. 9. Click OK. The Add Tooltip Value dialog closes and the newly added value is shown in the Tooltip property page. 10. Click Close. To show structures from an information link in tooltips: 1. Open the Properties dialog for the visualization. Comment: This is done by right-clicking on the visualization and selecting Properties from the pop-up menu. 2. Click on the Tooltip page in the list on the left. The Tooltip page displays. 3. Click Add. The Add Tooltip Value dialog displays. 4. Select an identifier Column. Comment: Here you select the identifier column in your data table used to match the identifier in the information link from which structures are to be retrieved. 5. Type a Name to display. Comment: This is the text that will be shown together with the expression value in the tooltip, and also will be shown in the list of available tooltip values. 6. Select Get content from: Structure Column. Comment: This specifies that rather than displaying the information from the selected Label by column directly, the selected column will be used as an identifier when retrieving data from an information link. 7. Click on the Settings button next to Get content from. The Structure Column Settings dialog displays. 8. Ensure the correct Key column is selected, click Browse. The Open from Library dialog displays. 9. Click to select the information link containing your structures and click Open. Note: Ensure sure that columns containing the key column data (in our example - structure IDs) and the data you would like to view in the virtual column (for example, molecular structures) are included in the information link. 10. Click OK. 11. Ensure that Show as is set to your current structure renderer. 12. If desired, change the Size of the tooltip image by moving the slider, Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 37 of 93

38 13. Clear the Include value name in tooltip check box if you only want to display the image in the tooltip and not the name. 14. Click OK. The Add Tooltip Value dialog closes and the newly added value is shown in the Tooltip property page. 15. Click Close. 7. Calculation of Chemical Properties Lead Discovery allows you to determine different chemical, topological, physical, and thermodynamic properties based on a chemical structure. Once calculations are complete, they can be used in other visualizations. You can insert chemical properties, based on a selected structure column, into the data table as new columns. This provides a quick interface for you to generate multiple chemical property columns simultaneously. In this case, the calculations are performed via custom Data Function(s). The column type of the new chemical property column inserted is Result type. You can also insert chemical properties using Calculated Columns in Spotfire. In this case, the column type of the new chemical property column is Calculated type. Only calculated columns support expression editing. The chemical property expression can be combined with other expressions allowing for customization of expressions. Chemical Properties are available anywhere expressions are available within Spotfire. Note: Overall, higher performance is seen when using Data Functions for the calculation of chemical properties. Calculating chemical properties for a structure column: 1. Right click on a structure column in the table visualization and select Insert Chemical Properties. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 38 of 93

39 Note: If the selected column is not a valid structure column, the Insert Chemical Properties option is not displayed in the right click context menu. The Insert Chemical Properties window opens. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 39 of 93

40 2. From the Structure column list, select the Structure column on which to perform the chemical property calculations. The first structure column, detected by Lead Discovery, is listed by default. 3. Select the chemical properties to calculate. Note: You can search for a Chemical property by entering a chemical property in the search field. The text box supports smart search and an abbreviated list of Chemical property matches is displayed for selection as you are typing. Clearing the search field will re-populate the list with all Chemical properties. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 40 of 93

41 4. Click OK. New columns are generated in the table for each calculated chemical property. If there is a row that does not contain a structure, a calculation is not shown for that row. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 41 of 93

42 In addition to the column name containing the name of the chemical property, it also displays the structure column and the units for the calculated property. 5. Via Edit > Column Properties, you can re-name the column. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 42 of 93

43 Additional complex computations, using Spotfire functionality, can be performed on the newly added columns. Inserting a Chemical Property using Calculated Columns 1. From the main menu, select Insert > Calculated Column. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 43 of 93

44 2. From the Functions drop down list, select Chemical Properties. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 44 of 93

45 3. Select a Chemical Property from the list, or type a chemical property name in the Search field. 4. Double click on the Chemical Property, or use the Insert Function button to insert the selected function (chemical property) at the current cursor position in the Expression field. 5. Select a structure column from the Available Columns list, and click on the Insert Column button. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 45 of 93

46 6. Specify a Column Name. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 46 of 93

47 7. Click on the OK button. A new column is generated based on the calculated chemical property. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 47 of 93

48 Note: Refer to the Chemical Properties Calculation section for a description of each calculation. 8. Structural Clustering Hierarchical clustering can be performed through a one-click operation on a structure or numerical column. It is available as a tool on the right-click menu on the table visualization. Clustering can be performed on tables with a maximum of 1000 rows. Clustering results dynamically reflect the filtered rows of the source table. The Hierarchical Structure clustering is based on the Tanimoto similarity between the chemical fingerprint of the structures in the selected column. Upon performing clustering, a new page ( Cluster by <column name> ) is generated containing 4 visualizations to display the results: A table visualization: containing the source data table upon which the clustering was performed. A dendrogram: displaying the clustering results in a tree-structured graph. 2D and 3D Scatter Plots: providing a visual representation of the clusters (indicating cluster size and similarity distance between clusters) present at the pruning line currently selected in the dendrogram. Note: To support the construction of the dendrogram, a column ( ClusteringMatch ) is added to the source data table and a new data table ( Clustering ) is added to the analysis. On each visualization, the appearance can be customized through the standard Spotfire visualization properties. However, it is not recommended to change the axes in the cluster plots, as doing so will invalidate the data displayed in the visualization. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 48 of 93

49 To perform a clustering analysis: 1. Right click on a structure or numeric column in the table visualization and select Cluster By. Note: If the table has more than 1000 rows, you will be notified that the selected column has more than 1000 rows and that this exceeds the maximum row limit for clustering. A new page ( Cluster by <column name> ) is generated containing 4 visualizations to display the results: Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 49 of 93

50 The scatter plots depend on the position of the dotted red cutoff line across the dendrogram (pruning line). Every node directly below the line is represented as a single ball in the scatter plot, with its size scaled to the number of leaves it contains. By moving the cut off line up and down, you vary between a coarse-grained view with few clusters, to a more detailed view with many. The clustering analysis can be removed by deleting the page containing the clustering results. 9. Structure Filtering 9.1. About the Structure Filter The Structure Filter is used to: Draw a chemical structure on which to filter the contents of a data table. Filter the contents based on full structure, substructure or similarity. Perform an R-Group decomposition analysis on the results of a substructure filter. Chemical structures loaded into Spotfire in ChemDraw s native file format (CDX) are supported in the Structure Filter provided ChemDraw is being used as the renderer and/or editor. The content is converted to MOLfiles or SMILES for renderers/editors that do not offer support. Note: The Structure Filter does not support all advanced query features, including variable attachment points when drawn in the ChemDraw editor. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 50 of 93

51 9.2. Accessing the Structure Filter To navigate to the Structure Filter: 1. Open data in Lead Discovery. 2. Click the Structure Filter button in the main toolbar. 3. The Structure Filter opens. By default, the Structure Filter opens above the Filters panel. Note: You can also select View > Structure Filter from the main menu to open the Structure Filter About the Structure Filter Toolbar The image below shows the toolbar for the Structure Filter. The following table explains the icons found on the Structure Filter toolbar, as shown in the image above. Button / Control Description Opens the Structure Editor to edit the current structure filter. Clears the current filter. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 51 of 93

52 Opens the Settings dialog for the selected renderer. Refer to Settings section. Opens the Historical Search drop down list. Insert/Remove R-Group Columns 9.4. Search Types The Structure Filter supports three structure search types: Full Structure Substructure Similarity A Full structure search finds a particular structure. A Substructure search finds structures containing a common structural component, plus any additional attachments at the open positions. An R-Group decomposition analysis can be performed on a data table following a substructure filter. Refer to the following section on R-Group Decomposition. Similarity searches are useful if you have a general idea of the types of compounds you are looking for, but do not have an accurate description of the target compound. Similarity searches find structures having features similar to the query structure. By default, a similarity search is performed based on a 90% degree of similarity. You can adjust the degree of similarity (from 0 to 100%) using the slider. The higher the value, the fewer hits found. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 52 of 93

53 Adding Similarity Score to the Table When performing a similarity search, you have to option to add Similarity Score to the table. If this option is enabled, an additional column will be added with the value of the similarity score of each matching row. The Similarity Score column is added to the table as a real column, and therefore you are able to sort or plot the Similarity Score column Performing a Structure Filter There are three different means by which you can filter a data table based on chemical structure: 1. Using a structure editor, draw the chemical structure in the Structure Filter pane, and specify the search type. Alternatively, you can copy and paste it into the Structure Editor window. 2. Filter directly from the current table visualization by selecting a chemical structure within the table, and specify the search type. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 53 of 93

54 3. Filter directly from the current scatter plot visualization by selecting a chemical structure within the scatter plot, and specify the search type. Each of these options is described below. A column named Structure Match is added to the data table after filtering is performed. This column contains the tags true and false If the structure matches the defined filtering criteria, then it will be tagged as true ; if not, it will be tagged as false. This column appears at the bottom of the applicable data table on the Spotfire Filters panel. By default, the tags are set to display the matches (true). You can select to view the structures that do not match the filter criteria (false), or both (true and false). In the case of a similarity search with the option to add similarity score to table enabled, an additional column will be added with the value of the similarity score of each matching row. Show Highlighting when Filtering When using the Structure Filter with the ChemDraw renderer, structures will be returned, by default, with the query molecule highlighted when performing a chemical substructure search. When the filter is cleared, the molecules are re-rendered without the highilighting. This feature can be enabled/disabled for each visualization via the Renderer Settings window. Refer to the Settings section. Monitoring Indexing and Filtering Progress Prior to filtering a data table for the first time, the structures undergo an indexing operation which may be time consuming depending on the number of structures. A progress bar is displayed indicating the indexing status. Similarly when filtering a data table, a similar progress bar may be displayed. In both cases, the Structure Filter panel is disabled. Note: If a data table is embedded in the analysis, when loading a saved Spotfire analysis (*.dxp file) which contains a filter, the index for that data table is persisted and therefore indexing is not performed again upon loading. The index is not persisted if the data is linked to the original data source when saved. Therefore, if the data is not embedded in the analysis, when loading a saved Spotfire analysis (*.dxp file) which contains a filter, the indexing will be performed again upon loading. Filtering a Data Set with multiple structure columns If the data file contains more than one structure column, you can select the column on which to filter. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 54 of 93

55 When the structure column is changed, the current filter is cleared. If there are no structure columns defined in a data table, the Structure Filter panel is disabled. A message will appear in the Structure Filter pane that no structure columns have been identified for the active data table. However, if there are columns containing structure strings in the data table, a column can be defined as a structure column by setting its content type property. At this point, the Structure Filter panel will be enabled. Filtering using the Structure Filter pane To create a new filter: 1. Open the Structure Filter. 2. Select the Filter Type from the drop down list. By default, Substructure is selected. If Similarity is selected, use the slider to specify the degree of similarity. Note that the filter operation is triggered upon release of the mouse button when using the slider bar. Also, if Similarity is selected, you can specify to add similarity score to the table. 3. Double click in the Structure Filter pane to open the Structure Editor. By default, the ChemDraw Structure Editor opens. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 55 of 93

56 Note: To select a different Structure Editor, close the ChemDraw Structure Editor, and click on the Edit filter button in the toolbar. A list of available editors is presented. The selection is then saved as a user preference, and will be opened by default the next time you double click on the Structure Filter pane. 4. Draw the query structure in the Structure Editor window using appropriate tools. You can also copy and paste a structure into the Structure Editor window. For example, a structure can be copied from the Structure Viewer, a table, or the Details-on-Demand panel, and paste it into the Structure Editor. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 56 of 93

57 5. Click OK to initiate the filter. Filtering directly from a table visualization Structures can be rather large and complex to draw. Existing structures in the current visualization table can be selected as the filter structure. To filter directly from a table: 1. Mark the row in the data table containing the structure on which to filter. 2. Right click on the row in the table visualization and select Structure Filter. Select the Filter Type (Full Structure, Substructure, and Similarity). If Similarity is selected as the Search Type, a 90% degree of similarity is used by default. You can adjust the degree of similarity (from 0 to 100%) using the slider in the Structure Filter panel. The filter operation is triggered upon release of the mouse button. Also, if Similarity is selected, you can specify to add similarity score to the table. Note: Filtering can be performed on only one row at a time. If more than one row is marked, or no rows are marked at all, then the filtering search types will not be available for selection. Filtering directly from a scatter plot Existing structures in the current scatter plot visualization can be selected as the filter structure. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 57 of 93

58 To filter directly from a scatter plot: 1. Mark the data point in the scatter plot representing the structure on which to filter. 2. Right click on the data point and select Structure Filter. Select the Filter Type (Full Structure, Sub-Structure, and Similarity). If Similarity is selected as the Search Type, a 90% degree of similarity is used by default. You can adjust the degree of similarity (from 0 to 100%) using the slider in the Structure Filter panel. The filter operation is triggered upon release of the mouse button. Also, if Similarity is selected, you can specify to add similarity score to the table. Note: Filtering can be performed on only one data point at a time. If more than one data point is marked, or no data points are marked, then the filtering search types will not be available for selection Editing a Filter To edit a filter: 1. Click on the Edit filter button in the toolbar to open the Structure Editor. If applicable, select the editor to edit the current structure. Alternatively, you can also double click in the Structure pane to open the editor for the current structure. 2. Edit the query structure in the Structure Editor window using appropriate tools. 3. Click OK to initiate the filter. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 58 of 93

59 Note: When editing a filter, all visualizations associated with the data table will be affected Clearing a Filter To clear a filter: 1. Click on the Clear filter button in the toolbar. The current filter is cleared and the Structure Match column is removed from the data table.. Note: The filter applies to the data table, therefore clearing a filter will clear the results for all visualizations associated with the data table. Clearing a filter does not clear the results of an R-Group decomposition Viewing Historical Structure Filters Lead Discovery retains the previous ten filters allowing you to re-do a previous filter without having to re-draw the chemical structure or set the filter conditions. These filters are accessible by clicking on the Previous Filters button the last ten searches is displayed similar to the example shown here. in the toolbar. A drop down displaying The structure, search type, date and time stamp and the structure column on which the filter was initially performed are displayed. Selecting a filter from this list re-populates the query structure, resets the filter conditions, and sets the associated filter column to display matching rows. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 59 of 93

60 9.9. Saving Structure Filters Structure filter definitions can be saved with a user defined names, persisting the tag column used to define the filter matches. This allows manipulation of multiple structure filters at once resulting in dynamic toggling between structures in the filter. Saving a structure filter 1. Perform a structure filter. 2. Enter a unique name for the filter search in the Structure Filter panel. If the name already exists, you will be prompted if you want to overwrite the existing filter name. 3. Click on the Save Filter button. All current filter settings are saved with the filter. The Structure Match column (tag column), added to the data table after filtering is performed, is re-named to the saved filter name. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 60 of 93

61 In addition, the column added to the applicable data table on the Spotfire Filters panel is also re-named to the saved filter name. The re-named tag column is not removed from the table when the filter is cleared. To remove this column, you need to delete the saved filter. Re-naming a saved structure filter An existing filter can be re-named by selecting the filter name from the list, and entering a new name for the filter. Click on the Save Filter Executing a saved structure filter button to save the newly named filter. When a saved filter is selected from the drop down list, the filter panel is updated with the filter settings of the saved filter. The table is filtered to reflect the saved structure filter settings. Note: If a structure filter was already in place at the time the saved search was selected, the saved filter will replace the other structure filter. However, the replaced filter (if not a previously saved filter) will still be available as part of the Historical Search list. Once a saved filter has been selected, further changes to the filter settings will create an additional Structure Match column to be added to table. If you want to save the new filter settings, you would need to create a saved filter. Using the Spotfire Filter panel, filter results can be combined for further analyses. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 61 of 93

62 Deleting a saved structure filter Saved filters can be deleted from the list by selecting the filter to delete and clicking on the Delete Filter button. You will be prompted to confirm the deletion. The tag column is removed from the data table. 10. R-Group Decomposition An R-Group decomposition analysis separates out the functional groups attached to a variable point of a specified substructure. Following a substructure filter on a data table, you can perform an R-Group decomposition on the filtered data. Note: You cannot perform an R-Group decomposition from a full structure or similarity search. The resultant R-Group template structure or scaffold is displayed in the Structure Filter panel under the R-Group Decomposition tab. Whether the functional group found at each Rn position is displayed in a real column or virtual column is based on a user defined R-Group Decomposition threshold. By default, this threshold is set to If the R-Group decomposition is performed on a number of rows below the threshold, the R-groups are rendered in real columns as SMILES. If the R-Group decomposition is performed on a number of rows above the threshold, you will be prompted to select if you want real columns to be generated (rendered as SMILES) for the R-Group Decomposition results. If you do not choose to generate real columns, the R-Group columns will be added as virtual columns. Virtual columns are populated on an as needed basis and consequently they are rendered more quickly than real columns. Although, they take considerably more time to generate, once in place, real columns can be sorted, filtered, and used in other visualizations. Note: If the threshold is set to zero, the columns will always be rendered as virtual columns, and you will not be prompted to select the column type (real vs. virtual). Note: R-Groups displayed in virtual columns are available for export using the Export to SDFile or Export to ChemDraw for Excel features in Lead Discovery. Refer to the section Exporting Setting the R-Group Decomposition Threshold Preference To set the R-Group Threshold: 1. Open the Spotfire client, and logon as a Spotfire Administrator. From the Tools menu, select the Administration Manager sub-menu item. The Administration Manager is only enabled if you logon connected to the Spotfire Server. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 62 of 93

63 The Administration Manager window opens. 2. Click on the Preferences tab. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 63 of 93

64 3. Select the Group Name to which the preferences should be applied. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 64 of 93

65 4. Expand the Structure filter. 5. Select the R-Group Decomposition preference. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 65 of 93

66 6. Click on the Edit button to open the Edit Preferences dialog. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 66 of 93

67 7. Enter a new value for the R-Group Decomposition Threshold. By default, this value is set to Note: If the threshold is set to zero, the columns will always be rendered as virtual columns, and you will not be prompted to select the column type (real vs. virtual). 8. Click OK. Note: It is recommended that you restart the Spotfire Client in order for the new Preference settings to take effect Performing an R-Group Decomposition Analysis To perform an R-Group Decomposition of a Data Table: 1. Perform a Substructure filter on a data table. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 67 of 93

68 2. From the Structure Filter toolbar, click on the Insert R-Group Columns button. A progress bar may be displayed indicating the analysis status. The Structure Filter panel is disabled during the analysis. The resultant R-Group template structure is displayed in the Structure Filter panel under the R-Group Decomposition tab, similar to the example shown below. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 68 of 93

69 The decomposition results are displayed as columns which are added to the table visualization. A new column is added for each of the R s. The rows are populated with the R s hits, similar to the example shown below. The column type (real vs. virtual) is dependent on the R-Group Decomposition threshold and user input at the time of generation. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 69 of 93

70 To remove R-Group columns from a data table: An R-Group analysis can be removed from a data table. A data table can only contain one R-Group Decomposition analysis, and therefore before a new R-Group decomposition can be performed on the same table, the R-Group analysis must be removed. 1. From the Structure Filter toolbar, click on the Remove R-Group Columns button. The R-Group columns, regardless if they are real or virtual, will be removed from the table visualization. R-Group columns do not need to be removed before performing different structure filters. This enables filtering to be performed on real RGD columns. Consequently, the RGD analysis may not necessarily apply to the current filter in place on the panel. If you open a table visualization after performing the R-Group Decomposition, and the virtual columns, if applicable, are not automatically added to the table visualization, they will need to be added manually. To add the virtual columns to a new table visualization: 1. Right-click on a table visualization and select Properties. You can also access the Table Properties by clicking on the Visualization Properties button Properties menu item. in the main toolbar, or via the Edit > Visualization 2. Select Virtual Columns and click on the Add button. 3. Select R-Group Decomposition Column. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 70 of 93

71 The virtual columns are now available to be added to the table visualization. Note: If the Add new columns automatically is set under Columns, the R-Group columns will have already been added to the table, and it is not necessary to continue with the remaining steps to add the columns to the visualization. 4. Select Columns. The virtual columns are listed under Available columns. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 71 of 93

72 5. Use Add >, to select virtual columns to add to the table visualization. 6. Use Move Up and Move Down to specify the order of columns in the table visualization. 7. Click Close. 11. Structure Alignment Two molecules can be aligned by rotating one onto the other so they have the best possible overlap. In order for the alignment to occur, the structures must have a common core or scaffold. The rendering of each molecule that contains a common scaffold can be modified to align with the selected structure. Lead Discovery allows you to modify the alignment of the structures in a table visualization so that they align with a selected structure in the table. Any visible structures in the Structure Viewer and Details on Demand panel are also aligned. In addition, when performing a Structure filter operation, Lead Discovery allows you to optionally modify the alignment of the structures in the table visualization such that they align with the drawn structure. The structures are aligned in the column that is used in the filtering operation. Note: Only the rendering of the structure is aligned. The structure data is not modified. Aligning Structures from a table visualization 1. Right click on the structure on which you want to align and select Align to This Structure. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 72 of 93

73 All structures in the column are aligned with the selected structure, similar to the example shown below. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 73 of 93

74 Realigning to a Structure If a column already has a structure alignment applied to it, you can realign the column to another structure in the column. 1. Right click on the structure in the table visualization on which you want to realign and select Realign to This Structure. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 74 of 93

75 Note: This menu option is only available if there is already an alignment applies to the selected column. Clearing Column Structure Alignment 1. Select the column with an applied structure alignment. 2. Right click on the column in the table visualization and select Clear Column Structure Alignment. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 75 of 93

76 Aligning structures from the Structure Filter 1. Perform a Substructure filter on a data table. 2. From the Structure Filter panel, check the Align to this structure checkbox. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 76 of 93

77 All structures in the specified structure column are aligned with the selected substructure, similar to the example shown below. Clearing All Structure Alignments 1. If there are multiple structure alignments applied to a table (multiple structure columns), you can clear all alignments simultaneously. From the Tools menu, select the Clear All Structure Alignments submenu item. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 77 of 93

78 12. Settings Supported Renderers Lead Discovery modules provide support for several different renderers to display molecular structures. For more information see the system requirements for Lead Discovery at: However, note that a few of the supported renderers can only be used to render structures in the table visualization, the Structure Viewer and the Structure Filter; they cannot be used to edit structures in the Structure Search tool. You can add one or more of these renderers to the list of default renderers, select any of them as default for a content type, and change the renderer settings. Note: The default Renderer settings for each content type are honored in all rendering contexts The settings defined for a default renderer are extended to the custom panels (e.g. Structure Viewer, Structure Filter). If a default Renderer is not configured for a supported content type, ChemDraw is automatically selected, by default, as the renderer. To add a renderer to the list of default renderers: 1. Select Tools > Options. 2. Select the Application tab. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 78 of 93

79 3. Click the Renderer Setting button. 4. Click Add. The Add Default Renderer dialog displays. 5. Specify the Content type and select the default renderer from the drop-down list in the dialog. Comment: You can only specify one default renderer per content type. See the table below for a description of content types. To change the default renderer for a certain content type: 1. Select Tools > Options. 2. Select the Application tab. 3. Click the Renderer Settings button. 4. Click to select the content type of interest and click Edit. The Edit Default Renderer dialog displays. 5. Select a new default renderer from the drop-down list. Note: The content type you enter can be an arbitrary string, but it is recommended that you use the MIME types defined for molfiles, CHIME strings, and SMILES strings as shown in the table below. Structure Format MDL molfile MDL Chime string Daylight SMILEs string ChemDraw Chemical Structure Exchange Content Type chemical/x-mdl-molfile chemical/x-mdl-chime chemical/x-daylight-smiles chemical/x-cdx To change the renderer and/or renderer settings for the structures displayed in the table visualization: 1. Right-click on a row in the table visualization and select Properties > Columns. 2. Select the column that contains chemical structures. 3. In the Renderer drop-down list, select the renderer to use. 4. Click the Settings button to change the renderer settings. The Renderer Settings dialog for the currently used renderer displays. 5. Change the renderer settings and click OK. To change the renderer used in Structure Viewer: 1. In the Structure Viewer pane of the Structure Viewer, right-click on the structure. 2. Select Renderer. 3. Select the renderer to use. To edit the renderer settings in the Structure Viewer: 1. In the Structure Viewer pane of the Structure Viewer, right-click on the structure. 2. Select Renderer > Settings. The Renderer Settings dialog for the currently used renderer displays. 3. Change the renderer settings and click OK. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 79 of 93

80 To change the renderer used in Structure Filter: 1. In the Structure Filter toolbar, click on the Renderer settings button in the toolbar. 2. Select the renderer to use. To edit the renderer settings in the Structure Filter: 1. In the Structure Filter toolbar, click on the Renderer settings button in the toolbar. 2. Select Settings. The Renderer Settings dialog for the currently selected renderer displays. 3. Change the renderer settings and click OK. Note: When the renderer settings are changed in a custom panel (e.g. Structure Viewer, Structure Filter), they overwrite the default settings, and are saved with the.dxp file Renderer Settings The renderer is the program responsible for the display of structures in Structure Viewer, Structure Search, and Structure Filter and also when structures are shown in visualizations. ChemDraw Renderer Settings The ChemDraw renderer does not require you to select the format of the structure string. It auto-detects the data format. CDX content in tables is displayed natively in the ChemDraw renderer. Show highlighting when filtering When using the Structure Filter with the ChemDraw renderer, structures will be returned, by default, with the query molecule highlighted when performing a chemical substructure search. Specifying a Template File You can select an existing ChemDraw Style Sheet file (.cds) for visualizing structures. To specify a template (.cds) file: 1. From the ChemDraw Settings dialog, click on the Load Settings button. 2. From the drop down list box, select an existing cds template file to apply to a structure visualization. Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 80 of 93

81 The selected.cds template file is displayed in the ChemDraw Settings dialog indicating that it was successfully loaded. 3. Click OK. If you select Default Settings from the drop down list, the factory settings are used. Selecting Other from the drop down list will open a Load Settings file browser from which you can browse for the.cds template. Note: The settings for the ChemDraw Editor and Renderer are separate. The Editor settings are defined through the ChemDraw application (File menu). The Renderer settings are defined as described here. For example, if a template is loaded into the ChemDraw renderer, the Structure Filter panel will display an existing structure Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 81 of 93

82 according to these settings. However, if the structure is edited using ChemDraw, although the structure is displayed in the editor using the same format as the renderer, any edits are displayed using the default ChemDraw editor template. Other Structure Renderers Other structure renderers auto detect the format to use for rendering, except if the data format is CHIME. Note: Other structure renderers may display different type of settings, hence, the dialog you see may look different from the example shown here (Symyx Draw (MDL) Settings). The table below describes the fields in the Structure Renderer Settings dialog. Option Structure string Show Hydrogens Description The structure string is auto detected with the exception of MDL CHIME. Activate the checkbox if the data format is CHIME. This checkbox is disabled if the renderer does not support the CHIME data format. Changes the hydrogen display settings. Possible options: For Symyx Draw (MDL) - Off, Hetero, Terminal, HeteroOrTerminal, All For Accord - True, False For Marvin - Off, Hetero, HeteroOrTerminal, All Copyright CambridgeSoft Corporation, a subsidiary of PerkinElmer, Inc. All rights reserved. 82 of 93