QSP Small Improvements

Certara's Quantitative Systems Pharmacology (QSP) platform offers advanced modeling and simulation tools to enhance drug development. This article highlights the latest updates, including implementation scope, unit changes, workspace paths, and verification warnings. Explore new features like parameter selection for fitting, sensitivity analysis, and more to streamline your workflows and improve research outcomes.

When copying a reaction graph from QSP Designer to a different workspace, unit system information is included. If units are missing or have different definitions, new unique units are added, and the graph is updated. The warning now includes detailed information about these unit changes.

A new button next to the quick search box on the menu bar shows a dropdown of successful quick searches from the current session. Clicking an item populates the search box and performs the search. Quick searches are not saved between sessions.

In the workspace comparison tool, the results tables feature a column labeled "Different Connections." This column indicates "False" if the corresponding entities in the two workspaces have equivalent generalized connections, and "True" if they do not. Previously, users were unable to access detailed information about these connection discrepancies. Now, when the column displays "True," users can access detailed differences through the Inspect context menu item.

When recently opened workspaces are displayed under File > Recent Workspaces, the full paths may be truncated to prevent items from being too wide. Now, users can view the full paths by hovering over the items to see a tooltip.

In QSP Designer, users can specify if assignments are "initial-only" (performed once at the start of the simulation) or "repeated" (performed throughout the simulation). Sometimes, users may mark a constant expression as "repeated," which can be misleading and cause unnecessary assignments. To address this, a verification warning now alerts users when the software detects such cases with certainty.

Previously, the workspace comparison tool identified differences in unit systems between workspaces but did not account for simulation base units. The updated Base Units table now includes a Simulation Base Unit column to explicitly display these differences when present.

Previously, the software assumed that all integer values in user-defined expressions could be converted to their opposite sign. However, in most programming languages, including C#, signed integers use a "two’s complement" representation, making this assumption incorrect. The software's handling of integers has been updated to accurately reflect the underlying data type.

In individual fitting, QSP Designer groups individuals to determine a single set of parameters. Previously, the fitting process was parallelized over different groups but not over individuals within a group. Now, parallelization also occurs over different individuals within groups.

Within the window for automatically determining and editing the simulation base units, additional editing options are provided:

When selecting the Weighted Least Square or Least Square With Error Models objective functions in the fitting wizard, users can choose to log-transform dependent variables (DVs) via the Options menu. A checkbox appears for each DV, allowing users to enable or disable log-transformation for that specific DV. This transformation converts each observation and prediction xx into ln⁡(x)ln(x) (natural logarithm) when calculating the objective function value during fitting. The same log-transformed values are also used for calculating confidence intervals if enabled.
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Search functionality in the parameters page of the fitting wizard and the outputs window has been enhanced to function like a quick search. If the user input is not found as a prefix, it will now search for the input as a sub-string within possible matches.

Previously, if a data overlay file for displaying simulation results was missing from the stored path, an error dialog was shown, leading users to mistakenly believe the simulation had failed. Now, if the data overlay files cannot be opened when the outputs window opens, the header of the Plot Options tab turns red, and validation errors are displayed on that tab. No error dialog is shown.

The software now remembers the folders from which different file types have been loaded or saved, specific to each file type. This path information is retained between sessions for each user on a given machine. The current file types include:

Within fitting, sensitivity, and parameter scanning, users can now use the "Control" and "Shift" keys to perform multiple selections when adding or removing parameters from the chosen set.

The Is Deactivated checkbox in the property inspector now appears and can be modified when multiple entities are selected, provided all selected entities have the Is Deactivated property.

The behavior of the following windows has been modified: Simulation > Solver Settings, Simulation > Verification Options, Edit > Index Order, and Edit > Configuration. Now, if there are pending edits in these windows when the user attempts to close them, a warning dialog will appear to alert them and ask whether they wish to continue and lose the edits.

On the final page of the Sensitivity Analysis wizard, a new control allows users to select a VPop file. If a valid VPop file is selected, the user will be prompted to choose an individual from the VPop file to apply to the simulations when the analysis is run.

Users now have the ability to run parameter scans on a selected subset of individuals from the loaded VPop (Virtual Population) file. The selection screen presented is identical to the one used for running VPop simulations, offering the following options:

The interface behavior remains consistent with the VPop simulation process. However, instead of simulating the selected individuals, they are chosen for the parameter scanner. The parameter scanner then operates exclusively on the selected individuals, rather than the entire VPop as previously.

Users can now save the most recent database generated by the parameter scanner for viewing in the outputs window. This database contains raw simulation data produced by the parameter scanner, where each "individual" corresponds to a single parameter set, leveraging VPop simulation functionality under-the-hood.

Additionally, users can export both input and output parameter sets in CSV format. This allows them to easily identify which parameter set corresponds to each "individual" in the saved database.

A new right-click context menu item has been added, allowing users to easily toggle the collapse or expansion of sub-graph definitions. This feature enhances user control and flexibility when managing sub-graphs, making it more convenient to navigate and organize complex graph structures.

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A new right-click context menu item has been added, enabling users to quickly find all usages of a given inline function. This feature streamlines the process of locating function references, enhancing code navigation and improving overall efficiency in managing and understanding codebases.

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It is now possible to place reactions that depend on indexed species in a manner where non-natural components of the substrates are referenced in rate expressions within compartments sharing the same indices. However, this can lead to unexpected results during the automatic determination of reaction compartments. The automatic determination process does not consider indices initially, and then projects the natural key of the reaction onto the compartment.

A realistic example of potential undesired behavior involves a reversible reaction with index mapping. In such cases, the compartment component used to multiply the reaction rate for the reverse reaction may not be the desired one.

To alert users to these potential issues, a verification warning has been added. This warning informs users of possible discrepancies and suggests resolving them by explicitly including volume factors.

A new right-click context menu item has been added, allowing users to quickly find all quantities associated with a given index. This feature enhances the ability to navigate and manage indexed data, improving efficiency and clarity when working with complex datasets.

In the Sampling Times tab of the Run Simulation window (accessed via Simulation > Simulate > Run With Options), a new checkbox labeled "Use Every Solver Step As Default" has been added. When this checkbox is selected, it enables "every solver step sampling" for all quantities that have the "Default" sampling times list selected during simulation. This feature ensures that every solver step is used for sampling, providing more granular data collection by default.

It is now possible to open a window with a read-only view of an imported workspace. This read-only view can be accessed via context menus on list items and nodes in the imports graph within the Edit > Imported Workspaces window, as well as through context menus on the workspace import nodes in the reaction graph. Additionally, further read-only view windows can be opened for workspace imports from within an existing read-only view window.

The save type of the file to which the currently loaded workspace was last saved or from which it was loaded is now displayed at the bottom of the first tab in the Workspace Report window. This enhancement provides users with clear information about the file type associated with their workspace, improving transparency and ease of file management.

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A new right-click context menu item has been added for workspace import nodes, allowing users to find all imported nodes that reference a specific workspace import node. This feature enhances navigation and management of workspace imports by providing a quick and efficient way to locate all references to a given import node.

A new right-click context menu item has been added for imported nodes, enabling quick jumps to the corresponding workspace import node. This feature enhances navigation within the workspace, making it easier to locate and manage related import nodes efficiently.

The software now allows canvas edits while the simulation results window is open. This enhancement enables continued interaction with the workspace, including editing the canvas, running additional simulations, or opening different workspaces, without needing to close the simulation results window.

To facilitate this, the outputs configuration is no longer automatically saved upon closing the results window. Instead, a button has been added to save the outputs configuration to the currently loaded workspace.

The method for determining equations for display within Grids has been improved to reduce the appearance of unnecessarily chained operators.

For example, where previously “- -” might have appeared, now just “+” will be displayed instead. This enhancement simplifies the visual representation of equations, making them easier to read and understand.

Tooltips now display numbers with commas as thousands separators (e.g., “1,000,000” instead of “1000000”) in tables within the software for displaying values in VPop files. This enhancement improves readability and clarity when viewing large numbers.

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Values in VPop tables within the software are now sorted numerically rather than alphabetically. For example, “40000” will correctly appear after “300.” This enhancement ensures accurate and logical ordering of numerical data, improving data analysis and interpretation.

The quick search dropdown has been modified to expand, allowing the full names of search results to be visible when those names exceed the default width. This enhancement improves usability by ensuring that longer search result names are fully displayed, making it easier to identify and select the desired results.

The progress indicator in Parameter Scanning has been improved for greater clarity and visibility. During simulation, the overall completion percentage and the total number of scans to be run are now displayed in the progress indicator. This enhancement provides a more transparent and informative view of the scanning process, making it easier to track progress.

A verification warning has been added for cases where a dosing plan includes indices that neither its times expression nor its dosed species have. In such scenarios, the same dose will be applied to the same unrolled state multiple times simultaneously, which is likely not intended. This warning helps identify and resolve potential issues with dosing plans to ensure accurate and intended dosing behavior.

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