Certara's QSP platform advances drug development with QSP Designer V3. This version offers powerful new features and enhancements to streamline workflows, improve simulation accuracy, and provide greater flexibility. With advanced parameter scanning and enhanced user interface options, QSP Designer V3 revolutionizes modeling and simulation of complex biological systems. Explore this groundbreaking release to elevate your research and development efforts.
QSP Notebook Domain-Specific Language Export
This update introduces a new export feature in QSP Designer, enabling the generation of scripts in the QSP Notebook domain-specific language (DSL).
Key Updates
User Interface Updates:
Added option for exporting a QSP Notebook DSL script and its associated files in the Generate Script window.
Related options added to the Options tab.
Generate Script Modal (Scripts Tab):
Expanded to include a new QSP Notebook section for managing DSL scripts.
Enables export of QSP Notebook DSL scripts and selection of a VPop file for conversion.
Generate Script Modal (Options Tab):
Enhanced with new settings for exporting QSP Notebook DSL scripts.
Added options: 'Generate QSP Notebook Dosing File' and 'Generate QSP Notebook Conversion File.'
Key Differences Between QSP Notebook DSL and QSP Designer:
Fixed Units: QSP Notebook DSL supports only fixed units.
ODE States as Amounts: All ODE states must correspond to amounts.
Parameter Restrictions: Parameters are non-time-varying inputs.
No 'Initial-Only' Assignments: Assignments are always evaluated if they reference time-varying variables.
Addressing Differences in Unit Systems:
Export script creates state variables as amounts in simulation base units.
Variables in the exported script are given a '_sim' suffix if their units differ from the original model.
Handling Model Parameters and Assignments:
Separate initialization quantities with '_init' suffixes manage parameters.
Parallel tree of 'initial-only' assignments ensures correct initial values.
Processing Model Features:
Model is transformed to remove unsupported features before exporting.
Converting VPop Files:
Converted VPop files contain values in simulation base units and use modified names with '_init' suffixes.
Defining Individual Dosing:
Individual dosing defined via a separate dosing file in QSP Notebook.
Conversion File Option:
Option to include a conversion file with unit conversion factors.
QSP Platform Enhancements
This update highlights new features and improvements, including unit changes, workspace paths, and verification warnings.
Key Updates
Unit Changes on Paste:
When copying a reaction graph 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.
Warnings now include detailed information about these unit changes.
View Recent Quick Searches:
A new button next to the quick search box 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.
Comparing Old and New Connections:
The workspace comparison tool now features a column labeled "Different Connections."
This column indicates "False" if entities have equivalent connections and "True" if they do not.
Users can access detailed differences through the Inspect context menu item when the column displays "True."
Recent Workspace Paths:
Recently opened workspaces displayed under File > Recent Workspaces may have truncated paths.
Users can view the full paths by hovering over the items to see a tooltip.
Verification Warning for Redundant Assignments:
Alerts users when constant expressions marked as "repeated" cause unnecessary assignments.
Simulation Base Units in Comparison Tool:
The updated Base Units table now includes a Simulation Base Unit column to display differences explicitly.
Improved Handling of Signed Integers:
Updated handling of signed integers to accurately reflect the "two’s complement" representation used in most programming languages.
Enhanced Parallelization in Individual Fitting:
Parallelization now occurs over different individuals within groups, in addition to different groups.
Enhanced Simulation Base Unit Editing Options:
Reset Button: Resets simulation base units to their default definitions.
Scaling Factor Option: Allows users to apply a target scaling factor for automatic determination, addressing problematic behavior with small numbers.
Log-Transformation of Dependent Variables in Fitting:
Users can choose to log-transform dependent variables (DVs) via the Options menu in the fitting wizard.
A checkbox allows enabling or disabling log-transformation for each DV.
Transforms observations and predictions into ln(x)ln(x) for calculating objective function values and confidence intervals.
Sub-String Search:
Enhanced search functionality in the parameters page of the fitting wizard and the outputs window.
Searches for user input as a sub-string within possible matches if not found as a prefix.
Improved Handling of Missing Data Overlay Files:
If data overlay files cannot be opened, the header of the Plot Options tab turns red, and validation errors are displayed.
No error dialog is shown, preventing mistaken belief that the simulation failed.
Default File Path Management:
Software now remembers folders from which different file types have been loaded or saved, specific to each file type.
Path information is retained between sessions for each user on a given machine.
Enhanced Parameter Selection for Fitting:
Users can use "Control" and "Shift" keys to perform multiple selections when adding or removing parameters from the chosen set.
Modifying Deactivation Status for Multiple Entities:
The Is Deactivated checkbox in the property inspector can be modified when multiple entities are selected, provided all selected entities have the Is Deactivated property.
Warning Dialog for Pending Edits:
If there are pending edits in certain windows, a warning dialog will appear to alert users and ask whether they wish to continue and lose the edits.
Selecting VPop Files in Sensitivity Analysis:
A new control allows users to select a VPop file on the final page of the Sensitivity Analysis wizard.
Users are prompted to choose an individual from the VPop file to apply to the simulations when the analysis is run.
Parameter Scanning:
Users can run parameter scans on a selected subset of individuals from the loaded VPop file.
Options include selecting all individuals, manual selection, and automatic sampling.
Database Saving and Exporting:
Users can save the most recent database generated by the parameter scanner for viewing in the outputs window.
Export both input and output parameter sets in CSV format.
Enhanced Sub-Graph Toggle Functionality:
A new right-click context menu item allows users to toggle the collapse or expansion of sub-graph definitions.
Inline Function Usage Finder:
A new right-click context menu item enables users to quickly find all usages of a given inline function.
Indexed Species Reaction Handling and Verification Warning:
Reactions that depend on indexed species can now be placed in compartments sharing the same indices.
A verification warning alerts users to potential discrepancies.
Indexed Quantity Finder:
A new right-click context menu item allows users to quickly find all quantities associated with a given index.
Default Solver Step Sampling Option:
A new checkbox in the Sampling Times tab enables "every solver step sampling" for all quantities with the "Default" sampling times list.
Read-Only View for Imported Workspaces:
Users can open a read-only view of an imported workspace via context menus.
Displaying Save Type in Workspace Report:
The save type of the file to which the workspace was last saved or loaded is now displayed in the Workspace Report window.
Find References for Workspace Import Nodes:
A new right-click context menu item allows users to find all imported nodes that reference a specific workspace import node.
Quick Navigation to Workspace Import Nodes:
A new right-click context menu item enables quick jumps to the corresponding workspace import node.
Enable Canvas Edits While Simulation Results Window Is Open:
Users can edit the canvas, run additional simulations, or open different workspaces without closing the simulation results window.
A button has been added to save the outputs configuration to the currently loaded workspace.
Simplified Equation Display in Grids:
Improved method for displaying equations, reducing unnecessary chained operators.
Example: “- -” now displayed as “+”.
Formatting Numbers with Commas:
Tooltips now display numbers with commas as thousands separators (e.g., “1,000,000” instead of “1000000”) in VPop tables.
Numerical Sorting in VPop Tables:
Values in VPop tables are now sorted numerically rather than alphabetically, ensuring accurate and logical data ordering.
Expanded Quick Search Dropdown:
Quick search dropdown now expands to show full names of search results, improving usability.
Enhanced Progress Indicator for Parameter Scanning:
Progress indicator now displays overall completion percentage and total number of scans during simulation.
Verification Warning for Dosing Plan Index Discrepancies:
Added verification warning for dosing plans with indices that neither its times expression nor its dosed species have, helping to identify and resolve potential issues.
QSP SimBiology Export Improvements
QSP Designer now supports exporting models with conditional assignments, event nodes, and parameterized or indexed stoichiometry expressions to SimBiology, enhancing translation capabilities.
Key Updates
User Interface:
Exporting models with conditional assignments, event nodes, and parameterized or indexed stoichiometry expressions no longer displays an error message or prevents the export.
Conditional Assignments:
Example:
addrule(model, 'p1 = (a > 0) * (a + b) + (!(a > 0)) * (a + c)', 'repeatedAssignment');
For initial-only assignments, use “initialAssignment.”
Events:
Example:
e1 = addevent(ModelObj, 'Tumor_cell < one_cell', 'flag = 0');
Parameterized or Indexed Stoichiometry Expressions:
Stoichiometry expressions are now statically evaluated during code generation, allowing their use in SimBiology exports.
Example:
An index “a” with 8 values results in stoichiometries: 8, 7, 6, 5, 4, 3, 2, 1.
This functionality applies to all cases where the stoichiometry expression can be statically evaluated. Any parameters may be used as part of the expression, provided the overall expression can be statically evaluated and is guaranteed to be constant-in-time.
QSP Improvements to Reversible Reactions
Enhancements to QSP software improve the handling of reversible reactions, enabling more accurate modeling and simulation.
Key Updates
Reverse Rate Property:
Introduced a "Reverse Rate" property for reaction nodes, allowing clear and uncluttered modeling of reversible reactions.
ODE Handling:
ODEs are solved for amounts rather than concentrations. The software automatically determines compartments and corresponding volumes for reactions, addressing mismatches in dimensionalities.
Enhanced Compartment Determination:
The automatic determination of reaction compartments now identifies compartments separately for forward and reverse components:
Species Referenced in Rate Expression: The reaction compartment is determined by the species' compartment. An error occurs if not all species are in the same compartment.
No Species Referenced: All in-scope species are considered. If none, all connected species are considered.
Improved Verification:
Some workspaces that previously failed verification will now pass and simulate correctly. Workspaces that previously passed verification will continue to do so with unchanged results.
QSP Improvements to Model Debugger
The model code debugger in QSP Designer has been enhanced to improve debugging capabilities and ease of use.
Key Updates
Debugging the Initialization Function:
Users can now debug the initialization function, allowing for thorough examination and troubleshooting.
Breakpoints can be set in the initialization function, but conditions cannot be applied until the model is fully initialized.
Search Functionality:
Users can search through the currently displayed function for strings of interest.
The search field is located at the top-right of the function view, with buttons to navigate between matches.
Matching results are highlighted, and the function view auto-scrolls to the focused match.
User Interface Changes:
The initialization function now behaves like other debuggable functions, allowing breakpoints to be set.
The Breakpoint Conditions tab in the Break Manager window does not permit the creation of conditions until the initialization function has fully executed.
Global Triggers remain supported and function as usual.
QSP Further Improvements to VPop Inference
Enhancements to VPop Inference improve the functionality and flexibility of Virtual Populations (VPops) in QSP Designer.
Key Updates
Treatment Response Functionality:
Added "Treatment response" mode to simulate/analyze each VPop subject against multiple defined treatments.
Works in both fitting mode (mutating parameters to adhere to observations) and non-fitting mode (filter-only).
Gate Definitions:
Users can now define gates manually or using error margins specified in the data file.
Gates can be defined on a per-treatment basis when combined with treatment response functionality.
Analysis Stage Enhancements:
Optional analysis stage following fitting-based simulation.
More relaxed filter criteria for mutated parameters.
Threshold for passed gates can be set per DV.
Automatic filtering stage option.
Enhanced plotting options and console area management.
Inclusion Probability Calculation:
Improved calculation of inclusion probabilities.
Generalized multivariate empirical distribution.
Ability to plot univariate distributions and virtual population samples.
Parameter Selection Interface:
Updated interface for selecting individual parameters to fit, mimicking the Parameter Estimation wizard.
New Treatment Response Mode:
New option to define treatments from INIT columns in the VPop Inference import page.
Different data file restrictions when the option is selected.
Gate definition screen now includes a "Treatment" drop-down.
Simulation and analysis take treatments into account.
Inclusion statistics calculation considers treatments.
New Gate Loading Functionality
The ability to load gates from the loaded data file has been added, enhancing the gate definition process in "New simulation" mode.
Key Updates
Load From Data File Button:
Added to the gate definitions overview screen.
Clears existing gates and loads gates defined in the data file's ERROR columns.
Gate Inference:
Gates are inferred from the ERROR column values or from ERROR_UPPER and ERROR_LOWER columns.
Example for DV "d":
If ERROR/d is present, gates are loaded with:
min = DV/d - e
max = DV/d + e
If ERROR_LOWER/d and ERROR_UPPER/d are present:
min = ERROR_LOWER/d
max = ERROR_UPPER/d
Treatment Association:
If "Defines treatments from INIT columns" is selected, inferred gates are associated with the matching treatment specified by the ID column.
Manual Gate Definition:
The "new gate definition" popup window allows manual gate definition.
Users can enter Time, Min, and Max values directly.
Observation-Based Gates:
Users can select "From observations" to define gates based on Time and Tolerance, calculated from the data file.
VPop Inference - Enhanced Gate Criteria and Analysis Options
Enhancements to VPop Inference improve gate criteria specification and analysis options in QSP Designer.
Key Updates
Relaxed Gate Criteria in Fitting Mode:
Users can now analyze with less strict gate criteria after fitting, specifying that only a threshold of gates needs to pass.
Improved Filter Criteria Specification:
Expanded analysis options with a dedicated screen for configuring thresholds.
Users can specify filter criteria for all DVs or chosen DVs, allowing different thresholds for different DVs.
Auto-Run Analysis Stage:
Option to automatically run the Analysis stage following simulation.
Default option is ON, but it resets once the VPop Inference window is closed.
Plotting Improvements:
Enhanced plotting options for both treatments mode and non-treatments mode.
Users can hide/show gates and observations, toggle grid lines, switch scales, edit colors, and export to Plotly HTML.
Graphs can be zoomed, and legends toggled on/off with additional information on hover.
Console Message Options:
Options to copy or clear console messages in the VPop Inference analysis screen.
Frequency Distributions for Inclusion Statistics:
New "Frequency" distribution type can be selected for each variable.
Users can define bins with names, min/max values, and weighted frequencies.
Errors in specification are displayed, preventing calculation of inclusion statistics.
Frequency distributions can be saved/loaded from CSV files.
Enhanced Plotting and Comparison for Inclusion Statistics
Enhancements to the inclusion screen improve plotting and comparison of univariate distributions and virtual population samples using calculated inclusion probabilities.
Key Updates
Compare Button:
Introduced on the inclusion screen, active once the proportionality constant is fitted.
Opens a window for sampling the population using calculated inclusion probabilities.
Sampling Options:
Users can select distributions or variables defined on the main screen.
Acceptance Sampling and Weighted Sampling options initiate sampling of successful individuals from the VPop Inference analysis stage.
Plotting Normal Distributions:
Plots specified empirical distribution (green line) and sampled individuals binned into intervals (blue bars).
Adjustable bin width for better visualization.
Line of best fit for the estimated distribution of sampled individuals (red curve).
Plotting Frequency Distributions:
Two binning modes: "Distribution bins" and "Fine-grained bins."
Distribution bins mode shows sampled individuals binned into empirically defined bins.
Fine-grained bins mode shows individuals binned into smaller intervals, color-coded to reflect empirical bins.
Plot Configuration:
Plots can be exported to Plotly HTML.
Users can toggle grid lines, switch scales, edit colors, zoom, and toggle legends.
Hovering over parts of the graph provides extra information.
Enhanced Parameter Selection Interface in VPop Inference Wizard
The parameter selection interface in the VPop Inference wizard has been updated to resemble the Parameter Estimation wizard, improving usability and functionality.
Key Updates
Parameter Selection:
Parameters can be selected from the bottom and added to the list of Selected Parameters using arrows.
Bound Enforcement:
Min/Max checkboxes replaced with "Enforce Lower Bound" and "Enforce Upper Bound."
Minimum and maximum input boxes replaced with "Lower Bound" and "Upper Bound."
Parameter Estimation:
All parameters in the Selected Parameters list are estimated during fitting. The previous option to check/uncheck "Estimate" has been removed.
Save/Load Functionality:
Selection can be saved or loaded from a CSV file using new Save and Load buttons.