Changelog

November 2024

Plates Table Redesign

• Tables have been redesigned to be more intuitive and cleaner.

• Column controls now have the ability to freeze a column in view, so that as you scroll horizontally, the column remains visible.

• You can now filter by condition for both text and number values.

• Add Plate button now appears at the top of the Plates table.

Projects Table Redesign

• Tables have been redesigned to be more intuitive and cleaner.

• Column controls now have the ability to freeze a column in view, so that as you scroll horizontally, the column remains visible.

• You can now filter by condition for both text and number values.

Visualization Changes

• The clustered heatmap now uses a complete-linkage method for clustering.

Other UI Changes

• Added link to End User License Agreement (EULA) in footer.

• Added Size column to display the total GBs used in each analysis.

• Simplified the breadcrumb path on the MS Data Files page.

• Users can now select multiple checkboxes in a table using SHIFT + click on the MS Data page.

Bug Fixes

• An error no longer appears when clicking Link to Plate in the MS Data Files page.

• Fixed a bug where excluded result information appeared in box plots.

• Users are no longer occasionally logged out when downloading files.

• An error no longer appears asking to save when no data is cached.

• Fixed heatmap colorization for normalized data.

• Fixed hierarchical clustering within heatmaps for N/A values.

• Fixed minor display issues with volcano plots.

• Other minor UI fixes.

October 2024

Group Analysis Improvements

• The Group Analysis wizard has been completely redesigned to be simpler and more powerful.

• The Group Analysis Setup page includes a live summary of the settings selected from the required and optional configurations. As each setting is made, the summary panel updates with the number of samples of each group that are included with the analysis.

• You can now run and save multiple group analyses on an analysis results dataset.

• If you leave an analysis record without saving the results of a group analysis, PAS caches the group analysis results and pre-populates the group analysis settings so that you can save or view its results.

• The most recently viewed group analysis data is cached and displays in the Data panel of its parent analysis.

• The Group Analyses panel displays a summary of the settings used to run it.

Data Table Redesign

• The tables on the Analyses and MS Data pages have been redesigned to be more intuitive and cleaner.

• Column controls now have the ability to freeze a column in view, so that as you scroll horizontally, the column remains visible.

• Additional column controls allow sorting in ascending or descending order and filtering using text or numeric operators based on the data type contained in the column.

Other Tables Redesign

• Column controls now have the ability to freeze a column in view, so that as you scroll horizontally, the column remains visible.

• You can now filter by condition for both text and number values.

Bug Fixes

• Selection boxes on the column head row now select or clear all boxes on all items, regardless of how many pages of items exist.

• The PPI network chart now functions correctly when viewing mouse data.

• Fixed an issue where Windows line-breaks in FASTA files could cause an analysis to fail.

• The clustered heatmap now correctly displays the clustered results.

• Box plots now correctly handle data from different samples with the same sample name.

• Fixed an issue where data did not display correctly in bar charts when the user selected particular settings.

• The UpSet plot now correctly updates when the user adjusts the Within Samples setting.

• The MS Instruments filtering of the QC charts now correctly filters the QC summary table.

• Other minor UI fixes.

July 2024

Additions

• Integrated CloudTrail.5 CloudTrail trails with Amazon CloudWatch Logs.

• Added IAM roles for each PAS account for better security.

Bug Fixes

• Fixed minor display issues with new UI components and error messages.

• Fixed an issue with some plots not updating correctly after changing inputs.

• Fixed an issue that prevented all boxplots appearing.

• Fixed an issue that prevented a new System Administrator from logging in.

• Fixed an issue where enabling two-factor authentication prevented login.

• Fixed an issue that allowed removed users continued access until logged out.

• Fixed an issue that prevented confirmation pop-ups when inviting new users.

• Fixed a rounding error issue that caused some items to get dropped from a group analysis Results table.

• Removed IAM policies from the backend STSUser for IAM.2 users.

• Fixed a display issue where after selecting Peptide for a PCA analysis, the Feature dropdown displayed as Protein.

• Fixed an issue where a user couldn’t add a plate with more than 80 files.

• Fixed an issue that prevented adding a plate after changing the space and updating the Plate ID.

• Fixed an issue where file sizes were expressed as terabytes instead of megabytes.

• Fixed issues affecting Demo users.

• Fixed various issues with VCF files.

• Fixed issues where some entries did not display immediately.

• Fixed an issue that caused PAS to stall when copying analysis protocols.

• Fixed an issue with the clustered heatmap that caused the browser to crash.

• Fixed an issue where user defined control limits were not applied in the QC charts.

June 2024

User Interface Overhaul

• Updated all pages of PAS to a new design.

• Removed the option for dark mode.

Group Analysis

• Removed the option to use Lowest Probability Imputation from the group analysis wizard.

Updates

• Fixed an issue that prevented users from downloading coverage plot PNG files.

• Fixed an issue where graph settings were cached between user sessions.

• Fixed an issue that caused projects to load slowly.

• Fixed field validation functionality when copying analysis protocols.

• Fixed an issue that allowed users to add plates to the wrong Space.

• Fixed and issue that prevented all search output files to download correctly.

• Fixed an issue that caused large DDA analyses to fail.

• Fixed an issue where the injection time was not being correctly loaded from a custom data file.

• Fixed the bulk data and time editing in the plates table view.

• Eliminated case sensitivity in waterfall and upset plot search.

• Fixed an issue with downloading intersection lists from the upset plot.

• Fixed security issues.

• Other minor UI fixes.

March 2024

Analysis Protocol limits

• Select analysis protocols and all user-modified derivative versions of them are limited to a maximum of 80 samples in a single analysis run to ensure system stability and enhance operational efficiency.

Bug Fixes

• Fixed a issue that prevented the user from selecting custom user-created analysis protocols when analyzing samples.

• Fixed an issue that allowed users to assign plates to an incorrect Space.

• Fixed an issue with group exclusion in the group analysis wizard.

• Fixed an issue with filtering the group analysis data panel by coverage.

• Fixed minor UI issues.

Updates

• Added a warning message when working with a capped system-provided analysis protocol to advise the limit of samples allowed.

• Fixed an issue where Tenant Admins could not update the phone number for their tenant.

November 2023

User Interface Fixes

• Fixed an issue where the Loading pop-up was not appearing during group analyses if the Remove peptides / proteins with missing values checkbox was not selected.

• Fixed an issue where the Enrichments dot plot results did not expand to the height of the window.

• Fixed an issue where default grouped-by text appeared in the Box Plots label when a group analysis had not yet been selected.

October 2023

Login and Logout

• User sessions are carried across any open and new windows or tabs accessing PAS. When logged in to PAS on one account, any attempt to log in again to a new window or tab displays a warning that the current user account is logged in and the user must log out to access a different account.

• Fixed an issue with user permissions where users were able to access functionality and data in the PAS demo.

Minor User Interface Improvements

• Fixed an issue with duplicated and unsorted columns in Processed Protein Group Intensities report.

• Fixed an issue where lengthy x-axis labels overwrote each other.

• Fixed an issue of missing x-axis labels in mini box plot mode.

• Fixed an issue to synchronize Box plot and Coverage plot graphs when multiple analyses are selected.

• Fixed an issue with the Group Analysis Wizard where it did not display any available groups when updating a group selection.

• Fixed an issue where a blank custom field would appear in the Demo account.

• Fixed an issue where the PCA plot color might repeat if a plate had fewer than 15 samples. PAS uses unique colors for up to 15 samples; colors will repeat when a plate contains more than 15.

• Fixed an issue where a datapoint’s information pane could extend off the visible area of the screen. Information panes are now constrained within the visualization.

September 2023

View changes to the Analysis page

New Analysis Protocol

• The new DIA-NN (1.8.1) — System Provided DIA Protocol, Ver Sep2023 analysis protocol includes a vastly improved spectral library built from DDA data collected using a ThermFisher Orbitrap Astral Mass Spectrometer and a new scalable version of match between runs (MBR) engineered by Seer’s team.

Analysis Results Reorganization

• The results and visualizations for each analysis have been reorganized to make it easier to quickly access biological insights. The analysis output content is now organized into the following tabs:

  • Analysis Results - aggregate results and visualizations as well as group analysis.

  • Analysis Metrics - sample by sample results as well as experiment quality control visualizations.

  • QC Charts (if applicable) - results specific to quality control samples.

• The raw data and group analysis results tables have been replaced by a single new Tabulated Results table that provides quick access to protein- and peptide-level analysis results.

• New export options are now available on the tabulated results table

  • the tabulated results in matrix format export file includes all data in the tabulated results table in either protein- or peptide-mode.

  • the processed intensities export file can be exported in matrix or long formats and includes raw log10 intensities as well as imputed and/or normalized log10 intensities if those we computed during group analysis.

• The results of group analyses will now be saved automatically. The panel will display the results of the most recent group analysis calculation performed per user.

Minor User Interface Improvements

• Non-significant data is now displayed on the volcano plot by default. The option to hide non-significant datapoints is now available in the volcano plot display options.

• A box plot is automatically displayed next to the volcano plot showing results from the data point with the highest -log10 adjusted p-value.

• Buttons to display graphs are now visible at all times. The buttons for graphs that are unavailable due to data limitations or that require data selection prior to display will be gray (inactive) by default.

• The protein groups and peptides graphs now display as bar charts by default. The line graph is no longer available.

• Nanoparticle-level visualizations are now hidden by default but can be unhidden in the display settings.

• The heatmap visualization is no longer available.

May 2023

New Spaces functionality

• Spaces offer an easy way to manage and segregate data for different external clients or internal teams

• Spaces are used to organize MS data files, VCF files, plates and samples, projects, and analyses into individual workspaces to which users can be assigned

• Administrators can assign users to multiple Spaces, and only those Spaces (as well as a general Space) are viewable when the users log in

• PAS tables can be filtered by Space, showing only the data for the selected Space

• Spaces replace the User Groups feature in PAS

Improvements to the Link to Plate setup workflow

• Added the ability to link up to 10 plates at a time

• Removed redundant buttons

• Added more supporting text to the user interface

• Added more checks throughout the workflow to notify users earlier if something is incorrect (e.g., wrong file type, missing files)

• Made the table of files on the Link to Plate dialog larger and easier to read

• Made other miscellaneous layout changes to the Link to Plate dialog

Improvements to the Analyses page

• Added a Reanalyze button to allow users to easily reanalyze previously analyzed datasets, typically with different analysis parameters (e.g., MS method, analysis protocol)

Improvements to the VCF Files page

• Added a new dialog for adding VCF files, making the process more intuitive

Improvements regarding search engines

• Added the ability for users to adjust more parameters of the DIA-NN search engine

• PAS now accepts .mzml files for all analysis protocols

Improvements to the Seer AutoUploader

• Added the ability to create and manage multiple connections between local folders on the MS controller computer where MS data files are stored and destination folders in PAS Spaces to which files are uploaded automatically

• Added a notification system for future customer alerts

Improvements to user assistance

• Added more tool tips in the PAS user interface

• Updated the PAS Help system

General improvements

• Improved the layout of menu buttons throughout

• Fixed an issue in the Setup Group Analysis dialog that was incorrectly assigning column headers

• Fixed an issue with exporting a violin plot of the Intensity Distributions graph (under Analysis Metrics) when viewed in dark mode

• Corrected the title of the Volcano graph (under Group Analysis)

• Made other minor bug fixes

January 2023

New analysis protocol

• Integration of MSFragger¹ version 3.5 database search engine for DDA library-based search

Improvements to existing analysis protocols

• Integration of the updated DIA-NN² version 1.8.1 analysis protocol for DIA library-based and library-free search

Improvements to user assistance

• Updated content in the PAS Help system

• Updated tooltips in the PAS user interface

General improvements

• Minor user interface improvements

• Minor bug fixes

¹Kong, Andy T., Leprevost, Felipe V., Avtonomov, Dmitry M., Mellacheruyu Dattatreya, and Nesvishskii, Alexey I. MSFragger: ultrafast and comprehensive peptide identification in mass spectrometry–based proteomics. 14 Nature Methods (April 2017): 513-520, doi:10.1038/nmeth.4256.

²Demichev, V., Messner, C.B., Vernardis, S.I. et al., “DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput.” 17 Nat Methods (January 2020): 41–44, doi.org/10.1038/s41592-019-0638-x.

July 2022

PAS Proteogenomics Workflow to identify and explore peptides with protein sequence altering genetic variants

• Build a custom peptide database

  • New feature to build a customized peptide sequence database using user-uploaded custom or sample-specific variant call files (VCF).

    • VCF files are used to annotate genetic variants that may result in amino acid variants (i.e., variant peptides) not captured in the canonical reference database.

  • Variant peptide sequences are combined with the reference database to generate customized peptide sequence databases.

• Search for variant peptides

  • Using the customized peptide sequence database, now users can search their DDA data for variant peptides using MSFragger.

• Variant Peptide Browser and Proteogenomics Data Explorer

  • Variant Peptide Browser — Identified variant peptides are summarized in interactive plots and table.

    • Summary table shows all identified variant peptides and can be sorted/filtered by sample, nanoparticle, protein, variant, and allele frequency. Each variant (row) links to a view within the Proteogenomics Data Explorer.

    • The number of variant peptides found across samples, conditions, and nanoparticles are shown. The distribution of variant peptide intensity is stratified by reference and alternative alleles and homozygous/heterozygous alleles across samples, conditions, and nanoparticles.

  • Proteogenomics Data Explorer — Interactive tool to explore peptide and variant peptide data maps in genomic space for entire proteins and at nucleic acid/amino acid resolution

    • Gene structure, protein structure, domain information, and functional region information are displayed.

    • Amino acid variants within variant peptides are highlighted, including both reference and alternative alleles.

Improvements to analysis protocols

• Integration of MSFragger database search engine.

  • Pre-installed MSFragger-based Proteogenomics protocol (DDA, VCF required).

• Enabled DIA-NN MBR feature¹.

Dashboard to monitor PAS account usage

• Track the total number of plates added, projects added, completed analyses, and data storage.

• Added links to most recently added plates, projects, completed analyses, and data storage.

Expansion and improvement of analysis visualizations

• Added additional background datasets and overlay for multiple samples in waterfall plots.

• Added ability to interact with sample correlation and similarity plots and visualize plots showing underlying data for each comparison.

• Added option to view and compare all metrics from plate map grid across all wells and across all plates analyzed.

• Added option to select order of comparison for differential abundance group analysis.

• Added new interactivity with differential abundance group analysis volcano plot display.

Changes to file and project management

• Added feature to multi-select projects when launching analyses.

• Added feature to collapse Analyses folders by project.

• Added project filtering capabilities.

Improvements to analysis stability and plot visualizations for large-scale study sizes

• Stability and browser performance upgrades.

• Analysis visualization and plot rendering speed improvements.

• Streamlined analysis summary menu improves navigation between visualizations.

Added PAS software end user license agreement (EULA)

Changes to help content

• Updated help system and user guide.

• Updated tooltips.

Other general improvements

• Sample Description File is now stored in Data Files.

• Minor bug fixes.

¹Demichev, V., et al. DIA-NN: Neural Networks and interference correction enable deep proteome coverage in high throughput. Nature Methods 17, 41–44 (2019).

October 2021

New analyses to visualize differences in peptide/protein group intensities between samples and groups

• New interactive table containing peptide/protein group intensities across samples/groups

• New heatmap plot for visualizing peptide/protein group intensities across samples/groups

New analysis to identify peptide/protein groups with significantly different intensities between groups (e.g., healthy vs. disease samples)

• Added new “Group analysis” sections to ‘Analysis’ section

• Guided comparison setup providing data filtering, normalization, imputation, and statistical test options

• Toggle for viewing only ‘Significant Peptides/Proteins’ in dataset

• Interactive plots and tables for exploratory expression analysis of significantly regulated targets with dynamic fold-change and p-value options

• New group analysis plots to visualize peptides/protein groups with statistically different intensities

  • Volcano plot – fold-change vs. statistical significance with coloring options to highlight proteins-of-interest

  • Coverage viewer – Amino acid sequence coverage by peptides display, including PTM detection

  • Clustered heatmap – visualizing peptide/protein group intensities across samples/groups with rows (peptide/protein groups) and columns (samples) ordered using hierarchical clustering

  • Protein-protein interaction – Visualization of PPIs (STRING db) of significant proteins

  • Intensity box plots – Compare significant peptide/protein group intensities between groups

Changes to plot visualizations

• Added ability to export plot source data to .csv files

• Improved plot rendering speeds

• Added user preferences to modify plots

New analysis protocols

• Integration of DIA-NN database search engine

  • Pre-installed DIA-NN library-based protocol (DIANN - System Provided DIA Protocol)¹

  • Expanded Seer human plasma spectral library file (4,011 protein groups; 62,687 precursors)

  • Optional in silico predicted library-free protocol

Changes to results summary

• Simplified peptide and protein group results tables

  • Panel level summary

  • NP level summary

Changes to help content

• Updated user guide

• Indexed online help

• Tooltips

New data file management

• New AutoUploader application allows automatic data transfer from LC-MS system to PAS account

¹Demichev, V., et al. DIA-NN: Neural Networks and interference correction enable deep proteome coverage in high throughput. Nature Methods 17, 41–44 (2019).

May 2021

Initial release