Bionano Access v1.1 Release Notes

Table of Contents Revision History... 3 Bionano Access... 3 Introduction... 3 Compatibility... 3 Improvements... 4 Experiment Design (Saphyr only)... 4 Project Browser... 6 Administration... 8 Visualization... 8 In Silico Digestion... 9 Tickets... 10 User Stories... 10 Defects... 12 Technical Assistance... 13 Page 2 of 13 30188 Rev C, Bionano Access v1.1 Release Notes

Revision History Revision Notes Rev A Initial release of document. Rev B Addition of updates for version 1.1.1 Rev C Addition of updates for version 1.1.2 Bionano Access This document describes the v1.1 release of Bionano Access TM. In this document we will provide an overview of what is changing with this release so that you may better understand the impact of moving to this version of our visualization software. Should you have any questions please contact support@bionanogenomics.com. Introduction Bionano Access v1.1 is a new release of our Bionano Access product. Bionano Access v1.1 supports Windows, Mac, and Linux systems. Data between users is shared using projects, and performance is much improved through rendering optimizations and graphics acceleration. This application is designed for install on a single centralized server that can be shared across an organization. For information about system requirements and installation please refer to the latest Bionano Access Installation Guide (part number 30170). Compatibility Bionano Access is compatible with data generated on both Irys and Saphyr instruments. Existing Irys Data generated via Auto Detect v2.1.4 or IrysSolve v2.1 pipeline can be uploaded into Bionano Access. Bionano access is compatible with Saphyr Control Software version 3.0 and 3.1. Bionano Access is designed to integrate directly with the Bionano Solve v3.1 pipeline running on the IrysSolve, Saphyr Compute and Bionano Compute servers (see the Bionano Access Installation Guide, part number 30170 for the configuration details). Compute configurations which are not directly compatible will continue to be supported from the command line, with a manual import of results into Bionano Access. 30188 Rev A, Bionano Access v1.1 Release Notes Page 3 of 13

Updates The following updates have been made to the 1.1 release of Bionano Access. Update Change Ticket v 1.1.1 v 1.1.2 Multiple simultaneous uploads fail randomly Experiments created before 1.1 show wrong sample Chip Run finishes, but molecule object not imported into project Cohort QC Foreign key constraint failure during installation Auto Assembly checkbox is not visible Duplicate dashboard data points when multiplexing Avg Label Density missing on MQR report IW-2682 IW-2652 IW-2664 IW-2683 IW-2666 IW-2694 IW-2693 Improvements Experiment Design (Saphyr only) Improvement Scan Column Update New Experiment List No Empty Cells Red color sample Support Red Only Workflow Multiplex Workflow Description We modified the scans column on the dashboard. It now shows the number of scans received and the number of scans done. The scans received reflects the number of scans submitted by Saphyr Control Software to Bionano Access. The Scans Done reflects the number of scans that have been converted to molecule data and had their metrics data generated. The experiment list has been modified. The list was too wide for some screens. The list now shows one row for each chip and you can expand the chip row to see what is in each flowcell. The Experiment Design module no longer allows the submission of chips with empty flowcells. Both flowcells must be populated before you can proceed. All flowcells of a cartridges must be loaded with a sample when running to avoid cross-contamination between flowcells. The Access system now supports experiments that use the red laser in the Saphyr instrument. These workflows are disabled by default, but they can be enabled with settings in your configuration file. For more information on enabling red color capability, contact support. If red support has been enabled, you will have the choice of using green or red when you are doing a Single Sample experiment. If red color workflow has been enabled, the Sample Multiplex workflow will be enabled in the Experiment Design module. This workflow is designed to process one sample using green and a second sample using red in the same flowcell. This workflow will generate separate dashboard metrics for each color. This workflow will also generate a separate bnx file for each color. It is possible to use the same sample for both red and green, but the molecules loaded should be labeled with only red or green not both. Page 4 of 13 30188 Rev C, Bionano Access v1.1 Release Notes

Dual Labeled Workflow Dual Labeled Dashboard If red is enabled, the Dual Labeled workflow in the experiment design module will be available. The Dual Labeled workflow is designed to process a single sample whose molecules have both green and red labels. The system will generate molecule metrics on the dashboard for each color individually. Users can provide separate references for each color, but only one reference will be associated with final merged bnx file. The user is prompted to select which reference (the primary) would be retained. The Dual Labeled workflow will generate a single Bnx file that contains both green and red labels. When chips with dual labeled samples are processed, the dashboard will display separate mapping metrics for each color because the labels will be different. The dashboard will display molecule metrics once for each sample because each color shares the same molecules. 30188 Rev A, Bionano Access v1.1 Release Notes Page 5 of 13

Project Browser Improvement BNX Merge Select All Export All Message Center Project Name Filter Dual Labeled Bnx Files Merged Inversions and Translocations Object Create Date Background SV Merge Job Error Reporting New BNX Merge Rules Description When merging molecule files there is now a select all option on the table that lists molecule files that can be merged together. When you export a project you are prompted to select which objects from the project you want to export. Some projects may contain an extensive number of objects. A selection all box was added to allow users to select all the objects in the project. At some sites access to email for system notifications was not possible. The message center was added to notify users through the Bionano Access interface directly when their background jobs have completed. In the web page header there is a mail icon. Clicking this icon will open the message center. The message center icon will show a red circle with a number indicate now many new messages are waiting. In the message center window you can read messages and delete them. Email notifications can be disabled in favor of the message center if desired. Some sites have an extensive list of projects. We added a filter to the project name column on the project list screen to help locate projects. Dual labeled bnx files will contain two channels. Each channel will have a fluorescent label (color) and recognition enzyme in the bnx file. Bionano Access was designed to only handle one reference per bnx file. By design if you had a dual labeled bnx file, you could have a reference two enzymes (one for each color) to match. However, the de novo assemblies currently only support alignment to a single enzyme. Associate a single enzyme reference with your two color bnx file on the channel you want aligned during de novo assembly. The object import, object edit, and de novo assembly input dialogs have been modified to allow you to specify the channel desired. The SV Merge operation now also merges translocations and inversions in addition to indels. In the Project Browser the object created date has been added to the object list. You can sort and filter the create date column. When you ran an SV Merge operation in Bionano Access v1.0 your browser was locked until the SV Merge operation completed. In Bionano Access v1.1 the SV Merge operation is completed in the background freeing your system to perform other operations. The SV Merge operation is now also completed on your compute server instead of the local web server making the operation faster and more consistent with other bioinformatics operations we perform. The system will message you when the SV Merge job has completed. Improvements are being made to better trap and return errors from bioinformatics operations to the user. If there was error returned an icon will appear next to the job number in the Object Details pane on the Project Browser page and next to the View Details link in the job list. Clicking the icon will show the error message that was returned. In Bionano Access v1.0 the Merge Molecule Objects operation would automatically select the molecule objects that you were likely to merge, but allowed the user to merge any Molecule Objects. Bionano Access v1.1 is more restrictive about what Molecule objects it will allow to be merged. Initially it will select Molecule objects with the same sample and recognition enzymes. The user can choose other molecule objects that do not have the same sample, but they must have the same recognition enzymes. Dual labeled bnx files can only be merged with dual labeled bnx files with matching recognition enzymes. Page 6 of 13 30188 Rev C, Bionano Access v1.1 Release Notes

Merge Variant Annotation Allow Project Leads to make References MQR Not Blocking Variant Annotation Download SV Merge Download SV Merge Error Message Import Compressed BNX File MQR Sub-Sampling Increased Special Character Fix for Variant Annotation Project Cookie Disabled Variant Annotation Moved In Bionano Access v1.1 it is possible to merge Variant Annotation containers. This works similar to merging SVs. Select one of the Variant Annotation containers and then select the merge operation. In the merge dialog select the second annotation you want to merge. The merge output will include the extra SV annotation columns in addition to the traditional smap data. Variant annotation containers can only be merged with other variant annotation containers. They cannot be merged with assemblies. The permissions have been modified on the reference list to allow users with the Project Lead role to manage the References available in the system. Whenever a bnx file is uploaded into the system it will automatically run MQR. When you edit the Molecule Object it will also run the MQR. While the MQR is running the user was not able to start an assembly or perform other operations using the bnx file. We have modified the system to make the MQR operation non-blocking. You can begin an operation with the bnx file while the MQR is still running if desired in Bionano Access v1.1. Download links have been added for Variant Annotation objects. We do not support the import of Variant Annotation objects yet. Download links have been added for SV Merge. We do not support the import of SV Merge objects yet. The error messaging has been improved to help customers understand they can only merge assemblies that have the same sample names. The Molecules Object import now supports uploading compressed bnx files in gzip (gz) format. The sub-sampling for MQR has been increased from 1,000 molecules to 10,000. The Variant Annotation operation failed in Bionano Access v1.0 if the name for the assemblies selected included special characters. This has been corrected in Bionano Access v1.1. Your last project selection was preserved so that you would automatically be forwarded to the project you selected last time. This design was based on the assumption that you would typically do work in the same project. For some customers this was problematic because they did work on numerous projects simultaneously so the project selection caching was removed. The back end scripts for the variant annotation pipeline have moved into the Bionano Solve product so the folder location for the scripts has been updated to reflect the new location. This will allow users to perform variant annotation from the command line also if desired. 30188 Rev A, Bionano Access v1.1 Release Notes Page 7 of 13

Administration Improvement Login Banner Config File Download HTTPS Support Configuration Issue SSH Connection Test Description Some customers expressed a need to display corporate policy and notices on the login screen. Users with the Administrator role can now define a message to appear on the Login screen. From the Settings page click the Login Banner button to access the Login Banner definition screen. We added the ability to download the configuration files in the system. From the configurations page click the filename link and you will be prompted to confirm you want to download the selected file. HTTPS support is available with release 1.1. Customers can acquire and install SSL certificates onto their Bionano Access server and enable https protocol with command line arguments when starting the web server. Contact support for details on enabling https support. We found that at some customer sites we needed to enable image detection (even though they are using Auto Detect instead) in their configuration for some bioinformatics operations to function. This has been corrected in Bionano Access v1.1. During startup the system will attempt to open an SSH connection to each sever in your access configuration to verify connectivity. Visualization Improvement Label Stretch Match Confidence Filter Change Dual Labeled Molecules in Viewer Viewer Quick Help Variant Molecule Alignments Match Tab Duplication Visualization Description In Release 1.1 it is possible to choose stretched alignment for molecule labels when viewing assemblies. Click the View Options icon. Then select the desired molecule alignment and click the Close button. The Unstretch view is the system default. The confidence filter in the viewer will now allow you to enter a value directly in addition to selecting existing ranged values from a list. If you choose to show molecules in the viewer and the molecules file is dual labeled the system will show the labels for both enzymes. Our viewer is packed with functionality. To help users realize and remember all the features available, a quick help menu that details all the hotkeys and actions possible within the viewer was added. Click the help icon on the viewer tool bar to open the shortcut quick help window. When you view the results of a variant annotation the system will display the assembly for the proband. When the user chooses to show molecules for a selected contig, the system will prompt the user to select which molecule alignment they wish to view. If the user performed a trio analysis they will be able choose to see the molecules for the Proband, Mother, or Father. The viewer now includes a Match tab that lists the contigs for an assembly. The table on the Match tab can be sorted and filtered. The table includes columns for the xmap ID, query ID, query start, query end, orientation, and confidence. The content for the Match tab is generated when the assembly is imported. So, only new assemblies generated or imported after the new version has been installed will show the Match tab. The system generates structural variations during a de novo assembly operation. In Bionano Access v1.1 the system will now generate duplication structural variations. Page 8 of 13 30188 Rev C, Bionano Access v1.1 Release Notes

In Silico Digestion Improvement Manage in silico Fasta Files Remove in silico Summary Improved in silico File Upload Copy in silico Result to References Description We have added the ability to manage FASTA files that have been uploaded into the in silico digestion tool. To access the FASTA file management screen click the file icon in the header on the in silico digestion screen. From the FASTA Management screen you can delete runs associated with the selected FASTA file and delete the FASTA file itself. In Bionano Access v1.0 you could expand each row of the completed runs table to view summary information about the digestion. This summary information was redundant with the summary file we provide for download so it was removed. The summary file is generated by the in silico digestion scripts. Some customers reported issues uploading large FASTA files into the in silico tool. This has been resolved in Bionano Access v1.1. Files larger than 1GB will now upload properly. In the completed runs table in the in silico digestion tool there is a new link, Add to References. Clicking the Add to References link will copy the FASTA file to the References List in Bionano Access. 30188 Rev A, Bionano Access v1.1 Release Notes Page 9 of 13

Tickets User Stories Summary Issue key [3 Level] Add Matches Tab IW-1954 [3 Level] Quick help menu IW-1925 [3 Level] Stretch Matches IW-10 [3 Level] allow user entred value for confidence score filter IW-1466 [Assembly] Update smap processing with masking rules IW-2123 [Auth v2] Modify User Profile IW-489 [Bnx Workflow] Add se, sf, and sr columns to cohorotqc IW-2063 [Bnx Workflow] Instrument embedded browser support IW-880 [Bnx Workflow] Population Index IW-1989 [Bnx Workflow] Version API IW-1258 [Bnx Workfow] Chip Stats API IW-1636 [Bnx Workflow] Add chip limits for offline processing IW-2422 [BnxMerge] New Merge Rules IW-1988 [Exp Design] New samples auto linked to experiment project IW-665 [General] Add port to log file IW-1852 [General] Message Center VAT-84 [General] change email / database configuration IW-1823 [General] Debug SSH connections on startup IW-2436 [Help] Add tutorial for bed files IW-1957 [Help] Add tutorial for confidence filter IW-1956 [Import] Bnx Import Reference Channel Designation IW-2062 [Import] Create "Select All" function for all objects when exporting a Project IW-1798 [Knickers] Clean up dead fasta files IW-2351 [Knickers] Remove Summary IW-2444 [Knickers] copy result to reference list IW-2367 [Multi-Prep] Add transform string to process cohort api IW-1256 [Multi-Prep] Change Dashboard IW-1860 [Multi-Prep] Chip Type Selection IW-1849 [Multi-Prep] Cohort Shell Script Changes BT-19 [Multi-Prep] Disable Red Workflows by Default IW-2454 [Multi-Prep] GetCohortQC to return array IW-1900 [Multi-Prep] Modify Experiment Design IW-1844 [Multi-Prep] Modify PSF Detect IW-890 [Multi-Prep] Modify Pending Experiments API IW-1856 [Multi-Prep] Modify Start Chip API IW-1859 [Multi-Prep] Modify Start Run API IW-1857 [Multi-Prep] Modify the Cohort Bnx Merge IW-892 [Multi-Prep] Modify the PreProcessor IW-889 [Multi-Prep] No empty flow cells permitted IW-1801 Page 10 of 13 30188 Rev C, Bionano Access v1.1 Release Notes

[Multi-Prep] Pending Experiments for Unlocked Chips [Multi-Prep] Two color molecules for Assembly [Multi-Prep] auto-assembly coverage by run instead of prep [Project Browser] Add Create date [Project Browser] Add Filter for Project Name [Project Browser] BNX Merge needs bulk check/uncheck [Project Browser] Delete all messages button [Project Browser] Remove Project Cookie [Project Browser] Variant Annotation moved to pipeline [SV Merge] Add Download link [SV Merge] Add molecule alignments for SV Annotations [SV Merge] Call SV Merge Wrapper Script [SV Merge] Column reduction [SV Merge] Move to compute server for processing [SV Merge] Run in background [SV22] Duplication Visualization [SV22] Import Duplication File [SV22] Merged Inversion/Translocation Visualization [SV22] SV Merge Output for SV Annotation [Variant] Add Caption to Variant Annotation Diagrams [Variant] Add overlapping genes script [Variant] Download output [Variant] Gene Overlay After SV Merge [Variant] Merge 2 Enzyme Results [Variant] Show molecule alignments [Variant] Support HG38 [Variant] localize files for molecule alignments IW-2025 IW-1851 IW-1325 IW-2001 IW-1832 IW-959 VAT-83 IW-1921 IW-2561 IW-1960 VAT-76 IW-1959 IW-1961 IW-1920 IW-1715 IW-1915 IW-1916 IW-1917 VAT-70 VAT-72 VAT-26 VAT-78 IW-1958 VAT-56 VAT-20 VAT-24 VAT-43 30188 Rev A, Bionano Access v1.1 Release Notes Page 11 of 13

Defects Summary [Assembly] Could not start assembly with psfdetectserver [Assembly] Cannot start because of enzyme mismatch [Assembly] Update SV Mask Files [Auth] Allow Project Leads to create references [Exp Design] Add scans received to dashboard [Exp Design] Change Scans Completed on Dashboard [Exp Design] Revisit Experiment and Chip Run lists [General] Password reset not working [Import] Allow.bnx.gz to be imported as molecules object too [Knickers] Cannot upload 3GB fasta file [Knickers] Change Copy to Access Link [MQR] Change sub-sampling [Multi-Prep] Add Prep Type to Pending Experiment API [Multi-Prep] Add population_idx column [Multi-Prep] Change Bnx Merge for 2 color [Multi-Prep] Dashboard shows duplicate values for Dual Labeled Samples [Multi-Prep] Double counting metrics [Multi-Prep] Enzyme Rule Check [Project Browser] MQR failure blocks assembly [Project Browser] job failures [Reference] Cannot download configuration files [SV Merge] Improve Error Message for Same Sample [Variant] Variant Annotation fails if Assembly Name has illegal characters Issue key IW-2053 IW-2112 IW-2501 IW-1554 IW-1640 IW-2122 IW-1981 IW-2504 IW-1876 IW-2184 IW-2139 IW-2411 IW-2126 IW-2125 IW-1975 IW-2129 IW-2121 IW-2023 IW-1639 IW-1985 IW-2002 IW-2011 VAT-79 Page 12 of 13 30188 Rev C, Bionano Access v1.1 Release Notes

Technical Assistance For technical assistance, contact Bionano Genomics Technical Support. You can retrieve documentation on Bionano products, Safety Data Sheets, certificates of analysis, frequently asked questions, and other related documents from the Support website or by request through e-mail and telephone. Type Email Phone Contact support@bionanogenomics.com Hours of Operation: Monday through Friday, 9:00 a.m. to 5:00 p.m., PST US: +1 (858) 888-7600 Website www.bionanongenomics.com/support 30188 Rev A, Bionano Access v1.1 Release Notes Page 13 of 13