Improvements

• When importing tracks, the history of the track now contains the full path name of the imported file.

Bug fixes

•  Fixed an issue with the Basic Variant Detection , Low Frequency Variant Detection  and Fixed Ploidy Variant Detection tools that could cause the count and frequency values to be too low for a small subset of those variants that are contained within a larger variant region (e.g. an MNV or deletion). For a variant to be affected by this problem, there needed to be at least two other potential variants nearby that were disregarded during the variant calling process. This circumstance and our testing suggest this is a rare issue.

• Fixed an issue in the Copy Number Variant Detection tool where the data in the “Fold-change (adjusted)” and “Fold-change (raw)” columns were reversed in the target-level output.

• Fixed a bug that in some cases would result in incorrect BaseQRankSum values being reported in the outputs of the Basic Variant Detection  , Low Frequency Variant Detection  and Fixed Ploidy Variant Detection tools.

• Fixed an issue that could cause the SRA search view to display an error when trying to show results.

• Fixed a problem with the identification of the correct sequence types from MLST schemes in cases where the schemes contained blank characters. This issue affected Workbenches with the QIAGEN CLC Microbial Genomics Module installed.
  

Improvements

• In cases where tools within a workflow have been renamed, it is now possible to filter for original tool names within the workflow configuration view of the workflow editing tool.

Bug fixes

• A timeout value that would lead a job to fail after 24 hours, which was introduced as part of optimizations to run on multiple threads in the Biomedical Genomics Workbench 3.5 has been extended to 7 weeks. The tools affected are Add Information from Variant Databases, Remove Variants Found in External Database, Remove Germline Variants, Add Exon Number, Add Flanking Region, Remove False Positives, Trio Analysis, Identify highly Mutated Gene Groups and Pathways, Add Information About Amino Acid Changes, Add Conservation Scores, Identify Variants with Effect on Splicing, Link Variants to 3D Protein Structure, QC for Targeted Sequencing, Identify Enriched Variants in Case vs Control Samples, Add Information from Overlapping Genes, Add information from Genomic Regions, Add Information from Overlapping Variants, Remove Variants Outside Genome Genome Regions, Remove Variants Outside Target Regions, Remove Variants Inside Genome Regions, Identify Mutated Genes, Remove Reference Variants, Identify Candidate Variants, Whole Genome Coverage Analysis, and InDels and Structural Variants.
• Fixed an issue in the RNA-Seq Analysis tool where running in EM mode, with a “Strand specific” setting of “Forward” or “Reverse” would result in the second read of a pair mapped as a broken pair being counted incorrectly if that read was mapped outside a region annotated as a transcript.
• Fixed an issue where an error arose when using the RNA-Seq Analysis tool with the EM option and a strand specific setting of “Forward” or “Reverse” in cases where the second read of mapped broken pair mapped to the opposite strand of the strand specific setting.
• Fixed an issue with the Basic Variant Detection, Low Frequency Variant Detection and Fixed Ploidy Variant Detection tools where the forward and/or reverse count for a longer variant, supported by paired reads with both children having the same direction, could be too low. The forward count and reverse count is now reported correctly.
• Fixed an issue with the InDels and Structural Variants tool where an incorrect insertion could be called when the optimal alignment of a read’s unaligned end around the breakpoint included a gap in the insertion sequence.
• Fixed an issue in the InDels and Structural Variants tool that would terminate analysis of large read mappings prematurely a fraction of the times.
• Fixed an issue with the Basic Variant Detection, Low Frequency Variant Detection and Fixed Ploidy Variant Detection tools where the count and read count could be reported as marginally higher than they actually were in a small minority of cases. For the affected variants, this could then also result in variant frequencies being reported that were slightly higher than they should have been, in some cases above 100%. Variants affected by this issue are a small subset of variants where the variant affected overlapped another potential variant and where only the affected variant was then reported. This change could lead to a small decrease in the number variants reported compared to earlier versions of the CLC software, due to a variant no longer passing the count or read count filtering constraints. The impact of this change is expected to be low. For example, in our tests, for a particular analysis that reported 250,000 variants, 30 fewer were reported with the same parameters and filters applied after this fix was implemented.
• Fixed an issue where the Basic Variant Detection, Fixed Ploidy Variant Detection, Low Frequent Variant Detection and Local Realignment tools could fail if a deletion was encountered at the end of a match between a read and the reference in the mapping used as input.
• Fixed an issue in the Basic Variant Detection, Fixed Ploidy Variant Detection and Low Frequent Variant Detection tools where the tools could stop with an error. The problem arose when a read split up within a mapping (e.g. to map to separate exons) was split into 4 or more parts, and at least 4 of those parts would map within a region of adjacent variants being considered as a possible multiple nucleotide variant (MNV). This infrequent problem was most likely to occur when using high coverage RNA-Seq mappings and looking for variants occurring at low frequency. It was introduced in the previous bugfix release of the Biomedical Genomics Workbench, version 3.5.3.
  

Advanced notice

• The Probabilistic Variant Detection (legacy) and Quality-based Variant Detection (legacy) tools will be removed from the Server and Workbenches in March 2017.
• Support for some older operating systems (OS), listed below, will be discontinued in March 2017. Software released at that time and later may still run without issue, but problems experienced due to using an unsupported OS will not be addressed. If you are concerned about the proposed change, please contact our Support team (AdvancedGenomicsSupport@qiagen.com), letting them know the OS being used and the products you are running on that OS.
  • Windows: Windows Vista and Windows Server 2008
  • Mac: Mac OS X 10.7 and 10.8
  • Linux:  Red Hat Enterprise Linux 5, SUSE Linux Enterprise Server 10 and 11 and Fedora 6 through 21

Improvements

• Server import and export locations shown in Workbench wizards now have tooltips giving the path to those locations.
• Various other minor improvements (e.g. improved tooltips)

Bugfixes

For the Basic Variant Detection, Fixed Ploidy Variant Detection and Low Frequency Variant Detection tools, the following have been addressed:

• Fixed an issue where the coverage of a longer variant that contained another variant was reported for both the longer variant and the contained variant. The coverage for the contained variant is now reported correctly.
• Fixed an issue affecting coverage calculation for SNVs without immediately adjacent variants when using paired read data: if the second read of a pair containing the variant did not meet the requirements of the quality filter, neither the first nor second read of that pair contributed to the coverage calculated for the variant.
• Fixed an issue where, for an SNV without immediately adjacent variants, overlapping reads of a pair that had conflicting base calls for that variant position contributed to the values calculated for coverage, read coverage, and read count of that variant.
• Fixed a bug where count, read count, and forward- and reverse read count could be incorrect for variants found in overlapping regions of a pair of reads and where the variant was originally identified as being adjacent to one or more other variants.

The above issues, including information on the products affected, are described on the public notification page: Coverage and count reporting for variants in certain circumstances are incorrect

For the Identify Known Mutations from Sample Mappings tool, the following issues have been addressed:

• Fixed an issue with the Identify Known Mutations from Sample Mappings tool where reads in a sample mapping were not identified as supporting the presence of a known variant in cases where the first position of the variant region in the mapped read contained a gap.
• Fixed an issue with the Identify Known Mutations from Sample Mappings tool where a read containing a variant longer than a known variant being tested for was counted as supporting the known variant in cases where the first part of the read’s variant sequence is identical to that of the known variant.
• Fixed an issue in the Identify Known Mutations from Sample Mappings tool where overlapping reads of a pair having conflicting base calls for a variant position could contribute to the coverage calculated for that variant.

Advanced notice

• The Probabilistic Variant Detection (legacy) and Quality-based Variant Detection (legacy) tools will be removed from the Server and Workbenches in early 2017.
• Support for some older operating systems (OS), listed below, will be discontinued in early 2017. Software released at that time and later may still run without issue, but problems experienced due to using an unsupported OS will not be addressed. If you are concerned about the proposed change, please contact our Support team (AdvancedGenomicsSupport@qiagen.com), letting them know the OS being used and the products you are running on that OS.
  • Windows: Windows Vista and Windows Server 2008
  • Mac: Mac OS X 10.7 and 10.8
  • Linux:  Red Hat Enterprise Linux 5, SUSE Linux Enterprise Server 10 and 11 and Fedora 6 through 21

Improvements

• SRA download functionality has been updated to support the upcoming NCBI transition to HTTPS.
• Updated the restriction enzyme list from REBASE.

Bug fixes

• Fixed a bug where running two or more concurrent instances of RNA-Seq Analysis with EM quantification could in some cases lead to incorrect results or error messages.
• Fixed an issue with running BLAST on macOS Sierra.
• Fixed an issue introduced in Biomedical Genomics Workbench 3.5 where enzymes listed alphabetically after RdeGBI were missing methylation information.
• Fixed an issue with running BLAST on macOS Sierra that would affect the use of the Link Variant to 3d Protein Structure tool.
• Various minor bugfixes.

Advanced Notice

• The Probabilistic Variant Detection (legacy) and Quality-based Variant Detection (legacy) tools will be removed from the Server and Workbenches in early 2017.
• Support for some older operating systems (OS), listed below, will be discontinued in early 2017. Software released at that time and later may still run without issue, but problems experienced due to using an unsupported OS will not be addressed. If you are concerned about the proposed change, please contact our Support team (AdvancedGenomicsSupport@qiagen.com), letting them know the OS being used and the products you are running on that OS.
  • Windows: Windows Vista and Windows Server 2008
  • Mac: Mac OS X 10.7 and 10.8
  • Linux:  Red Hat Enterprise Linux 5, SUSE Linux Enterprise Server 10 and 11 and Fedora 6 through 21

Bug fixes

• Fixed a serious issue that could arise when using Import | Illumina or Import | Ion Torrent to import gzip or bzip2 compressed files using Biomedical Genomics Workbench 3.5.
  
• Fixed a problem where launching a tool from the Quick Launch window after sorting led to the wrong tool being started.

New tools

• “Search for Reads in SRA …” allows search and download of reads from the SRA database. It is available from the Download menu.
• A new GFF3 importer is available as an option in the Import -> Tracks tool.
• A new option “Use EM estimation (recommended)” was added to the RNA-Seq Analysis tool. This enables the use of an expectation-maximization algorithm to distribute ambiguous reads between isoform/genes.

Improvements

Resequencing

• A RefSeq reference data set is now available in the reference data manager.
• The Local Realignment tool has a new option that can allow the use of guidance variants longer than 100bp.
• The InDels and Structural Variants tool now offers the option to include reads mapped as broken pairs in the analysis.
• The InDels and Structural Variants tool offers now the option for consensus calculation to ignore reads if their relative coverage or quality scores are too low.
• The COSMIC importer has been updated to support the latest version of the COSMIC database, release v77.
• Improved performance of a number of tools when run on systems with multiple cores: Add Information from Variant Databases, Remove Variants Found in External Database, Remove Germline Variants, Add Exon Number, Add Flanking Region, Remove False Positives, Trio Analysis, Identify highly Mutated Gene Groups and Pathways, Add Information About Amino Acid Changes, Add Conservation Scores, Identify Variants with Effect on Splicing, Link Variants to 3D Protein Structure, QC for Targeted Sequencing, Identify Enriched Variants in Case vs Control Samples, Add Information from Overlapping Genes, Add information from Genomic Regions, Add Information from Overlapping Variants, Remove Variants Outside Genome Genome Regions, Remove Variants Outside Target Regions, Remove Variants Inside Genome Regions, Identify Mutated Genes, Identify Candidate Variants, and Remove Reference Variants.

RNA-Seq

• The tools “Filter Based On Overlap” and “Add Information from Genomic Regions” now work with the Statistical Comparison Tracks produced by the Advanced RNA-Seq plugin.
• It is now possible to export expression tracks in BED format. The expression value will be exported as the score.
• Expression tracks are now colored according to a log-scale to ease visual interpretation of expression data.
• The track view of expression tracks dynamically rescales to make best use of the screen real estate. This change brings expression tracks in line with other track types.

Workflows

• Workflow outputs can now be configured so that subfolders to contain the outputs are created.
• New placeholders are available when defining the names of workflow outputs: {user}, {host}, and for elements of the timestamp of the output object, {year}, {month}, {day}, {hour}, {minute}, {second}.
• Placeholders within workflow output names that were previously available only as digits can now be specified using written names: {name} is a synonym for {1} and {input} is a synonyms for {2}.
• When using the {2} placeholder for custom naming in workflow output elements, only unlocked inputs will be included in the generated name.
• In the generated pdf showing all the configured parameters of a workflow, entries for parameters connected to a tool or an input element now list the names of the defining elements. Previously the parameter listings for such elements were left blank.
• Where a tool name has been altered in a workflow, the original name is now included alongside the changed name when exporting workflow parameters.
• The History view of data elements created using a workflow now includes information about the workflow that created them.
• The order of the tools in the workflow “Add Element” menu now matches the order in the Workbench Toolbox menu.
• Improved workflow validation to aid the user in identifying inputs that will be ignored due to the configuration of the workflow elements.

Launch

• The Quick Launch tool is now found under the Toolbox menu instead of the View menu and a button called Launch that brings up this tool has been added to the toolbar.
• Analyses can now be launched on data elements listed in the results table of a Local Search by selecting the elements of interest, right clicking with the mouse and navigating through the context menu that appears.

Metadata

• A “Remove Association(s)” option for removing metadata associations from selected data elements has been added sin the Metadata Elements view in a right click context menu.
• In the Metadata Find Associated Data view it is now also possible to use Find in Navigation Area when multiple rows are selected.
• When importing metadata from a spreadsheet with formulas in it, the result of the evaluation of the formula (as displayed in Excel) is now imported rather than the formula itself.

General

• The reference data manager has been reorganized, giving a better overview.
• The option “is not in list” has been introduced as a new table filtering option.
• The tool “Motif List” has been removed.
• The “Sort folder” tool now uses numerical sorting for filenames prefixed with a number.
• New placeholders are available when defining the names of exporter outputs:  {user}, {host}, and for elements of the timestamp of the output object, {year}, {month}, {day}, {hour, {minute}, {second}.
• Placeholders within export output names that were previously available only as digits can now be specified using written names: {input} is a synonym for {1}, {extension} is a synonym for {2} and {counter} is a synonym for {3}.
• The Trim Sequences tool now handles ambiguity codes in the adapter/primer sequences.
• The upper limit for the “discard reads above length” option of the Trim Sequences tool has been raised from 8000 to 99,999.
• Standard deviations in reports are now being calculated with a different algorithm than previously. This will have no noticeable effect in the overwhelming majority of cases.
• The Identify Graph Thresholds tool can now be configured to work on specified regions only.
• The Identify Graph Thresholds tool can now be run using only a lower or upper threshold limit, rather than having to specify both.
• All NCBI server communication is now encrypted. (NCBI will be moving all web services to the HTTPS protocol on September 30, 2016).
• Read group details are now shown on the Element Info view of sequence lists.
• The History view of variant, feature and expression tracks that are created by pressing the “Create Track from Selection” button on the table view of an existing track will now include details of any advanced filtering that was applied to the table at the time the new track was made.
• Improved the progress reporting for the import of large, gzip compressed Illumina and Ion-Torrent files.
• General speed and usability improvements.

Bug fixes

• Fixed an issue with the tools “Extract from Selection” and “Extract Reads Based on Overlap” so that they now correctly extract mapped reads that extend over the (arbitrarily chosen) ends of the 1D representation of a circular genome.
• Fixed an issue that caused characters in sequence names to be rendered incorrectly when a report was exported to Excel.
• The Create New Sequence List button in a broken pair table now works when multiple read groups are involved.
• Fixed an issue that would make the wizard for the Demultiplex Reads tool fail if an invalid bar code was entered.
• Fixed a bug that made graphics export of some plots from reports fail.
• Fixed a rarely occurring bug where rendering of a Read Mapping in a Track List would fail.
• The Find Binding Sites and Create Fragments tools now properly display mismatches when the primer input is in lower-case.
• Fixed an issue where, when viewing statistical comparison tracks together with read mapping tracks, the statistical comparison track annotations could sometimes be rendered as offset from their true genomic positions.
• Fixed an issue where sequences of length zero would cause the Create BLAST Database tool to throw an error. Such sequences are now skipped and will not included in the final database.
• Fixed a bug that prevented selecting custom Cytogenetic Ideograms files when building Custom Reference Data Sets.
• The Illumina High-Throughput Sequencing Import tool now correctly warns that zip files with multiple entries are not supported.
• Tables with more than 126 million entries now show a warning that they contain too much data to display instead of leaving the table empty.
• Fixed an issue in the wizard for the tool Create Entry Clone where a previously used data located on an unmounted location would result in an error message being shown.
• Fixed an issue where right-clicking on a graph in a report and choosing to show “Report”, “History” or “Element Info” triggered an error.
• Fixed an issue where it took a long time to open a workbench it it was previously closed when displaying an open table editor that had been sorted.
• Fixed a bug in the “Manage Enzymes” wizard that prevented a user from cancelling the action if “Save as new enzyme list” was enabled.
• Fixed a rare issue where some annotations could, but did not necessarily, go missing on sequences with greater than 1000 annotations of a given type on that sequence before the deletion and where the right-click context menu option “Delete selection” was used.
• Fixed an issue with links in tables to the PDB and dbEST databases.
• Fixed a rare issue that caused the “Extract from selection” right-click option not to work for a reads track in a track list.
• Fixed a bug where exporting to Wiggle on systems with specific system locales would produce files that could not be re-imported.
• Fixed an issue with the Import Metadata tool where, if a spreadsheet had already been loaded, then selecting the same spreadsheet again did not reload the spreadsheet content.
• Fixed an issue affecting the launching of workflows with multiple inputs in batch, where the workflow execution wizard did not update correctly when another metadata spreadsheet was selected.
• Fixed an issue where, when the Processes tab was hidden and then shown again, any processes listed before the tab was hidden were no longer shown.
• Fixed an issue where the save wizard dialog did not pre-select “Save in input folder” when that option was the most recently used one.
• Fixed an issue that could arise when migrating a workflow containing Create Sequencing QC Report where the workflow was originally created using the QIAGEN CLC Genomics Workbench 6.5 or older.
• Fixed an issue that made “Download and save” fail when invoked on a Blast editor.
• Updated the URL to use for links to UniProt databases.
• Various minor bugfixes.

Notice

From now on, only 64 bit versions of the QIAGEN CLC Genomics Server, QIAGEN CLC Genomics Workbench, Biomedical Genomics Workbench, CLC Bioinformatics Database and QIAGEN CLC Assembly Cell will be made available. 32 bit versions of these are discontinued.

Advance notice

The Probabilistic Variant Detection (legacy) and Quality-based Variant Detection (legacy) tools are scheduled to be removed from the Server and Workbench in spring, 2017.

Improvements

• New reference data added: Ensembl v83 and v84 are now available via the Reference Data Manager.
• Tutorial reference data sets have been added and others modified, in order to allow easy and quick run-through of all Biomedical Genomics Workbench tutorials.
• GATK reference data sets have been made available for use in the GATK Integration plugin.

Bug fixes

• Fixed an issue with the RNA-Seq Analysis tool that could arise when the “Genomes annotated with genes and transcripts” option was chosen: If two or more genes had the same name, and a transcript could be assigned to each from the mRNA track, then the value in the “Transcripts annotated” column in the GE track and in the TE track was 0. Furthermore, all counts for such genes were reported as zero, even when there were reads mapping to them.
• Fixed an issue where it was not possible to manage reference data “On Server”, even though the workbench was in fact connected to a server with reference data on it.
• Fixed an issue that arose when executing workflows with multiple inputs in batch, where changes to pre-defined, fixed inputs specified during the launch process were not applied.
• Fixed an exception in the Read Mapping Editor that could arise when working with mappings to circular references.
• Fixed an issue where sorting a folder while saving into it could trigger an error.
• Fixed a bug in the batch mode dialog that would lead to an error when problems related to the underlying file or data location were encountered.
• Fixed broken help link in Ion Torrent importer.

Advanced notice

• From the autumn 2016 release, only 64 bit versions of the QIAGEN CLC Genomics Server, QIAGEN CLC Genomics Workbench, Biomedical Genomics Workbench, CLC Bioinformatics Database and QIAGEN CLC Assembly Cell will be made available. 32 bit versions of these will be discontinued from that time.
• The Probabilistic Variant Detection (legacy) and Quality-based Variant Detection (legacy) tools will be removed from the Server and Workbenches in early 2017.

New tools

Import Metadata – basic and easy metadata import. This tool supplements the tools available in the Metadata Table Editor .

Improvements

Workflow

• Workflow inputs   can now be ordered via the Workflow Editor, affecting the order that input information is requested when setting up a Workflow run.
• Workflows with multiple input elements, where all input elements will be changed per batch, can now launched in batch by right-clicking on the installed workflow name and choosing the option “Run in Batch Mode…”.
• Tools in a Worfklow that have been renamed will have both the new tool name and the original tool name displayed in the Workflow Configuration editor.
• Made it possible to select files located on a CLC Server when using exporters in the Workflow Configuration editor of a CLC Workbench.

RNA-seq

• The RNA-Seq Analysis tool now computes Transcripts Per Million (TPM) values, which appear as an additional column in expression tracks.
• Faster analysis of multiple samples in the RNA-Seq Analysis tool due to caching of reference index files.
• Performance improvements for Expression Tracks in RNA-Seq .
• Expression track table views now have two new buttons for selecting or copying genes/transcripts names.
• Expression tracks now contain links to external databases when available.
• Transcript level expression tracks now contain the gene name for each transcript.

Mapping

• Match score can now be specified in the Map Reads to Reference and Map Reads to Contigs tools.
• Map Reads to Reference now outputs an empty read mapping and report when nothing mapped, and empty unmapped reads if everything mapped.
• Fixed threads being leaked in Map Reads to Reference when caching of indexed reference sequences was used.

Track

• The tool Create Mapping Graph can now create a coverage graph over the start positions of reads in a read mapping.
• Improved error messaging when trying to import malformed fasta files into tracks.

Metadata

• The use of partial or exact matching schemes can be chosen when associating data with metadata using the Associate Data Automatically option.
• It is now possible to change the type of a metadata column, even if it already contains values. Conversion is only possible when all existing values in the given column can be converted to the new data type.
• Usability enhancements in the Metadata Table Editor .

General

• Fixed an issue with the VCF-exporter resulting in inconsistent information being output to the exported VCF. The metadata field “##reference” field now contains a human readable string-representation identifying the reference genome the exported variants are based on. The metadata field “##fileOrigin” was added to contain a human readable string-representation identifing the exported variant track.
• The 3D Protein Structure Database has been updated. Please use the Download 3D Protein Structure Database  tool to work with the latest version.
• Improvements to the way Ensembl IDs  are parsed to links in tables: stable Ensembl IDs are now correctly parsed to links for all Ensembl-supported organisms (Ensembl release 83).
• Substantial speed improvements to BAM export .
• The options for saving the output from “batch jobs ” have been improved. Outputs can now be saved into a specified single folder in addition to the other established save options.
• All Excel sheets in a document are now imported and each sheet has a table created for its contents.
• The CSV, HTML and Excel table/tabular exporter now use “Inf” and “NaN” values to replace the ambiguous “?”.
• In the wizard for exporting a table in CSV format, when not exporting all columns, it is now possible to cancel or go back to the previous step while selected columns are loading.
• SAM records with CIGAR strings with no aligned residues can now be handled when importing SAM/BAM files
• An option has been added to allow the same print settings to be applied to all reports being exported to pdf format in a given export run.
• GFF Track Import now supports spaces in annotation names
• The “Manage Resources” tab has been removed from the the Plugin Manager.

Changes

Workflow

• The Create Scatter Plot tool is now Workflow enabled.
• The Create MA Plot tool is now Workflow enabled.

General

• The naming rules for the outputs of several tools have been changed to align with those applied by most other tools. The tools affected by these changes are: Local Realignment, Low Frequency Variant Detection , Fixed Ploidy Variant Detection, Basic Variant Detection as well as the legacy variant detection tools: Probabilistic Variant Detection and Quality-based Variant Detection .
• The BaseQRankSum value for variants is now negative to indicate that the qualities for the variant is below those for the reference allele. The BaseQRankSum is now calculated as a positive value when the qualities for the variant are above those for the reference allele.
• Export to clc format now truncates very long filenames.
• Versions of individual tools are now reported in the history of output objects.
• The default view of the expression tracks has been changed: the table view opens first by default, and some columns are hidden, to simplify the view.
• For the NGS importers, the paired reads minimum and maximum default interval has been updated to 1 – 1000.
• Plots without any data points will now be skipped when rendering reports.
• The annotations “Known variation”, “Validated by other experiment”, “Ancestral allele”, and “Phenotype related”, created by variant track import are not used and have therefore been removed from variant tracks.
• The QC for Read Mapping report statistics table is now showing previously missing values for regions with partial coverage. For fully covered regions these values cannot be calculated, and empty strings are replaced with coverage minimum, average and standard deviation. Numeric sorting is retained by inserting NaN values instead of empty strings, where calculations cannot be made.
• RPM package installers for Linux are no longer available.
• Associate Data Automatically accepts data elements (not folders) as input.
• The ‘Database Fields’ label shown in the ‘Show Element Info ‘ view has been renamed to ‘ Local Attribute Fields’.
• The “Metadata Role Override” parameter that was visible when creating Workflows has been removed.
• The user can no longer uncheck “export all columns” for input objects that do not support this option. This applies to command line functionality as well, where the user will now receive an error if this is attempted.

Retirements

• The Identify Candidate Variants (legacy) tool has been retired.

Bug fixes

• Fixed an error when running merge overlapping pairs on extremely short reads.
• BED Export: when exporting block list entries (such as connected exons from mRNA tracks), positions were absolute, but are now relative to the ‘chromStart’ position.
• A change was made to the rare disease ready-to-use workflows so that the variant contribution from both the mother and the father is now shown in the compound heterozygous variant table. Previously, only the variant from one of the patients was shown in the table.
• In the Ready-to-Use Workflow “Identify Somatic Variants form tumor normal pair (TAS)”, “Auto-detect paired distances” was selected in the normal sample and not the tumor sample. This has been aligned and the parameter is now deselected for both the tumor and the normal sample.
• Fixed a frame offset bug that occurred when translating reverse complemented CDS regions into protein sequences.
• In heat maps it is now possible again to show colors legend to the left and right of the heat map.
• Fixed an issue where the Export Workflow wizard had “ignore” as default for data reference instead of “reference” or “bundle”.
• Fixed an off-by-one error for read start positions in the ‘Find Broken Pair Mates…’ output table.
• Fixed a bug that caused the Excel importer to use column names as cell values of the first row.
• Fixed an issue where open tabs were not correctly ordered after splitting view horizontally or vertically using the View menu or keyboard shortcuts.
• Fixed an issue where an error was reported if the local realignment tool detected an insertion followed by a deletion in the original mapping. Such positions are now ignored.
• Fixed an issue where Workflows were not able to remove intermediate data from permission enabled locations unless the top folder was writable.
• Fixed a bug that prevented the output from certain tools to be used as input in the “References” channel of the Map Reads to Reference tool when used in workflows.
• Fixed an issue where the “Show results”option in the Processes tab would lead to an error if the results dataset was very large.
• Fixed an issue so that double clicking on clc:// urls on Mac OS X now opens the data element in a view in an installed CLC Workbench.
• Fixed in an issue where upgrading a workbench could cause the Download Reference Genome Data tool to fail the first time it was used.
• Fixed an issue where an error arose when renewing a borrowed network license.
• Fixed a bug that led to the creation of an empty folder for each excluded batch unit.
• Fixed a bug that  led to the inclusion of the number of excluded batch units in the count of the total number of batch units to be processed.
• In the ready-to-use workflow Identify Rare Disease Causing Mutations in Family of Four (WES), the read mapping output track for the sibling was named “Read Mapping Father”, this has been corrected.
• Added missing percentage signs for identities and gaps in Blast text exports.
• A Workbench Data Location pointing at a file on the system instead of a folder will now appear as unavailable in the Workbench Navigation area instead of throwing an error.
• When the InDels and Structural Variants tool is added to the workflow the “P-value Threshold” parameter did not show up in the Select settings wizard step under “Significance of unaligned ends breakpoints”. This has been fixed.
• Fixed a bug where it was possible to type non-number characters into a number field when starting up a job in the Workbench.
• An error was previously thrown when encountering blank annotation-values. Blank values are now ignored.
• Fixed an error that could appear when moving the mouse over annotations in a sequence annotation table.
• Fixed an issue with Open Copy of Workflow so it now works on all workspaces rather than just the first workspace.
• Fix an issue that could lead to an error when a job status description changed while a full description was being generated.
• Fixed an issue with handling dates when importing metadata from Excel format files using the Metadata Table Editor.
• When using two outputs from the same tool as input in a Genome Browser View, it was not possible to discriminate between the two inputs when changing the order of the tracks in the Genome Browser View as they had identical names. This has been fixed.
• Fixed an issue where, when the option to “Skip these updates” was checked in the plugin update information window, this information was not saved. This led to the same plugin update information being presented after each Workbench restart if the plugins were not updated.
• The “Extract and Count” tool in Small RNA analysis now only accepts sequences and sequence lists. Previously, it incorrectly accepted standalone read mappings or small RNA samples as well.
• Fixed an error that occurred when pressing the Print button in the Help dialog (Mac OS X only).
• Fixed an issue where the text area in error dialogs did not expand vertically when the dialog was expanded.
• Fixed an issue where sub-jobs were not resumed after pausing and resuming a batch process.
• Fixed an issue where the workflow installer creation keyboard shortcut could be used when it should have been disabled.
• Fixed a rare issue that could be triggered by switching editor view with a double click.
• Fixed a bug that was causing missing report text lines.
• A bug was fixed where no BaseQRankSum was calculated for insertions of length 1.

Plugin updates and fixes

All plugins need to be installed in the new Workbench for compatibility reasons.

Changes to freely available plugins

• A new RNA-Seq analysis plugin is now available: Advanced RNA-Seq
• Ingenuity Pathway Analysis: Expanded with a new tool supporting Statistical Comparisons and a Ready-to-Use Workflow for statistical analysis, visualization, and upload to QIAGEN IPA.
• Ingenuity Variant Analysis: Enforce diploid export has been exposed in the wizard and switched on as default option,in the drop-down options for “Analysis pipeline name”, “Personal genome” has been renamed to “Single sample”, and fixed an issue where the IVA plugin failed when it was given a genome with a non-circular MT chromosome.
• QIAGEN GeneRead Panel Analysis Plugin: Adjusted a number of parameter settings in the workflow and moved the workflow to the subfolder “Somatic cancer (TAS)” under “Targeted Amplicon Sequencing”.
• Batch rename: Fixed an issue where a warning was displayed for entries not modified.

Advanced notice

From the autumn 2016 release, only 64 bit versions of the QIAGEN CLC Genomics Server, QIAGEN CLC Genomics Workbench, Biomedical Genomics Workbench, CLC Bioinformatics Database and QIAGEN CLC Assembly Cell will be made available. 32 bit versions of these will be discontinued from that time.

All changes in this release have also been fixed on the Biomedical Genomics Workbench 4.x and 3.5.x lines at time of writing, with the exception of the one release note marked with an asterisk. That issue was fixed for Biomedical Genomics Workbench 4.0 and will be fixed in future in the Biomedical Genomics Workbench 3.5.x line. 

Improvements

• All NCBI server communication is now encrypted (uses HTTPS).
• Updated the URL to use for links to UniProt databases.
• Updated BLAST executables, used in the Link Variant to 3d Protein Structure tool, to be compatible with macOS Sierra. This change only affects Mac users.

Bug fixes

• For the Basic Variant Detection, Low Frequency Variant Detection and Fixed Ploidy Variant Detection tools 
  • Fixed an issue where the count and read count could be reported as marginally higher than they actually were in a small minority of cases. For the affected variants, this could then also result in variant frequencies being reported that were slightly higher than they should have been, in some cases above 100%. Variants affected by this issue are a small subset of variants where the variant affected overlapped another potential variant and where only the affected variant was then reported. This change could lead to a small decrease in the number variants reported compared to earlier versions of the CLC software, due to a variant no longer passing the count or read count filtering constraints. The impact of this change is expected to be low. For example, in our tests, for a particular analysis that reported 250,000 variants, 30 fewer were reported with the same parameters and filters applied after this fix was implemented.
  • Fixed an issue where the coverage of a longer variant that contained another variant was reported for both the longer variant and the contained variant. The coverage for the contained variant is now reported correctly.
  • Fixed a bug where count, read count, and forward- and reverse read count could be incorrect for variants found in overlapping regions of a pair of reads and where the variant was originally identified as being adjacent to one or more other variants.
    
  • Fixed an issue affecting coverage calculation for SNVs without immediately adjacent variants when using paired read data: if the second read of a pair containing the variant did not meet the requirements of the quality filter, neither the first nor second read of that pair contributed to the coverage calculated for the variant.
  • Fixed an issue where for a SNV without immediate neighboring variants, overlapping reads of a pair that had conflicting base calls for that variant position contributed to the values calculated for coverage, read coverage, and read count of that variant.
  • Fixed an issue where the forward and/or reverse count for a longer variant, supported by paired reads with both children having the same direction, could be too low. The forward count and reverse count is now reported correctly.
• For the Identify Known Mutations from Sample Mappings tool:
  • Fixed an issue where reads in a sample mapping were not identified as supporting the presence of a known variant in cases where the first position of the variant region in the mapped read contained a gap.
  • Fixed an issue where a read containing a variant longer than a known variant being tested for was counted as supporting the known variant in cases where the first part of the read’s variant sequence is identical to that of the known variant.
  • Fixed an issue where overlapping reads of a pair having conflicting base calls for a variant position could contribute to the coverage calculated for that variant.
• Fixed an issue with the InDels and Structural Variants tool where an incorrect insertion could be called when the optimal alignment of a read’s unaligned end around the breakpoint included a gap in the insertion sequence.
•  Fixed a rare issue where some annotations could, but did not necessarily, go missing on sequences with greater than 1000 annotations of a given type on that sequence before the deletion and where the right-click context menu option “Delete selection” was used.  
• Fixed a bug in the Manage Enzymes wizard that prevented a user from cancelling the action if “Save as new enzyme list” was enabled.
• Fixed a problem with the identification of the correct sequence types from MLST schemes in cases where the schemes contained blank characters. This issue affected workbenches with QIAGEN CLC Microbial Genomics Module installed.*
  

Bug fixes

• Fixed an issue with the RNA-Seq Analysis tool that could arise when the “Genomes annotated with genes and transcripts” option was chosen: If two or more genes had the same name, and a transcript could be assigned to each from the mRNA track, then the value in the “Transcripts annotated” column in the GE track and in the TE track was 0. Furthermore, all counts for such genes were reported as zero, even when there were reads mapping to them.
• Fixed an issue where it was not possible to manage reference data “On Server”, even though the workbench was in fact connected to a server with reference data on it
• Fixed problem that occurred when using the CNV tool in a workflow and choosing to output gene-level CNV track.

Advanced notice

• From the autumn 2016 release, only 64 bit versions of the QIAGEN CLC Genomics Server, QIAGEN CLC Genomics Workbench, Biomedical Genomics Workbench, CLC Bioinformatics Database and QIAGEN CLC Assembly Cell will be made available. 32 bit versions of these will be discontinued from that time.
• The Probabilistic Variant Detection (legacy) and Quality-based Variant Detection (legacy) tools will be removed from the Workbench in early 2017.

Bug fixes

• Fixed an issue with handling dates when importing metadata from Excel format files using the Metadata Table Editor.
• QC for Read Mapping tool: the Detailed mapping report statistics table is now showing previously missing values for regions with partial coverage. For fully covered regions these values cannot be calculated, and empty strings are replaced with coverage minimum, average and standard deviation. Numeric sorting is retained by inserting NaN values instead of empty strings, where calculations cannot be made.
• Bug fixed causing missing report text lines.
• Fixed an error when running Merge Overlapping Pairs on extremely short reads.
• Added support for a SAM record to be able to declare a CIGAR string, which leaves no residues left for aligning when importing SAM/BAM files.
• Fixed a frame offset bug that occurred when translating reverse complemented CDS regions into protein sequences.
• Fixed an issue where Workflows were not able to remove intermediate data from permission enabled locations unless the top folder was writable.
• The “Metadata Role Override” parameter that was visible when creating Workflows has been removed.
• Fixed threads being leaked in Map Reads to Reference when caching of indexed reference sequences was used.
• Fixed an issue where Map Reads to Reference would under rarely occurring circumstances report a persistence error.
• When the InDels and Structural Variants tool is added to the workflow the “P-value Threshold” parameter did not show up in the Select settings wizard step under “Significance of unaligned ends breakpoints”. This has been fixed.
• BED Export: when exporting block list entries (such as connected exons from mRNA tracks), positions were absolute. This has been fixed: positions are now relative to the ‘chromStart’ position.
• In cases where reference data download failed, half-downloaded references were left in the temp folder. This has been changed so that temp folders are now automatically cleaned up.
• Fixed a bug, where the reference data manager fails to open when the CLC_References folder is located on a resource (e.g. an external disk) currently not available (for example the disk might be unplugged/disconnected).
• Fixed an issue with renewing a borrowed license.

Bug fixes

• Fixed a bug that prevented concurrent download of multiple versions of the same reference data element.
• Fixed a bug where cancelling a download could lead to an incorrect download status for a Reference Data Set.
• Fixed bug that could result in an error message when collapsing the Reference Data Sets section of the Reference Data Management.
• Fixed a reference to mouse conservation score which should have been rat conservation score in the workflow “Compare Variants in DNA and RNA (R)“.
• Enabled tooltips for all parameters when configuring and executing workflows.
• Fixed a bug in ready-to-use workflows that use 1000 Genomes reference data. In some cases the default selection included other reference data types than the 1000 Genomes reference data.
• Fixed a bug where cancelling a download could lead to an incorrect download status for a Reference Data Set.
• Fixed a bug where a download of reference data that failed would result in temporary files being left in the temp folder. These are now removed.
• Fixed problem that occurred when the Reference Data Manager dialog is opened before the information about the reference data has been retrieved from the reference data server.
• Fixed an error happening when a Workbench Data Location was pointing at a file on the system instead of a folder. It will now appear as unavailable in the Workbench Navigation area.
• Fixed an issue leading to an error during VCF export where the data involved had originally been imported from VCF files and the values in the QUAL field were integers.
• Export of floating-point (decimal) numbers to VCF format were previously dependent on the specified locale. This has been fixed so that the decimal separator now always is a point.
• Fixed a bug where doing automatic association using a metadata table stored on a CLC Server would fail.
• Automatic association of metadata now handles association based on the a prefix of data names rather and exact matching to the whole data name.
• A metadata table no longer needs a key column for its rows to be manually associated with data elements.
• An option to override metadata roles previously visible in the configuration of Workflow outputs was removed.
• Fixed issue that caused locked parameters to be overwritten by a previously entered value, during workflow execution.
• Fixed a bug that prevented metadata manual information to be accessed from within the Workbench.
• The login process from a Workbench to a CLC Server must now complete before opening a clc url will begin.
• Fix a problem on Macs where the Workbench was not recognized as a custom protocol handler for clc:// urls.
• Resolved a rare occurring exception that could be triggered by switching editor view with a double click.
• Fixed a problem where after import of a large volume of data, using the “Show results” option in the process tab resulted in an error.
• Fixed an error that occurred when pressing the Print button in the Help dialog (Mac OS X only).

Improvements

• The rare disease hereditary disease workflows have been expanded and now also outputs recessive variants (heterozygous variants from both parents that are homozygous in the child).
• New reference data included: Ensembl version 81 has been added to the Reference Data Manager.
• Reference data found under “Data Management” have been restructured so that tutorial data sets and elements now have their own main categories.
• Information about reference data versions have been added to each of the reference data sets to make it easier to see which reference data versions have been included in a reference data set.
• When running the “Identify Causal Inherited Mutations…” workflows, information about “Count” and “Coverage” is now available in the “Putative Causal Variants Proband” variant table.
• Removed the tool “Remove variants outside targeted regions” from the ‘Identify Variants WES-HD and TAS-HD” workflows. This has no impact on the generated results as this step is already included in the Fixed Ploidy Variant Detection tool.
• The ready-to-use workflows “Identify Rare Disease Causing Mutations…”  no longer give compound heterozygous variant and gene contributions from the parents but now outputs “Recessive Variants”, “Gene List with Recessive Variants” and “Recessive Variants (Amino Acids)”.
• In the ready-to-use workflows “Identify Variants (WGS)”, “Identify Known Variants in One Sample (WGS)”, “Identify Somatic Variants from Tumor Normal Pair (WGS)”, and “Identify Variants (WGS-HD)”, the option to “Restrict calling to target regions” has been removed in the step “InDels and Structural Variants” as this is not relevant for WGS workflows.
• When applying a reference data set that has not yet been downloaded, a dialog now appears with information that workflows cannot be run before the data used by the workflow has been downloaded.
• In the output from the Trio Analysis tool, the inheritance option “Accumulative” has been renamed to “Recessive”.
• When doing automatic association of metadata, the log now shows which metadata rows were not associated with any data.

New features and improvements

• The BxWB now supports analysis of hereditary and rare diseases. A range of new ready-to-use workflows have been added to the toolbox, specifically designed to analyze hereditary diseases and to identify de novo mutations and compound heterozygous mutations.
• The Reference Data Manager has been redesigned and expanded with the human hg38 reference sequence as well as mouse and rat reference data.
• New ready-to-use workflows targeting mouse and rat sequencing data have been added in the Whole Transcriptome Sequencing category.
• New tool: Filter Based on Overlap. Allows filtering based on overlapping annotations.
• The tools “Create Filter Criteria” and “Identify Candidate Variants” have been merged into one tool: Identify Candidate Variants. The two original tools have been moved to the Legacy Tools in the Toolbox.
• When a track list is opened, the first variant track found is opened in table view in a split view. When a variant is selected in a table view, the track view zooms to selection.
• Batching on selected elements is now possible: it used to be restricted to selected folders.
• Fixed an issue with the Map Reads to Reference tool that could be extremely slow when included in workflows with multiple inputs.
• The performance of the “Link Variants to 3D Structure” tool has been significantly improved when running on a grid or on a remote server.
• Improved memory management when handling large report elements.
• Quality scores ( QUAL ) are now calculated and added as annotations for variants. These values are included in VCF exports.
• The Hierarchical Clustering of Samples tool can now be executed as part of a workflow and can be executed on a QIAGEN CLC Genomics Server.
• Improved use of multiple cores when running the QC for Read Mapping tool.
• Improved use of multiple cores in the InDels and Structural Variants tool.
• The QC for Sequencing Reads report now contains the total number of reads in the summary.
• The fastq exporter can now export sequences up to 500Kbp. The limit used to be 32Kbp.
• A cloning editor and a gel view have been added to the View tools of a cloning experiment.
• Annotation with COSMIC database has been removed from ready-to-use workflows.
• Numbers are no longer appended to the names of Workflow elements when creating a copy of a Workflow using “Open Copy of Workflow”.
• Metadata Management. Keep track of input files and import meta information for your samples.

Changes

Bug fixes

• Fixed a SOLiD NGS importer bug where import of very low quality, colorspace-encoded, paired-end sequence reads in fastq format could lead to paired sequence lists where the wrong reads were marked as pairs .
• The Add Information from Overlapping Genes tool no longer accepts incorrect types of input objects.
• Fixed bug in the variant callers that happened for certain genomes when using masking tracks.
• Fixed an issue whereby “Create Box Plot” and “Principal Component Analysis” could sometimes be run with illegal arguments, leading to an error message.
• Fixed automatically generated link to COSMIC website, which previously led to retired page.
• Fixed an issue where some filtering operations, such as “doesn’t contain” did not act correctly when filtering table cells that contained multiple pieces of information.
• Fixed an issue where annotations that spanned the ends of a circular sequence would be incorrectly placed in the Circular Sequence View.
• Fixed a bug that caused the workbench to freeze if certain sequences were displayed in circular view with radial rendering of labels.
• Fixed an issue with zoomFixed an issue where one could not zoom in after zooming out fully on very large workflows.ing out fully on very large workflows.
• Fixed an issue that prevented a root folder on Windows drives from being used as a File Location.
• Fixed an issue where updating an existing installation on Windows would result in the .vmoptions file being deleted, which makes the Workbench run with the default Java configuration.
• Fixed exported reports having the wrong author in certain situations.
• The list of Illumina adapters sequences has been removed from the Workbench.

Bug fixes

• Fixed a read mapper bug that caused some reads to be incorrectly reported as unmapped when global alignment was selected.
• Fixed a SOLiD NGS importer bug where import of very low quality, colorspace encoded paired-end sequence reads in fastq format could lead to paired sequence lists where the wrong reads area marked as pairs.
• Fixed an issue with the sort order for paired reads in SAM/BAM exports in high coverage regions.
• Fixed a rare occurring issue where the Workbench would display an error message when installing a 3rd party licensed plugin.
• Fixed an issue where an error would arise in some view types when a region of a sequence had been selected and then the “Zoom to selection” tool was used.
• Fixed an issue where the Local Realignment tool when run with RNA-seq mapping could occasionally report a match that did not meet internal requirements as a valid match. This had a downstream effect when variant calling tools were run, and then failed upon encountering such a position. This issue has also been addressed in this release.
• Fixed an issue where the Basic Variant Detection, Fixed Ploidy Variant Detection and Low Frequency Variant Detection tools would stop with an error when encountering a place in a read mapping containing a match that did not meet internal requirements of a valid match.
• Fixed an issue where an error would arise when using the Design Primers editor and clicking on an annotation on the sequence.
• In case of very low sample coverage, the Copy Number Variant Detection algorithm will now terminate the analysis early and an explanation is given in the reports.
• Fixed a bug that caused the mapper to enter an infinite loop if a reference of length 0 was used.
• Fixed a rare bug that sometimes made the read mapper halt prematurely when several seeds were identified at the same reference position.

Improvements

• The Illumina import now shows the file name on top of the process bar during the import.
• In the “SAM/BAM Mapping Files” import tool, any inconsistencies between the reference sequences in the BAM file and the reference sequences in the CLC software that are provided for the import of the BAM file are now highlighted in red in the “References in files” table.

Bug fixes

• The InDels and Structural Variants tool can now better detect variants when using target regions near the edge of the regions.
• The workflow Identify Somatic Variants from Tumor Normal Pair (WES) was missing an output variant track. This has now been fixed.
• The Basic Variant Detection tool could fail for certain input using default parameters, except for “Minimum Coverage” set to 3.
• The relative read direction filter in the Low Frequency Variant Detection tool is less strict on variants with large coverage.
• Fixed bug in which Local Realignment could produce an illegal read mapping. This only happened for RNA-data.
• The variant caller will now fail if it encounters an illegal RNA read mapping. If the variant caller fails with such a message, and if it was run on locally realigned data, then we suggest to re-run the local realignment to avoid the error.
• Added a work around to a java issue that occasionally resulted in the Workbench displaying an uninformative error and requiring a restart to continue working.
• Fixed a rare error in the QC for Targeted Sequencing tool. The error resulted in a failure when a target region only included the very last nucleotide of a chromosome.
• The variant callers could enter an infinite loop for certain inputs. This fix adds a check that was unfortunately missing in previous fix for this problem.
• Fix of potential wrong file being saved when editing a file found via the Local Search Editor.
• Fixed text inside variant boxes in the track view sometimes having a small font size.
• Plots inside reports are now shown with their saved side panel settings.
• Fixed saving different line colors in plots through the side panel.
• Side panel option to show legends for a plot with more than 10 samples is now enabled.
• Fixed an issue that led to an error when rendering plots for empty data sets.
• When installing a workflow with bundled data, it is no longer possible to select a read-only folder for storing the data.
• Transcriptomics experiment and sample tables can now be sorted, even with large numbers of rows.
• Fixed wrong display of “Supported format” when exporting elements from either the Folder Editor or the Local Search Editor.
• Fixed an issue where the “Empty Recycle Bin” option was sometimes incorrectly unavailable.

Biomedical Genomics Workbench is a new product from QIAGEN.

Besides the existing functionalities in CLC Cancer Research Workbench, the following was added, improved or fixed:

Major highlights

• The Copy Number Variant (CNV) Detection tool is included as an integrated tool in the Biomedical Research Workbench 2.1, and can be found in the ‘Resequencing’ toolbox. The CNV detection tool has existed as a beta plugin to the Cancer Research Workbench since last year, and moves out of beta status with this release. This update to the tool also includes several improvements and small bugfixes.
• New tool: Proportion-based Statistical Analysis has been added to identify differential expressed genes. The proportions-based tests are applicable in situations where your data samples consists of counts of a number of ‘types’ of data. This could e.g. be in a study where gene expression levels are measured by RNA-Seq or tag profiling.
• To help interpret whether a variant is likely pathogenic due to disruption of interfaces in a multi-subunit complex, the tool “Link Variants to 3D Protein Structure” now provides 3D visualizations of variants in a biomolecule context.
• The filtering option in the Extract Differentially Expressed Genes tool only considered the predicted fold-changes in the positive direction, so features that were reduced in expression were filtered out. This has now been fixed. The change also affects the workflow: “Identify and Annotate Differentially Expressed Genes and Pathways“, as the tool is also included in this workflow.
• Improved visualization and opening of results: The Genome Browser opens with a linked variant table.

Minor highlights

• Particular annotation types (columns) can now be specified for export in Excel, HTML and tab delimited formats.
• Increased the performance for gzip export.
• Added column to output of “Annotate and Merge Counts” in the “Small RNA Analysis” folder indicating 3′ or 5′ direction when using “grouping on mature” parameter.
• Transcriptomics experiment and sample tables can now be sorted, even with large numbers of rows.
• Improved how nucleotides are drawn inside variant track boxes, making letters smaller when zooming out.

Bug fixes

• Fixed an error that in rare cases would result in a division by zero error message when selecting rows in the Annotation Table view.
• Fixed an error that made it impossible to add an annotation via the Annotation Table view, if the table is empty.
• Fixed rare problem where a track list of reads tracks and graph tracks would break.
• Fixed bug where a left-click quickly followed by right-click was interpreted as double-click on OS X (in: the persistence search result list, in the toolbox tree, and in the workflow editor).
• Fixed an error affecting the “Cut Sequence Before/After Selection” tool in the Cloning editor.
• Fixed the SOLiD NGS importer to correctly import basespace encoded sequences in fastq files. It is still assumed that sequences originate from colorspace.
• It is now possible to filter tables based on content in the ‘Link to 3D Protein Structure’ column.
• Fixed an error that occurred when running the QC for Target Sequencing and requesting quality analysis reporting.
• Fixed an error that prevented the import of adapters from csv format.
• Fixed a rare error that caused the Amino Acid Change tool to crash if a CDS feature was less than 3 bases long.
• Resized Manage Reference Data dialog. Previously some of the text was hidden in the default size.
• Fixed a bug in the probabilistic variant caller that caused it to fail for certain input.

Please note: Biomedical Genomics Workbench was formally known as CLC Cancer Research Workbench

CLC Cancer Research Workbench 2.0

• ChIP-seq data analysis is now available. The tools for ChIP-seq analysis are found in the toolbox under “Epigenomics Analysis”.
• A highly sensitive Copy Number Variant Detection tool is available for targeted amplicon and exome sequencing data via the Plugin Manager.
• A new display of mutations at the amino acid level is available in the Genome Browser View.
• It is now possible to find out why a variant is pathogenic or if a variant could be pathogenic. This can be done by visualizing the effect of the mutation on the protein 3D structure using the tool Link Variants to 3D Protein Structure.

New tools

• Merge Read Mappings. This tool can be used to merge two read mappings if you have performed two mappings with the same reference sequences.
• Extract Reads Based on Overlap. This tool can be used to extract subsets of reads based on annotations.
• On Gaussian Data. The Gaussian based test (t-test and Anova) tool has been included.
• Cloning tools. A folder has been added to the toolbox with tools for cloning and restriction site analysis.
• ChIP-Seq Analysis. The tool for analysis of ChIP sequencing experiments is found under “Epigenomics Analysis”. The tool identifies genomic regions with significantly enriched read coverage and a read distribution with a characteristic shape.
• Annotate with Nearby Gene Information. This tool is part of the “Epigenomics Analysis” and can be used to create a copy of the annotation track used as input and add information about nearby genes.

• The Map Reads to Reference tool now supports both linear gap cost parameters and affine gap cost parameters. The addition of affine gap cost support allows you to get more accurate results for reads with stretches of insertions or deletions.
• The read mapper used in the RNA-Seq Analysis tool has been upgraded to use the affine gap cost read mapper described above. This upgrade enables you to run RNA-seq analysis with as little as 6 GB RAM and at the same time improves your end results. See our blog post for a further review.
• The tool Add Information about Amino Acid Changes has been expanded with an extra output that makes it possible to visualize amino acid changes in track format. The amino acid color schemes can be changed in the Side Panel under “Track layout” and “Amino acids track”.

• Chromosome bands/cytogenetic ideograms can now be downloaded to the Workbench via the Data Management. The ideogram can be added to Genome Browser Views to get a better overview of the data.

• Link Variants to 3D Protein Structure makes it possible to visualize amino acid changes on 3D protein structures. After running the tool on a variant table, variants can be visualized on 3D structures. 3D models are automatically built using structural templates from the PDB. The new tool can be found under ‘Tools | Add Information to Variants | Link Variants to 3D Protein Structure’.
• The “Identify Known Mutations from Sample Mappings” tool now supports ignoring broken reads and multi-match hits. The change in behavior is that conflicting broken paired reads now contribute to the overall “coverage” of the variant, but are still ignored in the counts.
• A 3D Molecule Viewer is now available for visualization of protein, RNA, DNA, and small molecules.

• Tracks:

  • Consistent output when enriching variant tracks and annotation tracks with extra table columns. Output tracks from these tools now have the same number of added table columns and the columns will always be in the same order. Previously, if an added column had empty values for all variant rows, it would have been removed from the final table, resulting in varying number and relative order of additional columns when multiple samples were processed with the same tools/workflows. All columns are retained now, facilitating downstream processing of exported tables, and providing immediate visual reference as to which enrichment/annotation tools have been applied, even if they did not produce any results for a particular sample.
  • Tables for variant tracks and annotation tracks can now sort and filter columns with cells containing multiple numbers.
  • Improved the track viewer for variant tracks to show the sequence alteration on the rendered variant.
  • Improved performance of creating variant tracks and annotation tracks.
  • Graph tracks now show negative values filled upwards to y=0 (as expected).
  • It is now possible to extract sequences from tracks. The sequence of interest can be selected by dragging the mouse over the region of interest followed by a right click on the reads and a click on Extract from selection.
    

     Workflows:

    • An extra optional output called “Create coverage graph“, that shows the coverage in each position of the targets, has been added to the tool QC for Target Sequencing.
    • When installing a workflow in the workflow manager, the newly installed workflow is automatically selected.
    • When creating a new workflow installer, it is now possible to include reference data without bundling the reference data with the workflow. Instead the reference data can be included by pointing at the CLC_References directory.
    • The “Run” button in the workflow editor does not require a saved workflow anymore to be enabled.
    • In the execution wizard of a workflow the “Reset to default” button is now active.
    • All icons in the workflow editor are now on the left side.
    • Introduction of snippets: Parts of workflows can now be saved as a snippet and reused in other workflows.
    • Installed workflows: It is now possible to create a copy of an installed workflow and open the copy in the view area by clicking once and then right-clicking on the installed workflow in the toolbox. This brings up the option “Open Copy of Workflow“.

• MA plots, scatter plots and histograms can now accept expression tracks as input
• Increased decimals for numbers when exporting table to CSV, tab delimited text, and Excel.
• Improved reporting of errors related to low disk space.
• Batching: Processes tab and analysis execution logs now display batch names in addition to analysis names for enhanced clarity.
• The External Application Client Plugin is now available directly from the Workbench Plugin Manager.
• Multiple target region tracks for the “Indels and Structural variants” can now be specified.

Bug fixes

• Fixed an error resulting in billions of reads being silently dropped when producing large read mappings against large counts of reference sequences. The error involves a read count overflow and the dropping of at least 2 billion reads per failure instance.
• Fixed display problem in read mappings showing too many hidden insertions (as vertical black lines) in certain overlapping paired reads.
• Fixed problem with links and text in tables that were being cut off when succeeding a link.
• The tool Identify Graph Threshold Areas can now use negative values to define its threshold.

• Workflows:

  • In the workflow editor the “Reset to default” now always reverts to the right names.
  • In the workflow editor the validation is now correctly triggered when changing the configuration of an input element.
  • The workflow editor can now open workflows in which the graphical view of the workflow is corrupt.
  • Fixed an exception which could occur during workflow migration.
  • Data with the same name can now be bundled multiple times in a workflow installer.
  • Previously when a plugin contained custom actions and a workflow, the workflow could not be installed. This has been fixed.
  • Fixed problem with unlocked output names that previously could not be configured during execution of a workflow.
  • A workflow with configured data from a server is now automatically validated when connected to the server (when opened in the editor). Previously the workflow had to be closed and reopened first.
  • The original workflow file included in a workflow installer can now be exported directly without having to restart the workbench in advance.”
• A problem with saved table settings that sometimes did not work has been fixed. The bug fix includes a more robust/generic way of saving table settings with different columns. To fix this problem, existing saved table settings should first be loaded on an object where it works (i.e. has the same columns as when it was saved); and then the table settings should be saved with the old name to overwrite the settings.
• Fixed an error that could cause batch processing to open all results rather than saving them.
• Fixed problem with import of BED files using external applications.
• SAM/BAM import will no longer fail for alignments with POS = 0, but instead import them as though they were unmapped.
  Fixed problem going back in the wizard for the “Find Binding Site and Create Fragments” tool.
• Fixed error occurring when removing an unsaved reads track from a track list.
• Fixed error when showing protein translations of annotations shorter than 3 bases.
• Fixed a bug in the Mapping Coverage exporter.
• Fixed reads tracks reads-amount indicators (the numbers between the reads track and the box with the tracks name and number of reads) that sometimes wrongly said 0.
• Small RNA Analysis -> Annotate and Merge Counts: When you choose to create a “grouped on mature” output, the small RNAs are grouped by both the 5’ and the 3’ mature sequences separately in the “grouped on mature” output. The column heading has therefore been changed to show “Mature” instead of “Mature 5′”.
• When using the RNA-Seq Analysis tool with the “One reference sequence per transcript” option, the “Maximum number of hits for a read” option was sometimes not taken into account for multi-hit reads. This has been fixed.
• Two problems with the F1 help has been fixed; 1) When pressing F1 in a workflow tool wizard more than one help window appeared, and 2) Fixed problems showing help by pressing the F1 key in tool wizards.
• Add Information about Amino Acid Change tool: In cases where an mRNA track does not overlap all annotations in the CDS track, “Coding Region Changes” were not added to variants that overlap a CDS but not an mRNA annotation. This has been fixed.
• Variant callers and the “Add Information about Amino Acid Changes” tool: In cases where variants overlapping an mRNA annotation but not a CDS annotation,”Coding Region Changes” were not added to variants overlapping an mRNA annotation but not a CDS annotation. This has been fixed.
• Fixed an error that in rare cases would prevent creation of tracks from references sequences.
• Hypergeometric test on annotations: Fixed a rare error that occurred for some datasets containing annotations of the form: ‘1234 // abc’.
• Fixed a bug for color space reads in the RNA-Seq Analysis tool that caused only exon-exon matches to be reported.
• An issue where an XSQ file containing both base space and color space versions of the same reads were incorrectly imported into the same sequence list, resulting in each read appearing twice has been addressed.
• Fixed an issue with mapping of paired-end reads, where these were erroneously reported as broken pairs when the fragment size derived from the alignments of the two ends of the pair was longer than reference sequence.
• Fixed issue where when the options  “Keep only selected annotations” in the “Remove information from variants” tool was selected, the Coverage, Count and Frequency columns did not appear in the output.

CLC Cancer Research Workbench 1.5.6

Release date: August 18, 2015

• Fixed a read mapper bug that caused some reads to be incorrectly reported as unmapped when global alignment was selected.
• Fixed a bug that caused the mapper to enter an infinite loop if a reference of length 0 was used.
• Fixed a rare bug that sometimes made the read mapper halt prematurely when several seeds were identified at the same reference position.
• Fixed a SOLiD NGS importer bug where import of very low quality, colorspace encoded paired-end sequence reads in fastq format could lead to paired sequence lists where the wrong reads area marked as pairs.
• Fixed sort order for paired reads in SAM/BAM exports in high coverage regions.
• The analysis/workflow execution system now handles search algorithms specially so that search results are not modified. This eliminates a host of concurrency issues.
• Minor improvements in persistence.

CLC Cancer Research Workbench 1.5.5

Release date: June 18, 2015

Bug fixes

• Fixed an issue introduced by a fix in the Cancer Research Workbench 1.5.4 restricting the use of the QC for Targeted Sequencing tool on tracks containing a larger number of nucleotides (>2147483647 bp) than could be supported for coverage table output. This check is no longer applied if coverage table output is not requested.
• Fixed bug in which Local Realignment could produce an illegal read mapping. This only happened for RNA-data.
• The variant caller will now fail if it encounters an illegal RNA read mapping. If the variant caller fails with such a message, and if it was run on locally realigned data, then we suggest to re-run the local realignment to avoid the error.
• Side panel option to show legends for a plot with more than 10 samples is now enabled.
• Fixed saving different line colors in plots through the side panel.
• Plots inside reports are now shown with their saved side panel settings.
• The automated paired distance estimate can no longer exceed the maximum distance accepted by read mapper (100,000 bp).
• Fixed an error that occurred when hovering the mouse cursor over the edge of a read mapping.
•  Read-only folders are no longer offered as potential locations to save data bundled with a Workflow.

CLC Cancer Research Workbench 1.5.4

Release date: April 23, 2015

Bug fixes

• The filtering option in the Extract Differentially Expressed Genes tool only considered the predicted fold-changes in the positive direction, so features that were reduced in expression were filtered out. This has now been fixed. The change also affects the workflow: “Identify and Annotate Differentially Expressed Genes and Pathways”, as the tool is also included in this workflow.
• When using the RNA-Seq Analysis tool with the “One reference sequence per transcript” option, the “Maximum number of hits for a read” option was sometimes not taken into account for multi-hit reads. This has been fixed.
• Fixed an issue with mapping of paired-end reads, where these were erroneously reported as broken pairs when the fragment size derived from the alignments of the two ends of the pair was longer than reference sequence.
• Fixed issue where when the options  “Keep only selected annotations” in the “Remove information from variants” tool was selected, the Coverage, Count and Frequency columns did not appear in the output.
• Fixed a bug in the probabilistic variant caller that caused it to fail for certain input.

CLC Cancer Research Workbench 1.5.3

Release date: February 17, 2015

Bug fixes

• Fixed reads tracks reads-amount indicators (the numbers between the reads track and the box with the tracks name and number of reads) that sometimes wrongly said 0.
• Fixed an error resulting in billions of reads being silently dropped when producing large read mappings against large counts of reference sequences. The error involves a read count overflow and the dropping of at least 2 billion reads per failure instance.
• Small RNA Analysis -> Annotate and Merge Counts: When you choose to create a “grouped on mature” output, the small RNAs are grouped by both the 5’ and the 3’ mature sequences separately in the “grouped on mature” output. The column heading has therefore been changed to show “Mature” instead of “Mature 5′”.
• Two problems with the F1 help has been fixed; 1) When pressing F1 in a workflow tool wizard more than one help window appeared, and 2) Fixed problems showing help by pressing the F1 key in tool wizards.
• Add Information about Amino Acid Changes tool: In cases where an mRNA track does not overlap all annotations in the CDS track, “Coding Region Changes” were not added to variants that overlap a CDS but not an mRNA annotation. This has been fixed.
• The Low Frequency Variant caller could end up in an infinite loop in certain corner cases. This is now fixed.
• Hypergeometric test on annotations: Fixed a rare error that occurred for some datasets containing annotations of the form: ‘1234 // abc’.
• Fixed a bug for color space reads in RNA-Seq Analysis that caused all exon-exon matches to be filtered away.
• Fixed “Export Graphics” default save-as directory.
• Fixed error when removing an unsaved reads track from a Genome Browser View.
• Fixed display problem showing too many hidden insertions in certain overlapping paired reads.
• Fixed a bug in the Mapping Coverage exporter.
• Fixed problem with import of BED files using external applications.
• Fixed a bug for color space reads in RNA-Seq Analysis that caused all exon-exon matches to be filtered away.
• Fixed problem going back in the wizard for the “Find Binding Site and Create Fragments” tool.

CLC Cancer Research Workbench 1.5.2

Release date: November 12, 2014

• On update of the QIAGEN GeneRead Panel analysis plugin, the plugin would not update the workflow it comes with. This has been fixed.

CLC Cancer Research Workbench 1.5.1

Release date: October 28, 2014

New features and improvements

• RNA-Seq Analysis: The ENSEMBL gene id of each gene, where available, has been added as an additional column to the gene expression track output.
• It is now possible to run a workflow without an optional input.

Bug fixes

• The AAC tool did not annotate variants in 3′ UTR with their DNA-level change using the HGVS c.xxx format. This affects any analysis done with Gx 7.5 or earlier based on ENSEMBL CDS tracks from older versons. The AAC analysis should be redone using Gx 7.5.1 for correct annotation. Important: Please also check the description in the CRWB 7.5 release notes of a bug fix in the translation of CDS annotations to protein sequences that was wrong in cases where the reading frame was not +1 or -1 in CDS annotations imported from ENSEMBL.
• A bug has been fixed in the Set Up Experiment tool. Exon-related expression values can now only be selected when present in the individual samples.
• When creating a subset of a paired experiment, the sub-experiment no longer appeared as being paired. This bug has been fixed and sub-experiments created in previous versions should recover the pairing information when accessed with this version of the workbench.
• Fixed problem importing VCF files using the AO and RO genotype field.
• Fixed problem importing certain VCF files.
• Fixed problem with scrolling to the relevant files when selecting objects as parameters in tool wizards.
• Fixed a bug in the Annotate and Merge Counts tool that in rare cases resulted in incorrect sorting and crash.
• Fixed problem with import of read mappings with supplementary alignments. When importing read mappings with supplementary alignments, supplementary alignments are not imported. Previously import of such read mappings caused import errors.
• Fixed rare problem with coverage that could occur in zoomed out reads tracks containing wrapped paired reads.
• Fixed rare error when sorting experiment tables.

CLC Cancer Research Workbench 1.5

Release date: August 28, 2014

New features and improvements

• New tools:
  • It is now possible to analyze RNA-Seq data in CLC Cancer Research Workbench. A new set of ready-to-use workflows have been added to the toolbox under “Ready-to-Use Workflows” -> “Whole Transcriptome Sequencing”:
    • Annotate Variants (WTS).
    • Compare Variants in DNA and RNA.
    • Identify Candidate Variants and Genes from Tumor Normal Pair.
    • Identify Differentially Expressed Genes Across Samples.
    • Identify Variants and Add Expression values.
  • Transcriptomics Analysis tools: A new folder called “Transcriptomics Analysis” has been added to the toolbox under “Tools”. This folder holds a range of different tools that can be used for the analysis of RNA-seq data.
  • Add Fold Changes is a new tool found under “Tools” in the folder “Add Information to Variants”…
  • Identify Differentially Expressed Gene Groups and Pathways is a new tool found under “Tools” in the folder “Identify Candidate Genes”. The tool can be used to investigate candidate differentially expressed genes for a common functional role.

• The ready-to-use workflows that perform read mapping and local realignment now also include detection of larger insertions and deletions.
• NGS Importers are now enabled for workflows.
• A new folder called “Legacy tools” has been added to the toolbox. The “Probabilistic Variant Detection” and the “Quality Based Variant Detection” tools have been moved to this folder as the three variant detectors; Basic Variant Detection, Fixed Ploidy Variant Detection, and Low Frequency Variant Detection have been moved out of beta.
• CLC Cancer Research Workbench can now be connected to a server with a Cancer Research Server Plugin, which is an add-on to the Genomics Server. In addition to the Genomics Server license you need a license for the CLC Cancer Research Server Plugin. This enables cancer related tools on the GxServer.
• The Search Editor is now capable of filtering on “Path”.
• Zoom tools redesign: The “zoom to selection” feature is now also available for sequences, sequence lists, alignments and read mappings.
• The tracks info panel, with track names in the left side of the track, now wraps information instead of showing a scroll bar.
• Saving/applying side-panel settings for tables now works for different tables that share some columns.
• Graph Tracks can now be exported to Wiggle file; the span option is now supported in the Wiggle import.
• SAM/BAM import. It is now possible to choose to ignore unmapped reads when importing SAM/BAM files.
• Fisher’s Exact Test. Added the following options for correction of p-value for multiple testing: Bonferroni correction and False Discovery Rate (FDR).
• Speedup: newly created expression tracks will display the graph faster.
• Copy operations can now be stopped.
• Import of Example Data and imports done through dragging files into the workbench and dropping them in the Navigation Area will no longer block the user interface while executing. Instead, the import happens as a background process that can be monitored and controlled via the Processes tab in the lower left corner.
• CLC workbenches now support high resolution displays such as Apple retina displays of all data shown in the View Area (including tooltips).
• Data Management for References in the ready-to-use workflows has undergone a small change, making it no longer modal, and adding two new statuses for detecting if reference data is inconsistent (e.g. not fully downloaded), or if different workflows use different versions. If you need to delete (suspected inconsistent) data, you can now do that from the Data Management as well. Furthermore, you can now see where new data is available (local and/or server), and it can be downloaded to both locations at the same time.
• Configuring ready-to-use workflows with your own reference data now helps you select data of the right type.
• The Data Management notification to download new references can now be dismissed (until next time something gets updated, at which point you can dismiss it again).
• Advanced filtering on tables now includes the option to filter for a space, comma or semi-colon delimited lists of terms.
• Improved error messages due to low disk space.
• Improved variant callers:
  •  The value that the “Read position filter” operates on is now added as an annotation.
  • Created a column on variants which contains “Forward/reverse read imbalance significance”.
  • The “mark as homopolymer” parameters were removed from the wizard and made into an annotation.
  • A “Maximum frequency” parameter has been added to the “Pyro filter”.
  • Added a parameter to the “Direction and position filters” parameters in the “Noise filters” wizard step.
  • Two new columns that are called ‘Read count’ and “Read coverage” were added to the variant table. These consider “reads” rather than fragments.
  • The way the filters are applied has been changed, so that, in the first iteration they are only applied at half their values, and only after joining are they applied at their full value.

Bug fixes

• Translation of CDS annotations to protein sequences was wrong in cases where the reading frame was not +1 or -1 in CDS annotations imported from ENSEMBL. This error affected the Translate to Protein tool, translation functionality in sequence viewers and their context menus, as well as the Amino Acid Consequences (AAC) variant annotation tool. We highly recommend redoing the AAC analysis for correct variant annotation, as CDS tracks typically are created from ENSEMBL data.
• A bug has been fixed in the Local Realignment tool. The bug materializes in extremely rare cases when applying the variant callers on locally realigned RNA-seq mappings with spliced reads. On these mappings, local realignment could generate invalid spliced reads (after local realignement, you could have spliced reads with segments that overlapped).
• Fixed rare error when sorting experiment tables.

Changes

• The start-up background canvas has been updated with the new RNA-seq analysis options.
• The concepts “Secondary Analysis”, “Tertiary Analysis”, and “Combined secondary and tertiary analysis” have been changed to “Data analysis”, “Interpretation”, and “Data analysis and interpretation”, respectively.

CLC Cancer Research Workbench 1.0.1

Release date: June 16, 2014

New features

• A new plugin for use with QIAGEN GeneRead panels is now available. Go to Help -> Plugins to download.

Bug fixes

• Fixed: When several tracks were available as reference data for a workflow, it was not possible to change the selection after the initial run of the workflow.

CLC Cancer Research Workbench 1.0

Release date: April 7, 2014