Data Sheet: Reproductive and Genetic Health

BlueFuse™ Multi Analysis Software forMolecular Cytogenetics
A powerful software package designed to detect and display areas of potential chromosomal
abnormality within the genome.
Highlights

Figure 1: Key Fields Available in BlueFuse
Software Sample Reports• Seamless Data Comparison
All tables and charts linked within the software for easy
viewing• Confident Answers
Optimized and validated algorithms and automated analysis
provide user-independent results• Scalable Software Platform
Single software package, with multi-user capabilities, provides
data and information management solutions

Introduction
Developmental delay is a common condition affecting 1–3% of thepopulation1. A number of causative disorders, including Down, CriDu-Chat, DiGeorge, and Williams syndromes, are known to have anassociated genetic or chromosomal abnormality. Recent advancesin microarray screening technologies have enabled identification offurther chromosomal microdeletions and microduplications as thecause of many other developmental delay disorders, expanding ourunderstanding of this complex condition.
To support the study of cytogenomic-relevant genes associatedwith congenital disorders, Illumina offers the Infinium® CytoSNP850K BeadChip. Providing a truly complete solution, the BeadChip
includes a license for BlueFuse Multi Analysis Software. BlueFuse
Software offers automated batch import from the primary scanner
files, data processing and segmentation using validated algorithms,
and automatic report generation for fast sample turnaround time andconfident results reporting.

Efficient Multiuser Software
BlueFuse Multi is a sophisticated software for analyzing andinterpreting results from molecular cytogenomic studies. Results ofeach analysis are stored and accessed in a multiuser shared
database. BlueFuse Software supports data import from CytoSNP
BeadChips, CytoChip Oligo arrays, and CytoChip Focus arrays forboth copy number and AOH (absence of heterozygosity) analysis, ifapplicable. With automated microarray processing, single-click

BlueFuse Software enables input of all sample information and links to experimental runs into one database. Data fields can be updated as needed.

batch import to reporting, and a clear, intuitive user interface,
BlueFuse Software generates accurate, user-independent results
quickly and efficiently.

Simple Sample-to-Sample Comparisons
The BlueFuse Software framework enables input of all sample
information and provides links to experimental runs into one database(Figure 1). Sample information includes sample type (e.g., blood,CVS, amniotic fluid), date of birth, pedigree number, and phenotype.
Related samples can be overlaid for data comparisons and regionsof change compared to phenotype.

Confident Copy Number and AOH Detection
BlueFuse Software uses optimized, validated algorithms to detect
copy number changes automatically and display areas of potential
abnormality within the genome. For applicable platforms, this includes
the ability to detect areas of AOH. Accurate, reliable results areachieved independent of the user.

Data Sheet: Reproductive and Genetic Health
Figure 2: View of the Genome from BlueFuse Software

Horizontal view of the entire genome showing copy number and B-allele data. The orange line in the LogR chart displays the median of the region.

Figure 3: Linked Data Between Charts and Tables

Linked data are indicated by the yellow region in the charts (left) and the highlighted blue row in the table (right).

Data Sheet: Reproductive and Genetic Health
Figure 4: Visualization of a Gene Deletion

A deletion within the DOCK8 gene covers three exons.

Clear Visualization for Rapid Data Confirmation
The key to rapid, confident results interpretation is clear, unambiguous
data presentation. In the BlueFuse Software, data can be viewed
horizontally or vertically (classical cytogenetics view). The opening
view shows the entire genome with the automated calling displayed,facilitating user confirmation of the calls. The user can zoom in to
any region on the genome for more detailed analysis at any timeby selecting the desired region or abnormality. The user may alsoannotate the data manually for segmental changes or override theautomated calls. The region comments box supplements any changes
with an explanation, enabling an audit trail and case history andfacilitating the addition of any other relevant information used in theanalysis (Figure 2).

Intuitive Navigation
BlueFuse Software links all data for each view, making navigation as
simple as a click of the mouse. For example, click a region in a chart
to see specific information in a table format, or click a line in a table tosee that data highlighted in the charts (Figure 3).

Helpful Data Interpretation
In addition to clear data presentation, BlueFuse Software helps users
understand the significance of any detected changes. This is achieved
through the import of a secondary file called the annotation database.
The annotation database is comprised of summary information fromthe key public databases (ISCA, DGV, Ensembl, and Decipher) and isupdated regularly. To make sure that the most recent information isused, BlueFuse Software facilitates direct link-out to the live websites
for region, gene, and OMIM searches, simply by right-clicking on therelevant region in the decision track. Laboratories can import custom
BED or TXT files to supplement this information. Visualization featuresin the decision tracks enable data comparison between current
experiments and published regions, and a closer look at gene andexon content within each region (Figure 4).

Full History of Laboratory Data
BlueFuse Software incorporates a number of measures to ensure atransparent audit trail of laboratory data and decisions made regarding
data interpretation.

Record of Data Assessment
The Region View dialog within BlueFuse Software provides alaboratory record of the decisions made for every region identified.
Every region can be assigned an assessment of Benign, Probably
Benign, Unknown, Probably Pathogenic, and Pathogenic, following
ISCA guidelines. Users can add specific comments regarding theassessment, supplying additional support of the decision. This nondeletable audit trail delivers a history of analysis and a paperlessformat of case management between users. All information appearson the generated report (Figure 5).

Sample and QC Comparison
Complete information for all samples is stored in a central database.
A summary of all regions found in all experiments, including frequency
of detection and previous region assessments, is available to guidedecisions. Data are permanently available and can be revisited andinterrogated at any time ensuring that any follow-up questions canbe readily answered. QC metrics for each experiment are also storedData Sheet: Reproductive and Genetic Healthwithin the database allowing laboratories to perform run-to-run, lotto-lot, and user-to-user comparisons to aid in the development andoptimization of QC\QA processes.

maintains write access to the database for full functionality. There arethree levels of user access (Figure 7):

Complete Audit Trail

2. Supervisor—write, annotate, and delete samples and experiments
to the database

From a laboratory record perspective, it is essential to track who
evaluates experiment performance and when in the process
this evaluation occurs. BlueFuse Software provides a “Sign-off”
functionality that logs this activity automatically. After a result isreviewed, the user will sign off on that experiment as a pass or a fail.
Each inspection includes a user name and time stamp to establish
the audit trail. The experiment is then passed to the next user andconfirmed before being signed-off by the senior members of theteam. This trail cannot be deleted or edited, even by an administrator,

1. User—write samples and experiments to the database only

3. Administrator—write, annotate, and delete samples andexperiments to the database; change global database settings

BlueFuse Server for Multi-User Write Accessproviding a robust audit trail of the sample (Figure 6).

BlueFuse Server is an optional install that enables multiple users towrite simultaneously to a central database. If this software is notinstalled, multiple users can log in with read-only access, but only one
person can write to the database at any given time.

Scalable Workflow

Rapid and Consistent Reporting

BlueFuse Software supports multiple users accessing the databaseat the same time to ensure fast workflows and ease of use. If installedwith the recommended (optional) BlueFuse Server, every user

BlueFuse Software automatically generates annotated reports for eachexperiment. Reports contain a breakdown for every copy number andAOH region, including user assessment and associated commentsFigure 5: Region View in BlueFuse Software

The Region View shows information regarding data assessment, including the region type, call assessment, reported status, location of the variation, and any usercomments. The additional tabs of “Overlapping CGH Regions” and “Reported Genes” enable rapid assessment of the region.

Data Sheet: Reproductive and Genetic Health
Figure 6: Sample Sign-Off Report

Figure 7: Configuring User Level in the Database

BlueFuse Software requires case sign-off for each report, creating a clear
audit trail for each sample.

plus details of the Human Genome Organisation Gene Nomenclature
Committee (HUGO/HGNC)2 and Online Mendelian Inheritance in Man(OMIM)3 genes, overlapping Database of Genomic Variants (DGV)
entries4, and International Standards for Cytogenomic Arrays (ISCA)
database of consensus regions5. Reports are updated when any
changes to the case are made, ensuring the reports are always up-todate based on the latest experiment actions and changes. In addition,
reports can be customized to make sure that only the desired
information is reported outside of the laboratory. All reports are easily
exported or copied to a laboratory-specific report as required. Reports
are also available as Web Reports using a standard internet browser
within the institute to maximize availability to all users*.

Integrated Framework
BlueFuse Software offers a single framework for analyzing data for
IVF and molecular cytogenetic applications. Developed by the clinicalgenomics community for the clinical genomics community, the clear
intuitive interface ensures that the unique needs of these laboratories
are met. In addition, the software supports analysis and visualizationof sequencing and array data on the same platform. This integrated
approach enables molecular cytogenetic laboratories to run a suite oftechnologies and expand their testing portfolios.

* When BlueFuse Server is installed.

BlueFuse Software supports multiple user access levels.

Summary
BlueFuse Multi Software enables rapid, accurate molecular
cytogenetics analysis. The ability to visualize and report copy numberand AOH data quickly and reliably allows laboratories to run multiple
tests per day with confidence and minimal hands-on time. In addition,
the integrated framework ensures that laboratories are able to scale
to higher volumes and offer new tests with minimal staff training.
Designated user login and profiles coupled with experiment sign-off
requirements allows the lab to control and track data throughout theworkflow and institute.

Ordering Information
BlueFuse Software is available free of charge to users of Illumina
cytogenetic and IVF technologies with unlimited licenses per site.
The software is not available as an open platform to other vendors orLDTs. Download the software from www.cambridgebluengome.com/
software. For license information, contact techsupport@illumina.com.

Data Sheet: Reproductive and Genetic Health

References
1.

Michelson DJ, Shevell MI, Sherr EH, Moeschler JB, Gropman AL, et al.
(2011) Evidence Report: Genetic and metabolic testing on children with
global developmental delay. Report of the Quality Standards Subcommitteeof the American Academy of Neurology and the Practice Committee of theChild Neurology Service. Neurology 77(17): 1629–1635.

2.

HGNC Home Page (wwwdev.genenames.org/) Accessed 09 June 2014.

3.

OMIM – Online Mendelian Inheritance in Man (omim.org/) Accessed
09 June 2014.

4.

Database of Genomic Variants (dgv.tcag.ca/dgv/app/home) Accessed
09 June 2014.

5.

Welcome to the ISCA Consortium web site (www.iscaconsortium.org/)
Accessed 09 June 2014.

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Pub. No. 1570-2014-057 Current as of 30 July 2014