Data Sheet: Reproductive and Genetic Health

BlueFuse™ Multi Analysis Software forPreimplantation Genetic Diagnosis
A powerful software package built by clinical geneticists for clinical geneticists offering quick,efficient, integrated analysis of array and sequencing data.
Highlights• Clear Data Interpretation
Optimized, validated algorithms produce accurate, easy-tovisualize haploblock charts• Rapid, Consistent Reporting
Automated report generation from barcoded data
• Scalable Software Platform
Single software package provides data and informationmanagement solutions

Introduction
Preimplantation genetic diagnosis (PGD) enables screening ofembryos for specific genetic conditions before an in vitro fertilization(IVF) procedure. Screening by PGD uses genetic markers locatedthroughout the genome to assess the likelihood of an embryo carrying
a mutated gene involved in a single-gene disorder. Karyomapping is
one method currently available for performing PGD.
Karyomapping uses advanced array-based technology to provide ahigh-density view of the chromosomes in an embryo to establish theparental origin of inherited chromosomal segments, or haploblocks.
Data generated through this reliable assay is analyzed using theBlueFuse Multi Analysis Software with karyomapping module.
BlueFuse Multi Software provides optimized algorithms for tracking
maternal and paternal inheritance patterns in the embryo for fast,
reliable results and reports.

Visualize Single-Gene Inheritance
BlueFuse Multi Software with karyomapping module is a sophisticatedmulti-user database for storing, analyzing, and interpreting
karyomapping results. From single-click batch import to automatedFigure 1: Haploblocks Showing Inheritance Patterns Surrounding the CFTR Region

Maternal and paternal inheritance patterns in the flanking regions around the CFTR gene (blue highlight) in the embryos.

Data Sheet: Reproductive and Genetic Health
Figure 2: Detailed SNP Information Used to Make an Inheritance Call

For each chromosome, key SNPs are displayed above the chromosome and non-key SNPs below the chromosome, enabling users to determine the accuracy ofhaploblock calling. SNPs failed to be called are displayed as white points in the middle of the chromosome.

reporting, BlueFuse Multi Software enables clinical laboratories toprocess large numbers of samples efficiently and store all cases ina central database.
The karyomapping module enables users to investigate and visualize
the inheritance of single genes within embryos. Starting with data
generated by the Infinium® HumanKaryomap-12 assay, a highly
validated algorithm tracks haploblocks from the parents for quick,clear assessment of the genetic status of each embryo. Automatic
report generation supports fast and easy data reporting.

Automated Algorithms for Rapid Interpretation
All PGD data are run through automated, validated algorithms toprovide accurate, reliable results, independent of user preferences andsettings. The proprietary karyomapping algorithm establishes which
haploblocks, either maternal or paternal, the embryo has inheritedacross the genome*. Identifying the parental source allows detectionof the likely phase and carrier status for each embryo for the gene, orregion, of interest.

Clear Visualization for Data Confirmation
Key to karyomapping data interpretation is the ability to compare
embryo inheritance to the status of a reference sample, such as aclose relative of known disease status. The BlueFuse karyomapping
module enables single-click zoom of a haploblock chart to show theinheritance pattern for all embryos of the gene, or region, of interest(Figure 1). Users can confirm the accuracy of the results by simply
clicking each embryo number to see detailed information regarding
key and informative SNPs in the haploblock (Figure 2). This clear,
unambiguous data presentation enables users to make quick,
informed decisions regarding the carrier status of each embryo. Ifneeded, automated calls can be overridden manually.

Automated Report Generation
BlueFuse Multi Software automatically generates individual reports
for each embryo as well as an overall case report. These reports are
updated as changes are made to the case, ensuring that they arealways up to date with the latest experiments.

Karyomapping Embryo Reports
A karyomapping embryo report is produced for every embryo. Thissimple report allows users to confirm that the assay has passed QC
before performing the analysis. Information from this report is alsoavailable in the full karyomapping case report.

Karyomapping Case Reports
The karyomapping case report contains final phasing of all embryos
along with biological and workflow details, information on all samples
analyzed, the gene or region of interest, software version, andessential QC metrics (Figure 3). This report is easily exported, copied,or printed, and ready to pass on to a clinician.

Scalable Workflow
BlueFuse Multi Software supports multi-user access to the databaseat the same time to ensure the fastest workflows and ease of use. If
installed with the recommended BlueFuse Server (optional), every user
maintains write access to the database for full functionality. There arethree levels of user access (Figure 4):
1. User—write samples and experiments to the database only
2. Supervisor—write, annotate, and delete samples and experiments
to the database
3. Administrator—write, annotate, and delete samples andexperiments to the database as well as change global databasesettings* To learn more, download “A Technical Guide to Karyomapping Calling” from support.illumina.com/downloads/humankaryomap-12-v1-technical-guide-15052496.ilmn.

Data Sheet: Reproductive and Genetic Health
Figure 3: Karyomapping Case Report Example

Excerpts from a BlueFuse summary report. For each SNP, the report lists assay success rate in accurately calling genotypes at the global level. A detailed section
shows additional SNP information from the flanking regions of the gene of interest.

BlueFuse Server for Multi-User Write Access
The BlueFuse Server is an optional install that enables multiple users
to write simultaneously to a central database. Without the BlueFuse
Server, multiple users can log in with read-only access, but only one
user can write to the database at any given time.

Complete Audit Trail Through Sample Sign-Off
It is critical that only high-quality data are used to generate the final
reports that inform patient-physician decisions. Users inspect eachexperiment and provide “sign-off” indicating whether the experimentpassed or failed. Each inspection includes a user name and timestamp to build an audit trail. The experiment is then passed to thenext user and confirmed before sign-off by senior members of theteam. BlueFuse Multi Software automatically tracks and stamps eachinteraction in the process. This trail cannot be deleted or edited, evenby an administrator, providing a high-integrity audit trail of the sample(Figure 5).

Figure 4: Configuring User Level in the Database

BlueFuse ensures access control by assigning three user levels withdifferent privileges and functions. The software supports multiple users at
each level and administrators can reassign access levels any time.

Centralized Database
Experimental results analyzed using BlueFuse Multi Software are stored
in a central database. Data are permanently available and can berevisited at any point in the future for comparison across multiple IVF
cycles, which may have a treatment or counseling impact. Data storage
also ensures that any follow-up questions can be readily answered.

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

Summary
BlueFuse Multi Software with karyomapping module enables rapid,
accurate visualization and reporting of PGD cases. Optimized
algorithms combined with automated report generation allow
laboratories to run multiple tests per day with confidence and minimalhands-on time. In addition, the integrated framework ensures thatlaboratories are able to scale rapidly 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 through the workflow and institute.

Data Sheet: Reproductive and Genetic Health
Figure 5: Sample Sign-Off Report

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

Ordering Information
Access to BlueFuse Multi Software is available free of charge to usersof Illumina cytogenetic and IVF technologies with unlimited licenses persite. The software is not available as an open platform to other vendors
or LDTs. Download the software from www.cambridgebluegnome.com/
software. For license information, contact techsupport@illumina.com.

Illumina • 1.800.809.4566 toll-free (U.S.) • +1.858.202.4566 tel • techsupport@illumina.com • www.illumina.com
FOR RESEARCH USE ONLY.
© 2014 Illumina, Inc. All rights reserved.
24sure, BlueFuse, Illumina, Genetic Energy, the pumpkin orange color, and the Genetic Energy streaming bases design are
trademarks or registered trademarks of Illumina, Inc. All other brands and names contained herein are the property of their respective
owners. Pub. No. 1570-2014-055 Current as of 10 September 2014