CUSTOMER SPOTLIGHT
NIR RAINY, PHD

Building a state-of-the-art clinicalresearch sequencing lab in Israel
Genomics center established in record time to combat
COVID-19 pandemic

The novel coronavirus disease (COVID-19) pandemic has spurredbiomedical innovation and motivated scientific collaboration. For
Shamir Medical Center in Israel, COVID-19 was the catalyst toestablish an onsite genomics center. Primarily focused onsequencing coronavirus variants, this next-generation sequencing(NGS) lab is developing innovative protocols for comprehensive
genomic profiling and other clinical research applications.

NIR RAINY, PHD
HEAD OF SHAMIR GENOME CENTER,SHAMIR MEDICAL CENTER, ISRAEL

Nir Rainy, PhD, who leads the new Shamir Genome Center, hasspent his career on the forefront of technology. With his expertisein biomedical automation and with support from Illumina andDanyel Biotech,* Dr. Rainy set up a fully operational genomics lab
in only three weeks. Shamir Genome Center is now the primary
COVID-19 testing site in Israel, sequencing more than 1600 samples
per week. We spoke with Dr. Rainy about what it takes to build ahigh-throughput genomics center, how his lab is aiding COVID-19
surveillance efforts in Israel, and his vision for the future of NGS inclinical research.

Q: What is the mission of Shamir Medical Center?
Nir Rainy (NR): Shamir Medical Center is the fourth largest public
hospital in Israel. We serve over one million patients and provide
personalized care to our patients in various specialty and subspecialty fields. In addition, Shamir Medical Center is a hub for
cutting-edge research and we strive to provide the best
technology and care for our patients.

* Danyel Biotech is the Illumina channel partner in Israel. As an authorized distribution partner,Danyel Biotech gives customers access to Illumina products while providing the same levelof sales, marketing, service, and support offered directly by Illumina.

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"I am attracted to the breadthof biological research doneat Shamir Medical Centerand believe cutting-edge
multidisciplinary projects will
require NGS and our dedicatedservices."

Q: Why was it important to establish a genomics lab atyour hospital?
NR: Over the past few years, the hospital discussed options toestablish an in-house NGS unit for pathology needs, as well asgenetics, molecular diagnostics, and research at the hospital.
The final push and catalyst to move forward was the COVID-19
pandemic. Shamir Medical Center was chosen to take part in thenational sequencing efforts starting in 2021. By sequencing highvolumes, Shamir Medical Center was able to build its own sequencing center and run the NextSeq™ 550 Systems at high capacity,
lowering the cost of sequencing. We adopted a bottom-to-top
approach in which we efficiently managed procurement, reagents,manpower—and overnight operations at times—to fully utilize
the hospital network topology. Our main customer for COVID-19
sequencing was the Ministry of Health of the state of Israel. Since
the establishment of the Shamir Genome Center, we have gained
additional customers from pathology, genetics, microbiome, andother departments, as well as external customers.

Q: What attracted you to joining the Shamir Genome Center?
NR: I am a technology early adopter and I spent most of my professional career integrating biological questions and innovative technology. I prefer looking at several scientific questions, for instancein immunology, molecular biology, and genetics, and then applying
state-of-the-art technologies to resolve some of those questions.
I am attracted to the breadth of biological research done at Shamir
Medical Center and believe cutting-edge multidisciplinary projects
will require NGS and our dedicated services.

Q: How did your background prepare you for this role?
NR: I hold a PhD in molecular immunology as well as extensive
training as a programmer and systems analyst. In the beginning of
my career I worked as an immuno-oncology scientist and I wasresponsible for screening ligand–receptor interactions. Afterdeveloping several tools and expanding the activity to a larger
scale, we implemented automation and I gained deep and thoroughknowledge of the automation process. Then, as an application
scientist for Beckman Coulter automation systems, I learned how to
do full-scale, automated NGS, how to write scripts, how to validate
and execute protocols. Currently at Shamir Medical Center, I verymuch enjoy applying my knowledge and passion for a wide rangeof biological questions. The experience I’ve gained helps Shamir
Medical Center ensure the best results for patients and customers.

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Q: Why did you choose Illumina sequencing systems for theShamir Genome Center?
NR: We chose Illumina sequencing systems based on our extensive
experience, the platform flexibility, quality of service, and ourexcellent relations with Illumina Israeli distributer, Danyel Biotech.
Illumina brings a very flexible solution that allows us to sequenceexomes or microbiomes—basically, you can do everything on thesame machine. In order to work quickly and with high efficiency,
even during a pandemic, it was important for us that the NGS
platform be able to utilize a wide range of reagents for the library
prep stage, and that’s exactly what we got with Illumina sequencing
systems.
In March 2021, we got the green light to purchase the first NextSeq
550 System and less than 3 weeks after that, our lab was fully
operational, running the Illumina COVIDSeq™ Test (RUO) with 384
samples per run. To comply with our main customer's demands (theIsraeli Ministry of Health), we spent days and nights in the lab until
validation was completed successfully. Dedication of the hospitalmanagement, IT, and laboratory workers was essential to oursuccess, as well as to rapid deployment.

"In March 2021, we got thegreen light to purchase thefirst NextSeq 550 System
and less than 3 weeks
after that, our lab was fully
operational, running theIllumina COVIDSeq Test (RUO)
with 384 samples per run."

Q: How did you implement a high-throughput NGS workflow
so quickly?
NR: We were able to make this happen due to our vast professional experience and prior knowledge. A lot of experience andknow-how, in short. Before we started our lab at Shamir MedicalCenter, I already had a predesigned plan for the workflow, including
what equipment would be needed. A Qubit fluorimeter, a plate
reader, and almost anything else that was needed to start the lab
was loaned to us at the beginning. It’s been difficult to get 384-wellplates, PCR plates, robot tips, etc, due to the high global demandfor plastic consumables. Very generous help from our collaborators and supporters in the Israeli biotech ecosystem enabled us toovercome these obstacles, and we thank them.
We got the first NextSeq 550 System from Illumina within a few
weeks, followed by rapid delivery of a Hamilton NGS Star liquidhandling robot. It took us less than a week from unpacking theequipment to post validation. Everything was achieved very quickly
because the entire management team in the hospital was absolutely dedicated, from procurement to IT to infrastructure management.
Red tape issues were resolved almost immediately, which was
unheard of at the time in a big public hospital in Israel.

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"We have excellent relations
and support services fromDanyel Biotech, the distributor
in Israel for both Illumina andHamilton. We appreciate theirexpertise and direct contact
with the application specialists.
We feel we are really in goodhands."

Q: How did Danyel Biotech support you as you were setting up
your lab?
NR: We have excellent relations and support services from Danyel
Biotech, the distributor in Israel for both Illumina and Hamilton. We
appreciate their expertise and direct contact with the application
specialists, both for automation and Hamilton. We feel we are reallyin good hands. During this very rapid, somewhat chaotic time ofestablishing the Shamir Genome Center, Danyel Biotech came into help, advise, and support by phone or remote access to theNextSeq 550 System, even on weekends. One weekend, we hada probe that was broken in the robot gripper and someone justcame and replaced it at noon on Friday before Shabbat started. Itis really amazing to have the safety net and level of service fromDanyel Biotech.

Q: How is Shamir Genome Center helping COVID-19 research andsurveillance efforts in Israel?
NR: Our COVID lab is open 24/7. We have a relatively short turnaround time from sample receipt to bioinformatics analysis to final
report. At the moment, we've implemented a seven- to eight-day
SLA† for each run. Our bioinformatics pipelines enable us todetermine COVID-19 variants in less than 24 hours, complete witha list of critical mutations and this later is integrated into a comprehensive demographic analysis. We then work another 24-48 hours
on the final report. We strive to improve this time but not at theexpense of quality control. We won't lessen the strict measures wetake in our process to ensure the results are accurate and that ourreport is crystal clear to decision makers in the Ministry of Health,Israel. Due to our dedication and level of service, the Ministry ofHealth asked us to remain onboard and further develop our sequencing capabilities. We are currently the busiest NGS COVID-19
sequencing lab in Israel and since March 2021 we have sequenced
more than 18,000 samples.

Q: How has your process impacted your results?
NR: The process has implications for failure rates and conciseresults. We only have around 7% failed libraries in each run, which
is an excellent benchmark. Based on past experience and speaking
with colleagues, a 9-11% failure rate is more typical. This success is† SLA, service level agreement

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mostly due to deep understanding of the limitations and potentialof automation. For example, if you see a gradient, then you knowthat you need to mix better. If the beads do not settle quickly, thenit means you need to extend step times. When you choose theright automation protocols, you can see better results. Additionally,
we have bioinformatics expertise. We’ve gained knowledge thatallows us to correctly assess samples even if their quality scoreis low. For example, if we get lower coverage of a region, but wesee some mutations that we know, we can score it and declare acertain variant.

"We strive to improve our time

Q: How are you using your sequencing systems?

our report is crystal clear to

NR: We have two NextSeq 550 Systems and one MiSeq™ System.
Our vision is to have a NovaSeq™ 6000 System by the end of
the next year. The NextSeq 550 Systems are going to support
COVID-19 for the next two years. In addition, they will support
TruSight™ Oncology 500 assays and the small-scale exome
sequencing we are planning to start later this year. With theMiSeq System, we are going to implement Archer panels, 16S,
18S, and also SOPHiA assays for hematology panels. The future
NovaSeq 6000 System will be used for interesting research withunique genomes and high-throughput exomes.

decision makers in the Ministry

but not at the expense ofquality control. We won't lessen
the strict measures we takein our process to ensure theresults are accurate and thatof Health."

Q: How have you used automation to improve your process?
NR: We use automation to maximize sample throughput andoverall flexibility. The automation script for the Hamilton robot
was developed by Danyel Biotech. Initially, it was designed for384 samples per run and Eppendorf tubes for the source material.
During the implementation we modified the script to support
96-well plates as the source. Mostly we are doing 384 samples,but we can do 24, 48, 72, or 96 samples and we have jumps of
96 samples after that. We have immense flexibility with automation
and also flexibility to use the mid-output or high-output flow cellon the NextSeq 550 System. On rare cases that require a quickanswer to identify a COVID-19 variant, we can do a manual library
preparation and run 24 samples on the MiSeq System.
We are also finalizing the validation and evaluation of TruSightOncology 500. In a few months, we will be the first certified NGS
lab in Israel that will fully automate this assay. Currently in Israel ittakes three to five weeks to get results for TruSight Oncology 500

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"Our versatile team arealways seeking new ideas tostretch the boundaries of ouror for exome sequencing for rare diseases. We are aiming to cutthat time in half and bring results to customers in two weeks.
Hopefully, we will grow and be able to serve more customers withthe best possible solution for them.

capabilities. In a sense, we are

Q: How else are you innovating?

a small start-up company inside

NR: Our success with COVID-19 sequencing has paved the way to
new collaborations with big pharma companies, academic
researchers, and defense organizations. Also, we dedicate 10%of our time for innovation—intriguing projects we want to do andthen try to develop into a product or a service. Our versatile teamare always seeking new ideas to stretch the boundaries of ourcapabilities. What can we do for the hospital? What can we do forresearchers? In a sense, we are a small start-up company inside a
big public hospital.

a big public hospital."

Q: What is your vision for Shamir Genome Center?
NR: Our vision: We are aiming to be the best genomic center inIsrael, in a few years, serving tailor-made solutions for various
customers. Innovation will allow us to be leaders in our field andexpand in other areas.

Q: Where are you taking NGS next?
NR: Taking NGS to the next level will have to include miniaturizing
tests and enhancing cost effectiveness. Being able to shorten thesequencing run time might help us shorten reporting time. Being
able to combine different tests on the same run, for example,
TruSight Oncology 500 and whole-exome panels together with 16S
amplicons will be very beneficial. Today, this is not feasible unless
you know how to calculate the molarity perfectly and have superprecision in pipetting. But most people will have failures and will
have some of the libraries overriding other libraries. We want todevelop tools that will allow us to do many tests on the same run.

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Learn more
NextSeq 550 System, illumina.com/systems/sequencing-platforms/nextseq.html
Illumina COVIDSeq Test (RUO), illumina.com/products/by-type/clinical-research-products/covidseq.html

1.800.809.4566 toll-free (US) | +1.858.202.4566 tel | techsupport@illumina.com | www.illumina.com© 2021 Illumina, Inc. All rights reserved. All trademarks are the property of Illumina, Inc. or their respective owners.
For specific trademark information, see www.illumina.com/company/legal.html.
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