{"id":11971,"date":"2019-01-30T23:39:30","date_gmt":"2019-01-30T23:39:30","guid":{"rendered":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/?p=11971"},"modified":"2019-01-31T02:54:03","modified_gmt":"2019-01-31T02:54:03","slug":"dr-charlotte-brasch-andersen-uses-cytoscan-products-to-improve-prenatal-screening","status":"publish","type":"post","link":"https:\/\/www.thermofisher.com\/blog\/behindthebench\/dr-charlotte-brasch-andersen-uses-cytoscan-products-to-improve-prenatal-screening\/","title":{"rendered":"Dr. Charlotte Brasch-Andersen Uses CytoScan Products to Improve Prenatal Screening"},"content":{"rendered":"
\"A

Dr. Charlotte Brasch-Andersen, Clinical Laboratory Geneticist, Odense University Hospital Associate Professor, University of Southern Denmark<\/p><\/div>\n

Dr. Charlotte Brasch-Andersen is a clinical laboratory geneticist at Odense University Hospital<\/a> in Southern Denmark and an associate professor in human genetics at the University of Southern Denmark\u2014a position she has held since 2010. Previously, she held positions as\u00a0a senior consultant at the National Genome Center<\/a> in Denmark, an assistant professor in pharmacogenetics at University of Southern Denmark<\/a>, and a board member of the Danish Society of Medical Genetics. Additionally,\u00a0Dr. Brasch-Andersen was the chairperson of a committee that implemented a formal education program for clinical laboratory geneticists in Denmark.<\/p>\n

Dr. Brasch-Andersen\u2019s clinical work focuses on examining copy number variations in DNA from blood or tissues that are implicated in intellectual disabilities, developmental delay, dysmorphisms, prenatal diagnostics and miscarriages. This interview with Dr. Brasch-Andersen discusses the process her lab underwent when choosing the best platform for her prenatal diagnostics workflow.<\/p>\n

Thermo Fisher Scientific: You were originally using the Agilent\u00a0platform\u00a0at\u00a0Odense.\u00a0What was it that first drew your attention to Applied Biosystems\u2122 CytoScan\u2122\u00a0products<\/a>?<\/p>\n

Dr. Brasch-Andersen: My team was using the 400K Comparative Genomic Hybridization (CGH) Microarray from\u00a0Agilent\u00a0for postnatal\u00a0samples,\u00a0but had to\u00a0start\u00a0running prenatal samples as well. Adding prenatal samples to the array workflow made me evaluate the present setup. So, I made a list of which factors were important to consider in a setup of both postnatal\u00a0and\u00a0prenatal\u00a0samples.\u00a0One\u00a0of the more\u00a0important\u00a0considerations\u00a0was in\u00a0clinical\u00a0applications,\u00a0I wanted to be able to detect polyploidy (an extra set of all chromosomes), which in rare cases can be seen in prenatal samples. To detect polyploidy, single-nucleotide polymorphisms (SNPs) are needed on the platform, as\u00a0without them the algorithms behind CGH will just normalize all the data resulting in a normal result. Back then, few CGH arrays had enough SNPs to detect polyploidy. Even though the ultrasound gynecologist said that they could tell by the ultrasound if the fetus was polyploid, I felt I needed a method that could detect it using molecular means.<\/p>\n

Another issue to consider was the workflow and staff in the lab. Time, or specifically report time, and economy is always an issue, even in a government-funded healthcare system like ours in Denmark. I didn\u2019t need the same array resolution for pre- and postnatal arrays, but I wanted an array solution and protocol where we could do postnatal\u00a0arrays at the same time as prenatal arrays. It wasn\u2019t optimal economically to have one group of technicians running one protocol and another running a different one. It wouldn\u2019t\u00a0be robust enough when people go on vacation or are sick. What\u2019s really neat about the CytoScan suite is that it is essentially the same protocol in the lab for the various array formats, so the only difference really is which cartridge\u00a0you load. The benefit of the same protocol is that it would allow us to run the postnatal arrays alongside the regular prenatal array batches. That gave a lot of flexibility and thus allowed potentially faster turnaround times on the postnatal arrays, as we run the prenatal analysis twice a week.<\/p>\n

\u201cThe CytoScan products require less DNA than a majority of the other products on the market that compete in the same space. The low DNA input requirement is a significant advantage of the CytoScan products<\/a> and was another factor that drove our decision to convert.\u201d<\/span><\/strong><\/p><\/blockquote>\n

The added flexibility also had an additional benefit: with the very different numbers and types of samples we were receiving every week, it meant we could allow for changes in volumes of each sample type more easily. Sometimes prenatal sample volumes are small and it is not possible to extract a lot of DNA. The CytoScan products<\/a> require less DNA than a majority of the other products on the market that compete in the same space. The low DNA input requirement is a significant advantage of the CytoScan products<\/a> and was another factor that drove our decision toc onvert.<\/p>\n

\n

\u201cThe CytoScan products and\u00a0ChAS<\/a>\u00a0have\u00a0both\u00a0a\u00a0CNV track and a SNP track, and I learned these\u00a0were\u00a0totally independent.\u00a0If I saw a deletion in the copy number variation track, then it was independently confirmed in the SNP track and I didn\u2019t have to verify it using another method.\u201d<\/span><\/strong><\/h1>\n<\/blockquote>\n

Another important feature is that CytoScan products<\/a> have two data tracks in the Applied Biosystems\u2122 ChAS<\/a> (Chromosome Analysis Software) analysis package compared to CGH; the CytoScan products<\/a> and ChAS have both a CNV track and a SNP track, and I learned these were totally independent. If I saw a deletion in the copy number variation track, then it was independently confirmed in the SNP track and I didn\u2019t have to verify\u00a0it using another method. I just had the confirmation right there.<\/p>\n

For all prenatal analysis, report and analysis time is really important so you need something that\u2019s super robust and provides an answer quickly, I felt that no other platform offered both of these advantages.<\/p>\n

Thermo Fisher Scientific: At which point were you convinced that you should switch to CytoScan arrays?<\/p>\n

Dr. Brasch-Andersen: I weighed the pros\u00a0and cons and I think the arguments were strong despite\u00a0CytoScan products<\/a> having a longer protocol compared to other products we were evaluating.<\/p>\n

Thermo Fisher Scientific: So it was the benefits of the systems that made you make the change?<\/p>\n

Dr. Brasch-Andersen: Absolutely, and I have to say, they are very robust systems. During the first six months of running it, we analyzed 27 prenatal arrays; as of October of this year we\u2019d already done 1,000. It\u2019s been an enormous increase. We are getting referrals from other hospitals too as the obstetricians can see that it is a robust system and few samples fail. It\u2019s the results that make the difference.<\/p>\n

Thermo Fisher Scientific: When you first introduced the CytoScan solution into the lab, what was it that\u00a0Thermo Fisher offered that made it easier to deploy within your department?<\/p>\n

Dr. Brasch-Andersen: Well, we got help from all of the support teams, including a dedicated applications scientist, and they ironed out any early troubles very quickly. We\u00a0also have a unique Nordic community involved with this application in the form of the Thermo Fisher Scientific<\/a>\u00a0cytogenomic user group. This group holds annual meetings facilitated by Thermo Fisher and is backed up strongly by all the users in the region. During the Nordic meetings,\u00a0we have open discussions around our applications and use of the system. I\u2019m of the conviction that if I find a problematic issue, then I\u2019m not the only one who has seen\u00a0it\u2014somebody else has probably had a similar finding. Open debates are discussed, and it\u2019s really been a great help to implement improvements in the lab and in the analytical stages. The user group meetings have provided a lot\u00a0of value.<\/p>\n

\u201cWe also have a unique Nordic community involved with this application \u2026 the user group meetings have provided a lot of value.\u201d<\/span><\/strong><\/p><\/blockquote>\n

Thermo Fisher Scientific: You mentioned earlier one of the main reasons you chose the CytoScan suite<\/a> of products was because of reliability.<\/p>\n

Dr. Brasch-Andersen: Yes, I think I can count on two hands\u00a0the\u00a0number\u00a0of arrays that we\u2019ve ever had fail. I\u00a0mean it is really\u00a0robust.<\/p>\n

Thermo Fisher Scientific: Is the robustness something that you saw in the other platforms?<\/p>\n

Dr. Brasch-Andersen: No, we had to redo a lot of arrays previously. We came from the 400,000 probe arrays\u00a0from Agilent, but we\u2019re now using the CytoScan suite of products for both prenatal<\/a> and postnatal<\/a>. We didn\u2019t\u00a0change to a system with more probes because we wanted to detect smaller aberrations, but because having more probes gives a stronger, more robust answer.<\/p>\n

\n

\u201cI\u00a0think\u00a0I can count on two hands the number of arrays that we\u2019ve ever had\u00a0fail.\u201d<\/span><\/strong><\/h1>\n<\/blockquote>\n

Thermo Fisher Scientific: What are your reasons for continuing to use the CytoScan suite?<\/p>\n

Dr. Brasch-Andersen: For a lot of the reasons that I\u2019ve mentioned already (independent SNP track, flexible protocol, low DNA input), but\u00a0mainly\u00a0because\u00a0of robustness. When you\u2019re conducting analysis and you have\u00a0people\u00a0waiting for rapid, accurate results\u2014and in\u00a0the majority of these cases pregnant women are worried because they have an abnormal risk assessment for the pregnancy\u2014robustness is important. It is just enormously important and nice not to have to tell the patient, \u201cI\u2019m sorry, your sample failed and now you\u2019re going to have to wait another five days.\u201d It just happens so rarely now. Even sometimes with samples from miscarriages, the DNA can be very degraded; but most of the time we\u2019re still able to get results for those samples, and it means a lot to the parents that they get an answer.<\/p>\n

\u201cEven sometimes with samples from miscarriages, the DNA can be very degraded \u2026 we\u2019re still able to get results \u2026 and it means a lot to the parents that they get an answer.\u201d<\/span><\/strong><\/p><\/blockquote>\n

Thermo Fisher Scientific: How do you view the future of arrays now that NGS applications<\/a> are developing in this field?<\/p>\n

Dr. Brasch-Andersen: We do see more and more\u00a0 analyses moving to NGS applications,<\/a>\u00a0but I think it is still going to be a while before genome sequencing will take over copy number arrays<\/a> in diagnostics. I see the methods coexisting for a while and even supplementing each other as\u00a0long\u00a0as exome\u00a0sequencing is the\u00a0preferred\u00a0NGS<\/a>\u00a0method for diagnosing rare diseases. I am uncertain if NGS<\/a> will replace\u00a0the\u00a0screening\u00a0of the\u00a0prenatal<\/a>\u00a0samples\u00a0from the first trimester, which are the majority of our samples now. So I\u2019m sure these robust arrays will be the core of our work for the foreseeable\u00a0future.<\/p>\n

\n

\u201cWe do see more and more analyses moving to NGS<\/a> applications, but I think it is still\u00a0going\u00a0to\u00a0be a while\u00a0before genome sequencing will\u00a0take over copy number\u00a0arrays\u00a0in diagnostics.\u201d<\/span><\/strong><\/h1>\n<\/blockquote>\n

Find out more at\u00a0thermofisher.com\/repro-health-research<\/a>.<\/strong>\u00a0\u00a0<\/strong><\/p>\n

For Research Use Only. Not for use in diagnostic procedures. <\/em><\/p>\n

<\/p>\n

<\/p>\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

Dr. Charlotte Brasch-Andersen is a clinical laboratory geneticist at Odense University Hospital in Southern Denmark and an associate professor in human genetics at the University of Southern Denmark\u2014a position she has held since 2010. Previously, she held positions as\u00a0a senior consultant at the National Genome Center in Denmark, an assistant professor in pharmacogenetics at 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