Hello, everyone, thank you for taking the time to attend today's webcast presentation. We are so excited to have all of you here with us today to show off our upcoming addition to VSClinical, the ACMG CNV workflow. My name is Delana Hawkins and I am the director of marketing and operations here at Golden Helix and will be the moderator for today's webcast. It is my pleasure to introduce today's presenters. Firstly, our field application scientist, Julia Love. Julia, welcome.
Hi, yeah, thanks, Delaina. I am happy to be here. And then also we have joining us our VP of product and engineering, Gabe Rudy. Gabe, thank you so much for joining us today as well.
Excited to be here.
Before I pass things over to you, I will remind our attendees that we will be having a live Q&A session at the end of your presentation. If you have a question that comes up, you can enter those directly into the questions pane of your Go to Webinar Panel. Now on the screen here, you can see where we are referring to in case there are any concerns. These will also be asked anonymously. So please enter those as they come up. I will be back later to announce some exciting news here at Golden Helix, but for now, I will go ahead and hand it over to you, Julia.
Thanks, Delaina, so yeah, I am really excited to share with all of you today some updates and new features that are being incorporated into this upcoming release of VarSeq. Recently, we have been talking a lot about the addition of the new ACMG guidelines, specifically for CNV analysis. But there is so much more that has been added to this, to VarSeq and the ACMG workflow. Many of these new features have been developed and incorporated from feedback from VarSeq users, which makes this even more exciting to talk about. But before we start deep-diving into the subject, I wanted to mention our appreciation for a recently received grant funding from the NIH. The research reported in this publication was supported by the National Institute of General Medical Sciences and the National Institutes of Health under these listed awards. Additionally, we are also grateful for receiving local funding from the state of Montana. Our PI is Dr. Andreas Scherer, who is also the CEO at Golden Helix and the content described today is the responsibility of the authors and does not officially represent the views of the NIH. Again, we are thankful for grants such as these, which support the advancement and development of our software to create the high-quality software that you will see today. So, with that covered, let's take a few minutes to talk a little bit about our company. So Golden Helix was founded back in 1998, and we are one of the few bioinformatics companies that can say we have 20 years of experience building solutions in the research and clinical space. And these solutions have a broad range of capabilities. We will not be able to cover all of these today, but they do cover a lot of use cases in both clinical and research realms. But what we will be focused on today is our VarSeq product suite, which focuses primarily on the clinical application of the software. VarSeq supports clinical analysis workflows in which you can filter and annotate variants and then evaluate those variants according to the ACMG and AMP guidelines. However, if you are interested in any of these other capabilities, please visit our website. We've recorded numerous webinars and other materials for you to browse through at your own pace. We have been cited in thousands of peer-reviewed publications, and we are always happy to celebrate the success of our customers in performing their research, using our tools. And, if you check out our blog, you will often see us highlighting those publications. We serve over 400 customers globally, and these customers span many different industries from academic institutions to research hospitals to commercial testing labs and government institutions. As a company, our software is being vetted by our large and established customer base and we have had many years to perfect the development process and are always incorporating feedback from our customers and their diverse set of needs and use cases. We are integrated into the scientific community, providing content in the form of e-books and webinars, much like this one. As a business, we want to be aligned with the success of our customers, and one way that we do that is to provide our software on a simple per-user subscription model that comes unlimited with training and support, as we are invested in supporting your research or setting up your test so that you can run as many samples through our software as possible. Since we are an established and trusted business in this space, you might already know someone who uses Golden Helix. But if not, we are happy to find a reference for you in your area. So before I jump into today's topic, I want to provide a conceptual overview of how VarSeq and more specifically VarSeq clinical fits into your analysis workflow. So conceptually, VarSeq's application comes into play for all tertiary analysis of variants and copy number variants, and VarSeq comes fully equipped with algorithms and annotations, metrics that help you understand the impact of your clinically relevant variants. So VSClinical can essentially be thought of as the second stage of analysis. So, after you've identified the clinically relevant variants, these variants can be evaluated with either the AMP or ACMG guidelines to determine pathogenicity and oncogenicity. VSClinical automates the application of these guidelines, simplifying what is normally a tedious and complex process. Then lastly, once the evaluation is complete, the interpretation can then be stored in your internal assessment catalogs and rendered into a clinical report. So together, VSClinical is an ideal paradigm to streamline analysis for clinical variants and CNVs. That said, there are many new features and updates to the ACMG guideline workflow that we want to cover. So, let us go ahead and get started. So many of the new features for the ACMG guidelines workflow that we are going to cover today come into play when you are setting up your project and evaluation and these new features are nicely then incorporated into clinical reports. So, I'll start by going through a few slides that will discuss VSClinical ACMG features that are now available. Some of these are new algorithms or new ways to catalog and save classifications or are improvements on the customization options for clinical evaluations. Then our VP of product development, Gabe Rudy, will deep dive into the new reporting capabilities for the ACMG workflow. The reports are now Word-based, and there are a couple of different templates to choose from to report your findings. And with that, the Word-based templates do offer some more opportunities to easily customize your clinical reports. Then lastly, for the product demonstration, we are going to allow you to see some of these features in action. So, first, I will walk you through setting up a new evaluation and customizing your workflow, and then I'll show you how to carry the variant CNV interpretations over into the new reports, and then finally, Gabe will demonstrate how users can easily customize those clinical reports. OK, so as some of you may know, the VSClinical uses the ACMG classifier algorithm, which computes classifications for each variant based on the ACMG guidelines. And so, these classifications are based on evidence such as population frequencies, conservation scores, splice site algorithms, and functional predictions. Since the publication of the original article describing the ACMG guidelines back in 2015, there have been a few updates and additional scoring options added to the guidelines. So, in particular, ClinGen, more specifically, the sequence variant interpretation working group refined at the scoring for PVS1 variants. So, the guidelines now elaborate on specific considerations for the different types of loss of function variants and provide decision-making pathways, assimilating information about the variant type, its location, or any additional evidence for the likelihood of a true null effect. The result of taking these nuances into account is that instead of a single, very strong criteria, the scoring allows null variants to range from supporting to very strong and VSClinical has been updated to automate the decision and suggest the appropriate strength for any given potential loss of function variant. On a related note, we have expanded the ability to change the evidence strength to many additional scoring criteria, allowing your lab to customize the scoring process to meet its own needs. Then the final edition to the ACMG sample CROSSFIRE algorithm is that you can include custom population frequency tracks like Caviar, Top Med, and, we had many requests for Gnomad genomes to be available to evaluate variants. Because it is such a large annotation track, we did not want to force users to download this track. But now it is available for those users who do work with whole genomes and they can opt into using it for their analysis. Then also, if you do have established your own population cohort, you can utilize that as well. So, if you want to include your own cohort for analysis, we do recommend that you have at least 2,000 samples. But even more exciting is the addition of the new CNV classifier algorithm for evaluating CNVs according to the ACMG guidelines. We have had previous discussions on the new ACMG CNV classifier, but now this can run scoring for CNVs just like the autoscoring that runs for variants. Going hand in hand with the ACMG CNV classifier is a second algorithm: the probability segregation algorithm, which will compute the expected copy number for each CNV column. It also identifies other samples that are likely to share the CNV. In the case of trios, it computes the probability that the CNV is present in the mother or father. So, these algorithms can be incorporated into your workflow to narrow down your search for variants, to be evaluated with the ACMG scoring criteria but integrated into the ACMG classifier algorithms and the ACMG workflow overall are the assessment catalogs. An essential component to the ACMG workflow is saving your variant interpretations and classifications for your reference, but also for application in future samples. So, for instance, if you have a previously evaluated variant and then you see that variant again in another sample, you will not have to classify this variant all over again. To be able to save even more information about the variants that are being evaluated, additional fields have been incorporated into the new ACMG assessment catalogs to capture every user-provided detail about the variant. Of course, with the addition of the CNV interpretation, with the ACMG guidelines, there is a need to save both CNV and gene interpretations as well. And this is important for CNV workflows as the information on certain genes or CNVs can be limited. So, the assessment catalogs allow your lab to essentially build an internal database for interpretations and classifications for the CNVs and the genes that you evaluate within VSClinical. Then setting up the assessment catalogs for saving variant and gene interpretations is the first step in the VSClinical workflow, and then the next step is to set up the project-specific details, defining how you will evaluate variants and regulate the information that is going to be included in your clinical report. Many new project options have been added to offer more customization for your workflow. I also want to mention that these options are also available in the AMP workflow for those of you listening in from the cancer space. But let us discuss some of these features and customization options now. So, some of you may be familiar with the ability to flag, track, and organize variants for analysis within the current version of VarSeq. These flags can now also be applied to CNVs and coverage regions. So, the flags are essential not only to track variants and CNVs within your VarSeq project, but they are also useful to preselect variants, CNVs, and coverage regions to be included in your clinical reports. There are many applications for these flags as they are fully customizable. But one example may be that you want to flag a specific region that had low-quality exon coverage and include this information in the clinical report. The next feature I want to mention is that you can now include custom gene lists and gene panels, even more, you can include the gene list in your report, and you can even calculate covered statistics based on that gene list and visualize coverage for those genes specifically. Next on the list here, you can see that you can still define custom thresholds for the ACMG criteria, like the allele frequency for a variant to be considered common in the control population, for example. However, you can now choose the HGBS representation notation for display and reporting. This is important, as I know, particularly in Europe, but there is a specific way that variants must be reported. So, the ability to control this display is essential. On a related note, we have included the option to score variants according to the ACGS guidelines, which are based more on European best practices. The difference between the ACGS guidelines is that they have potentially an improved way to sum up the scoring criteria when distinguishing between likely pathogenic and pathogenic classification for variants. But before we change gears to discuss the new reporting capability, there is one more new feature that I want to mention, and that is the ability to define and lock the annotations that are used in evaluations. So currently, VarSeq has been able to guarantee consistency in using the same annotation sources by having those versions incorporated into a project template. However, VSClinical has always used the latest version of the annotation source that's downloaded. But now, by default, VSClinical will remember all the sources used to create an evaluation, even if a newer version of that source is available, and to ensure those same versions are used, you can lock these. These will be used for future evaluations within the project, and then if you want to, you can continue to use the same annotation sources in other projects, as these locked sources can also be integrated into the project template as well. Like other features that we have talked about, these annotation source versions can now be appended to the clinical report. Speaking of reports, I am happy to introduce our VP of Product Development, Gabe Rudy, who will discuss the new reporting capabilities and how you can customize your clinical reports.
The second template we call the trio report template. Now, although we call it the trio report template, it would still work if you did not have a trio. But this template is really focused on the use case of having more than one sample or really having the pro-band and the parent information, and having a place in the header for the parent information, and having a place for the parents' genotypes and the parents' allele depths and variant allele frequency for every reported variant: so, all that sort of information that you would want to put in a report focused around maybe a trio diagnostic situation. This also just demonstrates a little bit different set up in terms of detail. This is sort of in the moderate level of detail. Again, the nice thing about having multiple report templates to start with is you can open all of these and be, oh, I like the way that this section kind of went into a little more detail. I am just going to copy and paste that into my other report and kind of mix and match, as you may choose to do. The third report template: we call this the Mendelian disorder report template. You might recognize this because this is also very similar to the report template, we have been advocating in our existing report system called our ACMG Report Template. It is very much focused on the maximum amount of detail where you might be starting from a situation of a whole genome or whole exome, so you expect to find secondary findings, which is very common in that situation. And if you are incidental findings are being reported, you might want to break them down into those that are of direct concern for sort of hereditary disease risks. These would be monogenic disorders with a dominant model versus those in which you're purely in a carrier status. So, all the variant is pathogenic. You only have essentially potentially one novel allele, and that might be critical for understanding the use case or might be critical for sort of interpreting the report. So, this is our most advanced, most detailed report template. So, what do you do with these templates? As I said, you can start with them as is, they are very easy to customize and when we get into the demonstration portion, we will demonstrate just a couple sort of cosmetic changes and even how to sort of customize the content itself. It is very easy to, for example, just change the header and logo. You basically open one Word file, and when you open the template Word file, it will look a little bit like this screenshot. And you can see basically you can do all the editing you want on here, but the text has some special text characters like these ones in brackets that will get replaced as basically almost like a find and replace with the content coming from your patients and your variants. Then custom logic can also be applied, even if we have an imagined way in which you potentially want to present the information or what piece of data you have. There is an enormous amount of raw data that is backing this report, and that raw data can be displayed, manipulated, summarized, tabulated, put into columns, all that type of stuff. And I think our different report templates give you examples of all those as a starting point. Of course, you can always reach out to our fantastic support team to do more advanced things or work with us to design a custom report. We are very excited about this new reporting capability and we think it would be a great default starting point for people who are using VSClinical.
Thanks, Gabe. We look forward to seeing some of that a little bit later, but first I want to go ahead and transition over to my VarSeq project. This project has three whole exome samples already imported and ready to go. I'm also going to be using a bone disease gene panel to narrow down to the clinically relevant variants and CNVs. So, go ahead and... OK, so you can see here in the three samples, I have about forty-five thousand variants that were imported and I can see all these variants displayed here in the variant table. Also in the variant table are any annotations and algorithms that were used in the project. We can see here, for example, the ACMG sample classifier. Any of these fields from within the variant table can be used to filter your variants down to those that are clinically relevant using the filter chain here that you see on the left. So, in this case, I have started filtering variants based on quality, but then you can see I apply my bone disease gene panel, which brings us to about 80 variants, which is still a lot of variants to have to go through. But once I leverage the classification output from the ACMG classifier algorithm, I essentially filter out the benign variants and that leaves us with 12 variants to analyze within VSClinical, which is very manageable considering we started with forty-five thousand. Also, in this project, I use the VarSeq CNV caller to call CNVs based on defined target regions which are displayed here in the coverage regions table. But just like for the variants, we have a CNV table displaying all the CNVs that were called from my samples, which looks to be around five hundred and fifty.
And then again, any of the CNV annotations and algorithms that are added to the project are displayed here as well. You can see here that after filtering on quality, I use the AC oh, let me switch over there. I use the CNV classifier to essentially ignore looking at those benign CNVs, and then I use that same bone disease gene panelist that I use for my variants to get us down to these six CNVs here that we can potentially evaluate with VSClinical. So, the first step to creating an evaluation: I have flagged a few of these variants and CNVs that we will take a look at. The first step to creating an evaluation is to create the assessment catalogs that are going to be used to capture the interpretations for our variants. So. Let us go ahead and do that now.
This first catalog here is to capture variant interpretations and then this middle one is for CNVs and then this last one will be to capture those gene interpretations. So, if you're a new VarSeq user, you will have to create each of these catalogs, and you'll do this by clicking on the create missing catalogs. You can see that when I do this, a catalog is automatically named and created in the assessment catalogs folder. For those of you who are existing VarSeq users, you may already have a catalog that you have been using to save your variant interpretations. You can continue to use this catalog as is, or alternatively, you will see this little notification here that you can add those additional fields to your existing catalog. And so, you can see when I click on this, you can see which fields will be added to the assessment catalog, and then any future variants that you evaluate will have interpretations for these fields. It looks like we are all set to go, so we will click OK, and then the next option that we see here is that we can choose to lock any of the annotation sources in our project.
Right now, I have got three sources here wherein there is a newer version available and I am using an older version, and so potentially I could update these, but I actually want to go ahead and lock these versions down to be used for this evaluation and future evaluations in this project so that I know I'm using the same sources to evaluate variants across my different samples and just maintain consistency there. At this point, we are just about ready to create our evaluation, but I have a few more opportunities to customize my workflow, so I will open the project options tab here, and the first tab is for the report sections. This is where you can create and choose those record sets or flags for reporting and tracking your variants and CNVs. I still need to create these for my CNVs, so I will go ahead and do that real quick. Just a quick click to do that and I will apply that and go back and project option. Sorry, I need to import my gene list so. I just got a text file here for my bone disease gene panel, and I will just go ahead and paste that in here. OK, and I'll click apply, and so that'll be good because we'll take a look at that when we create our evaluation, and we can look at the coverage for those genes. OK, so we will go ahead and start our evaluation, and in the evaluation tab here, I can see information about my sample and the sources that were used, but the main purpose for this tab is to add your CNVs and variants from your project. And so, as I mentioned, I did flag some of these variants for us to look at. So, I will go ahead and add those. And it looks like I can see here that these variants are present in the assessment catalog, so that means that they have been previously classified. So that is good because that will save us some time as we go through it. Now, let us go ahead and add our CNVs.
OK, and it looks like these have also been evaluated, too, and so this is really highlighting the value of the assessment catalogs. We are going to have some of our work cut out for us and I will show you what I mean here in a minute. But first, let us go ahead and look at the genes tab.
So, at the top here, you can see that we have a nice coverage summary based on the targets and the information from the BAM file, and then here from the project options, I chose my bone disease gene panel list. But when we scroll down here, we can start to see this gene coverage visually and I am going to go ahead and change this threshold down to 10x coverage for a minimum. And so, you can kind of see that the genes that passed as failed targets and genes that passed with good coverage kind of changed. So, the green bars here are those genes that meet that 10x required minimum coverage. The yellow bars are those that meet the 10x minimum, but they do not meet the desired 100x coverage that you can see here. And then the red bars are any of the genes with a depth below the 10x. And so, we can see here, for example, with this gene that the minimum coverage is 9, and so that is why that one's red. But if I do scroll down further, you can see here the list of genes that did not meet these thresholds that I just set and so I can have these also reported as failed regions.
But with that, let us go ahead and pop over and look at our variants and CNVs. So here we can see that the recommended scoring criteria for this WT1 variant have been evaluated and applied, and so these criteria lead us to a pathogenic classification, and we can see here all the interpretation filled in, it looks like, by my colleague Eli. And so, I want to be sure that I mark this variant as my primary findings for reporting, but then with that, we are pretty much ready to move on to our next variant here, which is our CBS variant, which has also been scored. But for this variant, I want to mark this as my secondary findings. Something else here, I can see that this is variant is a loss of function variant as PVS1 is being recommended. So, this is a great opportunity to look at the updated PVS1 scoring and how this looks in VSClinical so we can go ahead and jump to that section and look. So, this variant is a confirmed PVS1 variant and meets that very strong recommendation. However, in the case that the evidence is not so straightforward, VSClinical will automatically apply the logic that would potentially downgrade the recommendation to PVS1 strong or moderate or supporting. Conveniently, you can reference this logic tree for more information about how VSClinical is making these recommendations and in those decisions. All right, so since our variants are all scored and ready to go, let us take a quick look at our CNVs.
So, it looks like Eli has also scored our CNVs, but I just want to quickly mention that we do have webcams that do cover the details of the scoring process for variants and CNVs. So, you might want to check those out if you have not. But I am going to go ahead and start with this NR5A1 deletion, and if we scroll down here, we can see that this CNV does have evidence of haploinsufficiency and is scored a 2E in Section two as this deletion does disrupt the reading frame. I can see here, Section 5 is a sample-specific scoring section, so I would need to go through this for the sample, but for the sake of time, I am just going to go ahead and move on to our next CNV. This next CNV is a duplication in the OCRL gene, and now the CNV classification is of uncertain significance, but it is relevant to the patient's phenotype, so I do want to include this in the clinical report, but I will go ahead and include that in the section dedicated to uncertain, significant findings. So, if we take a quick look at this CNV, we can see that this gene is a haploinsufficient gene. However, it looks like this CNV is an in-frame insertion here, in exon 9, and it is not disrupting any protein function. We can kind of see this with its gene impact score and we are not getting any points there. But at this point, it looks like our variants and CNVs are ready for the report. So, let us go ahead and open up that report tab now.
If we quickly just look at some of these report sections, you get a nice summary of your results and patient information and sample information. But really, if you had to enter in all this information manually, you know, that takes a lot of time, and we do have a solution for this. When you import your samples, you can use a text file and have this information automatically fill in. And the VarSeq project has this available in the samples table, and so I can kind of pop over and show you really quick, you know, if you had a gene list associated with your samples or any phenotypes or, you know, disorders associated, those are not only displayed in the sample table, but they're also displayed here in the report and automatically fill in. But with that, I think now I would like to turn things back over to Gabe and he can talk a little bit more about reports and more specifically how you can customize these reports.
All right, so before we transition into answering some of your questions, I do want to again mention how grateful we are for grants like these, which just provide huge momentum in developing our software. But at this point, I will turn things back over to Delaina as she will talk about some Golden Helix updates, and then I think we'll go into the question and answer period.
Perfect. Yeah, thanks, Julia, and thanks to the both of you for that great overview. As she said, it looks like we need to give you guys a second to enter some questions. And as we wait, I will cover a few things happening here at Golden Helix. So first, I would like to feature the End of Year bundles that we recently announced, I think last month. This is a wonderful time to implement a Golden Helix solution if that is something you're considering. Listed here are the software packages we are offering. And then the number on the left of each bundle represents how many of those remain. So, for instance, the one on top, we only have three SVS imputation modules left. So, if you are interested, I highly advise reaching out to our team as soon as possible so we can make sure to put your name down on one of those before they run out. We have extended these bundles into the New Year, too, but to accommodate for budgets and Covid-19, but we do advise all of you who are interested to let us know whether you are considering making that purchase this year or next. I will go ahead and throw a link into the chat ping here so you can go to our website and learn more and request more information on those. You should see that pop up. There you go. And then just as a reminder to all our community, our Covid-19 assistance program is still running. This program allows all our customers to receive an additional licensed installation for those that are still working remotely, so you can continue to do your analysis wherever you might be. So, this is something that you would like to request or learn more about, you can either enter that into the questions pane and we'll follow up with you or you can get a hold of us on that same link I just sent. Perfect, and then next, I would like to mention Golden Helix was named to the Inc. 5000 list of fastest-growing private companies for our second consecutive year, and we are so honored to have received this recognition for two years in a row and just must thank all our customers and partners who have supported our sustained success throughout the years. So, thank you very much. Next is, if you are new to our webcasts or have not joined us for a while, our team has used our research platform SVS to publish several publications. On the top are the interviews and articles by our Golden Helix's president and CEO, Dr. Andreas Scherer. These discuss the use case of our platform in the space. Then on the bottom, we have published our work in two journals already using some of the statistical analysis features available in that SVS platform. So, if you are doing work in this space and would like to discuss these capabilities with our team, you can reach out to us and we'd love to show you on a more individualized demo, but we are very appreciative to be cited in so many of these publications. And then lastly, another exciting announcement, ClinGen recently identified the genomic analysis software platforms that meet their standard requirements to support data sharing. And if you look closely, Golden Helix is proud to say that we are included on this list and we are also the only vendor that was able to make the roster for meeting all the additional achievements with our VarSeq and VSClinical platforms. So, we are very appreciative to be able to share this list, and excited to be able to offer all of our customers a solution that meets all of these use cases. So that is it for my updates, and hopefully, that was enough time to give you guys some questions, but you can continue to enter those, and we will go ahead, Julia and Gabe, and get started with these.
So, first question is: Will the old report templates and reporting capabilities still be available in the new release?
Yeah, so you can still use the old templates and reporting system that you have been using previously, and because all of that capability is still there, if you prefer not to switch over to the Word-based report system.
Absolutely, and there is no reason that's ever going to go away, we don't want to break people's existing workflows. We want people to be able to, like anything in VarSeq, continue to use it if they have their system locked down and their process in place. We are finding that most people, some people have started to switch in our beta program because they wanted some of the flexibility and the layouts, and the translation was straightforward, especially with our report system having a design to match, very similar to the ones that we had in our old system. So, if you do want to make the switch, we expect it to be a moderate starting point or a moderate effort, depending on how close you are to the reports that we had in the old system.
Great, thank you. The next question is: Is there a director-level sign off for the clinical reports?
Yeah, there is, and, I can show this really quick in the software here, so right here in the report tab, you can see this nice green button here that you can sign out and finalize your report, and it gives you a nice little summary here. Then when you finalize and close that, when you go ahead and view this, it kind of goes into a disabled state where you can't make any of the edits, and it looks like I reopened it, but essentially, yes, you do have the opportunity to have a director sign-off on your reports and then they won't be able to be edited or changed around.
That sign-off information is brought into the render template as well. So, the templates I was rendering, for example, it would have said draft at the bottom of the footer until you get to that signed off state. And then it would say, you know, it is signed off by this person at this time automatically.
Great, thank you. We are coming up on the top of the hour, so I'm going to we have quite a few people asking, so I'm just going to summarize this one really quick: Does this Word-based feature also work with other operative systems, where Microsoft Word is not used.
Yeah. So that is a good question. So, we absolutely are running this in a way that we are not dependent on Word existing to create the file. We are creating a docx file and then we are just asking the operating system to open that. That turns out to work very well on Linux. We have several folks who are who have been using this on Linux. They are generating the report just fine, and it opens in the free LibreOffice Suite on Linux and is able to display this information because it is an open standard format. Then from there, you can save your file back out to a PDF and save that as part of your preserved project state. So, it works on Windows, it works on Linux, works on Mac. This is kind of the final sort of cool trick on this is it also works in our command line automated VSPipeline mode. So, if, for example, you wanted to generate a kind of draft report that just did all the automated analysis, prepare a bunch of variants that have maybe some classification based on the auto-classification system, you can get all the way to creating thatdocx report without the user doing a single thing, and then they might start from there and do some more work. So, it works in all those contexts.
Well, great. Thank you, Gabe, and thanks to both of you for this presentation, and like I said, we are up on our hour, so, unfortunately, we will have to go ahead and wrap things up. But we still have a lot of great questions to answer. We will have Julia and Gabe and I follow up with you all individually. But that is it, thank you, Gabe, and Julia, for this great demonstration. It is always great to have you guys. Absolutely. Thank you. Thanks. Then just to all our attendees, thank you as well for attending. In a moment, you will be shown a short two question survey about today's webcast that we hope all of you will give us your feedback on. But with that, I would like to thank you for attending and I hope to see you again on our next webcast in the New Year. So goodbye and see you later.