GenoLogics LIMS Helps EdgeBio Build Services Business

LIMS Supports ResEarch & clinical NGS services LAB GenoLogics LIMS Helps EdgeBio Build Services Business

LIMS Supports Research & Clinical NGS Services LAB GenoLogics LIMS Helps EdgeBio Build Services Business EdgeBio, one of the first purveyors of nucleic acid purification services, has used a commercial LIMS since it began offering sequencing services in 2009. At first, the company thought the bulk of its business would be Sanger-based sequencing. However, when the company decided to make a play to become one of the leading providers of next-generation sequencing (NGS) services, it realized it had outgrown its legacy LIMS particularly given an expanding lab environment that included three different sequencing platforms and associated, highly changeable workflows.»» A single point of entry and return for sequencing requests and results that has also enabled EdgeBio to be more deliberate and thorough in collecting necessary data from customers to drive sequencing and analysis»» Critical out-of-the-box support for standard Illumina sequencing workflows»» A flexible Rapid Scripting Application Programming Interface (API) that enabled the lab team to quickly automate routine manual inputs and implement workflows for the Ion PGM Sequencer. We needed something to solidify project management and organize sample data and metadata in a way that would help us work more efficiently and track what we were doing, said Justin Johnson, director of bioinformatics at EdgeBio. Implementing the GenoLogics LIMS has enabled EdgeBio to eliminate sources of manual, human error and improve overall lab efficiency, goals that have supported the company as it has applied for and successfully attained CLIA certification. EdgeBio recently replaced its legacy LIMS with the GenoLogics LIMS. The GenoLogics LIMS offered several advantages over EdgeBio s legacy system, including We knew we d need a LIMS to be successful with CLIA, because CLIA is all about... being able to reproducibly prove you are doing what you say you are doing, and that s what a LIMS does best. CLIA was the next logical step for our business, and we re excited about extending NGS services to clinicians so that they can help patients and gain a better understanding of genetic disease, said Johnson. And while I think our staff sometimes feels that they could do things faster if they didn t have to keep track of data, doing things manually simply isn t as accurate, particularly under CLIA. A LIMS slows you down in a good way, by making sure you re doing things right. Justin Johnson, Director of Bioinformatics, EdgeBio Page 13 2012 2011 GenoLogics Life Sciences Software, Inc.

Next-Gen Sequencing Equipment Requires Next-Gen LIMS EdgeBio s pioneering work in the 1990s led to the development of several innovative sequencing products, was more work to use the LIMS, Johnson explained. The legacy LIMS withered on the vine. including dye terminator removal products, highthroughput PCR purification products, sample preparation systems, bacterial competent cells; and an array of accessories. The company prides itself on being the sequencing purification provider of choice and maintains a solid commitment to providing highquality results and maintaining consistent communications with its customers. Sequencing at EdgeBio, however, continued to thrive. The lab began to scale up its NGS fleet and was up to seven SOLiDs and two Ion PGM Sequencers when it implemented the GenoLogics LIMS in 2011. We realized it was time to get organized, Johnson explained. We could finish a run in a matter of hours with the Ion PGM, and when you re doing 3, 4, 5, or 6 runs a day, it s a much bigger burden to keep up with all the data. For all of EdgeBio s experience in sequencing, Johnson is forthright about his organization s naiveté when it implemented its first LIMS in 2008. The thinking at the time was that if you wanted to run multiple sequencers, which we did, you needed to have a LIMS, said Johnson. But this type of thinking is usually a sign that you don t really understand your fundamental processes, and not understanding your fundamental processes, in turn, Additionally, EdgeBio was interested in pursuing CLIA certification. Having demonstrated our ability to offer research sequencing services that people would use and refer others to, the natural progression for our business was to bring NGS services to the clinic, said Johnson. Gearing up for its application required EdgeBio to take stock of its research processes and workflows. makes it hard to implement a LIMS, because a successful implementation is all about knowing what processes the LIMS needs to support. We wanted to start acting CLIA before we were CLIA so that we could adjust processes and understand what we were doing: What processes are fast, which are slow, how much Even as EdgeBio added more sequencers to its fleet, throughput was still such that lab scientists remained more comfortable tracking files using file folders or spreadsheets. When one run takes two weeks, and six months of data takes up about 10 rows in a spreadsheet, a LIMS feels like overkill our scientists ultimately felt it slower they are, how many more can we do in a week, said Johnson. EdgeBio knew that some organizations successfully achieve CLIA compliance tracking samples and processes using spreadsheets or documents. But its experience with its legacy LIMS demonstrated the need for something more robust. Page 2 2011 GenoLogics Life Sciences Software, Inc.

Figure 1 EdgeBio now runs a mixed fleet of nine machines comprising five SOLiD 4s and one SOLiD 5500 from Life Technologies, one Illumina HiSeq 2000, and two Ion PGM Sequencers. We knew we d need a LIMS to be successful with CLIA, because CLIA is all about tracking and process management being able to reproducibly prove you are doing what you say you are doing, and that s what a LIMS does best, said Johnson. The SOLiD 4 workflow was built from the ground up. We run more SOLiD sequencers than almost anyone in the country, so we offer a unique perspective that has helped GenoLogics evolve the workflow pipeline for these instruments, said Johnson. It was a really collaborative project. Supporting Next-Gen Sequencing Workflows EdgeBio opted to replace its legacy LIMS with the GenoLogics followed an iterative process that started with an initial look at EdgeBio s protocols and cycled through modifications and consultation before running configurations in a test environment. GenoLogics LIMS in order to accommodate a modern sequencing workflow. EdgeBio now runs a mixed fleet of nine machines comprising five SOLiD 4s and one SOLiD 5500 from Life Technologies, one Illumina HiSeq 2000, and two Ion PGM Sequencers. Out-of-the-box support for Illumina workflows and kits enabled EdgeBio to rapidly get the Illumina instrument up and running. However, EdgeBio was an early adopter of the Ion PGM, an instrument so new that workflows had not yet been created in the GenoLogics LIMS. The EdgeBio team was able to build out these workflows by adapting existing scripts using the GenoLogics LIMS API. Interestingly, Ion Torrent Systems has put a lot of thought into its on-board software and includes a lot of hooks for LIMS and other third-party systems, which made integration quite easy, noted Johnson. SOLiD had little or none of that initially, so it s clearly something machine We used scripts to ensure that the LIMS implementation mapped to some of their internal processes associated with labeling samples and also assisted with ensuring the LIMS interfaced correctly to driver files for the instrument, said Paul Jenkins, field implementation specialist at GenoLogics. Meanwhile EdgeBio leveraged When you re buying a system like a LIMS, you aren t just buying software, you re buying extensibility and the support of a technology partner. We definitely traded a product for a company. Justin Johnson, Director of Bioinformatics, EdgeBio vendors are starting to think about. Page 3 2012 GenoLogics Life Sciences Software, Inc.

Figure 2 Process wizard for the barcode printing process their relationship with Life Technologies and used our API to build out a backend integration to collect information directly off the instrument into the LIMS. So we each handled different aspects, but provided mutual support to ensure a smooth and painless implementation. Automating to Eliminate Errors Motivated by CLIA s insistence on tracking processes, EdgeBio was extremely interested in using the LIMS to automate data entry and streamline key workflow steps. When you re buying a system like a LIMS, you aren t just buying software, you re buying extensibility and the support of a technology partner, said Johnson. There aren t a lot of technical differences in most LIMS systems The LIMS helps by providing three things: A single point of data entry and results return, reduced data entry by scientists, and standardized workflows. today. But from the sales and technical staff all the way up in the organization, GenoLogics proved that even when the product isn t quite there yet, as was the case with the Ion PGM integration, the support is in place to get it where it needs to be. We definitely traded a product for a company. Every EdgeBio customer must enter its data through LabLink, a web portal that connects directly into the GenoLogics LIMS. The portal ensures that critical metadata is collected before sequencing even begins, including data necessary for downstream Page 4 2011 GenoLogics Life Sciences Software, Inc.

analyses. In the past, we often had to go back to clients and request certain material for an analysis, Johnson explained. Now, we can to some extent blame the LIMS to be sure we get everything we need upfront Sorry, but it s the LIMS it won t let us get started on your samples until you get us that information. scientists would use free text on the Ion PGM to enter information on the reference genomes and then upload the FASTA for alignment. Now, information on the reference genomes is stored in the LIMS, which populates the Ion PGM Sequencer directly when sequences are ready for alignment (see figure 3, pg 6). There s a drop-down menu of possible choices that scientists can select before sequencing begins, Reduced Data Entry by Scientists The GenoLogics LIMS interfaces with EdgeBio s barcode system, a capability that has significantly reduced the need for scientists to key in data manually (see figure 2, pg 4). We now have just one point where scientists have to manually enter sample data when they get the physical vials in and load them into the 96-well plates, said Johnson. Once samples are labeled, scientists proceed with follow-on steps by scanning barcoded plates and following standardized drop-down workflow options presented by the LIMS. The integration between the barcoding system and the LIMS has not only reduced error, but streamlined downstream procedures. Standardized naming schemes and other factors associated with barcoding means we can automate things that happen to samples post-lims. which keeps people from getting creative about how they perform alignment, explained Johnson. Another integration primarily benefits EdgeBio bioinformaticians. EdgeBio uses a specific cloud computing platform for some of its post-sequencing analysis. For analysis to proceed, bioinformaticians previously had to wait until sequencing was complete, then copy the data over and upload it to the cloud computing platform. The process could take 15 minutes or more because bioinformaticians often had to dig into the project management software to get key background on the project, such as submission details and the name of the researcher, said Johnson. The LIMS integration reduces all of this effort to a single button checked at the beginning of the project to indicate if the data should be analyzed on the cloud computing platform. When the box is checked, the LIMS automatically copies the data and uploads it to the cloud. Bioinformaticians receive an email Standardized Workflows The GenoLogics Rapid Scripting API has enabled EdgeBio to develop several key integrations tailored to its specific, unique workflows. For instance, EdgeBio has a standard set of genomes to which they align data when runs are complete. Prior to implementing the GenoLogics LIMS, EdgeBio when the cloud platform has performed the analysis. We save at least 15 minutes per sample, which doesn t sound like a lot until you factor in that there s probably 200 samples per analysis run, said Johnson. That s quite a bit of time saved on the backend. Plus, even a manual procedure that takes 15 minutes ultimately takes more than Page 5 2012 GenoLogics Life Sciences Software, Inc.

The LIMS has helped ensure that we can process samples more efficiently with less labor and time. Justin Johnson, Director of Bioinformatics, EdgeBio that. There s the 5-10 minutes someone will need to get their head out of what they were doing and into the manual activity, and then another 5-10 minutes to start something else. That s measurable time that adds up quickly when it s something my scientists are doing over and over again. Enabling Efficiencies and Improving Accuracy Ultimately, Johnson noted that the benefits of the LIMS aren t so much about speed as efficiency and accuracy. Our business model requires high-throughput, yes, because when someone comes to us with work, we need to be able to do it and do it well, he said. The LIMS hasn t made much of an impact on the number of samples we can process. But it has helped ensure that we can process those samples more efficiently with less labor and time. Figure 3 Process wizard for creating an Ion PGM run definition Prior to implementing the LIMS, we were probably making 2-3 data entry mistakes a week, Johnson continued. These errors did not prevent EdgeBio from working with the data or delivering quality results to customers, but they did require time to investigate and fix. Now, mistakes are rare. That s where we ve seen the value of the LIMS it keeps us more accurate. Page 6 2011 GenoLogics Life Sciences Software, Inc.

Implementing a LIMS has also supported EdgeBio s efforts to become CLIA certified. While being a CLIA lab doesn t require a LIMS, a LIMS makes it easier to demonstrate CLIA s documentation and consistency mandates than documents or spreadsheets. Additionally, EdgeBio also aspires to be CAP/CLIA accredited, which requires deeper and more rigorous certification and digital signatures not just from labs, but from their supporting instrumentation and software vendors. Now, mistakes are rare. That s where we ve seen the value of the LIMS it keeps us more accurate. Justin Johnson, Director of Bioinformatics, EdgeBio Given the level at which we want to be working, the LIMS not only lends credibility to our initiative as it s reviewed by governing bodies, but also helps in preventing sample issues and ensuring we are doing what we say we are, said Johnson. For lean organizations like EdgeBio, investing in a LIMS enables the organization to change workflows and, inevitably, mindsets. We have five people feeding our nine sequencers, and another five bioinformaticians to work with the data, said Johnson. So we wanted a system that offers balanced value: key functionality out of the box, the ability to adapt and extend the system over time, and professional help and support for the long haul. Prior to the LIMS, sample tracking and management was something our staff would get around to when they had time, Johnson concluded. We ve definitely changed the paradigm so that now sample tracking is something that our scientists and bioinformaticians do as a matter of course, and when they have time, they do something else. Page 7 2011 GenoLogics Life Sciences Software, Inc.

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