Virscidian’s advanced baselining algorithm (AsLS2) quantifiably gives higher quality and more accurate results than one of the older generation algorithms which we retain in the software. We found that the maximum deviation of the automatically calculated (AsLS2) Area% from an ideal result; ie: manually reviewed and integrated peak(s), gave no more than 0.5 % deviation in the returned Area% results. When compared with another more commonly used baseline algorithm, we found that the maximum deviation was as generally within 2% but had one data point which was almost 22% different. The results are shown graphically below in Figure 1

Figure 1: Plot of normalized Area% deviation for two different baseline algorithms that are included in Virscidian’s Analytical Studio Professional – Compund QC product. The key baseline of interest is the AsLS2 baseliner.

The supporting detail

Sometime back we promised to explore more on quality of results processing in our blog post “Does the physical task of having someone review the results of purity and concentration output for substance confirmation make a difference?”. As we can all see time passed, lots due to project, travel and other commitments, but mostly because to do the type of analysis we had planned was either going to be a bear of a manual project or required us to develop some tools to help us do the job properly. Needless to say we went the second route, but this we had to put a little on the back burner whilst we attended to other pressing business needs. While I might be prepared to delve hour after hour into the depths of numbers and manual data review {and have done on many occasions}, we have better things to do and thus waited until we could automate much of the data gathering.

So armed with an experimental implementation of a data collection package, which we have embedded into our Analytical Studio Professional – Compound QC and Analytical Studio Reviewer, we set about trying to quantify the performance of some aspects of our software, which we share here as a forerunner of more detailed studies we intend on performing over time and publishing here and in other appropriate venues.

Customers have told us anecdotally that “they are extremely happy and impressed with the accuracy of the results we produce for our Compound QC substance analysis” by LC/MS/UV/ELSD, CLND (or CAD), which is all well and good but is entirely unquantified.

Experimental summary

For Compound QC or substance analysis in support of library management or Medicinal Chemistry – synthetic chemists or purification of crude substance, the calculated Area% of the target substance is used as a powerful indicator of the implied purity of the substance using some chosen detector and some extracted channel of data for the 3D type detectors that are available (DAD/PDA or LC/MS). In this case we chose the DAD 310 nm extracted wavelength chromatogram.

These results are based on a pilot small scale study of 70 samples of varying complexity from relatively clean to crude mixtures with lots of closely eluting chromatographic peaks, which we wanted to share and get feedback on. The final results are based on 52 extracted target substance peaks on a subset of the original 70 samples. This was because there were a number of samples where the target substance was not found or was identified as maybe.

The same data (UV310) were processed firstly with the Peak Picker baseliner, then the AsLS2 baseliner and then finally all results were reviewed manually and reintegrated to produce our gold standard result. The peak area% of the target substance for each sample was then extracted from each of the three series of results. The Area% values for the peak picker algorithm were then differenced from the manually reviewed results, as were the AsLS2 results. The two final sets of data were then plotted as we see in figure 1, though for ease of visualization the outlier point of 21.9% deviation for the Peak Picker algorithm was excluded from display, so that the fine detail of the graph could be observed. No other changes were made to how the data were processed or reviewed. Nothing fancy in the overall treatment and presentation of the data and results.

Results

We can see that the maximum deviation from our graph above is 0.5% for the AsLS2 baseline and was actually 21.9% for one data point using the Peak Picker algorithm {though this was excluded from the graph above}. We can also observe that there is a much tighter cluster for the AsLS2 algorithm than for the Peak Picker as shown below in Table 1.

 

Table 1:- Summary of results for the comparison of AsLS2 and Peak Picker algorithm against a series of manually reviewed gold standard results

Figure 2:- Summary of results for the comparison of AsLS2 and Peak Picker algorithm against a manually reviewed gold standard results

Conclusions

Using a development statistical data gathering approach, it is now possible to capture important data features, which can then be used to design performance evaluation studies within Analytical Studio Professional – Compound QC and Analytical Studio Reviewer, and as a consequence we are now able to start quantifying the performance of our software and further allow us to quantify improvements we make to our processing algorithms.

We hope you find this short investigation interesting and welcome feedback on our results, approach and new experiments that would further help quantify the performance of our software.

Who is Virscidian and where did we come from?  Joseph Simpkins, President of Virscidian, has 15 years of experience in managing engineering and informatics projects in the pharmaceutical, chemical and food industry and was a cofounder of OpAns, LLC.  OpAns is a Contract Research Organization providing services to the pharmaceutical industry and focused on the application of mass spectrometry to a number of issues including quantitative analysis, structure and biomarker validation and determination of physicochemical properties.  At Opans Joseph applied his expertise to the development of software tools to support the needs of the laboratory and was able to produce a platform that excited the customers of OpAns.  With time, the customers were interested not only in the services provided by OpAns but also by the software platform, at that time branded as “Analytical Studio”.

What About Analytical Studio?

The technology was developed over the course of 7 years and during that period several large pharmaceutical companies invested in the software for their laboratories.  In that time, the software architecture underwent three major iterations until it settled on a powerful but flexible plug-in based architecture branded as “The Analytical Studio Framework” (to be discussed in depth in a seperate blog post).  In 2008, the progress of Analytical Studio caught the attention of folks in R&D at Agilent Technologies.  So, by mid-2008, a small limited subset of the software built on the Analytical Studio Framework was licensed by Agilent Technologies (to be discussed in a separate blog post).  The Analytical Studio Framework allows rapid development of full featured work-flow solutions.  Starting with vendor independent raw data reading and viewing.   Then data processing and review with integrated editing of results followed by reporting and publishing and archival of results and raw data.   In essence, it is a high-throughput tool that automates the conversion of raw data to results while allowing the flexibility of vendor independency and is a powerful and flexible viewing tool for some of the major formats adopted in the industry.

With seven years of stress-testing in large pharma labs and a CRO environment,  Analytical Studio has been optimized for performance, throughput and quality of results.   But without loosing the flexibility to adjust the software to be optimized for the customer’s workflow.   Analytical Studio is componentized and can be configured to provide solutions for different environments …this is how we have built solutions for Agilent to have an Analytical Studio Reviewer, why we can rollout a fully enabled version called the Analytical Studio Professional and why we can have an “Express” version for background processing, reporting and have Analytical Studio Repository for the publishing of data.

We will shortly start publishing some movies and presentations about Analytical Studio in its various flavors from highly customized solutions for research projects (parallel HPLC and biological deconvolution) to off-the shelf compound characterization and biomarker validation.

Welcome to the Virscidian Blog. It’s likely that you have not heard of Virscidian before but we believe that will change. Virscidian is a provider of analytical chemistry work-flow solutions to laboratories of all sizes and we already have a track-record of enabling laboratories world-wide to process more efficiently with greater accuracy while integrating with existing IT environments.  What does this mean and what do we stand for?

We built software focused on supporting analytical chemists.  Good software.  Software optimized around processes, throughput and designed with the user in mind based on user requirements and guidance.  This knowledge came from more than 10 years owning, managing and supporting analytical labs.  There are many analytical software packages on the market that have a lot of functionality.  These can be either hardware vendor or third party solutions and they offer a solution to many problems. Unfortunately many of these are complex to use and are not optimal for many of the environments and users they are delivered into.  This is not a surprise as they are trying to service thousands of laboratories with a single package.  We believe there is another way.  We have created a vendor neutral, modular (we call them plug-ins) solution that can be “wired” together to provide a complete targeted solution to address many of the needs of analytical laboratories in the Life Sciences industry specifically.  We already offer off-the-shelf solutions for LC-MS data processing, visualization and reporting but continue to deliver custom solutions for laboratories with specific needs for processing, reporting, integration to databases and much more.  With a platform built on tried and tested Microsoft platforms, and with a commitment to the .NET architecture, our software is efficient, scalable and affordable.  That’s our business – we deliver the complete solution to meet your needs.

We will introduce you to our science, our technologies and our “secret sauce” over the next few months. Welcome to Virscidian…come back and hear about what we’re up to…checkout these two posters as teasers.

Elimination of the LC/MS Data Analysis Workflow Bottlenecks Using Analytical Studio

Enabling High-Throughput MRM Based Biomarker Validation Studies Through a Vendor Neutral Application