Category: About LabKey

Biopharmaceuticals are increasingly being prescribed for a variety of diseases, from autoimmune disorders such as arthritis to neurological conditions like Alzheimer’s. Neutralizing antibody (NAb) assays are a critical component of biopharmaceutical development, helping inform researchers of potential product efficacy and patient safety. Having reproducible, repeatable NAb assay results will improve the product research pipeline and ultimately impact trial and patient outcomes. For this reason, efficient NAb data management is more important than ever to biomedical researchers.

With the advancement of plate and instrument technologies, NAb assays provide a high-throughput mechanism of evaluating the potential immunogenicity of the drugs they study. Teams must be able to set up plates accurately, produce consistent analyses, ensure appropriate quality controls, and keep track of data provenance in order to deliver NAb assay results that are reproducible, comparable, and reliable.¹ LabKey Server helps teams overcome core challenges in generating reliable NAb data in the following ways.

Facilitating Good Record Keeping Practices

LabKey Server helps scientists maintain good record keeping by:

• Directly importing instrument-derived results files and collating them into an analysis dashboard
• Improving data integrity by associating raw data files and results
• Providing a built-in graphical template designer that allows users to quickly create new plate layouts (supporting options for cross- or single-plate dilutions, and single- or multiple virus plates)

Streamlining NAb Data Analysis & QC

Improve the consistency and ease of NAb data management and analysis using LabKey Server by:

• Automatically calculating and generating neutralization curves and titers
• Removing ill-fitted and otherwise unsuitable data and maintaining those changes for future quality assurance
• Translating complex plate maps with dilutions and/or multiple viruses into the NAb dashboard so that results of each run may be viewed and graphed on a per-virus basis

Enabling Collaborative Analysis

LabKey Server can help researchers collaborate and share NAb data by:

• Centralizing raw file storage and analysis in a secure web-based interface
• Providing an interactive NAb Dashboard for collaborators to interrogate the data
• Integrating NAb data with other data types, presenting users with a comprehensive view

High-throughput 384-well NAb assays may contain hundreds of samples with dilutions across plates or within a single plate and the resulting graphs and views can be complex. The LabKey NAb Assay tools provide quick visual feedback allowing you to confirm a valid run or immediately correct and rerun if necessary. To learn more about using LabKey Server to manage NAb data, check out the NAb documentation library on the LabKey Support Portal or request a demo.

¹https://bmcimmunol.biomedcentral.com/articles/10.1186/1471-2172-12-33 

Project Background

In 2017, Harvard Pilgrim Health Care Institute (HPHCI) was selected by the U.S. Food and Drug Administration (FDA) through the FDA-Catalyst program to lead the development of a mobile application, called FDA MyStudies, that would facilitate the collection of real-world data directly from patients to support clinical trials, observational studies, and registries. The effort was funded by an award to FDA scientific staff from the Patient Centered Outcomes Research Trust Fund which is administered by the Associate Secretary for Planning and Evaluation (ASPE) of the Department of Health and Human Services. Harvard Pilgrim selected the mobile application development firm Boston Technology Corporation (BTC) and LabKey as their development partners for the project. BTC was tasked with developing a user friendly mobile interface while LabKey was tasked with building a secure back-end storage environment for collected data.

Why LabKey

LabKey Server was selected as the back-end data management solution for this project for a number of key reasons, one of which being the platform’s flexible, science-specific architecture. With the project’s long-term goal of expanding the use of real-world data across research programs, the application framework needed to support a broad range of potential healthcare topics through configuration as opposed to requiring development for each new project.

LabKey Server also stood out as an ideal solution because of the platform’s ability to handle PHI/PII data in a manner compliant with HIPAA and FISMA regulations. Finally, one of the project requirements outlined by the FDA was that the resulting application and storage architecture would need to be made available as open source to the scientific community. LabKey Server, an open source platform licensed under Apache 2.0, was able to support this distribution model without any changes to the existing licensing model.

The Implementation

The back-end storage environment is composed of three independent web applications:

1. Response Server: used to store data captured via the mobile application and provide secure access to these data for data analysis purposes.
2. Registration Server: used to manage participant authentication, preferences, notifications, and consents.
3. Web Configuration Portal: used to design study questionnaires and store study configuration information including consent forms, eligibility tests, surveys, and study resources.

This dispersed data model ensures secure partitioning of all identifying information from response data, helping ensure patient privacy. LabKey Server provides role-based governance of the data stored on the Registration and Response servers and ensures that data are only accessible by authorized users. When it comes time for analysis, data stored in the response server can be accessed by authorized users via a number of different methods including LabKey’s built in analytics capabilities, download to SAS or R, or export to Excel or other standard format.

The bulk of the components used in the development of the secure data storage environment were previously existing in the LabKey Server platform. However, three key areas of custom development and extension were required to support the project’s use:

• Enrollment Tokens: A unique token that is assigned to each participant upon registration that can be used to restrict their enrollment to a specific study cohort, as well as match the collected study data to external systems (e.g., EHRs).
• Automatic Schema Creation: Automatic generation of a new database schema when a study questionnaire is created, eliminating the need for manual schema development.
• Mobile App Response Handling: Capabilities to support automated parsing of the JSON responses sent by the mobile application were implemented, enabling the storage of results in the schema, in a scalable manner.

The LabKey team delivered these developments in a custom module using an agile development methodology, refining them based on client feedback in tandem with the development of the mobile application UI.

Results

To evaluate the usability and viability of the application and data storage environments, Harvard Pilgrim contracted with Kaiser Permanente Washington Health Research Network (KPWHRN) to launch a pilot study examining the medication use and healthcare outcomes of pregnant women throughout their pregnancy. For the pilot program, the Harvard Pilgrim team utilized LabKey’s Compliant Cloud hosting services to manage the storage of study data in a secure AWS cloud environment. Participants who successfully completed the study reported high levels of usability and comfort sharing sensitive information using the app. The pilot was deemed a success, and in Fall 2018 the FDA released the open source code and documentation publicly for use in other studies. Since its release, the FDA MyStudies platform has been selected to support a clinical trial as well as a disease registry.

Webinar Presentation

On May 9, 2019, subject matter experts from the FDA, HPHCI, BTC, and LabKey, presented an overview and many details about this project in a live webinar entitled: An Introduction to the FDA MyStudies App: An Open-Source, Digital Platform to Gather Real World Data for Clinical Trials and Research Studies.

Learn More Here!

Related Reading

https://www.fda.gov/downloads/Drugs/ScienceResearch/UCM625206.pdf

With massive increases in data collection, scientists must diligently apply Luminex data management practices, well-defined quality controls, and consistent analyses¹ in order to be efficient and effective. The Luminex xMAP technology is widely used in research, clinical trials, and diagnostics as it provides a multiplexed immunoassay platform to measure complex humoral responses. With instrumentation and bead technology improving, scientists are able to measure larger numbers of analytes on a greater number of samples.

Although typical Luminex xMAP exports are easy to read, they are often exported as multi-tab files that require human interaction and manipulation of the data in order to perform comprehensive analysis. Standard analysis mechanisms that involve manual processing of data are arduous and prone to errors. Results and visualizations of Luminex data are often shared without comprehensive annotations on how the analysis was performed; leaving out valuable background information such as well-exclusions, curve fits, and background calculations. Utilizing LabKey Server for Luminex data management helps standardize the workflow of transforming instrument-generated outputs into valuable data visualizations and ensures that valuable contextual information is preserved.

Enhancing Luminex Data Management

The LabKey Server software platform helps research teams enhance their management of Luminex data by:

• Providing support for multi-tabular excel output files and converting them into easy-to-read grids
• Allowing users to attach metadata about Luminex runs, increasing traceability of data
• Providing a single platform where raw data, transformed data, and analyzed data are linked and easy to track

Improving Quality Control of Luminex Data

LabKey Server’s Luminex data management tools help labs improve quality control of their data by:

• Automatically flagging outliers based on expected values
• Tracking data exclusions made by users
• Providing users with tools to track QC metrics across runs using Levey-Jennings plots

Ensuring Provenance & Reproducibility of Luminex Analyses

LabKey Server helps teams maintain data provenance and conduct reproducible analysis by:

• Logging changes to data records and allowing scientists to view the history of data transformations from the raw file to the analyzed results
• Providing built-in visualization tools that can be reused across runs
• Providing mechanisms to securely share data with colleagues, collaborators, or manuscript-reviewers

With the right tools, scientists can maintain a comprehensive, error-free catalog of Luminex data and analyses. To learn more about using LabKey Server to manage Luminex data, check out the Luminex documentation library  on the LabKey Support Portal or request a demo.

¹ Eckels J, Nathe C, Nelson EK, et al. Quality control, analysis and secure sharing of Luminex® immunoassay data using the open source LabKey Server platform. BMC Bioinformatics. 2013;14:145. Published 2013 Apr 30. doi:10.1186/1471-2105-14-145

Our Commitment to Cyber Security

The security of our users’ data is of utmost importance to us at LabKey. LabKey Server has functioned as a secure platform for research teams for 15+ years and the LabKey team works diligently to to adapt the platform in order overcome the evolving security challenges of a web-based world.

LabKey releases three major versions of the LabKey Server platform each year, each of which is subjected to extensive automated and manual testing to identify potential bugs and platform vulnerabilities for correction prior to each release. On rare occasion the LabKey team may identify or be notified of an issue that poses a risk to our users’ security. When this occurs, the LabKey team will assess the issue and determine a timeline for resolution based on the severity of the risk. Issues that pose a high security risk to our clients are corrected and delivered via a patched version of the current release to clients and community users as soon as possible.

Recent Security Vulnerabilities and Resolution

As a community driven platform, we welcome the collaboration of groups like Tenable, who recently brought to our attention several security vulnerabilities with the LabKey Server 18.2 release. These security issues were resolved in accordance with LabKey’s standard operating procedure for security vulnerabilities; the most serious was addressed with an immediate hotfix to the 18.2 release and the remaining issues patched in LabKey Server 18.3.0-61806.76, released January 16th.

The three vulnerabilities that were recently disclosed stemmed from different causes, with varying levels of risk. The most serious was a cross-site scripting (XSS) vulnerability that could have allowed a malicious entity to create a URL that, if accessed by a LabKey Server user (via a link in an unsolicited email, for example), would cause their browser to execute JavaScript of the attacker’s choice. This issue was hotfixed in version 18.2.

The second issue allowed a malicious entity to create a URL that would initially send a user to a LabKey Server installation, but then redirect them to a third-party server, such as one controlled by the attacker. Users might have inspected the link sufficiently to see that it went to a trusted LabKey Server deployment, but not realized that their browser would later be sent elsewhere.

The third issue was a bug that did not fully handle all possible inputs from a site administrator setting up a network drive mapping on LabKey Server installations on Windows. It would have allowed them to run command-line programs on the server. LabKey assessed this issue as a very low risk, since site administrators are implicitly trusted on all installations with the highest level of access possible within LabKey Server. While the likelihood of this bug resulting in a malicious attack was very low, the LabKey team chose to correct the issue in order to eliminate the risk.

While these specific issues are no longer a threat to the security of our users, we continue to evaluate the security of the platform and address risks as new malicious threats arise. We encourage users to always update to the latest version of LabKey Server to ensure that they have the most up-to-date protection against cyber security threats.

Flow cytometry data is widely used across diverse set of research areas including drug discovery and personalized medicine. Ongoing improvements to instrument technology allow scientists to generate more and more targeted reagents which in turn leads to increasing amounts of high-dimensional flow cytometry data. As the application of flow cytometry in immune monitoring becomes more prevalent, many scientists are finding themselves asking “what is the best way to manage flow cytometry data?”

As teams evaluate software tools for managing flow cytometry data, there are several things to keep in mind. Instrument-generated fcs files from cytometers are generally not useful to scientists on their own. Typically, users interrogate their data by creating an analysis file, either with manual gating through commercially-available tools like FlowJo and FCS Express, or by performing computational analyses via free software packages like Bioconductor. Ensuring that data provenance is maintained between fcs files and analysis is vital, and provides valuable information for groups looking to validate or re-analyze the raw data in the future.

Maintaining Comprehensive Data Records

The LabKey Server software platform help groups ensure data provenance and maintain comprehensive flow cytometry records by:

• Allowing for import of raw fcs files as well as analysis files
• Validating all fcs files are present when linking data to a FlowJo workspace file
• Auditing file upload for analysis data used in a LabKey study
• Surfacing run parameters and compensation values for further quality control

Adding Value to Runs

LabKey Server’s flow cytometry tools can also helps add value to runs by:

• Providing mechanisms to insert keywords and adding metadata
• Ensuring gate naming is consistent across workspaces
• Allowing administrators to merge gating strategies when necessary
• Visualizing statistics in Levy-Jennings plots for valuable quality control metrics

Improving Data Analysis Workflows

Using LabKey Server, scientists can achieve further improvements to their analysis workflow by:

• Integrating flow cytometry statistics and 2D plotting within the LabKey Server platform
• Creating easy integration mechanisms across flow cytometry runs, panels, and projects
• Providing built-in visualization tools for users to interrogate their data

With the right tools, scientists can maximize the insight derived from their flow cytometry data. To learn more about using LabKey Server to manage flow cytometry analysis, check out the flow cytometry documentation library or request a demo.