Enhancing Drug Discovery Collaboration with Advanced Scientific Software, Cambridge UK

Enhancing Drug Discovery Collaboration with Advanced Scientific Software, Cambridge UK

The Revvity Signals’ Roadshow Series offers current and prospective users of Revvity Signals Suite the opportunity to gain hands-on experience. The Roadshow came to Cambridge, UK with an interactive day of hand-on learning, discussions, and demos, all geared towards Enhancing Drug Discovery, to show how modern cloud-based software is transforming research.

Presenters

• Ben Bracke, Principal Field Application Scientist, Revvity Signals: Demonstrating the Chemical Research Integration Capabilities of Signals Notebook
• Linda Kewitsch, Senior Informatics Product Sales Specialist, Revvity: Demonstrating the Molecular Biology Capabilities of Signals Notebook
• Lewis Ibbotson PhD, INEOS Oxford Institute, University of Oxford: Development of Broad-Spectrum MBL Inhibitors – Integrating Signals Notebook for Advanced Data Management and Multisite Collaboration
• David McClymont, Head of Automation, Revvity Cambridge UK: Streamlining Research Projects: How Pre-Clinical Services Expands the Horizons of Signals Notebook for Greater Efficiency
• Alastair Pate PhD, Associate Director, Data Visualisation and Analytics, Exscientia (now Recursion): Using Spotfire to Optimise the Design, Make, Test and Learn Cycles for Drug Discovery

The Enhancing Drug Discovery event provided the combined opportunity to hear both from key users at the coal-face and from Revvity Signals Suite product experts. The event was attended by scientists from multiple sectors, ranging from chemicals to cell and gene therapy research. Delegates included teams already using Revvity Signals Suite solutions and those interested in leveraging the solutions to maximize and optimize collaboration for greater productivity, information-sharing, and innovation. The morning session focused on practical how-to demonstrations aimed at new and prospective users, while the afternoon reviewed real-world examples with presentations from current Revvity Signals users.Kicking-off the event, Ben Bracke and Linda Kewitsch from Revvity Signals presented high-level tours of the main capabilities of Signals Notebook. The key message was that drug discovery research is now a data-driven discipline. As more and more organizations move to fully digital operations, the connectivity, data integration, and analytical capabilities of solutions such as Signals Notebook are becoming critical components of successful drug discovery programs.

Resolving the Project Challenges of Chemical Research

Ben Bracke showed how Signals Research Suite can transform experimental design, moving away from the era of paper notebooks into a modern digital environment that offers an easy-to-use, intuitive user interface. As one delegate remarked, “In the past, the research community tended to accept poorly designed software that was difficult to use and didn’t provide effective analytics tools — and certainly did not offer AI capabilities. Signals Research Suite allows us to get on with the science.”

With a background in chemistry, Ben Bracke demonstrated the power of an integrated platform for building a unified workflow and collaborating with colleagues. For example, starting with the embedded ChemDraw application to describe the reaction, Signals Research Suite enables automated import of chemical metadata for solvents, reactants, catalysts, and more. As each reagent is added to the experiment, Signals Research Suite provides the location of the material and updates the stock remaining. For the experiment itself, data measured by digital devices —¬ such as mass, time, temperature, pressure —¬ can be passed directly to Signals Research Suite, and the outcome recorded.

Among many advantages of operating a single research platform, Signals Research Suite offers extensive collaboration tools through the Signals Synergy component, including powerful task assignment capabilities. Authorized users, no matter if they are in the lab next door or on another continent working as a contract manufacturer, can be assigned tasks and timings, with complete oversight of progress to help ensure projects move forward efficiently.

In addition, Signals Research Suite provides close control over data sharing at every level to protect intellectual property. For example, if a team does not want to share the drug target with a contract manufacturer, the task assignment can be restricted to purely the synthesis instructions, preserving confidentiality.

Managing Molecular Biology Projects More Effectively

With the growth in research modalities beyond traditional small molecules, the boundaries between research fields are rapidly blurring. The advent of antibody-drug conjugates clearly demonstrates the value of enabling cross-fertilization of ideas and techniques, and an integrated digital platform is an essential tool to gain the maximum possible synergy from diverse modalities.

Linda Kewitsch demonstrated the Signals Research functions that are particularly applicable to molecular biology, such as how automated connections to internal and external resources can transform drug discovery. Gene sequences can be imported from GenBank, for example, and modified with a complete and fully auditable track record of changes. Microscope images can similarly be ingested and annotated, with highlighted areas added to a task list for investigation by the relevant analyst. Requests are automatically sent to the selected analysts, and notifications triggered when tasks are accepted and completed, or are rejected and await reallocation.

Collaborative Working

Because modern research depends on globally dispersed teams and a complex network of suppliers and partners, task allocation and execution are very often reliant on a combination of highly organised project management as well as personal relationships. The Signals Synergy component supports user messaging with advanced social features complete with social media tools such as photos, avatars, and emojis. Ben Bracke showed delegates the collaboration capabilities of Signals Messenger to reach out within the community — in this case across the room, though it can easily be across the globe.

Underlying the messaging capability is a unified approach: data and communications are retained within an integrated environment, from experiment design to task allocation and message exchanges. Rather than spending time application-hopping, locating external resources, and wading through unfamiliar databases and spreadsheets, Signals Research Suite provides a single workspace to maximise scientific engagement.

Real-world examples

At the event, Dr Lewis Ibbotson reported on ongoing research into the development of broad-spectrum metallo-β-lactamase (MBL) inhibitors, supported by Signals Notebook.

To set the scene, Dr Ibbotson revealed the true extent of anti-microbial resistance (AMR), which contributes to around 4.95 million deaths annually (2019), and is estimated to rise to around 10 million by 2050. By comparison, the World Health Organization reports 7 million total cumulative deaths from COVID 19, which implies that AMR may soon become one of humanity’s biggest health threats.

The INEOS Oxford Institute (IOI) team, comprising of approximately 80 members, uses Signals solutions to assist their antibiotic drug development programs and studies into the spread of bacterial resistance and bacterial evolution. One area of research focuses on developing new compounds that target the resistance mechanism and bind to an active site zinc atom, and these compounds are undergoing preclinical development. From the ChemDraw description through to biochemical assays and interactive violin plots for inhibition analysis, the team uses Signals to map every research step.

“Across the team we found Signals easy to use and configure, with an intuitive, user-friendly interface, and from a comparatively small start we found that users adopted it enthusiastically,” commented Dr Ibbotson. “We work across multiple sites and with various partners, and Signals Notebook enables us to securely share exactly what we need both internally and externally.”

The IOI team and the Revvity Signals consultants customised the experimental templates to conform to the existing health and safety risk assessments at the University of Oxford. All experiments are logged with a signature and counter-signature before undertaking reactions.

“Countersigning to close the experiment helps with quality control when working across multiple groups,” explained Dr Ibbotson. “In addition, using Spotfire to visualize the very large data sets that we generate allows us to direct drug discovery towards promising targets far more quickly than before.”

Taking Advantage of Automation

To help research teams increase assay capacity, Signals Research Suite enables extensive automation and integrations through external actions. External actions are a powerful feature of Signals Research Suite that allows triggering of other systems from the context of the notebook page expanding the capabilities in almost limitless ways.

David McClymont, Head of Automation, Revvity Cambridge UK, showed how external actions can take the strain of designing and managing screening projects by taking user input as project requirements and writing a metadata description that enables Signals Notebook to create the experiments for specific assays automatically. Metadata information is loaded into tables in Signals Notebook, triggering actions for all the plates and the plate layouts required, writing instructions for the liquid handlers, and generating tasks for the assay.

The design language enables many hundreds or even thousands of different experiments to be created within Signals Notebook, scheduling hundreds of plates and tasks with a limited amount of user input. The system automates as many of the steps as possible programmatically; for example, in drug discovery it takes only the minimum amount of information needed to create a dose-response curve such as the number of replicates, the maximum and minimum concentration, the number of steps in the dilution series. The project description language uses a pool of digital workers to create experiments, plates, instructions, and tasks, and when assays are complete, data is sent to Signals Notebook for analysis.

External actions can also extend and integrate across multiple devices and systems and can be fully integrated into the Revvity ecosystem such as the automation workcell software, plate::works. With Signals Research Suite and external actions, teams can increase throughput capacity by automating processes, while focusing on the key make, test, decide steps of research.

Benefits of Data Visualization

Leading neatly on from Dr Ibbotson’s remarks on Spotfire, Dr Alastair Pate concluded the day with a strategic introduction to Exscientia (now merged with Recursion), a clinical-stage TechBio company decoding biology to industrialize drug discovery.

To pursue its drug discovery ambitions, the company develops sophisticated AI algorithms that mine vast data stores to design and identify new drug candidates, narrowing thousands of potential compounds to a shortlist of those with a high probability of success. The target molecules are synthesised and the predictions are then tested against reality, using the returned test data to fine-tune the next AI iteration.

“With our accelerated development cycle, Spotfire is our essential tool to visualize progress and to highlight bottlenecks in processes. With Spotfire, we can rapidly understand if a problem is specific to a single project or whether there are across-the-board issues to resolve,” explained Alastair Pate.

“One of the many great features of Spotfire is the ability to drill down to the underlying data even as it highlights the outliers that deserve investigation. We have created Spotfire dashboards that automatically send notifications when compounds are outstanding, automating and accelerating what was previously a manual process. We have found Spotfire to be an incredibly powerful tool for analytics, which helps to drive efficiencies in drug discovery at almost every level.”

Rounding up the roundup

The principal benefits gained from attending the Enhancing Drug Discovery event include the guidance gained from Revvity Signals experts, real-world insights from the customer presentations, and the positive human connection between delegates. By seeing multiple Revvity Signals solutions in action, complete with demo logins to enable click-by-click hands-on experience, the event revealed the power and scope of an integrated research platform, delivered as software-as-a-service (SaaS). With nothing more than a web browser and user log-in, delegates discovered how each of the Signals Research Suite components can transform drug discovery, and support data-driven, AI-fuelled innovations for tomorrow’s breakthrough therapies.

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