Over the course of the last thirty years, antibody drugs have become a central part of many drug discovery organizations’ research and development programs, and remain one of the biggest classes of biologic therapeutic types. As well as standard antibodies, with their conventional two heavy- and two light-chain protein sequences, there is now myriad antibody-derived therapeutic types, including bi- and tri-specifics, antibody drug conjugates, and fusion proteins, amongst a seemingly endlessly growing list of others. In fact, there seems no limit to the potential for scientific innovation around antibody-derived therapies.
This diversity provides a rich landscape upon which drug discovery organizations can strive for novel therapeutics. But it also presents challenges in working with the data created in these programs. Properly managing and tracking antibody discovery data requires a scientifically-literate and adaptable informatics system, that understands the nuances of antibody drugs, but which can also scale to handle the potentially large data volumes generated as part of these discovery programs.
The Dotmatics Platform fulfills these needs, providing antibody discovery scientists with the tools they need to innovate, and relieving them of mundane, repetitive tasks that distract them from their scientific endeavors and risk introducing errors in their data.
A comprehensive project status view
Antibody discovery programs are complex, comprehensive, collaborative endeavors that span months or years. Over that time, huge volumes of data are generated on hundreds of candidate therapeutics and stored in many distinct data repositories. Team members may join or leave the project during its full lifecycle. How can all the relevant information be aggregated, managed, tracked and accessed by the team, both individually and when working in concert? This capability is provided by Dotmatics Platform and the Browser search and browse interface, which forms the core of the Dotmatics suite. Browser solves the most fundamental problem facing discovery scientists – how do find and view your data, so that you can make effective, informed decisions.
Diverse needs for experimental design and tracking
Molecular biologists need to capture experiment design and execution in a structured yet flexible system. Electronic lab notebooks (ELNs), well established in small molecule drug discovery, provide immense advantages over alternate options such as paper lab notebooks and non-scientific electronic systems, both for scientists and the organizations they work for. However, biologists often find ELNs constraining when they’re engaged in discovery activities, such as performing target identification and validation studies or when innovating on new therapeutic types. Studies Notebook, the ELN from Dotmatics, solves this problem by supporting both ad hoc workflows for pure discovery, and structured templates for well-defined, standardized processes such as animal immunization, and protein production and purification workflows.
Registering diverse entity types, tracking relationships, and capturing intellectual property
A key facet of antibodies is the relationships that exist within both the antibody concept itself, and in the cycles of production, purification and subsequent modifications, in the drive towards a candidate therapeutic. Antibodies by their nature are hierarchical structures, made up of protein chains, which in turn are made up of amino acids, which are composed of atoms chemically bonded together. When researchers make an antibody, they have a batch of it, from which they draw samples for testing, evaluation, and characterization. To improve its characteristics as a therapeutic, and for developability, researchers create variants of the antibody. If they’re working on engineered/non-natural antibody-based structures, they may have chemical payloads and other non-sequence components to track. How can all these hierarchies, relationships, and lineages be managed so the organization collectively knows what it has, can protect its intellectual property, and researchers can reliably make their antibodies again and again? The answer is Bioregister, Dotmatics’ system for registering and tracking biological entities and related components of biologics discovery programs. Bioregister understands the structure of conventional antibodies and can easily be extended to manage non-natural antibody-based structures. With Bioregister, all related concepts can be tracked, biological sequences are understood at the molecular level for robust IP protection, and searching can be done by sequence, chemistry or other molecular properties and metadata.
Advanced automated screening
Screening assays are a critical component of the drug discovery process, whether they be simple single-point assays or multichannel dose-response assays. Transferring assay data from the source instruments into the scientific informatics system, to allow scientists to view and interpret the data, represents a potential bottleneck and locus for data quality issues to be introduced due to labor-intensive manual transfer of files and data within them, across non-integrated solutions. Dotmatics solves this problem with Studies assay data management, which integrates seamlessly with our partner organizations to automatically transfer instrument data files into the Dotmatics system, perform first-pass analysis, and present the partially analyzed data for scientists to review and finalize analyses.
Analyzing and visualizing antibody sequences and associated data
An antibody discovery project involves multiple candidate clones, each with multiple protein chains, and associated property and experimental data. How can researchers view, align, edit, and analyze that data to understand what they have and how to make it better? Dotmatics Vortex supports all these activities, providing a rich analytical environment that can easily handle large data objects and data volumes. Vortex supports CDR annotation, alternate numbering schemes (e.g., Kabat, Chothia), and alignment. Advanced analytical capabilities allow researchers to probe relationships between compounds and determine the effects of sequence variation on functional performance in assays. Because Vortex inherently understands both biology and chemistry, analysis and visualization of engineered antibody-based compounds is straightforward.