Epitope mapping is a critical component of therapeutic monoclonal antibody (mAb) development as it provides vital insights into mechanisms of action. It has also been used successfully to identify epitopes that sustain the effects of immunization, thereby accelerating the development of vaccines against several viral pathogens, such as chikungunya, dengue, Ebola, and Zika. More recently, proteome-wide epitope mapping techniques have helped identify antibodies vital to the detection and neutralization of SARS-CoV-2.
Much of the diagnostic and therapeutic potential of epitopes still remains unexplored as there are millions of antibodies and a severe lack of epitope information about most of them. As a result, the development of cost-effective, high-throughput, high-resolution epitope mapping techniques is an urgent priority in the field of bioinformatics.
There are several techniques, such as X-ray co-crystallography, cryogenic electron microscopy, high-throughput shotgun mutagenesis epitope mapping, cross-linking-coupled mass spectrometry, array-based oligo-peptide scanning, and hydrogen-deuterium exchange, that are currently used for epitope mapping.
However, there are still several limitations that make most approaches either inaccessible, inefficient, or inadequate. For instance, both X-ray co-crystallography and cryogenic electron microscopy are extremely effective in generating high-resolution maps of antibody-antigen interactions. But they are expensive and technically complex, making them largely inaccessible to the broader research community.
Similarly, techniques that facilitate high-throughput monitoring may be constrained by lack of resolution or their inability to compare millions of sequences, traverse multiple omics dimensions, or scale disparate biological datasets.
The limitations of conventional epitope mapping techniques translate into consequential challenges for epitope researchers and slow down epitope research.
The BioStrand R&R platform provides an accessible and cost-effective solution that can seamlessly scale across millions of sequences, all omics layers, and multiple databases without compromising speed, efficiency, or accuracy.
The aim of this workflow is to demonstrate how the BioStrand platform enables researchers to start with a specific isotope and then proceed to identify all homolog epitopes using its intuitive features and capabilities.
For the purposes of this demonstration, we will start with a particular antigen expressed in humans and then qualify the steps involved in:
For this walkthrough, we start with this particular antigen:
|Antigen: IEDB:BCR2102||Data Source: IEDB|
Description: bcr_3d_assays: antigen name =shiga-like toxin II B subunit encoded by bacteriophage BP-933W [Escherichia coli O157:H7 str. EDL933] organism name =Escherichia coli O157:H7 str. EDL933
Top Concepts: antigen name, bacteriophage bp-933w, bcr_3d_assays, edl933, escherichia coli o157:h7 str, organism name, Shiga-like toxin ii b subunit
We start by simply copying and pasting the antigen sequence mentioned above into the BioStrand Search Bar and hit return.
In the Alignment View, we now use the Filter feature to apply the relevant filters that will allow us to drill down to data related exclusively to epitopes.
Thus far, we have used BioStrand’s simple Search/Filter functionality to significantly narrow down the list of potential epitopes that are relevant to our research. We can now drill further down into any of the potential candidates. In this case, we want to explore the sixth sequence in the list of eight retrieved from the last search.
Next, we will further focus our search on finding matches only from the Protein Data Bank (PDB)
As we can see, “modulation of host virulence by virus” is one of the main features revealed by applying the Go Definition filter.
Using Search History on the R&R home page, we navigate to the candidate epitopes generated in Step 2. We then select the next epitope candidate we want to investigate, launch a search focused on the PDB data source.
This workflow demonstrates how the BioStrand R&R platform vastly simplifies and streamlines complex multi-omics homology searches.
A comprehensive array of built-in filters empowers researchers to click and filter through complex multilayered datasets, including metadata, to focus on pathways pertinent to their study without having to wrangle with a single line of code.
The process is as simple as a Google search and all relevant results are delivered instantly in an intuitive, interactive, and clickable dashboard that is simple, easy to understand, and visually informative.
BioStrand R&R addresses many of the limitations associated with conventional epitope mapping techniques.
It is the only solution that facilitates high-level integrated analysis across 440 million pre-indexed sequences and across all omics layers. With the functionality to scale across multiple databases, the platform can concurrently look up disparate topic- and domain-centric data sets, thereby generating a universal set of relevant results for any epitope.
The solution provides researchers with the flexibility to launch their homology search with either a small epitope or a longer antigen, without having to account for differences in local and global alignment.
By automatically translating all corresponding DNA and RNA into protein code, the platform ensures that all DNA-RNA are integrated into the analysis even if they are not explicitly denoted as a protein sequence. This significantly expands the scope of the search and returns a more exhaustive selection of pertinent sources of information.
Since the solution takes all cross-domain translations into account, researchers can now compare all cross-species DNA sequences that produce the same protein.
Most importantly, the BioStrand platform’s modern, intuitive, digital user interface allows even non-technical users to access all these sophisticated capabilities, and the SaaS delivery model enables anytime-anywhere pay-per-use access that maximizes productivity as well as cost-effectiveness.
Let us know of your epitope-related research challenges so that we can demonstrate how the BioStrand R&R platform can help.