Epitopedia: identifying molecular mimicry between pathogens and known immune epitopes

Abstract

Motivation: Upon infection, pathogen epitopes stimulate the host immune system to produce antibodies targeting the pathogen. Molecular mimicry (structural similarity) between an infecting pathogen and host proteins or pathogenic proteins the host has previously encountered can impact the immune response of the host. The ability to identify potential molecular mimicry for a pathogen can illuminate immune effects with importance to pathogen treatment and vaccine design. Summary: Epitopedia allows for identification of regions with three-dimensional molecular mimicry between a protein in a pathogen with known epitopes in the host. Results: SARS-CoV-2 Spike returns molecular mimicry with 14 different epitopes including integrin beta-1 from Homo sapiens, lethal factor precursor from Bacillus anthracis, and pollen allergen Phl p 2 from Timothy grass. Availability: Epitopedia is primarily written in Python and relies on established software and databases. Epitopedia is available at https://github.com/cbalbin-FIU/Epitopedia under the opensource MIT license and is also packaged as a docker container at https://hub.docker.com/r/cbalbin/epitopedia.

EMoMiS: A Pipeline for Epitope-based Molecular Mimicry Search in Protein Structures with Applications to SARS-CoV-2

“…Other predicted events of antibody cross-reactivity of SARS-CoV-2 Spike with HPV-16, HIV-1, and Dengue virus were suggested by previous literature (Demirbaş et al, 2021;Mannar et al, 2021;Lustig et al, 2021). Unlike previous studies (Balbin et al, 2021;Ludin et al, 2011;Doxey and McConkey, 2013), the EMoMiS pipeline can predict the exact site of molecular mimicry, thus opening the door for further experimentation. Most importantly, the results should be seen as an attempt to explain observed phenomena in terms of partial immunity and the COVID-19-associated complications and side effects.…”

“…Another approach for molecular mimicry search is to look for similar structural motifs (Kristensen et al ., 2006). A recent tool called Epitopedia combined sequence and structural similarity searches for improved scoring of molecular mimicry candidates of known epitopes (Balbin et al ., 2021). However, sequence and structural similarity of epitopes from two proteins do not guarantee antibody cross-reaction.…”

Potential autoimmunity resulting from molecular mimicry between SARS-CoV-2 Spike and human proteins

“…We used Epitopedia (Balbin et al, 2021) to predict molecular mimicry for the structure of the SARS-CoV-2 Spike protein (PDB id: 6XR8, chain A (Cai et al, 2020)) against all linear epitopes in IEDB, excluding those from Coronaviruses. Epitopedia returned 789 sequence-based molecular mimics (termed as “1D-mimics”).…”

“…We present an extended application of Epitopedia (Balbin et al, 2021) to identify molecular mimicry between Spike and known epitopes. We do not attempt to discover all possible epitopes for Spike but focus on epitopes with positive assays from the IEDB (Vita et al, 2019).…”

“…To identify known epitopes with positive assays, we used Epitopedia (Balbin et al, 2021) with a Cryo-EM structure of Spike from SARS-CoV-2 (PDB id: 6XR8, chain A (Cai et al, 2020)) as input. Hits containing 5 or more consecutive residues with 100% sequence identity where at least 3 of the input residues are surface accessible are considered sequence-based molecular mimics (termed as “1D-mimics”).…”