Graph-based optimization of epitope coverage for vaccine antigen design
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States); New Mexico Consortium, Los Alamos, NM (United States)
Epigraph is a recently developed algorithm that enables the computationally efficient design of single or multi-antigen vaccines to maximize the potential epitope coverage for a diverse pathogen population. Potential epitopes are defined as short contiguous stretches of proteins, comparable in length to T-cell epitopes. This optimal coverage problem can be formulated in terms of a directed graph, with candidate antigens represented as paths that traverse this graph. Epigraph protein sequences can also be used as the basis for designing peptides for experimental evaluation of immune responses in natural infections to highly variable proteins. The epigraph tool suite also enables rapid characterization of populations of diverse sequences from an immunological perspective. Fundamental distance measures are based on immunologically relevant shared potential epitope frequencies, rather than simple Hamming or phylogenetic distances. Here, we provide a mathematical description of the epigraph algorithm, include a comparison of different heuristics that can be used when graphs are not acyclic, and we describe an additional tool we have added to the web-based epigraph tool suite that provides frequency summaries of all distinct potential epitopes in a population. Lastly, we also show examples of the graphical output and summary tables that can be generated using the epigraph tool suite and explain their content and applications.
- Research Organization:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Organization:
- National Institutes of Health (NIH); USDOE; Bill and Melinda Gates Foundation
- Grant/Contract Number:
- AC52-06NA25396
- OSTI ID:
- 1343714
- Report Number(s):
- LA-UR-16-26417
- Journal Information:
- Statistics in Medicine, Vol. 37, Issue 2; ISSN 0277-6715
- Publisher:
- WileyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
Balancing sensitivity and specificity in distinguishing TCR groups by CDR sequence similarity
|
journal | January 2019 |
Role of Dendritic Cells in Exposing Latent HIV-1 for the Kill
|
journal | December 2019 |
Balancing sensitivity and specificity in distinguishing TCR groups by CDR sequence similarity
|
journal | May 2019 |
Vaccinations for Colorectal Cancer: Progress, Strategies, and Novel Adjuvants
|
journal | July 2019 |
Similar Records
Candidate mosaic proteins for a pan-filoviral cytotoxic T-Cell lymphocyte vaccine
Designing and Testing Broadly-Protective Filoviral Vaccines Optimized for Cytotoxic T-Lymphocyte Epitope Coverage