Development of a novel clustering tool for linear peptide sequences

Dhanda, Sandeep Kumar; Vaughan, Kerrie; Schulten, Véronique; Grifoni, Alba; Weiskopf, Daniela; Sidney, John; Peters, Bjoern; Sette, Alessandro

doi:10.1111/imm.12984

Cited by 82 publications

(76 citation statements)

References 53 publications

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“…IEDB epitope cluster analysis tool was applied to group all HLA-I and HLA-II epitopes in clusters (10). Minimum sequence identity threshold was 70% and cluster-break algorithm was applied.…”

Section: Clusteringmentioning

confidence: 99%

Molecular Insights into the Contagious Nature of Pandemic Novel Coronavirus 2019-nCoV

Mishra

2020

Preprint

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2019-novel coronavirus (nCoV), the virus causing Covid19 disease, is a highly contagious virus and has created a pandemic. In efforts to combat this virus, subunit vaccine designing using immunoinformatics tools was undertaken. During these studies, new hypotheses began to emerge, the prominent among these was that the newly acquired ORF10 protein may be the key protein responsible for its highly contagious nature. ORF10 is a hitherto unknown protein with no homology to any known protein in organisms present till date. Through immunoinformatics studies, it has been observed that among all ten 2019-nCoV proteins, ORF10 presents amongst the highest number of immunogenic, promiscuous CTL epitopes. These epitopes are part of a cluster with HTL epitopes, suggesting that there is a high degree of epitope conservation in ORF10. Conservation of protein sequence across organisms is not seen, and there is no known structural template on which to model and derive a structure to get structural and functional insights. Because there is altogether no conservation of its sequence, or structure, it may be presented as a novel protein to the immune system. Further, the human body may not have been able to utilize any memory B and T cells generated against other microorganisms to target ORF10 and fight this pathogen, contributing to its deadly, contagious nature.

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Section: Clusteringmentioning

confidence: 99%

Molecular Insights into the Contagious Nature of Pandemic Novel Coronavirus 2019-nCoV

Mishra

2020

Preprint

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“…IEDB epitope cluster analysis tool was applied to group all HLA-I and HLA-II epitopes in clusters (13). Minimum sequence identity threshold was 70% and cluster-break algorithm was applied.…”

Section: Clusteringmentioning

confidence: 99%

Molecular Insights into the Contagious Nature of Pandemic Novel Coronavirus 2019-nCoV

Mishra

2020

Preprint

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This article stems from the author's observations that ORF10, a protein with no sequence and structural conservation, provides with a high number of potentially immunogenic, promiscuous epitopes. With high degree of epitope conservation across CTL and HTL epitopes of ORF10, its existence in the 2019-nCoV genome is largely seen as particularly contributing to the highly contagious nature of this virus.<br>

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“…Epitope cluster analysis tool from IEDB (Dhanda et al, 2018) was used to identify the overlapping peptides among the top CTL, HTL and BCL epitopes at minimum sequence identity threshold of 100%. The identified clusters and singletons (unique epitopes) were utilized in a sequential manner to design the final vaccine constructs.…”

Section: Epitope Cluster Analysis and Vaccine Constructionmentioning

confidence: 99%

Conglomeration of highly antigenic nucleoproteins to inaugurate a heterosubtypic next generation vaccine candidate against Arenaviridae family

Azim

Lasker

Akter

et al. 2019

Preprint

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Arenaviral infections often resulting in lethal Hemorrhagic Fevers (HF) affect primarily African and South American regions. To date, there is no FDA-approved licensed vaccine against arenaviruses and treatments have been limited to supportive therapies. Hence, the study was employed to design a highly immunogenic heterosubtypic vaccine candidate against Arenaviridae family. The whole proteomes of Lassa virus (LASV), Lymphocytic Chorio Meningitis Virus (LCMV), Lujo virus and Guanarito virus were retrieved from NCBI database and assessed to determine the most antigenic viral proteins. Only the conserved sequences were used for T cell and B cell epitope prediction to ensure protective response against a wide range of viral strains. For each virus, nucleoproteins were identified as most antigenic which generated a plethora of antigenic epitopes. The proposed epitopes were highly conserved (up to 100%) and showed high cumulative population coverage. Moreover, results revealed that among the top epitopes, T cell epitope GWPYIGSRS were conserved in Argentine mammarenavirus (Junin virus) and Brazilian mammarenavirus (Sabia virus), while B cell epitope NLLYKICLSG were conserved in Bolivian mammarenavirus (Machupo virus) and Brazilian mammarenavirus (Sabia virus), indicating the possibility of final vaccine constructs to confer broad range immunity in the host. A total 3 constructs were designed by the combination of top epitopes from each protein along with suitable adjuvant and linkers. Different physicochemical properties revealed the superiority of construct V1 in terms of safety and efficacy. Docking analysis of the refined vaccine structure with different MHC molecules and human immune receptors were also biologically significant. The vaccine receptor complex (V1-TLR3) showed minimal deformability at molecular level. Moreover, construct V1 was compatible for insertion into pET28a(+) vector and heterologous cloning in E. coli srain K12. However, the results were based on different sequence analysis and various immune databases. Further wet lab based studies using model animals are highly recommended for the experimental validation of the designed vaccine candidates.

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Development of a novel clustering tool for linear peptide sequences

Cited by 82 publications

References 53 publications

Molecular Insights into the Contagious Nature of Pandemic Novel Coronavirus 2019-nCoV

Molecular Insights into the Contagious Nature of Pandemic Novel Coronavirus 2019-nCoV

Molecular Insights into the Contagious Nature of Pandemic Novel Coronavirus 2019-nCoV

Conglomeration of highly antigenic nucleoproteins to inaugurate a heterosubtypic next generation vaccine candidate against Arenaviridae family

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