Mining Trypanosoma cruzi Genome Sequences for Antigen Discovery and Vaccine Development

2019 ◽  
pp. 23-34 ◽  
Author(s):  
Christian Teh-Poot ◽  
Eric Dumonteil
Keyword(s):  
Trypanosoma Cruzi ◽  
Vaccine Development ◽  
Genome Sequences ◽  
Antigen Discovery

scholarly journals Correlates of SARS-CoV-2 Variants on Deaths, Case Incidence and Case Fatality Ratio among the Continents for the Period of 1 December 2020 to 15 March 2021

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1061
Author(s):  
Wajdy J. Al-Awaida ◽  
Baker Jawabrah Al Hourani ◽  
Samer Swedan ◽  
Refat Nimer ◽  
Foad Alzoughool ◽  
...  
Keyword(s):  
Negative Correlation ◽  
Significant Positive Correlation ◽  
Vaccine Development ◽  
Case Fatality ◽  
Significant Negative Correlation ◽  
Reference Sequence ◽  
Genome Sequences ◽  
Positive Correlation ◽  
Case Fatality Ratio ◽  
Epidemiological Surveys

The outbreak of coronavirus disease 2019 (COVID-19), by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly developed into a worldwide pandemic. Mutations in the SARS-CoV-2 genome may affect various aspects of the disease including fatality ratio. In this study, 553,518 SARS-CoV-2 genome sequences isolated from patients from continents for the period 1 December 2020 to 15 March 2021 were comprehensively analyzed and a total of 82 mutations were identified concerning the reference sequence. In addition, associations between the mutations and the case fatality ratio (CFR), cases per million and deaths per million, were examined. The mutations having the highest frequencies among different continents were Spike_D614G and NSP12_P323L. Among the identified mutations, NSP2_T153M, NSP14_I42V and Spike_L18F mutations showed a positive correlation to CFR. While the NSP13_Y541C, NSP3_T73I and NSP3_Q180H mutations demonstrated a negative correlation to CFR. The Spike_D614G and NSP12_P323L mutations showed a positive correlation to deaths per million. The NSP3_T1198K, NS8_L84S and NSP12_A97V mutations showed a significant negative correlation to deaths per million. The NSP12_P323L and Spike_D614G mutations showed a positive correlation to the number of cases per million. In contrast, NS8_L84S and NSP12_A97V mutations showed a negative correlation to the number of cases per million. In addition, among the identified clades, none showed a significant correlation to CFR. The G, GR, GV, S clades showed a significant positive correlation to deaths per million. The GR and S clades showed a positive correlation to number of cases per million. The clades having the highest frequencies among continents were G, followed by GH and GR. These findings should be taken into consideration during epidemiological surveys of the virus and vaccine development.

Systems Biology-Based Approaches Applied to Vaccine Development

Data Mining ◽  
2013 ◽  
pp. 1131-1148
Author(s):  
Patricio A. Manque ◽  
Ute Woehlbier
Keyword(s):  
Gene Expression ◽  
Systems Biology ◽  
Vaccine Development ◽  
Cost Effective ◽  
Host Responses ◽  
Effective Vaccine ◽  
Antigen Discovery ◽  
Genomic Technologies ◽  
History Of ◽  
Genomic Revolution

Vaccines represent one of the most cost-effective ways to prevent and treat diseases. The use of vaccines in the control of viral diseases represents an important milestone in the history of medicine. The genomic revolution brought us the possibility to scan genomes in the search of new and more effective vaccine candidates and the advancement of bioinformatics provided the framework for the application of strategies that were focused not only on antigen discovery but also on comparative genomics, and pathogenic factor identification and data mining. In addition, the progress in post-genomic technologies including gene expression technologies such as microarray and proteomics gave us the opportunity to explore the host responses to vaccines leading to a better understanding of immune responses to pathogens and/or to vaccines, assisting in the development of new and better vaccines and adjuvants. This chapter will review how systems biology-based approaches including genomics, gene expression technologies, and bioinformatics have changed the way of thinking about antigen discovery and vaccine development. In addition, the chapter will discuss how the study of the host responses in combination with “in silico” approaches could help predict immunogenicity and improve the efficacy of vaccines.

scholarly journals Streamlined Subpopulation, Subtype, and Recombination Analysis of HIV-1 Half-Genome Sequences Generated by High-Throughput Sequencing

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Bhavna Hora ◽  
Naila Gulzar ◽  
Yue Chen ◽  
Konstantinos Karagiannis ◽  
Fangping Cai ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Vaccine Development ◽  
Consensus Sequence ◽  
Cost Effective ◽  
Recombination Analysis ◽  
Genome Sequences ◽  
Single Genome ◽  
Hiv 1

ABSTRACT High-throughput sequencing (HTS) has been widely used to characterize HIV-1 genome sequences. There are no algorithms currently that can directly determine genotype and quasispecies population using short HTS reads generated from long genome sequences without additional software. To establish a robust subpopulation, subtype, and recombination analysis workflow, we amplified the HIV-1 3′-half genome from plasma samples of 65 HIV-1-infected individuals and sequenced the entire amplicon (∼4,500 bp) by HTS. With direct analysis of raw reads using HIVE-hexahedron, we showed that 48% of samples harbored 2 to 13 subpopulations. We identified various subtypes (17 A1s, 4 Bs, 27 Cs, 6 CRF02_AGs, and 11 unique recombinant forms) and defined recombinant breakpoints of 10 recombinants. These results were validated with viral genome sequences generated by single genome sequencing (SGS) or the analysis of consensus sequence of the HTS reads. The HIVE-hexahedron workflow is more sensitive and accurate than just evaluating the consensus sequence and also more cost-effective than SGS. IMPORTANCE The highly recombinogenic nature of human immunodeficiency virus type 1 (HIV-1) leads to recombination and emergence of quasispecies. It is important to reliably identify subpopulations to understand the complexity of a viral population for drug resistance surveillance and vaccine development. High-throughput sequencing (HTS) provides improved resolution over Sanger sequencing for the analysis of heterogeneous viral subpopulations. However, current methods of analysis of HTS reads are unable to fully address accurate population reconstruction. Hence, there is a dire need for a more sensitive, accurate, user-friendly, and cost-effective method to analyze viral quasispecies. For this purpose, we have improved the HIVE-hexahedron algorithm that we previously developed with in silico short sequences to analyze raw HTS short reads. The significance of this study is that our standalone algorithm enables a streamlined analysis of quasispecies, subtype, and recombination patterns from long HIV-1 genome regions without the need of additional sequence analysis tools. Distinct viral populations and recombination patterns identified by HIVE-hexahedron are further validated by comparison with sequences obtained by single genome sequencing (SGS).

scholarly journals Analysis of Whole Genome Sequences and Homology Modelling of a 3C Like Peptidase and a Non-Structural Protein of the Novel Coronavirus COVID-19 Shows Protein Ligand Interaction with an Aza-Peptide and a Noncovalent Lead Inhibitor with Possible Antiviral Properties

2020 ◽  
Author(s):  
Arun Shanker ◽  
Divya Bhanu ◽  
Anajani Alluri
Keyword(s):  
Binding Sites ◽  
Tertiary Structure ◽  
Vaccine Development ◽  
Homology Modelling ◽  
Whole Genome ◽  
The Novel ◽  
Structural Protein ◽  
Genome Sequences ◽  
Ligand Interaction ◽  
Percent Identity

The family of viruses belonging to Coronaviridae mainly consist of virulent pathogens that have a zoonotic property, Severe Respiratory Syndrome (SARS-CoV) and Middle East Respiratory Syndrome (MERS-CoV) of this family have emerged before and now the Novel COVID-19 has emerged in China. Characterization of spike glycoproteins, polyproteins and other viral proteins from viruses are important for vaccine development. Homology modelling of these proteins with known templates offers the opportunity to discover ligand binding sites and possible antiviral properties of these protein ligand complexes. Any information emerging from these protein models can be used for vaccine development. In this study we did a complete bioinformatic analysis, sequence alignment, comparison of multiple sequences and homology modelling of the Novel COVID-19 whole genome sequences, the spike protein and the polyproteins for homology with known proteins, we also analysed receptor binding sites in these models for possible vaccine development. Our results showed that the tertiary structure of the polyprotein isolate COVID-19 _HKU-SZ-001_2020 had 98.94 percent identity with SARS-Coronavirus NSP12 bound to NSP7 and NSP8 co-factors. Our results indicate that a part of the viral genome (residues 254 to 13480 in Frame 2 with 4409 amino acids) of the Novel COVID-19 virus isolate Wuhan-Hu-1 (Genbank Accession Number MN908947.3) when modelled with template 2a5i of the PDB database had 96 percent identity with a 3C like peptidase of SARS-CoV which has ability to bind with Aza-Peptide Epoxide (APE) which is known for irreversible inhibition of SARS-CoV main peptidase. The part of the genome when modelled with template 3e9s of the PDB database had 82 percent identity with a papain-like protease/deubiquitinase which when complexed with ligand GRL0617 acts as inhibitor which can block SARS-CoV replication. It is possible that these viral inhibiters can be used for vaccine development for the Novel COVID-19.

scholarly journals Immunity and vaccine development efforts against Trypanosoma cruzi

Acta Tropica ◽  
2019 ◽  
Vol 200 ◽  
pp. 105168 ◽  
Author(s):  
Lizette E. Rios ◽  
Juan Carlos Vázquez-Chagoyán ◽  
Antonio Ortega Pacheco ◽  
M. Paola Zago ◽  
Nisha J. Garg
Keyword(s):  
Trypanosoma Cruzi ◽  
Vaccine Development

scholarly journals Immunomics: a 21st century approach to vaccine development for complex pathogens

Parasitology ◽  
2016 ◽  
Vol 143 (2) ◽  
pp. 236-244 ◽  
Author(s):  
KARINA P. DE SOUSA ◽  
DENISE L. DOOLAN
Keyword(s):  
Multidisciplinary Approach ◽  
Vaccine Development ◽  
Antigen Discovery ◽  
Molecular Immunology ◽  
Molecular Databases ◽  
Causative Agents ◽  
Rational Vaccine Design ◽  
Host Parasite ◽  
Over Time ◽  
21St Century Approach

SUMMARYImmunomics is a relatively new field of research which integrates the disciplines of immunology, genomics, proteomics, transcriptomics and bioinformatics to characterize the host-pathogen interface. Herein, we discuss how rapid advances in molecular immunology, sophisticated tools and molecular databases are facilitating in-depth exploration of the immunome. In our opinion, an immunomics-based approach presides over traditional antigen and vaccine discovery methods that have proved ineffective for highly complex pathogens such as the causative agents of malaria, tuberculosis and schistosomiasis that have evolved genetic and immunological host-parasite adaptations over time. By using an integrative multidisciplinary approach, immunomics offers enormous potential to advance 21st century antigen discovery and rational vaccine design against complex pathogens such as the Plasmodium parasite.

scholarly journals Complete molecular genome analyses of equine rotavirus A strains from different continents reveal several novel genotypes and a largely conserved genotype constellation

2012 ◽  
Vol 93 (4) ◽  
pp. 866-875 ◽  
Author(s):  
Jelle Matthijnssens ◽  
Samuel Miño ◽  
Hajnalka Papp ◽  
Christiaan Potgieter ◽  
Luis Novo ◽  
...  
Keyword(s):  
South Africa ◽  
Working Group ◽  
Vaccine Development ◽  
Phylogenetic Analyses ◽  
Genome Sequences ◽  
Geographical Isolation ◽  
Rotavirus A ◽  
Genotype Constellation ◽  
Group A ◽  
Genome Analyses

In this study, the complete genome sequences of seven equine group A rotavirus (RVA) strains (RVA/Horse-tc/GBR/L338/1991/G13P[18], RVA/Horse-wt/IRL/03V04954/2003/G3P[12] and RVA/Horse-wt/IRL/04V2024/2004/G14P[12] from Europe; RVA/Horse-wt/ARG/E30/1993/G3P[12], RVA/Horse-wt/ARG/E403/2006/G14P[12] and RVA/Horse-wt/ARG/E4040/2008/G14P[12] from Argentina; and RVA/Horse-wt/ZAF/EqRV-SA1/2006/G14P[12] from South Africa) were determined. Multiple novel genotypes were identified and genotype numbers were assigned by the Rotavirus Classification Working Group: R9 (VP1), C9 (VP2), N9 (NSP2), T12 (NSP3), E14 (NSP4), and H7 and H11 (NSP5). The genotype constellation of L338 was unique: G13-P[18]-I6-R9-C9-M6-A6-N9-T12-E14-H11. The six remaining equine RVA strains showed a largely conserved genotype constellation: G3/G14-P[12]-I2/I6-R2-C2-M3-A10-N2-T3-E2/E12-H7, which is highly divergent from other known non-equine RVA genotype constellations. Phylogenetic analyses revealed that the sequences of these equine RVA strains are related distantly to non-equine RVA strains, and that at least three lineages exist within equine RVA strains. A small number of reassortment events were observed. Interestingly, the three RVA strains from Argentina possessed the E12 genotype, whereas the three RVA strains from Ireland and South Africa possessed the E2 genotype. The unusual E12 genotype has until now only been described in Argentina among RVA strains collected from guanaco, cattle and horses, suggesting geographical isolation of this NSP4 genotype. This conserved genetic configuration of equine RVA strains could be useful for future vaccine development or improvement of currently used equine RVA vaccines.

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