Pathogen Proteins Eliciting Antibodies Do Not Share Epitopes with Host Proteins: A Bioinformatics Approach

The best way to prevent diseases caused by pathogens is by the use of vaccines. The advent of genomics enables genome-wide searches of new vaccine candidates, called reverse vaccinology. The most common strategy to apply reverse vaccinology is by designing subunit recombinant vaccines, which usually generate an humoral immune response due to B-cell epitopes in proteins. A major problem for this strategy is the identification of protective immunogenic proteins from the surfome of the pathogen. Epitope mimicry may lead to auto-immune phenomena related to several human diseases. A sequence-based computational analysis has been carried out applying the BLASTP algorithm. Therefore, two huge databases have been created, one with the most complete and current linear B-cell epitopes, and the other one with the surface-protein sequences of the main human respiratory bacterial pathogens. We found that none of the 7353 linear B-cell epitopes analysed shares any sequence identity region with human proteins capable of generating antibodies, and that only 1% of the 2175 exposed proteins analysed contain a stretch of shared sequence with the human proteome. These findings suggest the existence of a mechanism to avoid autoimmunity. We also propose a strategy for corroborating or warning about the viability of a protein linear B-cell epitope as a putative vaccine candidate in a reverse vaccinology study; so, epitopes without any sequence identity with human proteins should be very good vaccine candidates, and the other way around

Gene expression patterns within cell lines are predictive of chemosensitivity

Abstract Background The NCI has undertaken a twenty-year project to characterize compound sensitivity patterns in a selected set of sixty tumor derived cell lines. Previous studies have explored the relationship between compound sensitivity patterns to gene expression, protein expression, and DNA copy number for these same cell lines. A strong correlation between the pattern of expression of a biomarker and sensitivity to a compound could suggest a clinically interesting biological relationship between the two. Results We isolated RNA's and measured expression of 40000 genes using cDNA microarrays from the fifty-nine publicly available cell lines. Analysis of this data set in comparison with published gene expression data sets demonstrates a high degree of reproducibility in expression level measurements even using completely independent RNA preparations and array technologies. Using the fifty-nine cell lines for discovery and an additional seven cell lines for which extensive compound sensitivity data were available as a test set, we determined that gene-compound pairs with a correlation coefficient above 0.6 had a false discovery rate of approximately 5%. Large scale features of the gene expression and chemosensitivity data, such as tissue of origin and other physiological factors, did not seem to explain the majority of correlations between gene and compound patterns. Conclusion A comparison of gene expression and compound sensitivity in panels of cell lines was demonstrated to have a relatively high validation and low false discovery rate supporting the use of this approach and datasets for identifying candidate biomarkers and targeted biologically active compounds.</p

Atmospheric mercury measurements at a suburban site in the Mid-Atlantic United States: Inter-annual, seasonal and diurnal variations and source-receptor relationships

AbstractDifferent atmospheric mercury forms have been measured at a suburban site in Beltsville, Maryland in the Mid-Atlantic United States since 2007 to investigate their inter-annual, seasonal and diurnal variabilities. Average concentrations and standard deviations of hourly measurements from 2007 to 2015 were 1.41 ± 0.23 ng m−3 for gaseous elemental mercury (GEM), 4.6 ± 33.7 pg m−3 for gaseous oxidized mercury (GOM), and 8.6 ± 56.8 pg m−3 for particulate-bound mercury (PBM). Observations show that on average, the rates of decrease were 0.020 ± 0.007 ng m−3 yr−1 (or 1.3 ± 0.5% yr−1, statistically significant, p-value < 0.01) for GEM, 0.54 ± 0.19 pg m−3 yr−1 (or 7.3 ± 2.6% yr−1, statistically significant, p-value < 0.01) for GOM, and 0.15 ± 0.35 pg m−3 yr−1 (or 1.6 ± 3.8% yr−1, statistically insignificant, p-value > 0.01) for PBM over this nine-year period. In addition, the collocated annual mercury wet deposition decreased at a rate of 0.51 ± 0.24 μg m−2 yr−2 (or 4.2 ± 1.9% yr−1, statistically insignificant, p-value > 0.01). Diurnal variation of GEM shows a slight peak in the morning, likely due to the shallow boundary layer. Seasonal variation of GEM shows lower levels in fall. Both diurnal variations of GOM and PBM show peaks in the afternoon likely due to the photochemical production of reactive mercury from the oxidation of GEM and the influence of boundary layer processes. Seasonally, GOM measurements show high levels in spring and constant low levels in the other three seasons, while PBM measurements exhibit higher levels from late fall to early spring and lower levels from late spring to fall. These measurement data were analyzed using the HYSPLIT back trajectory model in order to examine possible source-receptor relationships at this suburban site. Trajectory frequency analysis shows that high GEM/GOM/PBM events were generally associated with high frequencies of the trajectories passing through areas with high mercury emissions, while low GEM/GOM/PBM levels were largely associated the trajectories passing through relatively clean areas. This study indicates that local and regional sources appear to have a significant impact on the site and these impacts appear to have changed over time, as the local/regional emissions have been reduced

Physikalisch-chemische Aspekte immunologischer und anderer reversibler Assoziations-Reaktionen

Peer Reviewe