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Khrustalev V.V.,Belarussian State Medical University
Molecular Immunology | Year: 2010

We showed that nucleotide sequences coding for linear B-cell epitopes of human immunodeficiency virus type 1 (HIV1) gp120 protein are enriched with codons containing cytosine and guanine in their first and second codon positions. Guanine and cytosine are the most mutable nucleotides in HIV1 genes (due to APOBEC3 and APOBEC1 editing of viral DNA and RNA, respectively, as well as due to reverse transcriptase preference to incorporate 8-oxo-G against C). We introduced all the possible G to A, C to U, C to A and G to U single nonsynonymous nucleotide mutations in gp120 coding region from the HIV1 reference strain. The BepiPred algorithm (www.cbs.dtu.dk/services/BepiPred) was used for the linear B-cell epitopes predictions. Results of this " in-silico directed mutagenesis" showed that: (i) single nonsynonymous G to A transitions will cause partial or complete destruction of linear epitopes in 18% of 229 possible cases; (ii) single nonsynonymous C to U transitions will cause partial or complete destruction of linear epitopes in 58% of 142 possible cases; (iii) single nonsynonymous C to A transversions will cause partial or complete destruction of linear epitopes in 28% of 184 possible cases; (iv) single nonsynonymous G to U transversions will cause partial or complete destruction of linear epitopes in 37% of 240 possible cases. Moreover, single transition of C to U direction leading to amino acid replacement inside an epitope will cause partial or complete destruction of this epitope at a probability of 98%. © 2010 Elsevier Ltd. Source


Khrustalev V.V.,Belarussian State Medical University | Khrustaleva T.A.,National Academy of Sciences of Belarus | Barkovsky E.V.,Belarussian State Medical University
Biochimie | Year: 2013

In this study we classified regions of random coil into four types: coil between alpha helix and beta strand, coil between beta strand and alpha helix, coil between two alpha helices and coil between two beta strands. This classification may be considered as natural. We used 610 3D structures of proteins collected from the Protein Data Bank from bacteria with low, average and high genomic GC-content. Relatively short regions of coil are not random: certain amino acid residues are more or less frequent in each of the types of coil. Namely, hydrophobic amino acids with branched side chains (Ile, Val and Leu) are rare in coil between two beta strands, unlike some acrophilic amino acids (Asp, Asn and Gly). In contrast, coil between two alpha helices is enriched by Leu. Regions of coil between alpha helix and beta strand are enriched by positively charged amino acids (Arg and Lys), while the usage of residues with side chains possessing hydroxyl group (Ser and Thr) is low in them, in contrast to the regions of coil between beta strand and alpha helix. Regions of coil between beta strand and alpha helix are significantly enriched by Cys residues. The response to the symmetric mutational pressure (AT-pressure or GC-pressure) is also quite different for four types of coil. The most conserved regions of coil are "connecting bridges" between beta strand and alpha helix, since their amino acid content shows less strong dependence on GC-content of genes than amino acid contents of other three types of coil. Possible causes and consequences of the described differences in amino acid content distribution between different types of random coil have been discussed. © 2013 Elsevier Masson SAS. All rights reserved.. Source


Grant
Agency: Cordis | Branch: FP7 | Program: NoE | Phase: HEALTH.2010.2.3.2-3 | Award Amount: 15.96M | Year: 2011

Over the past 15 years, EU-funded cohorts and collaborations (EuroSIDA, CASCADE and PENTA), have played a central role in developing our understanding of HIV progression and the effects of ART, enabling European expertise to contribute directly to the advances in patient diagnosis and management worldwide, and providing a continued surveillance mechanism for detection of emerging problems at a European level. Furthermore, we also established COHERE (Collaboration Of HIV Epidemiologic Research in Europe), a new European-wide cohort collaboration encompassing virtually all European HIV cohorts which were not included in the EU-funded networks. COHERE provides us with sufficient statistical power to address questions that cannot be addressed by existing cohorts and networks alone. Together, these collaborations form the foundation of a proposed Network of Excellence, which we have named EuroCoord. EuroCoord currently has access to data from over 250,000 HIV-infected individuals across the European continent, and beyond, both male and female, from neonates to geriatric populations, infected through sex between men, sex between men and women, injecting drug use, nosocomially and from mother to child, with and without co-infection with hepatitis viruses, of different ethnic and socio-economic backgrounds, from indigenous and migrant populations, in settings with varying levels of access to care and laboratory techniques. Our multidisciplinary research will thus allow us to address key areas of HIV research aimed at improving the management and life of HIV-infected individuals, whilst allowing us to explore differences within sub-groups. EuroCoord is in a position to mobilise European HIV cohort research, bringing it within one truly pan-European network of cohort studies with a strong and increasing presence in the Central- and Eastern European region. The structure of our network, maintaining autonomy within each individual network but within one common research platform, ensures that the most competitive science is performed whilst allowing us to pool our expertise and resources to undertake new initiatives within an integrated collaborative structure.


Khrustalev V.V.,Belarussian State Medical University | Barkovsky E.V.,Belarussian State Medical University
Genomics, Proteomics and Bioinformatics | Year: 2010

The number of completely sequenced archaeal genomes has been sufficient for a large-scale bioinformatic study. We have conducted analyses for each coding region from 36 archaeal genomes using the original CGS algorithm by calculating the total GC content (G+C), GC content in first, second and third codon positions as well as in fourfold and twofold degenerated sites from third codon positions, levels of arginine codon usage (Arg2: AGA/G; Arg4: CGX), levels of amino acid usage and the entropy of amino acid content distribution. In archaeal genomes with strong GC pressure, arginine is coded preferably by GC-rich Arg4 codons, whereas in most of archaeal genomes with G+C<0.6, arginine is coded preferably by AT-rich Arg2 codons. In the genome of Haloquadratum walsbyi, which is closely related to GC-rich archaea, GC content has decreased mostly in third codon positions, while Arg4>>Arg2 bias still persists. Proteomes of archaeal species carry characteristic amino acid biases: levels of isoleucine and lysine are elevated, while levels of alanine, histidine, glutamine and cytosine are relatively decreased. Numerous genomic and proteomic biases observed can be explained by the hypothesis of previously existed strong mutational AT pressure in the common predecessor of all archaea. © 2010 Beijing Genomics Institute. Source


Khrustalev V.V.,Belarussian State Medical University | Barkovsky E.V.,Belarussian State Medical University
Journal of Theoretical Biology | Year: 2010

We studied usage of cytosine and guanine in 914 genes from completely sequenced genomes of five Simplex- and seven Varicelloviruses. In genes with total GC-content higher than 50% usage of cytosine is usually higher than usage of guanine (an average difference for genes with G+C higher than 70% reaches 4.0%). This difference is caused mostly by the elevated usage of cytosine in two-fold degenerated sites situated in third codon positions relatively to the usage of guanine in two-fold degenerated sites situated in third codon positions (an average difference for genes with G+C higher than 70% is equal to 28.2%). The usage of amino acids that are encoded by codons containing cytosine in two-fold degenerated sites situated in third codon positions (AA2TC) is much higher than the usage of amino acids encoded by codons containing guanine in two-fold degenerated sites situated in third codon positions (AA2AG). The usage of AA2AG declines much more steeply with the growth of GC-content than the usage of AA2TC. This effect is the consequence of the nature of genetic code and of the negative selection. In GC-rich genes the usage of cytosine in four-fold degenerated sites is only a little (but significantly) higher than the usage of guanine (in genes with G+C higher than 70% an average difference is equal to 4.3%). This difference may be caused by transcription-associated mutational pressure. © 2010 Elsevier Ltd. Source

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