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1.
J Health Care Poor Underserved ; 32(3): 1320-1338, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421034

RESUMO

To describe the dynamics and forecast the main parameters of the COVID-19 pandemic, the time series of daily cases in the World Health Organization African Region (WHOAR) from February 26th to December 29th, 2020 was analyzed. Estimates for expected values of parameters characterizing an epidemic (size of the epidemic, turning point, maximum value of daily cases, and basic reproductive number) were provided for both the first and the second wave, and for the entire ongoing pandemic in WHOAR. To this aim, the classical SIR (Susceptible-Infected-Removed) model and its approximations were applied to each identified wave. Our results suggest that the turning point of the COVID-19 first wave took place around July 20th, 2020. The first wave was expected to disappear by mid-December 2020, with a total of 1,200,000 expected cases. The second wave apparently started around August 19th, with an expected turning point by January 12th, 2021. The second wave is expected to end by August 9th, 2021, with 1,800,000 cumulative cases, and mounting up to 3,000,000 total cases between February 2020 and August 2021. Estimated basic reproduction numbers (R0) were 1.27 (first wave) and 1.15 (second wave); the expected total number of deaths is around 66,000 victims.


Assuntos
COVID-19/epidemiologia , África ao Sul do Saara/epidemiologia , Número Básico de Reprodução , Humanos , Modelos Biológicos , Pandemias , SARS-CoV-2 , Organização Mundial da Saúde
2.
Bioessays ; 42(11): e2000051, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32830350

RESUMO

Properties of non-canonical GC base pairs and their relations with mechanochemical cleavage of DNA are analyzed. A hypothesis of the involvement of the transient GC wobble base pairs both in the mechanisms of the mechanochemical cleavage of DNA and epigenetic mechanisms involving of 5-methylcytosine, is proposed. The hypothesis explains the increase in the frequency of the breaks of the sugar-phosphate backbone of DNA after cytosines, the asymmetric character of these breaks, and an increase in break frequency in CpG after cytosine methylation. As an alternative hypothesis, probable implication of GC+ Hoogsteen base pairs is considered, which now exemplify the best-studied non-canonical GC base pairs in the DNA double helix. Also see the video abstract here https://youtu.be/EUunVWL0ptw.

3.
Sci Rep ; 10(1): 8635, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451390

RESUMO

In the course of sample preparation for Next Generation Sequencing (NGS), DNA is fragmented by various methods. Fragmentation shows a persistent bias with regard to the cleavage rates of various dinucleotides. With the exception of CpG dinucleotides the previously described biases were consistent with results of the DNA cleavage in solution. Here we computed cleavage rates of all dinucleotides including the methylated CpG and unmethylated CpG dinucleotides using data of the Whole Genome Sequencing datasets of the 1000 Genomes project. We found that the cleavage rate of CpG is significantly higher for the methylated CpG dinucleotides. Using this information, we developed a classifier for distinguishing cancer and healthy tissues based on their CpG islands statuses of the fragmentation. A simple Support Vector Machine classifier based on this algorithm shows an accuracy of 84%. The proposed method allows the detection of epigenetic markers purely based on mechanochemical DNA fragmentation, which can be detected by a simple analysis of the NGS sequencing data.


Assuntos
Metilação de DNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Linhagem Celular Tumoral , Ilhas de CpG , Fragmentação do DNA , Bases de Dados Genéticas , Humanos , Meduloblastoma/genética , Meduloblastoma/patologia , Neoplasias/genética , Neoplasias/patologia , Análise de Sequência de DNA , Máquina de Vetores de Suporte
4.
BMC Genomics ; 17(1): 973, 2016 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-27884105

RESUMO

BACKGROUND: The general structure and action of all eukaryotic and archaeal RNA polymerases machinery have an astonishing similarity despite the diversity of core promoter sequences in different species. The goal of our work is to find common characteristics of DNA region that define it as a promoter for the RNA polymerase II (Pol II). RESULTS: The profiles of a large number of physical and structural characteristics, averaged over representative sets of the Pol II minimal core promoters of the evolutionary divergent species from animals, plants and unicellular fungi were analysed. In addition to the characteristics defined at the base-pair steps, we, for the first time, use profiles of the ultrasonic cleavage and DNase I cleavage indexes, informative for internal properties of each complementary strand. CONCLUSIONS: DNA of the core promoters of metazoans and Schizosaccharomyces pombe has similar structural organization. Its mechanical and 3D structural characteristics have singular properties at the positions of TATA-box. The minor groove is broadened and conformational motion is decreased in that region. Special characteristics of conformational behavior are revealed in metazoans at the region, which connects the end of TATA-box and the transcription start site (TSS). The intensities of conformational motions in the complementary strands are periodically changed in opposite phases. They are noticeable, best of all, in mammals. Such conformational features are lacking in the core promoters of S. pombe. The profiles of Saccharomyces cerevisiae core promoters significantly differ: their singular region is shifted down thus pointing to the uniqueness of their structural organization. Obtained results may be useful in genetic engineering for artificial modulation of the promoter strength.


Assuntos
Regiões Promotoras Genéticas , RNA Polimerase II/química , RNA Polimerase II/genética , Animais , Sequência de Bases , Clivagem do DNA , Variação Genética , Humanos , Motivos de Nucleotídeos , Schizosaccharomyces/genética , TATA Box , Sítio de Iniciação de Transcrição
5.
Bioinformatics ; 32(17): i552-i558, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27587674

RESUMO

MOTIVATION: Target-specific hybridization depends on oligo-probe characteristics that improve hybridization specificity and minimize genome-wide cross-hybridization. Interplay between specific hybridization and genome-wide cross-hybridization has been insufficiently studied, despite its crucial role in efficient probe design and in data analysis. RESULTS: In this study, we defined hybridization specificity as a ratio between oligo target-specific hybridization and oligo genome-wide cross-hybridization. A microarray database, derived from the Genomic Comparison Hybridization (GCH) experiment and performed using the Affymetrix platform, contains two different types of probes. The first type of oligo-probes does not have a specific target on the genome and their hybridization signals are derived from genome-wide cross-hybridization alone. The second type includes oligonucleotides that have a specific target on the genomic DNA and their signals are derived from specific and cross-hybridization components combined together in a total signal. A comparative analysis of hybridization specificity of oligo-probes, as well as their nucleotide sequences and thermodynamic features was performed on the database. The comparison has revealed that hybridization specificity was negatively affected by low stability of the fully-paired oligo-target duplex, stable probe self-folding, G-rich content, including GGG motifs, low sequence complexity and nucleotide composition symmetry. CONCLUSION: Filtering out the probes with defined 'negative' characteristics significantly increases specific hybridization and dramatically decreasing genome-wide cross-hybridization. Selected oligo-probes have two times higher hybridization specificity on average, compared to the probes that were filtered from the analysis by applying suggested cutoff thresholds to the described parameters. A new approach for efficient oligo-probe design is described in our study. CONTACT: shabalin@ncbi.nlm.nih.gov or olga.matveeva@gmail.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Genoma , Hibridização de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , Razão Sinal-Ruído , Sondas de DNA , Perfilação da Expressão Gênica , Genômica , Oligonucleotídeos , Sensibilidade e Especificidade
6.
Sci Rep ; 4: 4532, 2014 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-24681819

RESUMO

Next Generation Sequencing (NGS) technology is based on cutting DNA into small fragments, and their massive parallel sequencing. The multiple overlapping segments termed "reads" are assembled into a contiguous sequence. To reduce sequencing errors, every genome region should be sequenced several dozen times. This sequencing approach is based on the assumption that genomic DNA breaks are random and sequence-independent. However, previously we showed that for the sonicated restriction DNA fragments the rates of double-stranded breaks depend on the nucleotide sequence. In this work we analyzed genomic reads from NGS data and discovered that fragmentation methods based on the action of the hydrodynamic forces on DNA, produce similar bias. Consideration of this non-random DNA fragmentation may allow one to unravel what factors and to what extent influence the non-uniform coverage of various genomic regions.

7.
Biophys J ; 100(1): 117-25, 2011 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-21190663

RESUMO

We investigated the phenomenon of ultrasonic cleavage of DNA by analyzing a large set of cleavage patterns of DNA restriction fragments using polyacrylamide gel electrophoresis. The cleavage intensity of individual phosphodiester bonds was found to depend on the nucleotide sequence and the position of the bond with respect to the ends of the fragment. The relative intensities of cleavage of the central phosphodiester bond in 16 dinucleotides and 256 tetranucleotides were determined by multivariate statistical analysis. We observed a remarkable enhancement of the mean values of the relative intensities of cleavage (cleavage rates) in phosphodiester bonds following deoxycytidine, which diminished in the row of dinucleotides: d(CpG) > d(CpA) > d(CpT) >> d(CpC). The cleavage rates for all pairs of complementary dinucleotides were significantly different from each other. The effect of flanking nucleotides in tetranucleotides on cleavage rates of all 16 types of central dinucleotides was also statistically significant. The sequence-dependent ultrasonic cleavage rates of dinucleotides are consistent with reported data on the intensity of the conformational motion of their 5'-deoxyribose. As a measure of local conformational dynamics, cleavage rates may be useful for characterizing functional regions of the genome.


Assuntos
DNA/genética , DNA/metabolismo , Ultrassom/métodos , Sequência de Bases , DNA/química , Eletroforese em Gel de Poliacrilamida , Fenômenos Físicos , Maleabilidade , Soluções
8.
PLoS One ; 5(4): e10180, 2010 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-20422034

RESUMO

Prediction of efficient oligonucleotides for RNA interference presents a serious challenge, especially for the development of genome-wide RNAi libraries which encounter difficulties and limitations due to ambiguities in the results and the requirement for significant computational resources. Here we present a fast and practical algorithm for shRNA design based on the thermodynamic parameters. In order to identify shRNA and siRNA features universally associated with high silencing efficiency, we analyzed structure-activity relationships in thousands of individual RNAi experiments from publicly available databases (ftp://ftp.ncbi.nlm.nih.gov/pub/shabalin/siRNA/si_shRNA_selector/). Using this statistical analysis, we found free energy ranges for the terminal duplex asymmetry and for fully paired duplex stability, such that shRNAs or siRNAs falling in both ranges have a high probability of being efficient. When combined, these two parameters yield a approximately 72% success rate on shRNAs from the siRecords database, with the target RNA levels reduced to below 20% of the control. Two other parameters correlate well with silencing efficiency: the stability of target RNA and the antisense strand secondary structure. Both parameters also correlate with the short RNA duplex stability; as a consequence, adding these parameters to our prediction scheme did not substantially improve classification accuracy. To test the validity of our predictions, we designed 83 shRNAs with optimal terminal asymmetry, and experimentally verified that small shifts in duplex stability strongly affected silencing efficiency. We showed that shRNAs with short fully paired stems could be successfully selected by optimizing only two parameters: terminal duplex asymmetry and duplex stability of the hypothetical cleavage product, which also relates to the specificity of mRNA target recognition. Our approach performs at the level of the best currently utilized algorithms that take into account prediction of the secondary structure of the target and antisense RNAs, but at significantly lower computational costs. Based on this study, we created the si-shRNA Selector program that predicts both highly efficient shRNAs and functional siRNAs (ftp://ftp.ncbi.nlm.nih.gov/pub/shabalin/siRNA/si_shRNA_selector/).


Assuntos
Algoritmos , Desenho de Fármacos , Estabilidade de RNA , RNA Interferente Pequeno/química , Bases de Dados de Ácidos Nucleicos , Inativação Gênica , Conformação de Ácido Nucleico , Interferência de RNA , Termodinâmica
9.
J Biomol Struct Dyn ; 26(2): 187-96, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18597540

RESUMO

Unselective and reversible adsorption of ligands on DNA for a model of binding proposed by Zasedatelev, Gursky, and Volkenshtein is considered. In this model, the interaction between neighboring ligands located at the distance of i binding centers is characterized by the statistical weight ai. Each ligand covers L binding centers. For this model, expressions for binding averages are represented in a new simple form. This representation is convenient for the calculation of the fraction of inter-ligand distances of i binding centers fd(i) and the fraction of binding centers included in the distances of i binding centers fbc(i) for various types of interaction between bound ligands. It is shown that, for non-cooperative binding, contact cooperativity and long-range cooperativity, the fraction of the zero inter-ligand distance fd(0) is maximal at any relative concentration of bound ligands (r). Calculations demonstrate that, at low r, fd(0) approximately r.ao, and fd(i) approximately r at 11/r-L, then fd(i) rapidly decreases with i at any r for all types of inter-ligand interaction. At high ligand concentration (r is close to rmax=L(-1)), fd(0) is close to unity and fd(i) rapidly decreases with i for any type of inter-ligand interaction. For strong contact cooperativity, fd(0) is close to unity in a much lager r interval ((0.5-1).rmax), and fd(1) approximately ao(-1) at r approximately 0.5.rmax. In the case of long-range interaction between bound ligands, the dependence fd(i) is more complex and has a maximum at i approximately (1/r-L)1/2 for anti-cooperative binding. fbc(i) is maximal at i approximately 1/r-L for all types of binding except the contact cooperativity. A strong asymmetry in the influence of contact cooperativity and anticooperativity on the ligand distribution along DNA is demonstrated.


Assuntos
DNA/metabolismo , Ligantes , Modelos Teóricos , Matemática
10.
Nucleic Acids Res ; 35(8): e63, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17426130

RESUMO

Current literature describes several methods for the design of efficient siRNAs with 19 perfectly matched base pairs and 2 nt overhangs. Using four independent databases totaling 3336 experimentally verified siRNAs, we compared how well several of these methods predict siRNA cleavage efficiency. According to receiver operating characteristics (ROC) and correlation analyses, the best programs were BioPredsi, ThermoComposition and DSIR. We also studied individual parameters that significantly and consistently correlated with siRNA efficacy in different databases. As a result of this work we developed a new method which utilizes linear regression fitting with local duplex stability, nucleotide position-dependent preferences and total G/C content of siRNA duplexes as input parameters. The new method's discrimination ability of efficient and inefficient siRNAs is comparable with that of the best methods identified, but its parameters are more obviously related to the mechanisms of siRNA action in comparison with BioPredsi. This permits insight to the underlying physical features and relative importance of the parameters. The new method of predicting siRNA efficiency is faster than that of ThermoComposition because it does not employ time-consuming RNA secondary structure calculations and has much less parameters than DSIR. It is available as a web tool called 'siRNA scales'.


Assuntos
RNA Interferente Pequeno/química , Software , Algoritmos , Composição de Bases , Bases de Dados Genéticas , Internet , Modelos Lineares , Nucleotídeos/química
11.
Int J Biol Macromol ; 36(1-2): 103-15, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15979700

RESUMO

We describe the formation and properties of nanoconstruction that consists of the double-stranded DNA molecules located at distance of 35-50 A in the spatial structure of particles of their cholesteric liquid-crystalline dispersions and cross-linked by artificial nanobridges. The resulting nanostructures possess the peculiar spatial and optical properties.


Assuntos
Quitosana/química , DNA/química , Conformação de Ácido Nucleico , Dicroísmo Circular , Cobre/química , Reagentes para Ligações Cruzadas/farmacologia , Relação Dose-Resposta a Droga , Íons , Substâncias Macromoleculares/química , Microscopia de Força Atômica , Modelos Químicos , Modelos Moleculares , Nanoestruturas/química , Nanotecnologia , Ácidos Nucleicos , Polímeros , Temperatura
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