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Periodicity of SNP distribution around transcription start sites
Koichiro Higasa, Kenshi Hayashi
BMC Genomics , 2006, DOI: 10.1186/1471-2164-7-66
Abstract: A spectrum analysis of SNP density distribution in the genomic regions around transcription start sites (TSSs) revealed a remarkable periodicity of 146 nucleotides. This periodicity was observed in the regions that were associated with CpG islands (CGIs), but not in the regions without CpG islands (nonCGIs). An analysis of the sequence divergence of the same genomic regions between humans and chimpanzees also revealed a similar periodical pattern in CGI. The occurrences of any mono- or di-nucleotide sequences in these regions did not reveal such a periodicity, thus indicating that an interpretation of this periodicity solely based on the sequence-dependent susceptibility to mutation is highly unlikely.The periodical patterns of nucleotide variability suggest the location of nucleosomes that are phased at TSS, and can be viewed as the genetic footprint of the chromatin state that has been maintained throughout mammalian evolutionary history. The results suggest the possible involvement of the nucleosome structure in the promoter function, and also a fundamental functional/structural difference between the two promoter classes, i.e., those with and without CGIs.Several million single nucleotide polymorphisms (SNPs) have already been collected and deposited in public databases [1] and these are important resources not only for use as markers to identify disease-associated genes [2], but also for an understanding of the mechanisms that underlie the diversification of the organism. The nucleotide diversity of human genome sequence appears to fluctuate from region to region [3-5]. The majority of the SNPs are believed to have no biological consequence, and therefore their diversity is primarily determined by the mutation rate within the germ cells, although it may be affected by the selective pressure that operates at the individual level [6]. In this study, we used a spectral analysis approach to identify the pattern of nucleotide variability around the transcription sta
SinicView: A visualization environment for comparisons of multiple nucleotide sequence alignment tools
Arthur Shih, DT Lee, Laurent Lin, Chin-Lin Peng, Shiang-Heng Chen, Yu-Wei Wu, Chun-Yi Wong, Meng-Yuan Chou, Tze-Chang Shiao, Mu-Fen Hsieh
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-103
Abstract: In this paper, we present a versatile alignment visualization system, called SinicView, (for Sequence-aligning INnovative and Interactive Comparison VIEWer), which allows the user to efficiently compare and evaluate assorted nucleotide alignment results obtained by different tools. SinicView calculates similarity of the alignment outputs under a fixed window using the sum-of-pairs method and provides scoring profiles of each set of aligned sequences. The user can visually compare alignment results either in graphic scoring profiles or in plain text format of the aligned nucleotides along with the annotations information. We illustrate the capabilities of our visualization system by comparing alignment results obtained by MLAGAN, MAVID, and MULTIZ, respectively.With SinicView, users can use their own data sequences to compare various alignment tools or scoring systems and select the most suitable one to perform alignment in the initial stage of sequence analysis.With exponentially increasing genomic sequences available in the public domain [1-5] comparative genomics demonstrates its power to help biologists identify novel conserved and functional regions in genomes [6-9]. Based on the comparison of cross-species genomic sequences, biologists can understand the evolutionary relationship of genomic regions among species, discover conserved regions between different genomes, such as yeast species genomes [10], metazoan genomes [11], vertebrate genomes [12], and mammalian genomes [13], discover regulatory motifs in the yeast [14] and human promoters [15] or identify potential conserved non-genic sequences (CNGs) [16].However, genomic sequences can be megabase long and thus the traditional sequence alignment tools based on dynamic programming would not work efficiently due to their time and space complexities. To better tackle this problem, several tools for genomic sequence alignment have been proposed, such as pairwise sequence aligners like MUMmer [17], GS-Aligner [18]
Internucleotide correlations and nucleotide periodicity in Drosophila mtDNA: New evidence for panselective evolution
Valenzuela,Carlos Y;
Biological Research , 2010, DOI: 10.4067/S0716-97602010000400014
Abstract: analysis for the homogeneity of the distribution of the second base of dinucleotides in relation to the first, whose bases are separated by 0, 1, 2,... 21 nucleotide sites, was performed with the vih-1 genome (cdna), the drosophila mtdna, the drosophila torso gene and the human p-globin gene. these four dna segments showed highly significant heterogeneities of base distributions that cannot be accounted for by neutral or nearly neutral evolution or by the "neighbor influence" of nucleotides on mutation rates. high correlations are found in the bases of dinucleotides separated by 0, 1 and more number of sites. a periodicity of three consecutive significance values (measured by the x29) was found only in drosophila mtdna. this periodicity may be due to an unknown structure or organization of mtdna. this non-random distribution of the two bases of dinucleotides widespread throughout these dna segments is rather compatible with panselective evolution and generalized internucleotide co-adaptation.
Internucleotide correlations and nucleotide periodicity in Drosophila mtDNA: New evidence for panselective evolution  [cached]
Carlos Y Valenzuela
Biological Research , 2010,
Abstract: Analysis for the homogeneity of the distribution of the second base of dinucleotides in relation to the first, whose bases are separated by 0, 1, 2,... 21 nucleotide sites, was performed with the VIH-1 genome (cDNA), the Drosophila mtDNA, the Drosophila Torso gene and the human p-globin gene. These four DNA segments showed highly significant heterogeneities of base distributions that cannot be accounted for by neutral or nearly neutral evolution or by the "neighbor influence" of nucleotides on mutation rates. High correlations are found in the bases of dinucleotides separated by 0, 1 and more number of sites. A periodicity of three consecutive significance values (measured by the x29) was found only in Drosophila mtDNA. This periodicity may be due to an unknown structure or organization of mtDNA. This non-random distribution of the two bases of dinucleotides widespread throughout these DNA segments is rather compatible with panselective evolution and generalized internucleotide co-adaptation.
Periodicity of DNA in exons
Stephen T Eskesen, Frank N Eskesen, Brian Kinghorn, Anatoly Ruvinsky
BMC Molecular Biology , 2004, DOI: 10.1186/1471-2199-5-12
Abstract: We have shown that simulated coding sequences, which were composed using codon usage frequencies only, demonstrate DNA periodicity very similar to the observed in real exons. It was also found that DNA periodicity disappears in the simulated sequences, when the frequencies of codons become equal.Frequencies of the nucleotides (and the dinucleotide AG) at each location along phase 0 exons were calculated for C. elegans, D. melanogaster and H. sapiens. Two models were used to fit these data, with the key objective of describing periodicity. Both of the models showed that the best-fit curves closely matched the actual data points. The first dynamic period determination model consistently generated a value, which was very close to the period equal to 3 nucleotides. The second fixed period model, as expected, kept the period exactly equal to 3 and did not detract from its goodness of fit.Conclusion can be drawn that DNA periodicity in exons is determined by codon usage frequencies. It is essential to differentiate between DNA periodicity itself, and the length of the period equal to 3. Periodicity itself is a result of certain combinations of codons with different frequencies typical for a species. The length of period equal to 3, instead, is caused by the triplet nature of genetic code. The models and evolutionary algorithm used for characterising DNA periodicity are proven to be an effective tool for describing the periodicity pattern in a species, when a number of exons in the same phase are analysed.Periodicity of DNA in exons, with the period being equal to 3 nucleotides, has been well known for some time [1-6]. This periodicity reflects correlations between nucleotide positions along coding sequences [7], which is caused by the asymmetry in base composition at the three coding positions [8]. This periodicity has also been suggested as a reading-frame monitoring device during translation, due to interrupted periodic patterns matching with frame shifts downstream whe
Sequence periodicity of Escherichia coli is concentrated in intergenic regions
Sergey Hosid, Edward N Trifonov, Alexander Bolshoy
BMC Molecular Biology , 2004, DOI: 10.1186/1471-2199-5-14
Abstract: Here we demonstrate that practically only ApA/TpT dinucleotides contribute to overall dinucleotide periodicity in Escherichia coli. The noncoding sequences reveal this periodicity much more prominently compared to protein-coding sequences. The sequence periodicity of ApC/GpT, ApT and GpC dinucleotides along the Escherichia coli K-12 is found to be located as well mainly within the intergenic regions.The observed concentration of the dinucleotide sequence periodicity in the intergenic regions of E. coli suggests that the periodicity is a typical property of prokaryotic intergenic regions. We suppose that this preferential distribution of dinucleotide periodicity serves many biological functions; first of all, the regulation of transcription.DNA sequence periodicity with the period about 10–11 base pairs (bp) has been long known in eukaryotic DNA sequences. It was discovered recently in prokaryotic sequences as well [1-6]. The periodicity in Eubacteria sequences usually shows the period close to 11 bp [1]. This period is clearly different from the structural helical period of 10.5–10.6 bp/turn [7,8]. The difference was interpreted [1,2] as a possible reflection of the sequence dependent writhe of prokaryotic DNA. In the work [9] it was demonstrated that the periodicity in the bacterial genomes, in E. coli as well, is distributed in a non-uniform way, in scattered segments of the size 100–150 bases. It was also known for a long time that quite a few DNA promoter regions of E. coli possess the sequence periodicity of AA and TT dinucleotides [10].The sequence periodicity of AA/TT dinucleotides is frequently associated with sequence-dependent DNA curvature, which is known to play an important role in the initiation of transcription of many genes (for reviews, see [11-15]). Using different models and approaches for prediction of intrinsic DNA curvature it was shown that many E. coli promoters have upstream curved sequences [16,17]. Pedersen et al. [18] showed that promoter
A Hybrid Technique for the Periodicity Characterization of Genomic Sequence Data
Julien Epps
EURASIP Journal on Bioinformatics and Systems Biology , 2009, DOI: 10.1155/2009/924601
Abstract: The detection of structure within the DNA sequence has long captivated the interest of the research community. Among the various statistical characterizations of sequence data, one measure of structure within sequences is the degree of correlation or periodicity at various displacements along the sequence. Periodicity characterization of sequence data provides a compact and informative representation that has been used in many studies of structure within genomic sequences, including DNA sequence analysis [1], gene and exon detection [2], tandem repeat detection [3], and DNA sequence search and retrieval [4].To measure such periodicity, autocorrelation has been widely employed [1, 5–11]. Similarly, Fourier analysis and its variants have been used for periodicity characterization of sequences [4, 9, 12–24]. In some cases [25, 26], the Fourier transform of the autocorrelation sequence has also been computed, however using existing symbolic-numeric mappings such as binary indicator sequences [27], this transform can also be calculated without first determining the autocorrelation. Other recent promising approaches to periodicity characterization for biological sequences include the periodicity transform [28], the exactly periodic subspace decomposition [3], and maximum-likelihood statistical periodicity [29], however these techniques have yet to be adopted by biologists for the purposes of sequence structure characterization.Studies of structure within sequences, such as those referenced above, have tended to use either the autocorrelation or the Fourier transform, and to the author's knowledge, the limitations of each have not been compared in this context. In this paper, the limitations of both approaches are investigated using synthetic symbolic sequences, and caveats to their characterization of sequence data are discussed. A hybrid approach to periodicity characterization of symbolic sequence data is introduced, and its use is illustrated in a comparative manner on
Exon First Nucleotide Mutations in Splicing: Evaluation of In Silico Prediction Tools  [PDF]
Lucie Grodecká, Pavla Lockerová, Barbora Rav?uková, Emanuele Buratti, Francisco E. Baralle, Ladislav Du?ek, Tomá? Freiberger
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089570
Abstract: Mutations in the first nucleotide of exons (E+1) mostly affect pre-mRNA splicing when found in AG-dependent 3′ splice sites, whereas AG-independent splice sites are more resistant. The AG-dependency, however, may be difficult to assess just from primary sequence data as it depends on the quality of the polypyrimidine tract. For this reason, in silico prediction tools are commonly used to score 3′ splice sites. In this study, we have assessed the ability of sequence features and in silico prediction tools to discriminate between the splicing-affecting and non-affecting E+1 variants. For this purpose, we newly tested 16 substitutions in vitro and derived other variants from literature. Surprisingly, we found that in the presence of the substituting nucleotide, the quality of the polypyrimidine tract alone was not conclusive about its splicing fate. Rather, it was the identity of the substituting nucleotide that markedly influenced it. Among the computational tools tested, the best performance was achieved using the Maximum Entropy Model and Position-Specific Scoring Matrix. As a result of this study, we have now established preliminary discriminative cut-off values showing sensitivity up to 95% and specificity up to 90%. This is expected to improve our ability to detect splicing-affecting variants in a clinical genetic setting.
SVARAP and aSVARAP: simple tools for quantitative analysis of nucleotide and amino acid variability and primer selection for clinical microbiology
Philippe Colson, Catherine Tamalet, Didier Raoult
BMC Microbiology , 2006, DOI: 10.1186/1471-2180-6-21
Abstract: We first tested SVARAP to improve a strategy of identification of streptococci species of the Viridans Group targeting the groESL gene. Two regions with <500 nucleotides were identified, one being significantly more discriminant than one of a similar length used in a previous study (mean number of nucleotide differences between species, 113 (range: 12–193) vs. 77 (range: 14–109); p < 10-3). Secondly, aSVARAP was tested on reverse transcriptase (RT) sequences from 129 HIV-1 clinical strains to identify natural polymorphisms and drug-selected mutations emerging under nucleoside RT inhibitor (NRTI)-selective pressure. It revealed eleven of the 18 RT mutations considered in a reference HIV-1 genotypic NRTI-resistance interpretation algorithm.SVARAP and aSVARAP are simple, versatile and helpful tools for analysis of sequence variability, and are currently being used in real practice in our clinical microbiology laboratory.Sequence variability is a major parameter when designing primers and probes for a new PCR assay, even if various other factors such as string-based alignment scores, melting temperature, primer length and GC contents are also critical [1]. Indeed, nucleotide primers are designed to specifically target a nucleotide region that must be conserved as much as possible in order to ensure their hybridization. Conversely, when nucleotide sequences are used to identify or classify strains, the amplified and then sequenced region has to be divergent enough for discrimination. Variability is also a very informative property of nucleotide and protein sequences. For instance, it may indicate if a region is targeted or not by a given selective pressure or if mutations are occurring under drug-selective pressure.The analysis of the variability of a genetic or protein region is generally impractical, exacting, and based upon non-objective criteria when performed visually from a multiple sequence alignment. Difficulties are compounded by the length of sequences and thei
Using Periodicity of Nucleotide Sequences  [PDF]
Rick B. Jenison
Computer Science , 2013,
Abstract: Withdrawn by arXiv administrators due to content entirely plagiarized from other authors (not in arXiv).
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