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Facing the explosive growth of biological sequences unearthed in the post-genomic age, one of the most important but also most difficult problems in computational biology is how to express a biological sequence with a discrete model or a vector, but still keep it with considerable sequence-order information or its special pattern. To deal with such a challenging problem, the ideas of "pseudo amino acid components" and "pseudo K-tuple nucleotide composition" have been proposed. The ideas and their approaches have further stimulated the birth for "distorted key theory", "wenxing diagram", and substantially strengthening the power in treating the multi-label systems, as well as the establishment of the famous "5-steps rule". All these logic developments are quite natural that are very useful not only for theoretical scientists but also for experimental scientists in conducting genetics/genomics analysis and drug development. Presented in this review paper are also their future perspectives; i.e., their impacts will become even more significant and propounding.

The fluorescence dye SYBR Green II(SG II) has been frequently used in rolling circle amplification(RCA) based analyses of nucleic acids. However, a good amount of inconsistencies have been reported in regards the quality and reproducibility of RCA reactions. To properly examine this experimental issue, here we utilized a series of synthetic oligonucleotides and circular templates to investigate the impact of SG II in RCA reactions. The results indicate that SG II enables a strong fluorescence signal only when complexing with guanosine(G) residue. In RCA reactions, long single-stranded RCA products, enriched with G residues, result in higher fluorescence emission when compared with the addition of other nucleotide residues. These results suggest that the nucleotide composition of the reaction can affect the amplification results and, eventually, can lead to inconsistent fluorescence of the RCA products. This work indicates that particular attention should be given when circular templates are designed for the quantitative analysis of nucleic acids, to further allow the signal reproducibility of RCA-based experiments.

Identification of the sites of post-translational modifications (PTMs) in protein, RNA, and DNA sequences is currently a very hot topic. This is because the information thus obtained is very useful for in-depth understanding the biological processes at the cellular level and for developing effective drugs against major diseases including cancers as well. Although this can be done by means of various experimental techniques, it is both time-consuming and costly to determine the PTM sites purely based on experiments. With the avalanche of biological sequences generated in the post-genomic age, it is highly desired to develop bioinformatics tools for rapidly and effectively identifying the PTM sites. In the last few years, many efforts have been made in this regard, and considerable progresses have been achieved. This review is focused on those prediction methods that have the following two features. (1) They have been developed by strictly observing the 5-steps rule so that they each have a user-friendly web-server for the majority of experimental scientists to easily get their desired data without the need to go through the detailed mathematics involved. (2) Their cornerstones have been based on Pseudo Amino Acid Composition (PseAAC) or Pseudo K-tuple Nucleotide Composition (PseKNC), and hence the prediction quality is generally higher than most of the other PTM prediction methods.

The original version of this article unfortunately contained a mistake. One character was missing in the title, which was therefore incorrectly given as “A Two-Layer Computational Model for Discrimination of Enhancer and Their Types Using Hybrid Features Pace of Pseudo K-Tuple Nucleotide Composition”.

Nautilus pompilius has been listed as an endangered species by CITES due to low fecundity and overfishing. In this study, its whole circular mitochondrial genome (15,693 bp) was determined by polymerase chain reaction method. It contained the typical mitogenome gene set of 22 tRNAs, 13 protein coding genes (NAD1-6, NAD4L, COX1-3, Cob, ATP6 and ATP8), two rRNAs (rrnS and rrnL) and the non-coding A+T-rich region. The nucleotide composition was asymmetric with an obvious bias towards A and T (60.2%). Phylogenetic analysis revealed that N. pompilius is closely related to Nautilus macromphalus as expected. The complete mitochondrial genome of Nautilus pompilius will provided valuable information for corresponding conservation genetic studies.

At the chromosomal level of evolution, recombination is a major factor for genetic variations. However, recombination does not occur with equal frequency at various regions of genome. The recombination has the tendency to occur at specific region with higher frequency and with low frequency at other regions, and former regions are named as hot recombination regions whereas later are called cold regions for recombination. In this paper, we have developed supervised machine learning-based models using artificial neural network, support vector machine and Naive Bayes for efficient and effective classification of such hot and cold recombination regions based on the nucleotide composition of sequences. All models were validated and tested using tenfold cross-validation. Furthermore, neural network model was validated using leave one out and random sampling techniques in addition to tenfold cross-validation. Moreover, models were evaluated using receiver-operating curve. Our results indicate that artificial neural network achieves the best result.

Background Pseudouridylation is the most prevalent type of posttranscriptional modification in various stable RNAs of all organisms, which significantly affects many cellular processes that are regulated by RNA. Thus, accurate identification of pseudouridine (Ψ) sites in RNA will be of great benefit for understanding these cellular processes. Due to the low efficiency and high cost of current available experimental methods, it is highly desirable to develop computational methods for accurately and efficiently detecting Ψ sites in RNA sequences. However, the predictive accuracy of existing computational methods is not satisfactory and still needs improvement. Results In this study, we developed a new model, PseUI, for Ψ sites identification in three species, which are H. sapiens, S. cerevisiae, and M. musculus. Firstly, five different kinds of features including nucleotide composition (NC), dinucleotide composition (DC), pseudo dinucleotide composition (pseDNC), position-specific nucleotide propensity (PSNP), and position-specific dinucleotide propensity (PSDP) were generated based on RNA segments. Then, a sequential forward feature selection strategy was used to gain an effective feature subset with a compact representation but discriminative prediction power. Based on the selected feature subsets, we built our model by using a support vector machine (SVM). Finally, the generalization of our model was validated by both the jackknife test and independent validation tests on the benchmark datasets. The experimental results showed that our model is more accurate and stable than the previously published models. We have also provided a user-friendly web server for our model at http://zhulab.ahu.edu.cn/PseUI, and a brief instruction for the web server is provided in this paper. By using this instruction, the academic users can conveniently get their desired results without complicated calculations. Conclusion In this study, we proposed a new predictor, PseUI, to detect Ψ sites in RNA sequences. It is shown that our model outperformed the existing state-of-art models. It is expected that our model, PseUI, will become a useful tool for accurate identification of RNA Ψ sites. Electronic supplementary material The online version of this article (10.1186/s12859-018-2321-0) contains supplementary material, which is available to authorized users.

Background The HIV-1 RNA genome has a biased nucleotide composition with a surplus of As. Several hypotheses have been put forward to explain this striking phenomenon, but the A-count of the HIV-1 genome has thus far not been systematically manipulated. The reason for this reservation is the likelihood that known and unknown sequence motifs will be affected by such a massive mutational approach, thus resulting in replication-impaired virus mutants. We present the first attempt to increase and decrease the A-count in a relatively small polymerase (pol) gene segment of HIV-1 RNA. Results To minimize the mutational impact, a new mutational approach was developed that is inspired by natural sequence variation as present in HIV-1 isolates. This phylogeny-instructed mutagenesis allowed us to create replication-competent HIV-1 mutants with a significantly increased or decreased local A-count. The local A-count of the wild-type (wt) virus (40.2%) was further increased to 46.9% or reduced to 31.7 and 26.3%. These HIV-1 variants replicate efficiently in vitro, despite the fact that the pol changes cause a quite profound move in HIV–SIV sequence space. Conclusions Extrapolating these results to the complete 9 kb RNA genome, we may cautiously suggest that the A-rich signature does not have to be maintained. This survey also provided clues that silent codon changes, in particular from G-to-A, determine the subtype-specific sequence signatures.

Understanding the extent and pattern of codon bias and the forces affecting codon usage are the key steps towards elucidating choice of codons at the level of individual genes. In the present study, codon usage pattern among 3,703 genes of nitrogen fixing bacterium, Rhizobium etli CFN 42 was analyzed. The study aims to identify the factors responsible for codon usage bias and highly expressed genes of this bacterium. Multivariate statistical analysis revealed a single major explanatory axis accounting for codon usage variation among the genes. Correlation analysis suggested that the axis has strong significant positive correlation with GC3s i.e. GC content at the third codon position. A significant negative correlation between effective number of codons and GC3s content was observed suggesting that the codon usage was affected by gene nucleotide composition. These findings suggested mutational role as the major factor in shaping codon usage bias among the genes. Further, correspondence analysis of Relative Synonymous Codon Usage revealed cluster of highly expressed genes. Notably, 26 codons were determined as the ‘optimal codons’ that were significantly more frequent among the highly expressed genes tested by χ2 test (P < 0.01). Such results may add value to the efforts of developing bio-fertilizers based on symbiotic or non-symbiotic bacteria for improving soil fertility.

Enhancers are cis elements that play an important role in regulating gene expression by enhancing it. Recent study of modifications revealed that enhancers are a large group of functional elements with many different subgroups, which have different biological activities and regulatory effects on target genes. As powerful auxiliary tools, several computational methods have been proposed to distinguish enhancers from other regulatory elements, but only one method has been considered to clustering them into subgroups. In this study, we developed a predictor (called EnhancerPred) to distinguish between enhancers and nonenhancers and to determine enhancers’ strength. A two-step wrapper-based feature selection method was applied in high dimension feature vector from bi-profile Bayes and pseudo-nucleotide composition. Finally, the combination of 104 features from bi-profile Bayes, 1 feature from nucleotide composition and 9 features from pseudo-nucleotide composition yielded the best performance for identifying enhancers and nonenhancers, with overall Acc of 77.39%. The combination of 89 features from bi-profile Bayes and 10 features from pseudo-nucleotide composition yielded the best performance for identifying strong and weak enhancers, with overall Acc of 68.19%. The process and steps of feature optimization illustrated that it is necessary to construct a particular model for identifying strong enhancers and weak enhancers.

Background RNA viruses have genomes with a distinct nucleotide composition and codon usage. We present the global characteristics of the RNA genome of Zika virus (ZIKV), an emerging pathogen within the Flavivirus genus. ZIKV was first isolated in 1947 in Uganda, caused a widespread epidemic in South and Central America and the Caribbean in 2015 and has recently been associated with microcephaly in newborns. Methods The nearly 11 kb positive-stranded RNA genome of ZIKV was analyzed for its nucleotide composition, also in the context of the folded RNA molecule. Nucleotide trends were investigated along the genome length by skew analyses and we analyzed the codons used for translation of the ZIKV proteins. Results ZIKV RNA has a biased nucleotide composition in being purine-rich and pyrimidine-poor. This preference for purines is a general characteristic of the mosquito-borne and tick-borne flaviviruses. The virus-specific nucleotide bias is further enriched in the unpaired, single-stranded regions of the structured ZIKV RNA genome, thus further imposing this ZIKV-specific signature. The codons used for translation of the ZIKV proteins is also unusual, but we show that it is the underlying bias in nucleotide composition of the viral RNA that largely dictates these codon preferences. Conclusions The ZIKV RNA genome has a biased nucleotide composition that dictates the codon usage of this flavivirus. We discuss the evolutionary scenarios and molecular mechanisms that may be responsible for these distinctive ZIKV RNA genome features.

Despite Springer’s (1964) revision of the sharpnose sharks (genus Rhizoprionodon), the taxonomic definition and ranges of Rhizoprionodon in the western Atlantic Ocean remains problematic. In particular, the distinction between Rhizoprionodon terraenovae and R. porosus, and the occurrence of R. terraenovae in South American waters are unresolved issues involving common and ecologically important species in need of fishery management in Caribbean and southwest Atlantic waters. In recent years, molecular markers have been used as efficient tools for the detection of cryptic species and to address controversial taxonomic issues. In this study 415 samples of the genus Rhizoprionodon captured in the western Atlantic Ocean from Florida to southern Brazil were examined for sequences of the COI gene and the D-loop and evaluated for nucleotide differences. The results on nucleotide composition, AMOVA tests, and relationship distances using Bayesian-likelihood method and haplotypes network, corroborates Springer’s (1964) morphometric and meristic finding and provide strong evidence that supports consideration of R. terraenovae and R. porosus as distinct species. info:eu-repo/semantics/publishedVersion

One of the key problems in the study of ancient DNA is that of authenticating sequences obtained from PCR amplifications of highly degraded samples. Contamination of ancient samples and postmortem damage to endogenous DNA templates are the major obstacles facing researchers in this task. In particular, the authentication of sequences obtained from ancient human remains is thought by many to be rather challenging. We propose a novel approach, based on the c statistic, that can be employed to help identify the sequence motif of an endogenous template, based on a sample of sequences that reflect the nucleotide composition of individual template molecules obtained from ancient tissues (such as cloned products from a PCR amplification). The c statistic exploits as information the most common form of postmortem damage observed among clone sequences in ancient DNA studies, namely, lesion-induced substitutions caused by cytosine deamination events. Analyses of simulated sets of templates with miscoding lesions and real sets of clone sequences from the literature indicate that the c-based approach is highly effective in identifying endogenous sequence motifs, even when they are not present among the sampled clones. The proposed approach is likely to be of general use to researchers working with DNA from ancient tissues, particularly from human remains, where authentication of results has been most challenging.

Many coronaviruses are capable of interspecies transmission. Some of them have caused worldwide panic as emerging human pathogens in recent years, e.g., severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In order to assess their threat to humans, we explored to infer the potential hosts of coronaviruses using a dual-model approach based on nineteen parameters computed from spike genes of coronaviruses. Both the support vector machine (SVM) model and the Mahalanobis distance (MD) discriminant model achieved high accuracies in leave-one-out cross-validation of training data consisting of 730 representative coronaviruses (99.86% and 98.08% respectively). Predictions on 47 additional coronaviruses precisely conformed to conclusions or speculations by other researchers. Our approach is implemented as a web server that can be accessed at http://bioinfo.ihb.ac.cn/seq2hosts.

Binding of short fluorescently labeled AT-containing DNA duplexes with modified oligocytidylates is studied. The latter are modified to contain nonnatural α-anomers along with natural β-nucleotides; the nucleotide composition is selected according to the putative scheme of noncanonical triplex formation between duplex and oligomer bases. Nondenaturing gel electrophoresis is used to study the interaction of fluorescent duplexes with cytidyl oligomers and oligocytidylate self-association at low temperatures. A DNA duplex of random AT composition is shown to bind with an excess of the corresponding oligocytidylate in 0.1 M Tris-HCl in the presence of Mg2+. Binding is observed at neutral pH values, while more basic pH (8.0) prevents binding of the AT duplex and oligocytidylate. Unlike oligonucleotides of random composition, a regular dA30:dT30 duplex does not bind with the dC strand. It is also shown that an alternating self-complementary duplex d(AT)16 and oligocytidylate d(CβCα)15 do not form complexes, and poly-dC self-associates are formed instead. The effect of 2′-O-methylation of the third strand on complex formation and self-association is also analyzed. The results suggest that a modified oligocytidylate binds with a random-composition duplex, albeit with lower efficiency.

Seven strains with similar characteristics from the laboratory collection of yeasts isolated from forest substrates collected in the central part of European Russia corresponded to none of the known yeast species. Based on the study of their life cycle, physiological characteristics, and the nucleotide composition of their DNA and taking into account the data of PCR analysis with universal primers, the strains were ascribed to a new psychrophilic yeast species, Mrakia curviuscula sp. nov.

We report the nucleotide sequences of Australian Grapevine Viroid and Grapevine Yellow Speckle Viroid (type 1) isolated from grapevine trees in a Tunisian vineyard. Our data confirm the worldwide spread of these viroids and record their occurrence in Africa. This is the first description of Australian Grapevine Viroid sequences isolated from its natural host. Moreover, the sequences of these new natural variants suggests that the previous use of an indicator plant to amplify a viroid does not alter its nucleotide composition. In addition, we also present several new features of these two distinct quasi-species.

Cold-induced decondensation of heterochromatic regions (CSR-bands) in Paris hainanensis(=Daiswa hainanensisMerrill Takht.) (2n= 10; 10 + b) was studied. The comparison of CSR-banding patterns with those obtained by nucleotide-specific staining with fluorochromes DAPI and chromomycin A3demonstrated that low temperatures induced decondensation only of large AT-rich heterochromatic regions. It is suggested that this is characteristic of all plant species.

We have generated secA sequence data from a number of photosynthetic prokaryotes and carried out a phylogenetic analysis using secA sequences from prokaryotes, green plants, and red and brown algae. We have studied the substitution patterns that give rise to the apparent phylogenetic structure. We show that the high AT content of the plastid sequences significantly affects the amino-acid composition. We also show that most of the apparent evidence for an edge separating red and brown plastids from green plants within the phylogenetic tree is due to differences in nucleotide composition. The remaining apparent evidence is likely to be due, at least in part, to differences in the distribution of sites free to vary. We discuss the implications of this study for hypotheses of plastid origins.

We have performed several kinds of DNA walks which often are the first steps for further analysis of DNA structure and long range correlations. The DNA walks analysing frequency of G+C versus A+T cannot indicate the coding strand while purine versus pyrimidine DNA walks or two-dimensional (A-T,G-C) DNA walks in some instances can indicate the coding strand but cannot resolve the coding frame. The modified two-dimensional (A-T,G-C) DNA walks respecting the three-nucleotide codon structure show very high correlation in nucleotide composition of DNA coding sequences. They can distinguish between coding and non-coding sequences and indicate the strand and the phase in which DNA is coding.

Recent developments in the understanding of paralogous evolution have prompted a focus not only on obviously advantageous genes, but also on genes that can be considered to have a weak or sporadic impact on the survival of the organism. Here we examine the duplicative behavior of a category of genes that can be considered to be mostly transient in the genome, namely laterally transferred genes. Using both a compositional method and a gene-tree approach, we identify a number of proposed laterally transferred genes and study their nucleotide composition and frequency of duplication. It is found that duplications are significantly overrepresented among potential laterally transferred genes compared to the indigenous ones. Furthermore, the GC3 distribution of potential laterally transferred genes was found to be largely uniform in some genomes, suggesting an import from a broad range of donors. The results are discussed not in a context of strongly optimized established genes, but rather of genes with weak or ancillary functions. The importance of duplication may therefore depend on the variability and availability of weak genes for which novel functions may be discovered. Therefore, lateral transfer may accelerate the evolutionary process of duplication by bringing foreign genes that have mainly weak or no function into the genome.

The DNA's ofMicrococcus lysodeikticus andClostridium perfringens were fragmented to about 7 000 nucleotide pairs long by shear and fractionated with respect to buoyant density of mercury complexes in Cs2SO4. The distribution of G + C content in both DNA's was characteristically asymmetric. InM. lysodeikticus DNA, low G + C fragments were more numerous than high G + C fragments, whereas inC. perfringens DNA, high G + C fragments were more numerous than low G + C fragments. The G + C content of fragments ofM. lysodeikticus DNA varied from 70 to 77%, with a mean and standard deviation of 73.7 ± 1.92% G + C and that ofC. perfringens DNA varied from 27 to 34%, with a mean and standard deviation of 29.8 ± 1.34% G + C. The standard deviation was smaller than that ofEscherichia coli DNA fragments of similar size. Biological meanings of relatively low heterogeneity in nucleotide composition inM. lysodeikticus andC. perfringens are discussed.

1. Methods have been described for the separation and assay of various phosphorus-containing fractions ofDrosophila. 2. In the mutant, “lethal-translucida”, total acid-soluble phosphorus and ATP are present in normal amounts on a wet weight basis, or in excessive amounts on a dry weight basis; total phospho-lipid, nucleic acid, and residual phosphorus are deficient on a wet weight basis, or substantially normal on a dry weight basis; 5′-AMP is grossly deficient on a wet weight basis, and is substantially lower than normal even on a dry weight basis. The significance of these findings in relation to the abnormality of protein metabolism inltr is discussed. 3. Within experimental error, the ribonucleic acid of “lethal-translucida” has the same nucleotide composition as that of wild typeDrosophila.

1. t-RNA, t-RNA, and RNA of the AU type have been isolated from pea plants by fractional extraction and chromatography on methylated albumin and have been studied. The last-mentioned type is heterogeneous with respect to molecular weight, nucleotide composition, metabolic activity, and physicochemical state.

Between Panckow's description of Lycogala and De Bary's exposition of the Myxomycete life cycle, two centuries elapsed in which these forms were considered Gasteromycetes. From De Bary onward they have been recognized as a separate group with probably protozoan affinities. The Acrasieae were first recognized by Brefeld, but an error in interpreting the life cycle has kept them artificially allied with the Myxomycetes as “Slime Moulds”. It appears that the Acrasieae consist of two distinct groups, the Guttulinaceae and Dictyosteliaceae. The Acrasieae differ from the Myxomycetes in the absence of a flagellate swarmer stage, no known sexuality, and in the cellular structure of the fructification, which in the Myxomycetes is secreted. A third group, the minute Protostelida, recently described by Olive appears to be related to the Myxomycetes. The Myxobacteria in their flexuousness to some degree resemble the Cyanophyceae. But the nucleoids resemble more closely those of the Eubacteria. In nucleotide composition the true fruiting Myxobacteria form a very coherent group.

THE recent finding of relatively large concentrations of inosine triphosphate (ITP) (44–51 µg of phosphorus/g of haemoglobin) in erythrocytes obtained from two members of a family1 led to a closer investigation of the nucleotide composition of normal erythrocytes. A detailed analysis of several samples of fresh human erythrocytes revealed the presence of small amounts of ITP in an average concentration of 1.8 µg of phosphorus/g of haemoglobin2. From these studies it was concluded that ITP is a normal constituent of human erythrocytes.