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Chun-Ting Zhang

Publications and source records attributed to Chun-Ting Zhang.

At least 19 recordsLinked to original sources
PubMed2006

GC-Profile: a web-based tool for visualizing and analyzing the variation of GC content in genomic sequences.

In order to understand the evolution, structure and function of genomes, it is important to know the general compositional features of DNA sequences. Based on the quadratic divergence, a new segmentation algorithm to partition a given genome or DNA sequence into compositionally distinct domains has been put forward. With the aid of the technique of cumulative GC profile, the distribution of segmentation points can be displayed intuitively. We have therefore developed them into GC-Profile, an interactive web-based software system, which can be used to segment prokaryotic and eukaryotic genomes. GC-Profile provides a quantitative and qualitative view of genome organization. Based on the obtained results, the relationships between the G+C content and other genomic features, such as distributions of genes and CpG islands, can be analyzed in a perceivable manner. It shows that GC-Profile would be an appropriate starting point for analyzing the isochore structure of higher eukaryotic genomes, and an intuitive tool for identifying genomic islands in prokaryotic genomes. GC-Profile is freely available at the website http://tubic.tju.edu.cn/GC-Profile/. In addition, precompiled binaries, together with examples and documentation, can also be freely downloaded for a local execution.

Algorithms↗
PubMed2006

The impact of comparative genomics on infectious disease research.

The past decade has witnessed a revolution in infectious disease research, fuelled by the accumulation of a huge amount of DNA sequence data. The avalanche of genome sequence information has largely promoted the development of comparative genomics, which exploits available genome sequences to perform either inter- or intra-species comparisons of bacterial genome contents, or performs comparisons between the human genome and those of other organisms. This review aims to summarize how comparative genomics is being extensively used in infectious disease research, such as in the studies to identify virulence determinants, antimicrobial drug targets, vaccine candidates and new markers for diagnostics. These applications hold considerable promise for alleviating the burden of infectious diseases in the coming years.

Bacteria↗
PubMed2006

ZCURVE_V: a new self-training system for recognizing protein-coding genes in viral and phage genomes.

BACKGROUND: It necessary to use highly accurate and statistics-based systems for viral and phage genome annotations. The GeneMark systems for gene-finding in virus and phage genomes suffer from some basic drawbacks. This paper puts forward an alternative approach for viral and phage gene-finding to improve the quality of annotations, particularly for newly sequenced genomes. RESULTS: The new system ZCURVE_V has been run for 979 viral and 212 phage genomes, respectively, and satisfactory results are obtained. To have a fair comparison with the currently available software of similar function, GeneMark, a total of 30 viral genomes that have not been annotated by GeneMark are selected to be tested. Consequently, the average specificity of both systems is well matched, however the average sensitivity of ZCURVE_V for smaller viral genomes (< 100 kb), which constitute the main parts of viral genomes sequenced so far, is higher than that of GeneMark. Additionally, for the genome of Amsacta moorei entomopoxvirus, probably with the lowest genomic GC content among the sequenced organisms, the accuracy of ZCURVE_V is much better than that of GeneMark, because the later predicts hundreds of false-positive genes. ZCURVE_V is also used to analyze well-studied genomes, such as HIV-1, HBV and SARS-CoV. Accordingly, the performance of ZCURVE_V is generally better than that of GeneMark. Finally, ZCURVE_V may be downloaded and run locally, particularly facilitating its utilization, whereas GeneMark is not downloadable. Based on the above comparison, it is suggested that ZCURVE_V may serve as a preferred gene-finding tool for viral and phage genomes newly sequenced. However, it is also shown that the joint application of both systems, ZCURVE_V and GeneMark, leads to better gene-finding results. The system ZCURVE_V is freely available at: http://tubic.tju.edu.cn/Zcurve_V/. CONCLUSION: ZCURVE_V may serve as a preferred gene-finding tool used for viral and phage genomes, especially for anonymous viral and phage genomes newly sequenced.

Algorithms↗
PubMed2006

Isochore structures in the chicken genome.

The availability of the complete chicken genome sequence provides an unprecedented opportunity to study the global genome organization at the sequence level. Delineating compositionally homogeneous G + C domains in DNA sequences can provide much insight into the understanding of the organization and biological functions of the chicken genome. A new segmentation algorithm, which is simple and fast, has been proposed to partition a given genome or DNA sequence into compositionally distinct domains. By applying the new segmentation algorithm to the draft chicken genome sequence, the mosaic organization of the chicken genome can be confirmed at the sequence level. It is shown herein that the chicken genome is also characterized by a mosaic structure of isochores, long DNA segments that are fairly homogeneous in the G + C content. Consequently, 25 isochores longer than 2 Mb (megabases) have been identified in the chicken genome. These isochores have a fairly homogeneous G + C content and often correspond to meaningful biological units. With the aid of the technique of cumulative GC profile, we proposed an intuitive picture to display the distribution of segmentation points. The relationships between G + C content and the distributions of genes (CpG islands, and other genomic elements) were analyzed in a perceivable manner. The cumulative GC profile, equipped with the new segmentation algorithm, would be an appropriate starting point for analyzing the isochore structures of higher eukaryotic genomes.

Algorithms↗
PubMed2005

Segmentation algorithm for DNA sequences.

A new measure, to quantify the difference between two probability distributions, called the quadratic divergence, has been proposed. Based on the quadratic divergence, a new segmentation algorithm to partition a given genome or DNA sequence into compositionally distinct domains is put forward. The new algorithm has been applied to segment the 24 human chromosome sequences, and the boundaries of isochores for each chromosome were obtained. Compared with the results obtained by using the entropic segmentation algorithm based on the Jensen-Shannon divergence, both algorithms resulted in all identical coordinates of segmentation points. An explanation of the equivalence of the two segmentation algorithms is presented. The new algorithm has a number of advantages. Particularly, it is much simpler and faster than the entropy-based method. Therefore, the new algorithm is more suitable for analyzing long genome sequences, such as human and other newly sequenced eukaryotic genome sequences.

Algorithms↗
PubMed2005

Coronavirus phylogeny based on a geometric approach.

A novel coronavirus has been identified as the cause of the outbreak of severe acute respiratory syndrome (SARS). Previous phylogenetic analyses based on sequence alignments show that SARS-CoVs form a new group distantly related to the other three groups of previously characterized coronaviruses. In this paper, a geometric approach based on the Z-curve representation of the whole genome sequence is proposed to analyze the phylogenetic relationships of coronaviruses. The evolutionary distances are obtained through measuring the differences among the three-dimensional Z-curves. The Z-curve is approximately described by its geometric center and the associated three eigenvectors, which indicate the center position and the trend of the Z-curve, respectively. Although some information is lost due to the approximate description of the Z-curve, the phylogenetic tree constructed based on these parameters is consistent with those of previous analyses. The present method has the merits of simplicity and intuitiveness, but it is still in its premature stage. Because the phylogenetic relationships are inferred from the whole genome, instead of some individual genes, the present method represents a new direction of phylogeny study in the post-genome era.

Algorithms↗
PubMed2005

Genomic islands in the Corynebacterium efficiens genome.

Corynebacterium efficiens is a gram-positive nonpathogenic bacterium which can grow and produce glutamate at 40 degrees C or above. By using the cumulative GC profile method, we have identified four genomic islands which have many unifying genomic island-specific features in the C. efficiens genome. The presence of the gene encoding an aspartate kinase in a genomic island helps explain the unexpected low thermal stability of this enzyme; i.e., the adaptive mutations have not occurred extensively due to the recent horizontal gene transfer.

Aspartate Kinase↗
PubMed2005

Identification of replication origins in archaeal genomes based on the Z-curve method.

The Z-curve is a three-dimensional curve that constitutes a unique representation of a DNA sequence, i.e., both the Z-curve and the given DNA sequence can be uniquely reconstructed from the other. We employed Z-curve analysis to identify one replication origin in the Methanocaldococcus jannaschii genome, two replication origins in the Halobacterium species NRC-1 genome and one replication origin in the Methanosarcina mazei genome. One of the predicted replication origins of Halobacterium species NRC-1 is the same as a replication origin later identified by in vivo experiments. The Z-curve analysis of the Sulfolobus solfataricus P2 genome suggested the existence of three replication origins, which is also consistent with later experimental results. This review aims to summarize applications of the Z-curve in identifying replication origins of archaeal genomes, and to provide clues about the locations of as yet unidentified replication origins of the Aeropyrum pernix K1, Methanococcus maripaludis S2, Picrophilus torridus DSM 9790 and Pyrobaculum aerophilum str. IM2 genomes.

Archaea↗
PubMed2004

Gene recognition based on nucleotide distribution of ORFs in a hyper-thermophilic crenarchaeon, Aeropyrum pernix K1.

The 2694 ORFs originally annotated as potential genes in the genome of Aeropyrum pernix can be categorized into three clusters (A, B, C), according to their nucleotide composition at three codon positions. Coding potential was found to be responsible for the phenomenon of three clusters in a 9-dimensional space derived from the nucleotide composition of ORFs: ORFs assigned to cluster A are coding ones, while those assigned to clusters B and C are non-coding ORFs. A "codingness" index called the AZ score is defined based on a clustering method used to recognize protein-coding genes in the A. pernix genome. The criterion for a coding or non-coding ORF is based on the AZ score. ORFs with AZ > 0 or AZ < 0 are coding or non-coding, respectively. Consequently, 620 out of 632 ORFs with putative functions based on the original annotation are contained in cluster A, which have positive AZ scores. In addition, all 29 ORFs encoding putative or conserved proteins newly added in RefSeq annotation also have positive AZ scores. Accordingly, the number of re-recognized protein-coding genes in the A. pernix genome is 1610, which is significantly less than 2694 in the original annotation and also much less than 1841 in the RefSeq annotation curated by NCBI staff. Annotation information of re-recognized genes and their AZ scores are available at: http://tubic.tju.edu.cn/Aper/.

Aeropyrum↗
PubMed2004

Identification of replication origins in the genome of the methanogenic archaeon, Methanocaldococcus jannaschii.

Methanocaldococcus jannaschii has been notorious as an archaeon in which the replication origins are difficult to identify. Although extensive efforts have been exerted on this issue, the locations of replication origins still remain elusive 7 years after the publication of its complete genome sequence in 1996. Ambiguous results were obtained in identifying the replication origins of M. jannaschii based on all theoretical and experimental approaches. In the genome of M. jannaschii, we found that an ORF (MJ0774), annotated as a hypothetical protein, is a homologue of the Cdc6 protein. The position of the gene is at a global minimum of the x component of the Z curve, i.e., RY disparity curve, which has been used to identify replication origins in other Archaea. In addition, an intergenic region (694,540-695,226 bp) that is between the cdc6 gene and an adjacent ORF shows almost all the characteristics of known replication origins, i.e., it is highly rich in AT composition (80%) and contains multiple copies of repeat elements and AT stretches. Therefore, these lines of evidence strongly suggest that the identified region is a replication origin, which is designated as oriC1. The analysis of the y component of the Z curve, i.e., MK disparity curve, suggests the presence of another replication origin corresponding to one of the peaks in the MK disparity curve at around 1,388 kb of the genome.

Amino Acid Sequence↗
PubMed2004

Comparison of various algorithms for recognizing short coding sequences of human genes.

MOTIVATION: Since the early 1980s of the twentieth century, there has been great progress in the development of computational gene-finding algorithms. Some problems, however, have not yet been solved currently. Recognizing short genes in prokaryotes and short exons in eukaryotes is one of such problems. The paper is devoted to assessing various algorithms, including those currently available and the new ones proposed here, in order to find the best algorithm to solve the issue. RESULTS: The databases consisting of phase-specific coding and non-coding sequences of human genes with length of 192, 162, 129, 108, 87, 63 and 42 bp, respectively, have been established. Based on the databases and a standard benchmark, 19 algorithms were evaluated, which include the methods of Markov models with orders of 1 through 5, codon usage, hexamer usage, codon preference, amino acid usage, codon prototype, Fourier transform and 8 Z curve methods with various numbers of parameters. Consequently, the Z curve methods with 69 and 189 parameters are the best ones among them, based on the databases constructed here. In addition to the highest recognition accuracy confirmed by 10-fold cross-validation tests, the Z curve methods are much simpler computationally than the second best one, the fifth-order Markov chain model, in which 12 288 parameters are used. We hope that the Z curve methods presented in this paper would be beneficial to the further development of gene-finding algorithms. AVAILABILITY: The programs of various Z curve methods are available on request.

Algorithms↗
PubMed2004

A systematic method to identify genomic islands and its applications in analyzing the genomes of Corynebacterium glutamicum and Vibrio vulnificus CMCP6 chromosome I.

MOTIVATION: Some genomic islands contain horizontally transferred genes, which play critical roles in altering the genotypes and phenotypes of organisms, and horizontal gene transfer has been recognized as a universal event throughout bacterial evolution. A windowless method to display the distribution of genomic GC content, the cumulative GC profile, is proposed to identify genomic islands in genomes whose complete genome sequences are available. Two new indices are proposed to assess the codon usage bias and amino acid usage bias in genomic islands. RESULTS: A 211 kb genomic island (CGGI-1) has been identified in the genome of Corynebacterium glutamicum, and three genomic islands VVGI-1, VVGI-2 and VVGI-3, with lengths 167, 40 and 33 kb, respectively, have been identified in the genome of Vibrio vulnificus CMCP6 chromosome I. The CGGI-1 is flanked by two approximately 500 bp direct repeats, and utilizes a Val-tRNA as the integration site. For the VVGI-1 and VVGI-2, each has an integrase gene at 5' junction. All the identified genomic islands show unusual GC content, codon usage and amino acid usage, compared with the rest of the genomes. In addition, it is found that genomic islands are fairly homogenous in terms of GC content variation. An index, h, to quantify the homogeneity of GC content for genomic islands is proposed, and it is shown that h is less than 0.1 for all the genomic islands analyzed. The cumulative GC profile, as well as various indices to assess the codon usage bias, amino acid usage bias and homogeneity of the genomic islands, will be useful in the analysis of other genomes. AVAILABILITY: Programs used in this work and numerical results are available upon request.

Algorithms↗
PubMed2004

DEG: a database of essential genes.

Essential genes are genes that are indispensable to support cellular life. These genes constitute a minimal gene set required for a living cell. We have constructed a Database of Essential Genes (DEG), which contains all the essential genes that are currently available. The functions encoded by essential genes are considered a foundation of life and therefore are likely to be common to all cells. Users can BLAST the query sequences against DEG. If homologous genes are found, it is possible that the queried genes are also essential. Users can search for essential genes by their function or name. Users can also browse and extract all the records in DEG. Essential gene products comprise excellent targets for antibacterial drugs. Analysis of essential genes could help to answer the question of what are the basic functions necessary to support cellular life. DEG is freely accessible from the website http://tubic.tju.edu.cn/deg/.

Computational Biology↗
PubMed2004

Isochore structures in the genome of the plant Arabidopsis thaliana.

Arabidopsis thaliana is an important model system for the study of plant biology. We have analyzed the complete genome sequences of Arabidopsis by using a newly developed windowless method for the GC content computation, the cumulative GC profile. It is shown that the Arabidopsis genome is organized into a mosaic structure of isochores. All the centromeric regions are located in GC-rich isochores, called centromere-isochores, which are characterized by a high GC content but low gene and T-DNA insertion densities. This characteristic distinguishes centromere-isochores from the other class of GC-rich isochores, called GC-isochores, which have high gene and T-DNA insertion densities. Consequently, 15 isochores have been identified, i.e., 7 AT-isochores, 3 GC-isochores, and 5 centromere-isochores. The genes in centromere-isochores, which have the highest GC content, have much shorter intron lengths and lower intron numbers, compared to those of the other two types. There is also considerable difference in the numbers and lengths of transposable elements (TEs) between AT and GC-isochores, i.e., the TE number (length) of AT-isochores is 6.3 (7.3) times that of GC-isochores. It is generally believed that TEs are accumulated in the regions surrounding the centromeres. However, within these TE-rich regions, there are regions of extremely low TE numbers (TE deserts), which correspond to the positions of centromere-isochores. In addition, a heterochromatic knob is located at the boundary of an AT-isochore. Furthermore, we show that the differences in GC content among isochores are mainly due to the GC content variation of introns, the third codon positions and intergenic regions.

Analysis of Variance↗
PubMed2004

GS-Finder: a program to find bacterial gene start sites with a self-training method.

In this paper, a self-training method is proposed to recognize translation start sites in bacterial genomes without a prior knowledge of rRNA in the genomes concerned. Many features with biological meanings are incorporated, including mononucleotide distribution patterns near the start codon, the start codon itself, the coding potential and the distance from the most-left start codon to the start codon. The proposed method correctly predicts 92% of the translation start sites of 195 experimentally confirmed Escherichia coli CDSs, 96% of 58 reliable Bacillus subtilis CDSs and 82% of 140 reliable Synechocystis CDSs. Moreover, the self-training method presented might also be used to relocate the translation start sites of putative CDSs of genomes, which are predicted by gene-finding programs. After post-processing by the method presented, the improvement of gene start prediction of some gene-finding programs is remarkable, e.g., the accuracy of gene start prediction of Glimmer 2.02 increases from 63 to 91% for 832 E. coli reliable CDSs. An open source computer program to implement the method, GS-Finder, is freely available for academic purposes from http://tubic.tju.edu.cn/GS-Finder/.

Algorithms↗
PubMed2004

A nucleotide composition constraint of genome sequences.

Let a, c, g and t denote the occurrence frequencies of A, C, G and T, respectively, in a genome. We calculated the statistical quantity S = a2 + c2 + g2 + t2 for each of 809 genomes (11 archaea, 42 bacteria, 3 eukaryota, 90 phages, 36 viroids and 627 viruses) and 236 plasmids. We found that S < 1/3 is strictly valid for almost all of the above genomes or plasmids. As a direct deduction of the above observation, it is shown that (i) the statistical quantity S is a kind of genome order index, which is negatively correlated with the Shannon H function; (ii) S < 1/3 suggests that a minimal value of the Shannon H function is required for each genome; (iii) S defined above would be a new biological statistical quantity, useful to describe the composition features of genomes; (iv) By jointly considering the Chargaff Parity Rule 2, it is shown that the genomic G + C content should be in between 0.211 and 0.789.

Animals↗
PubMed2004

Isochore structures in the mouse genome.

The distribution of the G+C content in the mouse genome has been studied using a windowless technique. We have found that: (i). Abrupt variations of the G+C content from a GC-rich region to a GC-poor region, and vice versa, occur frequently at some sites along the sequence of the mouse genome. (ii). Long domains with relatively homogeneous G+C content (isochores) exist, which usually have sharp boundaries. Consequently, 28 isochores longer than 1 Mb have been identified in the mouse genome. A homogeneity index was used to quantify the variations of the G+C content within isochores. The precise boundaries, sizes, and G+C contents of these isochores have been determined. The windowless technique for the G+C content computation was also used to analyze the DNA sequence containing the mouse MHC region, which has a GC-poor isochore. This isochore is located at the central part of the sequence with boundaries at 468459 and 812716 bp, where the sequence is extended from the centromeric end to the telomeric end. In addition, the analysis of a segment of the rat genome shows that the rat genome also has clear isochore structures.

Algorithms↗