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1.
Interdiscip Sci ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817803

RESUMO

In 2002, our research group observed a gene clustering pattern based on the base frequency of A versus T at the second codon position in the genome of Vibrio cholera and found that the functional category distribution of genes in the two clusters was different. With the availability of a large number of sequenced genomes, we performed a systematic investigation of A2-T2 distribution and found that 2694 out of 2764 prokaryotic genomes have an optimal clustering number of two, indicating a consistent pattern. Analysis of the functional categories of the coding genes in each cluster in 1483 prokaryotic genomes indicated, that 99.33% of the genomes exhibited a significant difference (p < 0.01) in function distribution between the two clusters. Specifically, functional category P was overrepresented in the small cluster of 98.65% of genomes, whereas categories J, K, and L were overrepresented in the larger cluster of over 98.52% of genomes. Lineage analysis uncovered that these preferences appear consistently across all phyla. Overall, our work revealed an almost universal clustering pattern based on the relative frequency of A2 versus T2 and its role in functional category preference. These findings will promote the understanding of the rationality of theoretical prediction of functional classes of genes from their nucleotide sequences and how protein function is determined by DNA sequence.

2.
Comput Struct Biotechnol J ; 19: 4042-4048, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527183

RESUMO

Studies on codon property would deepen our understanding of the origin of primitive life and enlighten biotechnical application. Here, we proposed a quantitative measurement of codon-amino acid association and found that seven out of 13 physicochemical properties have stronger associations with the nucleotide identity at the second codon position, indicating that protein structure and function may associate more closely with it than the other two sites. When extending the effect of codon-amino acid association to protein level, it was found that the correlation between the second codon position (measured by the relative frequencies of nucleobase T and A at this codon site) and hydrophobicity (by the form of GRAVY value) became stronger with 96% genomes having R > 0.90 and p < 1e-60. Furthermore, we revealed that informational genes encoding proteins have lower GRAVY values than operational proteins (p < 3e-37) in both prokaryotic and eukaryotic genomes. The above results reveal a complete link from codon identity (A2 versus T2) to amino acid property (hydrophilic versus hydrophobic) and then to protein functions (informational versus operational). Hence, our work may help to understand how the nucleotide sequence determines protein function.

3.
Brief Bioinform ; 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30496347

RESUMO

Essential genes have attracted increasing attention in recent years due to the important functions of these genes in organisms. Among the methods used to identify the essential genes, accurate and efficient computational methods can make up for the deficiencies of expensive and time-consuming experimental technologies. In this review, we have collected researches on essential gene predictions in prokaryotes and eukaryotes and summarized the five predominant types of features used in these studies. The five types of features include evolutionary conservation, domain information, network topology, sequence component and expression level. We have described how to implement the useful forms of these features and evaluated their performance based on the data of Escherichia coli MG1655, Bacillus subtilis 168 and human. The prerequisite and applicable range of these features is described. In addition, we have investigated the techniques used to weight features in various models. To facilitate researchers in the field, two available online tools, which are accessible for free and can be directly used to predict gene essentiality in prokaryotes and humans, were referred. This article provides a simple guide for the identification of essential genes in prokaryotes and eukaryotes.

4.
Genome Biol Evol ; 10(8): 2072-2085, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30060177

RESUMO

Pandemic cholera is a major concern for public health because of its high mortality and morbidity. Mutation accumulation (MA) experiments were performed on a representative strain of the current cholera pandemic. Although the base-pair substitution mutation rates in Vibrio cholerae (1.24 × 10-10 per site per generation for wild-type lines and 3.29 × 10-8 for mismatch repair deficient lines) are lower than that previously reported in other bacteria using MA analysis, we discovered specific high rates (8.31 × 10-8 site/generation for wild-type lines and 1.82 × 10-6 for mismatch repair deficient lines) of base duplication or deletion driven by large-scale copy number variations (CNVs). These duplication-deletions are located in two pathogenic islands, IMEX and the large integron island. Each element of these islands has discrepant rate in rapid integration and excision, which provides clues to the pandemicity evolution of V. cholerae. These results also suggest that large-scale structural variants such as CNVs can accumulate rapidly during short-term evolution. Mismatch repair deficient lines exhibit a significantly increased mutation rate in the larger chromosome (Chr1) at specific regions, and this pattern is not observed in wild-type lines. We propose that the high frequency of GATC sites in Chr1 improves the efficiency of MMR, resulting in similar rates of mutation in the wild-type condition. In addition, different mutation rates and spectra were observed in the MA lines under distinct growth conditions, including minimal media, rich media and antibiotic treatments.


Assuntos
Pareamento de Bases/genética , Cólera/epidemiologia , Cólera/microbiologia , Deleção de Genes , Duplicação Gênica , Pandemias , Vibrio cholerae/genética , Cromossomos Bacterianos/genética , Meios de Cultura , Período de Replicação do DNA/efeitos dos fármacos , Ilhas Genômicas , Humanos , Taxa de Mutação , Reprodutibilidade dos Testes , Rifampina/farmacologia , Vibrio cholerae/efeitos dos fármacos
5.
Bioinformatics ; 33(12): 1758-1764, 2017 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-28158612

RESUMO

Motivation: Previously constructed classifiers in predicting eukaryotic essential genes integrated a variety of features including experimental ones. If we can obtain satisfactory prediction using only nucleotide (sequence) information, it would be more promising. Three groups recently identified essential genes in human cancer cell lines using wet experiments and it provided wonderful opportunity to accomplish our idea. Here we improved the Z curve method into the λ-interval form to denote nucleotide composition and association information and used it to construct the SVM classifying model. Results: Our model accurately predicted human gene essentiality with an AUC higher than 0.88 both for 5-fold cross-validation and jackknife tests. These results demonstrated that the essentiality of human genes could be reliably reflected by only sequence information. We re-predicted the negative dataset by our Pheg server and 118 genes were additionally predicted as essential. Among them, 20 were found to be homologues in mouse essential genes, indicating that some of the 118 genes were indeed essential, however previous experiments overlooked them. As the first available server, Pheg could predict essentiality for anonymous gene sequences of human. It is also hoped the λ-interval Z curve method could be effectively extended to classification issues of other DNA elements. Availability and Implementation: http://cefg.uestc.edu.cn/Pheg. Contact: fbguo@uestc.edu.cn. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Composição de Bases , Genes Essenciais , Análise de Sequência de DNA/métodos , Software , Animais , Eucariotos/genética , Humanos , Camundongos , Modelos Genéticos
6.
Biomed Res Int ; 2016: 7639397, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27660763

RESUMO

Investigation of essential genes is significant to comprehend the minimal gene sets of cell and discover potential drug targets. In this study, a novel approach based on multiple homology mapping and machine learning method was introduced to predict essential genes. We focused on 25 bacteria which have characterized essential genes. The predictions yielded the highest area under receiver operating characteristic (ROC) curve (AUC) of 0.9716 through tenfold cross-validation test. Proper features were utilized to construct models to make predictions in distantly related bacteria. The accuracy of predictions was evaluated via the consistency of predictions and known essential genes of target species. The highest AUC of 0.9552 and average AUC of 0.8314 were achieved when making predictions across organisms. An independent dataset from Synechococcus elongatus, which was released recently, was obtained for further assessment of the performance of our model. The AUC score of predictions is 0.7855, which is higher than other methods. This research presents that features obtained by homology mapping uniquely can achieve quite great or even better results than those integrated features. Meanwhile, the work indicates that machine learning-based method can assign more efficient weight coefficients than using empirical formula based on biological knowledge.

7.
Genome Biol Evol ; 8(8): 2624-31, 2016 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-27521813

RESUMO

The differences in evolutionary patterns of young protein-protein interactions (PPIs) among distinct species have long been a puzzle. However, based on our genome-wide analysis of available integrated experimental data, we confirm that young genes preferentially integrate into ancestral PPI networks, and that this manner is consistent in all of six model organisms with widely different levels of phenotypic complexity. We demonstrate that the level of restrictions placed on the evolution of biological networks declines with a decrease of phenotypic complexity. Compared with young PPI networks, new co-expression links have less evolutionary restrictions, so a young gene with a high possibility to be coexpressed other young genes relatively frequently emerges in the four simpler genomes among the six studied. However, it is not favorable for such young-young coexpression in terms of a young gene evolving into a coexpression hub, so the coexpression pattern could gradually decline. To explain this apparent contradiction, we suggest that young genes that are initially peripheral to networks are temporarily coexpressed with other young genes, driving functional evolution because of low selective pressure. However, as the expression levels of genes increase and they gradually develop a greater effect on fitness, young genes start to be coexpressed more with members of ancestral networks and less with other young genes. Our findings provide new insights into the evolution of biological networks.


Assuntos
Evolução Molecular , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Animais , Archaea/genética , Bactérias/genética , Fungos/genética , Aptidão Genética , Genoma , Humanos , Fenótipo
8.
Shanghai Kou Qiang Yi Xue ; 21(6): 718-20, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23364564

RESUMO

This study was to compare the difference of the existing course materials of basic restorative dental with the past materials, found out the weakness of teaching mode before the reform, and explored the reform in education through teaching content, method and evaluation, in order to improve the teaching quality.


Assuntos
Restauração Dentária Permanente , Educação em Odontologia , Tecnologia Odontológica , Materiais Dentários , Humanos
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