The basic unit in life is cell.?It contains many protein molecules located at its different organelles. The growth and reproduction of a cell as well as most of its other biological functions are performed via these p...The basic unit in life is cell.?It contains many protein molecules located at its different organelles. The growth and reproduction of a cell as well as most of its other biological functions are performed via these proteins. But proteins in different organelles or subcellular locations have different functions. Facing?the avalanche of protein sequences generated in the postgenomic age, we are challenged to develop high throughput tools for identifying the subcellular localization of proteins based on their sequence information alone. Although considerable efforts have been made in this regard, the problem is far apart from being solved yet. Most existing methods can be used to deal with single-location proteins only. Actually, proteins with multi-locations may have some special biological functions that are particularly important for drug targets. Using the ML-GKR (Multi-Label Gaussian Kernel Regression) method,?we developed a new predictor called “pLoc-mGpos” by in-depth extracting the key information from GO (Gene Ontology) into the Chou’s general PseAAC (Pseudo Amino Acid Composition)?for predicting the subcellular localization of Gram-positive bacterial proteins with both single and multiple location sites. Rigorous cross-validation on a same stringent benchmark dataset indicated that the proposed pLoc-mGpos predictor is remarkably superior to “iLoc-Gpos”, the state-of-the-art predictor for the same purpose.?To maximize the convenience of most experimental scientists, a user-friendly web-server for the new powerful predictor has been established at http://www.jci-bioinfo.cn/pLoc-mGpos/, by which users can easily get their desired results without the need to go through the complicated mathematics involved.展开更多
A GoBlast system was built to predict gene function by integrating Blast search and Gene Ontology (GO) annotations together. The operation system was based on Debian Linux 3.1, with Apache as the web server and Mysql ...A GoBlast system was built to predict gene function by integrating Blast search and Gene Ontology (GO) annotations together. The operation system was based on Debian Linux 3.1, with Apache as the web server and Mysql database as the data storage system. FASTA files with GO annotations were taken as the sequence source for blast alignment, which were formatted by wu-formatdb program. The GoBlast system includes three Bioperl modules in Perl:a data input module, a data process module and a data output module. A GoBlast query starts with an amino acid or nucleotide sequence. It ends with an output in an html page, presenting high scoring gene products which are of a high homology to the queried sequence and listing associated GO terms beside respective gene poducts. A simple click on a GO term leads to the detailed explanation of the specific gene function. This avails gene function prediction by Blast. GoBlast can be a very useful tool for functional genome research and is available for free at http://bioq.org/goblast.展开更多
Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported t...Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.展开更多
通过寻找共突变基因对,可以研究在癌症的发生与发展过程中被共同扰动的生物学功能,为揭示癌症的发生机制提供新的线索。目前,此类研究主要利用京都基因与基因组百科全书数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)。由于KEG...通过寻找共突变基因对,可以研究在癌症的发生与发展过程中被共同扰动的生物学功能,为揭示癌症的发生机制提供新的线索。目前,此类研究主要利用京都基因与基因组百科全书数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)。由于KEGG数据库倾向于定义粗泛的通路,因此,利用该数据库无法判定是通路整体还是其中的一部分与癌症相关。相反,Gene Ontology数据库在从宽泛到细致的不同层面上定义生物学功能,因此,基于GeneOntology功能类来研究癌症过程中生物学功能的共扰动是一种合理的选择。本文提出了一种算法,寻找Gene Ontology功能类间注释了非随机多的共突变基因对的功能对。由于GeneOntology功能类之间的依赖关系,导致找到的功能对之间存在冗余关系,本文提出了去冗余算法,以寻找非冗余的典型功能对。根据肺腺癌基因组体细胞突变扫查数据,我们找到了78对典型的共突变功能对。这些功能对包含宽泛和细致的生物学功能,更精确地定义了被共同扰动的生物学功能的范围,为研究肺腺癌的发生机制提供了新的线索。展开更多
Background Clustering is a useful exploratory technique for interpreting gene expression data to reveal groups of genes sharing common functional attributes. Biologists frequently face the problem of choosing an appro...Background Clustering is a useful exploratory technique for interpreting gene expression data to reveal groups of genes sharing common functional attributes. Biologists frequently face the problem of choosing an appropriate algorithm. We aimed to provide a standalone, easily accessible and biologically oriented criterion for expression data clustering evaluation. Methods An external criterion utilizing annotation based similarities between genes is proposed in this work. Gene ontology information is employed as the annotation source. Comparisons among six widely used clustering algorithms over various types of gene expression data sets were carried out based on the criterion proposed. Results The rank of these algorithms given by the criterion coincides with our common knowledge. Single-linkage has significantly poorer performance, even worse than the random algorithm. Ward＇s method archives the best performance in most cases. Conclusions The criterion proposed has a strong ability to distinguish among different clustering algorithms with different distance measurements. It is also demonstrated that analyzing main contributors of the criterion may offer some guidelines in finding local compact clusters. As an addition, we suggest using Ward＇s algorithm for gene expression data analysis.展开更多
Background Although biomedical ontologies have standardized the representation of gene products across species and databases, a method for determining the functional similarities of gene products has not yet been deve...Background Although biomedical ontologies have standardized the representation of gene products across species and databases, a method for determining the functional similarities of gene products has not yet been developed. Methods We proposed a new semantic similarity measure based on Gene Ontology that considers the semantic influences from all of the ancestor terms in a graph. Our measure was compared with Resnik＇s measure in two applications, which were based on the association of the measure used with the gene co-expression and the protein- protein interactions. Results The results showed a considerable association between the semantic similarity and the expression correlation and between the semantic similarity and the protein-protein interactions, and our measure performed the best overall. Conclusion These results revealed the potential value of our newly proposed semantic similarity measure in studying the functional relevance of gene products.展开更多
Clustering is perhaps one of the most widely used tools for microarray data analysis. Proposed roles for genes of unknown function are inferred from clusters of genes similarity expressed across many biological condit...Clustering is perhaps one of the most widely used tools for microarray data analysis. Proposed roles for genes of unknown function are inferred from clusters of genes similarity expressed across many biological conditions. However, whether function annotation by similarity metrics is reliable or not and to what extent the similarity in gene expression patterns is useful for annotation of gene functions, has not been evaluated. This paper made a comprehensive research on the correlation between the similarity of expression data and of gene functions using Gene Ontology. It has been found that although the similarity in expression patterns and the similarity in gene functions are significantly dependent on each other, this association is rather weak. In addition, among the three categories of Gene Ontology, the similarity of expression data is more useful for cellular component annotation than for biological process and molecular function. The results presented are interesting for the gene functions prediction research area.展开更多
DNA methylation is a critical epigenetic regulator in the occurrence and development of diseases and is closely related to various functional responses in relation to spinal cord injury.To investigate the role of DNA ...DNA methylation is a critical epigenetic regulator in the occurrence and development of diseases and is closely related to various functional responses in relation to spinal cord injury.To investigate the role of DNA methylation in spinal cord injury,we constructed a library with reduced-representation bisulfite sequencing data obtained at various time points(day 0-42)after spinal cord injury in mice.Global DNA methylation levels,specifically non-CpG(CHG and CHH)methylation levels,decreased modestly following spinal cord injury.Stages post-spinal cord injury were classified as early(day 0-3),intermediate(day7-14),and late(day 28-42)based on similarity and hie rarchical cluste ring of global DNA methylation patterns.The non-CpG methylation level,which included CHG and CHH methylation levels,was markedly reduced despite accounting for a minor proportion of total methylation abundance.At multiple genomic sites,including the 5’untranslated regions,promoter,exon,intron,and 3’untranslated regions,the non-CpG methylation level was markedly decreased following spinal cord injury,whereas the CpG methylation level remained unchanged at these locations.Approximately one-half of the differentially methylated regions were located in intergenic areas;the other differentially methylated regions in both CpG and non-CpG regions were cluste red in intron regions,where the DNA methylation level was highest.The function of genes associated with differentially methylated regions in promoter regions was also investigated.From Gene Ontology analysis results,DNA methylation was implicated in a number of essential functional responses to spinal cord injury,including neuronal synaptic connection creation and axon regeneration.Notably,neither CpG methylation nor non-CpG methylation was implicated in the functional response of glial or inflammatory cells.In summary,our work elucidated the dynamic pattern of DNA methylation in the spinal co rd following injury and identified reduced nonCpG methylation as an epigenetic target after spinal cord injury in mice.展开更多
Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate trau...Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.展开更多
文摘The basic unit in life is cell.?It contains many protein molecules located at its different organelles. The growth and reproduction of a cell as well as most of its other biological functions are performed via these proteins. But proteins in different organelles or subcellular locations have different functions. Facing?the avalanche of protein sequences generated in the postgenomic age, we are challenged to develop high throughput tools for identifying the subcellular localization of proteins based on their sequence information alone. Although considerable efforts have been made in this regard, the problem is far apart from being solved yet. Most existing methods can be used to deal with single-location proteins only. Actually, proteins with multi-locations may have some special biological functions that are particularly important for drug targets. Using the ML-GKR (Multi-Label Gaussian Kernel Regression) method,?we developed a new predictor called “pLoc-mGpos” by in-depth extracting the key information from GO (Gene Ontology) into the Chou’s general PseAAC (Pseudo Amino Acid Composition)?for predicting the subcellular localization of Gram-positive bacterial proteins with both single and multiple location sites. Rigorous cross-validation on a same stringent benchmark dataset indicated that the proposed pLoc-mGpos predictor is remarkably superior to “iLoc-Gpos”, the state-of-the-art predictor for the same purpose.?To maximize the convenience of most experimental scientists, a user-friendly web-server for the new powerful predictor has been established at http://www.jci-bioinfo.cn/pLoc-mGpos/, by which users can easily get their desired results without the need to go through the complicated mathematics involved.
文摘A GoBlast system was built to predict gene function by integrating Blast search and Gene Ontology (GO) annotations together. The operation system was based on Debian Linux 3.1, with Apache as the web server and Mysql database as the data storage system. FASTA files with GO annotations were taken as the sequence source for blast alignment, which were formatted by wu-formatdb program. The GoBlast system includes three Bioperl modules in Perl:a data input module, a data process module and a data output module. A GoBlast query starts with an amino acid or nucleotide sequence. It ends with an output in an html page, presenting high scoring gene products which are of a high homology to the queried sequence and listing associated GO terms beside respective gene poducts. A simple click on a GO term leads to the detailed explanation of the specific gene function. This avails gene function prediction by Blast. GoBlast can be a very useful tool for functional genome research and is available for free at http://bioq.org/goblast.
基金supported by the National Natural Science Foundation of China,No.81870975(to SZ)。
文摘Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.
文摘通过寻找共突变基因对,可以研究在癌症的发生与发展过程中被共同扰动的生物学功能,为揭示癌症的发生机制提供新的线索。目前,此类研究主要利用京都基因与基因组百科全书数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)。由于KEGG数据库倾向于定义粗泛的通路,因此,利用该数据库无法判定是通路整体还是其中的一部分与癌症相关。相反,Gene Ontology数据库在从宽泛到细致的不同层面上定义生物学功能,因此,基于GeneOntology功能类来研究癌症过程中生物学功能的共扰动是一种合理的选择。本文提出了一种算法,寻找Gene Ontology功能类间注释了非随机多的共突变基因对的功能对。由于GeneOntology功能类之间的依赖关系,导致找到的功能对之间存在冗余关系,本文提出了去冗余算法,以寻找非冗余的典型功能对。根据肺腺癌基因组体细胞突变扫查数据,我们找到了78对典型的共突变功能对。这些功能对包含宽泛和细致的生物学功能,更精确地定义了被共同扰动的生物学功能的范围,为研究肺腺癌的发生机制提供了新的线索。
文摘Background Clustering is a useful exploratory technique for interpreting gene expression data to reveal groups of genes sharing common functional attributes. Biologists frequently face the problem of choosing an appropriate algorithm. We aimed to provide a standalone, easily accessible and biologically oriented criterion for expression data clustering evaluation. Methods An external criterion utilizing annotation based similarities between genes is proposed in this work. Gene ontology information is employed as the annotation source. Comparisons among six widely used clustering algorithms over various types of gene expression data sets were carried out based on the criterion proposed. Results The rank of these algorithms given by the criterion coincides with our common knowledge. Single-linkage has significantly poorer performance, even worse than the random algorithm. Ward＇s method archives the best performance in most cases. Conclusions The criterion proposed has a strong ability to distinguish among different clustering algorithms with different distance measurements. It is also demonstrated that analyzing main contributors of the criterion may offer some guidelines in finding local compact clusters. As an addition, we suggest using Ward＇s algorithm for gene expression data analysis.
文摘Background Although biomedical ontologies have standardized the representation of gene products across species and databases, a method for determining the functional similarities of gene products has not yet been developed. Methods We proposed a new semantic similarity measure based on Gene Ontology that considers the semantic influences from all of the ancestor terms in a graph. Our measure was compared with Resnik＇s measure in two applications, which were based on the association of the measure used with the gene co-expression and the protein- protein interactions. Results The results showed a considerable association between the semantic similarity and the expression correlation and between the semantic similarity and the protein-protein interactions, and our measure performed the best overall. Conclusion These results revealed the potential value of our newly proposed semantic similarity measure in studying the functional relevance of gene products.
基金Project supported by the Key Program of Basic Research of Science ＆ Technology Commission of Shanghai Municipality （No. 04dz14004） and the Shanghai Natural Science Foundation （No. 03ZR14065）. Dedicated to Professor Xikui Jiang on the occasion of his 80th birthday.
文摘Clustering is perhaps one of the most widely used tools for microarray data analysis. Proposed roles for genes of unknown function are inferred from clusters of genes similarity expressed across many biological conditions. However, whether function annotation by similarity metrics is reliable or not and to what extent the similarity in gene expression patterns is useful for annotation of gene functions, has not been evaluated. This paper made a comprehensive research on the correlation between the similarity of expression data and of gene functions using Gene Ontology. It has been found that although the similarity in expression patterns and the similarity in gene functions are significantly dependent on each other, this association is rather weak. In addition, among the three categories of Gene Ontology, the similarity of expression data is more useful for cellular component annotation than for biological process and molecular function. The results presented are interesting for the gene functions prediction research area.
基金National Key Research and Development Program of China,No.2016YFA0100800(to LC)International(Regional)Cooperation and Communication Program of the National Natural Science Foundation of China,No.81820108013(to LC)+3 种基金State Key Program of the National Natural Science Foundation of China,No.81330030(to LC)National Natural Science Foundation of China,Nos.82071370(to ZW),81301042(to LC)Shanghai Pujiang Program,No.19PJ1409200(to ZW)Shanghai Sailing Program,No.21YF1442400(to CL)。
文摘DNA methylation is a critical epigenetic regulator in the occurrence and development of diseases and is closely related to various functional responses in relation to spinal cord injury.To investigate the role of DNA methylation in spinal cord injury,we constructed a library with reduced-representation bisulfite sequencing data obtained at various time points(day 0-42)after spinal cord injury in mice.Global DNA methylation levels,specifically non-CpG(CHG and CHH)methylation levels,decreased modestly following spinal cord injury.Stages post-spinal cord injury were classified as early(day 0-3),intermediate(day7-14),and late(day 28-42)based on similarity and hie rarchical cluste ring of global DNA methylation patterns.The non-CpG methylation level,which included CHG and CHH methylation levels,was markedly reduced despite accounting for a minor proportion of total methylation abundance.At multiple genomic sites,including the 5’untranslated regions,promoter,exon,intron,and 3’untranslated regions,the non-CpG methylation level was markedly decreased following spinal cord injury,whereas the CpG methylation level remained unchanged at these locations.Approximately one-half of the differentially methylated regions were located in intergenic areas;the other differentially methylated regions in both CpG and non-CpG regions were cluste red in intron regions,where the DNA methylation level was highest.The function of genes associated with differentially methylated regions in promoter regions was also investigated.From Gene Ontology analysis results,DNA methylation was implicated in a number of essential functional responses to spinal cord injury,including neuronal synaptic connection creation and axon regeneration.Notably,neither CpG methylation nor non-CpG methylation was implicated in the functional response of glial or inflammatory cells.In summary,our work elucidated the dynamic pattern of DNA methylation in the spinal co rd following injury and identified reduced nonCpG methylation as an epigenetic target after spinal cord injury in mice.
基金Acknowledgments This research was supported by the Natural National Science Foundation of China （No. 30571173, No. 31201274）, National High Technology Research and Development Program of China （863 Program） （No. 2012AA10A307）.
基金supported by the National Natural Science Foundation of China,No.81771355the Natural Science Foundation of Chongqing Science and Technology Bureau,Nos.CSTC2015jcyjA10096,cstc2021jcyj-msxmX0262(all to ZL)。
文摘Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.
