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A Human DNA methylation site predictor base on SVM
(2009)
Sun, Yi-Ming
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Liu, Baw-Jhiune
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Liao, Wei-Li
;
Chang, Cheng-Wei
;
Huang, Hsien-Da
During gene expression, transcription factors are unable to bind to a transcription binding site (TFBS) involved in regulation if DNA methylation has occurred at the TFBS. Methyl-CpG-binding proteins may also occupy the TFBS and prevent the functioning of a transcription factor. Thus, the methylation status of CpG sites is an important issue when trying to understand gene regulation and shows strong correlation with the TFBS involved. In addition, CpG islands would seem to undergo cell-specific and tissue-specific methylation. Such differential methylation is presented at numerous genetic loci that are essential for development. Current DNA methylation site prediction tools need to be improved so that they include TFBS features and have greater accuracy in terms of the DNA region that is involved in methylation. We developed models that compare the differences across these regions and tissues. The TFBSs, DNA properties and DNA distribution were used as features for this classification. From the results, we found some TFBSs that were able to discriminate whether a sequence was methylated or not. The sensitivity, specificity and accuracy estimated using 10-fold cross validation were 90.8%, 80.54%, and 86.07%, respectively. Thus, for these four regions and twelve tissues, the performance levels (ACC) were all greater than 80%. We propose that the differential features or methylations vary between the different regions because the features common to each DNA region made up only 50% of the top 70 features. An online predictor based on EpiMeP is available at http://140.115.51.41/EpiMeP/. Supplementary file is available at http://140.115.51.41/EpiMeP/supplementary.doc.
RiboSW - a web server for identifying RNA riboswitches
(2009)
Chang, Tzu-Hao
;
Wu, Li-Ching
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Yeh, Chi-Ta
;
Chang, Cheng-Wei
;
Liu, Baw-Jhiune
Riboswitches are cis-acting genetic regulatory elements within a specific mRNA, and can regulate both transcription and translation by interacting with their corresponding metabolites. Recently, more and more riboswitches were identified and investigated about their roles in regulatory functions in different species. Both of the sequence contexts and structural conformations are important characteristics of riboswitches. None of previous developed tools, such Covariance Models (CMs), Riboswitch finder, and RibEx, provides a web server for efficiently searching homologous instances to known riboswitches and considers two crucial characteristics of each riboswitch, such as structural conformations and sequence contexts of functional regions. Therefore, we developed a systematic method to identify twelve kinds of riboswitches. The method is implemented and provided as a web server, RiboSW, to efficiently and conveniently identify riboswitches within messenger RNA sequences. RiboSW is now available on the web at http://bioinfo.csie.ncu.edu.tw/RiboSW/. The predictive accuracy of the proposed method is comparable with other previous tools. The efficiency of the proposed method for identifying riboswitches was improved in order to achieve a reasonable computational time required for the prediction. That makes it possible to have an accurate and convenient web server for biologists to obtain their analyzing results in a given mRNA sequence. The supplementary data is available on the web at http://bioinfo.csie.ncu.edu.tw/RiboSW/sup.pdf.
Prediction of small non-coding RNA in bacterial genomes using support vector machines
(2010-08-01)
Chang, Tzu-Hao
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Wu, Li-Ching
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Lin, Jun-Hong
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Huang, Hsien-Da
;
Liu, Baw-Jhiune
Small non-coding RNA genes have been shown to play important regulatory roles in a variety of cellular processes, but prediction of non-coding RNA genes is a great challenge, using either an experimental or a computational approach, due to the characteristics of sRNAs, which are that sRNAs are small in size, are not translated into proteins and show variable stability. Most known sRNAs have been identified in Escherichia coli and have been shown to be conserved in closely related organisms. We have developed an integrative approach that searches highly conserved intergenic regions among related bacterial genomes for combinations of characteristics that have been extracted from known E. coli sRNA genes. Support vector machines (SVM) were then used with these characteristics to predict novel sRNA genes. (c) 2010 Elsevier Ltd. All rights reserved.
EuLoc: a web-server for accurately predict protein subcellular localization in eukaryotes by incorporating various features of sequence segments into the general form of Chou's PseAAC
(2013-01-01)
Chang, Tzu-Hao
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Wu, Li-Ching
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Lee, Tzong-Yi
;
Chen, Shu-Pin
;
Huang, Hsien-Da
The function of a protein is generally related to its subcellular localization. Therefore, knowing its subcellular localization is helpful in understanding its potential functions and roles in biological processes. This work develops a hybrid method for computationally predicting the subcellular localization of eukaryotic protein. The method is called EuLoc and incorporates the Hidden Markov Model (HMM) method, homology search approach and the support vector machines (SVM) method by fusing several new features into Chou's pseudo-amino acid composition. The proposed SVM module overcomes the shortcoming of the homology search approach in predicting the subcellular localization of a protein which only finds low-homologous or non-homologous sequences in a protein subcellular localization annotated database. The proposed HMM modules overcome the shortcoming of SVM in predicting subcellular localizations using few data on protein sequences. Several features of a protein sequence are considered, including the sequence-based features, the biological features derived from PROSITE, NLSdb and Pfam, the post-transcriptional modification features and others. The overall accuracy and location accuracy of EuLoc are 90.5 and 91.2 %, respectively, revealing a better predictive performance than obtained elsewhere. Although the amounts of data of the various subcellular location groups in benchmark dataset differ markedly, the accuracies of 12 subcellular localizations of EuLoc range from 82.5 to 100 %, indicating that this tool is much more balanced than other tools. EuLoc offers a high, balanced predictive power for each subcellular localization. EuLoc is now available on the web at http://euloc.mbc.nctu.edu.tw/.
An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs
(2013-01-21)
Chang, Tzu-Hao
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Huang, Hsi-Yuan
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Hsu, Justin Bo-Kai
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Weng, Shun-Long
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Horng, Jorng-Tzong
Background: Functional RNA molecules participate in numerous biological processes, ranging from gene regulation to protein synthesis. Analysis of functional RNA motifs and elements in RNA sequences can obtain useful information for deciphering RNA regulatory mechanisms. Our previous work, RegRNA, is widely used in the identification of regulatory motifs, and this work extends it by incorporating more comprehensive and updated data sources and analytical approaches into a new platform. Methods and results: An integrated web-based system, RegRNA 2.0, has been developed for comprehensively identifying the functional RNA motifs and sites in an input RNA sequence. Numerous data sources and analytical approaches are integrated, and several types of functional RNA motifs and sites can be identified by RegRNA 2.0: (i) splicing donor/acceptor sites; (ii) splicing regulatory motifs; (iii) polyadenylation sites; (iv) ribosome binding sites; (v) rho-independent terminator; (vi) motifs in mRNA 5'-untranslated region (5'UTR) and 3'UTR; (vii) AU-rich elements; (viii) C-to-U editing sites; (ix) riboswitches; (x) RNA cis-regulatory elements; (xi) transcriptional regulatory motifs; (xii) user-defined motifs; (xiii) similar functional RNA sequences; (xiv) microRNA target sites; (xv) non-coding RNA hybridization sites; (xvi) long stems; (xvii) open reading frames; (xviii) related information of an RNA sequence. User can submit an RNA sequence and obtain the predictive results through RegRNA 2.0 web page. Conclusions: RegRNA 2.0 is an easy to use web server for identifying regulatory RNA motifs and functional sites. Through its integrated user-friendly interface, user is capable of using various analytical approaches and observing results with graphical visualization conveniently. RegRNA 2.0 is now available at http://regrna2.mbc.nctu.edu.tw.
An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs
(2013-01-21)
Chang, Tzu-Hao
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Huang, Hsi-Yuan
;
Hsu, Justin Bo-Kai
;
Weng, Shun-Long
;
Horng, Jorng-Tzong
Background: Functional RNA molecules participate in numerous biological processes, ranging from gene regulation to protein synthesis. Analysis of functional RNA motifs and elements in RNA sequences can obtain useful information for deciphering RNA regulatory mechanisms. Our previous work, RegRNA, is widely used in the identification of regulatory motifs, and this work extends it by incorporating more comprehensive and updated data sources and analytical approaches into a new platform. Methods and results: An integrated web-based system, RegRNA 2.0, has been developed for comprehensively identifying the functional RNA motifs and sites in an input RNA sequence. Numerous data sources and analytical approaches are integrated, and several types of functional RNA motifs and sites can be identified by RegRNA 2.0: (i) splicing donor/acceptor sites; (ii) splicing regulatory motifs; (iii) polyadenylation sites; (iv) ribosome binding sites; (v) rho-independent terminator; (vi) motifs in mRNA 5'-untranslated region (5'UTR) and 3'UTR; (vii) AU-rich elements; (viii) C-to-U editing sites; (ix) riboswitches; (x) RNA cis-regulatory elements; (xi) transcriptional regulatory motifs; (xii) user-defined motifs; (xiii) similar functional RNA sequences; (xiv) microRNA target sites; (xv) non-coding RNA hybridization sites; (xvi) long stems; (xvii) open reading frames; (xviii) related information of an RNA sequence. User can submit an RNA sequence and obtain the predictive results through RegRNA 2.0 web page. Conclusions: RegRNA 2.0 is an easy to use web server for identifying regulatory RNA motifs and functional sites. Through its integrated user-friendly interface, user is capable of using various analytical approaches and observing results with graphical visualization conveniently. RegRNA 2.0 is now available at http://regrna2.mbc.nctu.edu.tw.
Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data
(2011-11-01)
Chien, Chia-Hung
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Sun, Yi-Ming
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Chang, Wen-Chi
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Chiang-Hsieh, Pei-Yun
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Lee, Tzong-Yi
MicroRNAs (miRNAs) are critical small non-coding RNAs that regulate gene expression by hybridizing to the 3'-untranslated regions (3'-UTR) of target mRNAs, subsequently controlling diverse biological processes at post-transcriptional level. How miRNA genes are regulated receives considerable attention because it directly affects miRNA-mediated gene regulatory networks. Although numerous prediction models were developed for identifying miRNA promoters or transcriptional start sites (TSSs), most of them lack experimental validation and are inadequate to elucidate relationships between miRNA genes and transcription factors (TFs). Here, we integrate three experimental datasets, including cap analysis of gene expression (CAGE) tags, TSS Seq libraries and H3K4me3 chromatin signature derived from high-throughput sequencing analysis of gene initiation, to provide direct evidence of miRNA TSSs, thus establishing an experimental-based resource of human miRNA TSSs, named miRStart. Moreover, a machine-learning-based Support Vector Machine (SVM) model is developed to systematically identify representative TSSs for each miRNA gene. Finally, to demonstrate the effectiveness of the proposed resource, an important human intergenic miRNA, hsa-miR-122, is selected to experimentally validate putative TSS owing to its high expression in a normal liver. In conclusion, this work successfully identified 847 human miRNA TSSs (292 of them are clustered to 70 TSSs of miRNA clusters) based on the utilization of high-throughput sequencing data from TSS-relevant experiments, and establish a valuable resource for biologists in advanced research in miRNA-mediated regulatory networks.
Biological data warehousing system for identifying transcriptional regulatory sites from gene expressions of microarray data
(2006-07-01)
Tsou, Ann-Ping
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Sun, Yi-Ming
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Liu, Chia-Lin
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Huang, Hsien-Da
;
Horng, Jorng-Tzong
Identification of transcriptional regulatory sites plays an important role in the investigation of gene regulation. For this propose, we designed and implemented a data warehouse to integrate multiple heterogeneous biological data sources with data types such as text-file, XML, image, MySQL database model, and Oracle database model. The utility of the biological data warehouse in predicting transcriptional regulatory sites of coregulated genes was explored using a synexpression group derived from a microarray study. Both of the binding sites of known transcription factors and predicted over-represented (OR) oligonucleotides were demonstrated for the gene group. The potential biological roles of both known nucleotides and one OR nucleotide were demonstrated using bioassays. Therefore, the results from the wet-lab experiments reinforce the power and utility of the data warehouse as an approach to the genome-wide search for important transcription regulatory elements that are the key to many complex biological systems.
RNAMST: efficient and flexible approach for identifying RNA structural homologs
(2006-07-01)
Chang, Tzu-Hao
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Huang, Hsien-Da
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Chuang, Tzu-Neng
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Shien, Dray-Ming
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Horng, Jorng-Tzong
RNA molecules fold into characteristic secondary structures for their diverse functional activities such as post- translational regulation of gene expression. Searching homologs of a pre-defined RNA structural motif, which may be a known functional element or a putative RNA structural motif, can provide useful information for deciphering RNA regulatory mechanisms. Since searching for the RNA structural homologs among the numerous RNA sequences is extremely time- consuming, this work develops a data preprocessing strategy to enhance the search efficiency and presents RNAMST, which is an efficient and flexible web server for rapidly identifying homologs of a pre-definedRNAstructuralmotifamongnumerous RNA sequences. Intuitive user interface are provided on the web server to facilitate the predictive analysis. By comparing the proposed web server to other tools developed previously, RNAMST performs remarkably more efficiently and provides more effective and flexible functions. RNAMST is now available on the web at http://bioinfo.csie.ncu.edu.tw/similar to rnamst/.
Database to dynamically aid probe design for virus identification
(2006-10-01)
Lin, Feng-Mao
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Huang, Hsien-Da
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Chang, Yu-Chung
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Tsou, Ann-Ping
;
Chan, Pak-Leong
Viral infection poses a major problem for public health, horticulture, and animal husbandry, possibly causing severe health crises and economic losses. Viral infections can be identified by the specific detection of viral sequences in many ways. The microarray approach not only tolerates sequence variations of newly evolved virus strains, but can also simultaneously diagnose many viral sequences. Many chips have so far been designed for clinical use. Most are designed for special purposes, such as typing enterovirus infection, and compare fewer than 30 different viral sequences. None considers primer design, increasing the likelihood of cross hybridization to similar sequences from other viruses. To prevent this possibility, this work establishes a platform and database that provides users with specific probes of all known viral genome sequences to facilitate the design of diagnostic chips. This work develops a system for designing probes online. A user can select any number of different viruses and set the experimental conditions such as melting temperature and length of probe. The system then returns the optimal sequences from the database. We have also developed a heuristic algorithm to calculate the probe correctness and show the correctness of the algorithm.

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