Browsing by Author "Chien, Chia-Hung"

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Identifying transcriptional start sites of human microRNAs based on high-throughput sequencing data
(2012-04-15)
Tsou, Ann-Ping
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Chien, Chia-Hung
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Chiang-Hsieh, Pei-Yun
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Tsai, Wei-Chih
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Huang, Hsien-Da
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.
Large-Scale Investigation of Human TF-miRNA Relations Based on Coexpression Profiles
(2014)
Chien, Chia-Hung
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Chiang-Hsieh, Yi-Fan
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Tsou, Ann-Ping
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Weng, Shun-Long
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Chang, Wen-Chi
Noncoding, endogenous microRNAs (miRNAs) are fairly well known for regulating gene expression rather than protein coding. Dysregulation of miRNA gene, either upregulated or downregulated, may lead to severe diseases or oncogenesis, especially when the miRNA disorder involves significant bioreactions or pathways. Thus, how miRNA genes are transcriptionally regulated has been highlighted as well as target recognition in recent years. In this study, a large-scale investigation of novel cis- and trans-elements was undertaken to further determine TF-miRNA regulatory relations, which are necessary to unravel the transcriptional regulation of miRNA genes. Based on miRNA and annotated gene expression profiles, the term "coTFBS" was introduced to detect common transcription factors and the corresponding binding sites within the promoter regions of each miRNA and its coexpressed annotated genes. The computational pipeline was successfully established to filter redundancy due to short sequencemotifs for TFBS pattern search. Eventually, we identified more convinced TF-miRNA regulatory relations for 225 human miRNAs. This valuable information is helpful in understanding miRNA functions and provides knowledge to evaluate the therapeutic potential in clinical research. Once most expression profiles of miRNAs in the latest database are completed, TF candidates of more miRNAs can be explored by this filtering approach in the future.
miRTar: an integrated system for identifying miRNA-target interactions in human
(2011-07-26)
Hsu, Justin Bo-Kai
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Chiu, Chih-Min
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Hsu, Sheng-Da
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Huang, Wei-Yun
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Chien, Chia-Hung
Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that are similar to 22-nt-long sequences capable of suppressing protein synthesis. Previous research has suggested that miRNAs regulate 30% or more of the human protein-coding genes. The aim of this work is to consider various analyzing scenarios in the identification of miRNA-target interactions, as well as to provide an integrated system that will aid in facilitating investigation on the influence of miRNA targets by alternative splicing and the biological function of miRNAs in biological pathways. Results: This work presents an integrated system, miRTar, which adopts various analyzing scenarios to identify putative miRNA target sites of the gene transcripts and elucidates the biological functions of miRNAs toward their targets in biological pathways. The system has three major features. First, the prediction system is able to consider various analyzing scenarios (1 miRNA: 1 gene, 1: N, N: 1, N: M, all miRNAs: N genes, and N miRNAs: genes involved in a pathway) to easily identify the regulatory relationships between interesting miRNAs and their targets, in 3'UTR, 5'UTR and coding regions. Second, miRTar can analyze and highlight a group of miRNA-regulated genes that participate in particular KEGG pathways to elucidate the biological roles of miRNAs in biological pathways. Third, miRTar can provide further information for elucidating the miRNA regulation, i.e., miRNA-target interactions, affected by alternative splicing. Conclusions: In this work, we developed an integrated resource, miRTar, to enable biologists to easily identify the biological functions and regulatory relationships between a group of known/putative miRNAs and protein coding genes. miRTar is now available at http://miRTar.mbc.nctu.edu.tw/.
miRTarBase: a database curates experimentally validated microRNA-target interactions
(2011-01-01)
Hsu, Sheng-Da
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Lin, Feng-Mao
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Wu, Wei-Yun
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Liang, Chao
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Huang, Wei-Chih
MicroRNAs (miRNAs), i.e. small non-coding RNA molecules (similar to 22 nt), can bind to one or more target sites on a gene transcript to negatively regulate protein expression, subsequently controlling many cellular mechanisms. A current and curated collection of miRNA-target interactions (MTIs) with experimental support is essential to thoroughly elucidating miRNA functions under different conditions and in different species. As a database, miRTarBase has accumulated more than 3500 MTIs by manually surveying pertinent literature after data mining of the text systematically to filter research articles related to functional studies of miRNAs. Generally, the collected MTIs are validated experimentally by reporter assays, western blot, or microarray experiments with overexpression or knockdown of miRNAs. miRTarBase curates 3576 experimentally verified MTIs between 657 miRNAs and 2297 target genes among 17 species. miRTarBase contains the largest amount of validated MTIs by comparing with other similar, previously developed databases. The MTIs collected in the miRTarBase can also provide a large amount of positive samples to develop computational methods capable of identifying miRNA-target interactions. miRTarBase is now available on http://miRTarBase.mbc.nctu.edu.tw/, and is updated frequently by continuously surveying research articles.
PlantPAN 2.0: an update of plant promoter analysis navigator for reconstructing transcriptional regulatory networks in plants
(2016-01-04)
Chow, Chi-Nga
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Zheng, Han-Qin
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Wu, Nai-Yun
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Chien, Chia-Hung
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Huang, Hsien-Da
Transcription factors (TFs) are sequence-specific DNA-binding proteins acting as critical regulators of gene expression. The Plant Promoter Analysis Navigator (PlantPAN; http://PlantPAN2.itps.ncku.edu.tw) provides an informative resource for detecting transcription factor binding sites (TFBSs), corresponding TFs, and other important regulatory elements (CpG islands and tandem repeats) in a promoter or a set of plant promoters. Additionally, TFBSs, CpG islands, and tandem repeats in the conserve regions between similar gene promoters are also identified. The current PlantPANrelease (version 2.0) contains 16 960 TFs and 1143 TF binding site matrices among 76 plant species. In addition to updating of the annotation information, adding experimentally verified TF matrices, and making improvements in the visualization of transcriptional regulatory networks, several new features and functions are incorporated. These features include: (i) comprehensive curation of TF information (response conditions, target genes, and sequence logos of binding motifs, etc.), (ii) co-expression profiles of TFs and their target genes under various conditions, (iii) protein-protein interactions among TFs and their co-factors, (iv) TFtarget networks, and (v) downstream promoter elements. Furthermore, a dynamic transcriptional regulatory network under various conditions is provided in PlantPAN 2.0. The PlantPAN 2.0 is a systematic platform for plant promoter analysis and reconstructing transcriptional regulatory networks.
RegRNA: an integrated web server for identifying regulatory RNA motifs and elements
(2006-07-01)
Huang, Hsi-Yuan
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Chien, Chia-Hung
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Jen, Kuan-Hua
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Huang, Hsien-Da
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生物科技學系
Numerous regulatory structural motifs have been identified as playing essential roles in transcriptional and post- transcriptional regulation of gene expression. RegRNA is an integrated web server for identifying the homologs of regulatory RNA motifs and elements against an input mRNA sequence. Both sequence homologs and structural homologs of regulatory RNA motifs can be recognized. The regulatory RNA motifs supported in RegRNA are categorized into several classes: ( i) motifs in mRNA 50- untranslated region ( 50- UTR) and 30- UTR; ( ii) motifs involved in mRNA splicing; ( iii) motifs involved in transcriptional regulation; ( iv) riboswitches; ( v) splicing donor/ acceptor sites; ( vi) inverted repeats; and ( vii) miRNA target sites. The experimentally validated regulatory RNA motifs are extracted from literature survey and several regulatory RNA motif databases, such as UTRdb, TRANSFAC, alternative splicing database ( ASD) and miRBase. A variety of computational programs are integrated for identifying the homologs of the regulatory RNA motifs. An intuitive user interface is designed to facilitate the comprehensive annotation of user-submitted mRNA sequences. The RegRNA web server is now available at http://RegRNA.mbc.NCTU.edu.tw/.
Studies on the annealing and antibacterial properties of the silver-embedded aluminum/silica nanospheres
(2014-06-17)
Pan, Ko-Ying
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Chien, Chia-Hung
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Pu, Ying-Chih
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Liu, Chia-Ming
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Hsu, Yung-Jung
Substantial silver-embedded aluminum/silica nanospheres with uniform diameter and morphology were successfully synthesized by sol-gel technique. After various annealing temperatures, the surface mechanisms of each sample were analyzed using scanning electron microscope, transmission electron microscope, and X-ray photoelectron spectroscopy. The chemical durability examinations and antibacterial tests of each sample were also carried out for the confirmation of its practical usage. Based on the result of the above analyses, the silver-embedded aluminum/silica nanospheres are eligible for fabricating antibacterial utensils.