Browsing by Author "Huang, Wei-Chih"

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A new method for post Genome-Wide Association Study (GWAS) analysis of colorectal cancer in Taiwan
(2013-04-10)
Wang, Hwei-Ming
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Chang, Tzu-Hao
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Lin, Feng-Mao
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Chao, Te-Hsin
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Huang, Wei-Chih
Recently, single nucleotide polymorphisms (SNPs) located in specific loci or genes have been identified associated with susceptibility to colorectal cancer (CRC) in Genome-Wide Association Studies (GWAS). However, in different ethnicities and regions, the genetic variations and the environmental factors can widely vary. Therefore, here we propose a post-GWAS analysis method to investigate the CRC susceptibility SNPs in Taiwan by conducting a replication analysis and bioinformatics analysis. One hundred and forty-four significant SNPs from published GWAS results were collected by a literature survey, and two hundred and eighteen CRC samples and 385 normal samples were collected for post-GWAS analysis. Finally, twenty-six significant SNPs were identified and reported as associated with susceptibility to colorectal cancer, other cancers, obesity, and celiac disease in a previous GWAS study. Functional analysis results of 26 SNPs indicate that most biological processes identified are involved in regulating immune responses and apoptosis. In addition, an efficient prediction model was constructed by applying Jackknife feature selection and ANOVA testing. As compared to another risk prediction model of CRC for European Caucasians population, which performs 0.616 of AUC by using 54 SNPs, the proposed model shows good performance in predicting CRC risk within the Taiwanese population, i.e., 0.724 AUC by using 16 SNPs. We believe that the proposed risk prediction model is highly promising for predicting CRC risk within the Taiwanese population. In addition, the functional analysis results could be helpful to explore the potential associated regulatory mechanisms that may be involved in CRC development. (c) 2012 Elsevier B.V. All rights reserved.
A panel of eight microRNAs is a good predictive parameter for triple-negative breast cancer relapse
(2020-01-01)
Hong, Hsiao-Chin
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Chuang, Cheng-Hsun
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Huang, Wei-Chih
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Weng, Shun-Long
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Chen, Chia-Hung
Rationale: Triple-negative breast cancer (TNBC), which has the highest recurrence rate and shortest survival time of all breast cancers, is in urgent need of a risk assessment method to determine an accurate treatment course. Recently, miRNA expression patterns have been identified as potential biomarkers for diagnosis, prognosis, and personalized therapy. Here, we investigate a combination of candidate miRNAs as a clinically applicable signature that can precisely predict relapse in TNBC patients after surgery. Methods: Four total cohorts of training (TCGA_TNBC and GEOD-40525) and validation (GSE40049 and GSE19783) datasets were analyzed with logistic regression and Gaussian mixture analyses. We established a miRNA signature risk model and identified an 8-miRNA signature for the prediction of TNBC relapse. Results: The miRNA signature risk model identified ten candidate miRNAs in the training set. By combining 8 of the 10 miRNAs (miR-139-5p, miR-10b-5p, miR-486-5p, miR-455-3p, miR-107, miR-146b-5p, miR-324-5p and miR-20a-5p), an accurate predictive model of relapse in TNBC patients was established and was highly correlated with prognosis (AUC of 0.80). Subsequently, this 8-miRNA signature prognosticated relapse in the two validation sets with AUCs of 0.89 and 0.90. Conclusion: The 8-miRNA signature predictive model may help clinicians provide a prognosis for TNBC patients with a high risk of recurrence after surgery and provide further personalized treatment to decrease the chance of relapse.
A Three-MicroRNA Signature as a Potential Biomarker for the Early Detection of Oral Cancer
(2018-03-01)
Chang, Yi-An
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Weng, Shun-Long
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Yang, Shun-Fa
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Chou, Chih-Hung
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Huang, Wei-Chih
Oral squamous cell carcinoma (OSCC) is often diagnosed at a late stage and may be malignantly transformed from oral leukoplakia (OL). This study aimed to identify potential plasma microRNAs (miRNAs) for the early detection of oral cancer. Plasma from normal, OL, and OSCC patients were evaluated. Small RNA sequencing was used to screen the differently expressed miRNAs among the groups. Next, these miRNAs were validated with individual samples by quantitative real-time polymerase chain reaction (qRT-PCR) assays in the training phase (n = 72) and validation phase (n = 178). The possible physiological roles of the identified miRNAs were further investigated using bioinformatics analysis. Three miRNAs (miR-222-3p, miR-150-5p, and miR-423-5p) were identified as differentially expressed among groups; miR-222-3p and miR-423-5p negatively correlated with T stage, lymph node metastasis status, and clinical stage. A high diagnostic accuracy (Area under curve = 0.88) was demonstrated for discriminating OL from OSCC. Bioinformatics analysis reveals that miR-423-5p and miR-222-3p are significantly over-expressed in oral cancer tissues and involved in various cancer pathways. The three-plasma miRNA panel may be useful to monitor malignant progression from OL to OSCC and as potential biomarkers for early detection of oral cancer.
Bacterial Communities in Semen from Men of Infertile Couples: Metagenomic Sequencing Reveals Relationships of Seminal Microbiota to Semen Quality
(2014-10-23)
Weng, Shun-Long
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Chiu, Chih-Min
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Lin, Feng-Mao
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Huang, Wei-Chih
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Liang, Chao
Some previous studies have identified bacteria in semen as being a potential factor in male infertility. However, only few types of bacteria were taken into consideration while using PCR-based or culturing methods. Here we present an analysis approach using next-generation sequencing technology and bioinformatics analysis to investigate the associations between bacterial communities and semen quality. Ninety-six semen samples collected were examined for bacterial communities, measuring seven clinical criteria for semen quality (semen volume, sperm concentration, motility, Kruger\'s strict morphology, antisperm antibody (IgA), Atypical, and leukocytes). Computer-assisted semen analysis (CASA) was also performed. Results showed that the most abundant genera among all samples were Lactobacillus (19.9%), Pseudomonas (9.85%), Prevotella (8.51%) and Gardnerella (4.21%). The proportion of Lactobacillus and Gardnerella was significantly higher in the normal samples, while that of Prevotella was significantly higher in the low quality samples. Unsupervised clustering analysis demonstrated that the seminal bacterial communities were clustered into three main groups: Lactobacillus, Pseudomonas, and Prevotella predominant group. Remarkably, most normal samples (80.6%) were clustered in Lactobacillus predominant group. The analysis results showed seminal bacteria community types were highly associated with semen health. Lactobacillus might not only be a potential probiotic for semen quality maintenance, but also might be helpful in countering the negative influence of Prevotella and Pseudomonas. In this study, we investigated whole seminal bacterial communities and provided the most comprehensive analysis of the association between bacterial community and semen quality. The study significantly contributes to the current understanding of the etiology of male fertility.
Clinical detection of human probiotics and human pathogenic bacteria by using a novel high-throughput platform based on next generation sequencing
(2013)
Chiu, Chih-Min
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Lin, Feng-Mao
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Chang, Tzu-Hao
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Huang, Wei-Chih
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Liang, Chao
The human body plays host to a vast array of bacteria which are harmful or beneficial. Next generation sequencing technology have increased its accuracy in identifying bacteria. This work develops a novel platform for rapidly detecting probiotics and pathogens based on sequencing results of 16S rRNA. A database that recorded the species of probiotics and pathogens from literature was constructed, along with a modified Smith-Waterman algorithm for assigning the taxonomy of the sequenced 16S rRNA sequences. A bacteria disease risk model for seven diseases was constructed based on 98 samples. Applicability of the proposed platform is demonstrated by collecting the microbiome in human gut of 13 samples. The proposed platform provides a relatively easy means of identifying a certain amount of bacteria and their species for clinical microbiology applications. Detecting how probiotics and pathogens inhabit humans and affect their health significantly contributes to develop a diagnosis and treatment method.
Controlled mechanical cleavage of bulk niobium diselenide to nanoscaled sheet, rod, and particle structures for Pt-free dye-sensitized solar cells
(2014)
Ibrahem, Mohammed Aziz
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Huang, Wei-Chih
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Lan, Tian-wey
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Boopathi, Karunakara Moorthy
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Hsiao, Yu-Chen
In this study, we report a one-step process for the preparation of NbSe2 nanosheets, nanorods and nanoparticles from pristine materials under the effects of shear and friction forces. Nevertheless, simple and facile methods for the large-scale syntheses of well-defined NbSe2 nanostructures in high yield have yet to be realized and that will have a great impact in a wide range of applications. For example, developing platinum (Pt)-free and highly efficient counter electrodes is meaningful and necessary for the cost reduction of dye-sensitized solar cells (DSSCs). By integrating this approach with a simple method of thin film preparation (spray coating) allowed us to prepare large-area, conductive, semitransparent flexible thin films of NbSe2. We have used microscopic and macroscopic methods to examine the morphologies, compositions, crystallinity, and electrical and optical properties of the converted NbSe2 nanostructures. DSSCs with NbSe2 nanosheet counter electrodes (CEs) achieved a conversion efficiency of 7.73%, superior to an efficiency of 7.01% for Pt-based CEs. Our NbSe2 nanostructure provides a cost-effective CE alternative to the noble metal Pt in DSSCs.
Development of a computational promoter with highly efficient expression in tumors
(2018-04-27)
Ho, Shu-Yi
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Chang, Bo-Hau
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Chung, Chen-Han
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Lin, Yu-Ling
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Chuang, Cheng-Hsun
Background: Gene therapy is a potent method to increase the therapeutic efficacy against cancer. However, a gene that is specifically expressed in the tumor area has not been identified. In addition, nonspecific expression of therapeutic genes in normal tissues may cause side effects that can harm the patients' health. Certain promoters have been reported to drive therapeutic gene expression specifically in cancer cells; however, low expression levels of the target gene are a problem for providing good therapeutic efficacy. Therefore, a specific and highly expressive promoter is needed for cancer gene therapy. Methods: Bioinformatics approaches were utilized to analyze transcription factors (TFs) from high-throughput data. Reverse transcription polymerase chain reaction, western blotting and cell transfection were applied for the measurement of mRNA, protein expression and activity. C57BL/6JNarl mice were injected with pD5-hrGFP to evaluate the expression of TFs. Results: We analyzed bioinformatics data and identified three TFs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), cyclic AMP response element binding protein (CREB), and hypoxia-inducible factor-1 alpha (HIF-1 alpha), that are highly active in tumor cells. Here, we constructed a novel mini-promoter, D5, that is composed of the binding sites of the three TFs. The results show that the D5 promoter specifically drives therapeutic gene expression in tumor tissues and that the strength of the D5 promoter is directly proportional to tumor size. Conclusions: Our results show that bioinformatics may be a good tool for the selection of appropriate TFs and for the design of specific mini-promoters to improve cancer gene therapy.
DNA Methyltransferases Modulate Hepatogenic Lineage Plasticity of Mesenchymal Stromal Cells
(2017-07-11)
Lee, Chien-Wei
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Huang, Wei-Chih
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Huang, Hsien-Da
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Huang, Yi-Hsiang
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Ho, Jennifer H.
The irreversibility of developmental processes in mammalian cells has been challenged by rising evidence that de-differentiation of hepatocytes occurs in adult liver. However, whether reversibility exists in mesenchymal stromal cell (MSC)-derived hepatocytes (dHeps) remains elusive. In this study, we find that hepatogenic differentiation (HD) of MSCs is a reversible process and is modulated by DNA methyltransferases (DNMTs). DNMTs are regulated by transforming growth factor beta 1 (TGF beta 1), which in turn controls hepatogenic differentiation and de-differentiation. In addition, a stepwise reduction in TGF beta 1 concentrations in culture media increases DNMT1 and decreases DNMT3 in primary hepatocytes (Heps) and confers Heps with multi-differentiation potentials similarly to MSCs. Hepatic lineage reversibility of MSCs and lineage conversion of Heps are regulated byDNMTs in response to TGF gamma 1. This previously unrecognized TGF beta 1-DNMTs-MSC-HD axis may further increase the understanding the normal and pathological processes in the liver, as well as functions of MSCs after transplantation to treat liver diseases.
Enterotype-based Analysis of Gut Microbiota along the Conventional Adenoma-Carcinoma Colorectal Cancer Pathway
(2019-07-29)
Yang, Tzu-Wei
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Lee, Wei-Hsiang
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Tu, Siang-Jyun
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Huang, Wei-Chih
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Chen, Hui-Mei
The dysbiosis of human gut microbiota is strongly associated with the development of colorectal cancer (CRC). The dysbiotic features of the transition from advanced polyp to early-stage CRC are largely unknown. We performed a 16S rRNA gene sequencing and enterotype-based gut microbiota analysis study. In addition to Bacteroides-and Prevotella-dominated enterotypes, we identified an Escherichia-dominated enterotype. We found that the dysbiotic features of CRC were dissimilar in overall samples and especially Escherichia-dominated enterotype. Besides a higher abundance of Fusobacterium, Enterococcus, and Aeromonas in all CRC faecal microbiota, we found that the most notable characteristic of CRC faecal microbiota was a decreased abundance of potential beneficial butyrate-producing bacteria. Notably, Oscillospira was depleted in the transition from advanced adenoma to stage 0 CRC, whereas Haemophilus was depleted in the transition from stage 0 to early-stage CRC. We further identified 7 different CAGs by analysing bacterial clusters. The abundance of microbiota in cluster 3 significantly increased in the CRC group, whereas that of cluster 5 decreased. The abundance of both cluster 5 and cluster 7 decreased in the Escherichia-dominated enterotype of the CRC group. We present the first enterotype-based faecal microbiota analysis. The gut microbiota of colorectal neoplasms can be influenced by its enterotype.
Haptoglobin expression correlates with tumor differentiation and five-year overall survival rate in hepatocellular carcinoma
(2017-02-03)
Tai, Chun-San
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Lin, Yan-Ren
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Teng, Tsung-Han
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Lin, Ping-Yi
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Tu, Siang-Jyun
Elevated serum haptoglobin (Hp) is identified as a prognostic marker in multiple types of solid tumors, which is correlated with poor prognosis. HCC is one of the major causes of cancer deaths in worldwide, which remains poor prognosis and is clinically urgent for discovering early diagnostic markers. However, except for serum Hp, the correlation of tumor Hp expression with hepatocellular carcinoma (HCC) progression is still unclear. In this study, we evaluated and identified the tissue Hp expression as a prognostic marker to predict the survival rate of HCC patients. To evaluate the prognostic value of Hp expression for HCC, two cohorts were enrolled in our study, including total 130 matched pair tissue sections (both adjacent non-tumorous and tumor tissue derived from same patient) of HCC patients from Changhua Christian Hospital (CCH) and total 316 RNA-seq data with clinical information of HCC patients from The Cancer Genome Atlas (TCGA) database. In contrast to other types of cancers, HCC tumor tissues have lower Hp protein expression in CCH cohort and have lower Hp mRNA expression in TCGA cohort as compared with adjacent non-tumorous tissues (p < 0.001). Moreover, lower Hp expression is significantly correlated with different stages of HCC cancer differentiation in CCH cohort (one-way ANOVA, p < 0.001). Most importantly, lower Hp expression is highly correlated with poor five-year overall survival rate in TCGA cohort (p < 0.01). Based on our data, we conclude that tissue Hp expression positively correlates with better HCC tumor differentiation and increased five-year overall survival rate of HCC patients. The results indicated that tissue Hp is potentially a prognostic marker for HCC patients. Our findings may further provide a new insight of effective treatments along with biopsy diagnosis of HCC patients.
Interplay between potassium doping and bandgap profiling in selenized Cu(In,Ga)Se-2 solar cells: A functional CuGa: KF surface precursor layer
(2018-05-01)
Cai, Chung-Hao
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Chen, Rong-Zhi
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Chan, Ting-Shan
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Lu, Ying-Rui
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Huang, Wei-Chih
The progress of selenized Cu(In,Ga)Se-2 (CIGSe) solar cells is limited by low open-circuit voltage (Voc), which results from the Ga-deficient surface and undesirable bandgap profile after selenization. Controlling the Ga grading, especially on the CIGSe surface, is challenging but critical for further efficiency improvement. Here, the simple sputtering route with K incorporation is presented to engineer single-or double-graded bandgap. The K incorporation through sputtered precursors can considerably affect the Ga profile in CIGSe during selenization, essentially distinct from reported KF post-deposition treatment, in which the Ga profile keeps unchanged. Using synchrotron-based X-ray absorption spectroscopy and first-principle calculations, we verify that Ga diffusion via Cu vacancies is restrained due to the presence of K-Cu defects. Therefore, by introducing a CuGa:KF surface layer on the bi-layer precursors, the surface Ga content of CIGSe is increased effectively, achieving a notch-like Ga distribution after selenization. This unique CuGa: KF layer significantly boosts the Voc and yields over 15% efficiency, even with a low reactive Se vapor for selenization. Our approach, completely compatible with the existing fabrication process, offers a new direction for engineering band structure without sulfurization.
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.
SVAD: A genetic database curates non-ischemic sudden cardiac death-associated variants
(2020-08-19)
Huang, Wei-Chih
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Huang, Hsin-Tzu
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Chen, Po-Yuan
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Wang, Wei-Chi
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Ko, Tai-Ming
Sudden cardiac death (SCD) is an important cause of mortality worldwide. It accounts for approximately half of all deaths from cardiovascular disease. While coronary artery disease and acute myocardial infarction account for the majority of SCD in the elderly population, inherited cardiac diseases (inherited CDs) comprise a substantial proportion of younger SCD victims with a significant genetic component. Currently, the use of next-generation sequencing enables the rapid analysis to investigate relationships between genetic variants and inherited CDs causing SCD. Genetic contribution to risk has been considered an alternate predictor of SCD. In the past years, large numbers of SCD susceptibility variants were reported, but these results are scattered in numerous publications. Here, we present the SCD-associated Variants Annotation Database (SVAD) to facilitate the interpretation of variants and to meet the needs of data integration. SVAD contains data from a broad screening of scientific literature. It was constructed to provide a comprehensive collection of genetic variants along with integrated information regarding their effects. At present, SVAD has accumulated 2,292 entries within 1,239 variants by manually surveying pertinent literature, and approximately one-third of the collected variants are pathogenic/likely-pathogenic following the ACMG guidelines. To the best of our knowledge, SVAD is the most comprehensive database that can provide integrated information on the associated variants in various types of inherited CDs. SVAD represents a valuable source of variant information based on scientific literature and benefits clinicians and researchers, and it is now available on.
Systematic Analysis of the Association between Gut Flora and Obesity through High-Throughput Sequencing and Bioinformatics Approaches
(2014)
Chiu, Chih-Min
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Huang, Wei-Chih
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Weng, Shun-Long
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Tseng, Han-Chi
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Liang, Chao
Eighty-one stool samples from Taiwanese were collected for analysis of the association between the gut flora and obesity. The supervised analysis showed that the most, abundant genera of bacteria in normal samples (from people with a body mass index (BMI) <= 24) were Bacteroides (27.7%), Prevotella (19.4%), Escherichia (12%), Phascolarctobacterium(3.9%), and Eubacterium (3.5%). The most abundant genera of bacteria in case samples (with a BMI >= 27) were Bacteroides (29%), Prevotella (21%), Escherichia (7.4%), Megamonas (5.1%), and Phascolarctobacterium (3.8%). A principal coordinate analysis (PCoA) demonstrated that normal samples were clustered more compactly than case samples. An unsupervised analysis demonstrated that bacterial communities in the gut were clustered into two main groups: N-like and OB-like groups. Remarkably, most normal samples (78%) were clustered in the N-like group, and most case samples (81%) were clustered in the OB-like group (Fisher\'s P value = 1.61E-07). The results showed that bacterial communities in the gut were highly associated with obesity. This is the first study in Taiwan to investigate the association between human gut flora and obesity, and the results provide new insights into the correlation of bacteria with the rising trend in obesity.
The aquatic animals' transcriptome resource for comparative functional analysis
(2018-05-09)
Chou, Chih-Hung
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Huang, Hsi-Yuan
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Huang, Wei-Chih
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Hsu, Sheng-Da
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Hsiao, Chung-Der
Background: Aquatic animals have great economic and ecological importance. Among them, non-model organisms have been studied regarding eco-toxicity, stress biology, and environmental adaptation. Due to recent advances in next-generation sequencing techniques, large amounts of RNA-seq data for aquatic animals are publicly available. However, currently there is no comprehensive resource exist for the analysis, unification, and integration of these datasets. This study utilizes computational approaches to build a new resource of transcriptomic maps for aquatic animals. This aquatic animal transcriptome map database dbATM provides de novo assembly of transcriptome, gene annotation and comparative analysis of more than twenty aquatic organisms without draft genome. Results: To improve the assembly quality, three computational tools (Trinity, Oases and SOAPdenovo-Trans) were employed to enhance individual transcriptome assembly, and CAP3 and CD-HIT-EST software were then used to merge these three assembled transcriptomes. In addition, functional annotation analysis provides valuable clues to gene characteristics, including full-length transcript coding regions, conserved domains, gene ontology and KEGG pathways. Furthermore, all aquatic animal genes are essential for comparative genomics tasks such as constructing homologous gene groups and blast databases and phylogenetic analysis. Conclusion: In conclusion, we establish a resource for non model organism aquatic animals, which is great economic and ecological importance and provide transcriptomic information including functional annotation and comparative transcriptome analysis.