Publications

@article{Chiu2021,

title = {Vaginal microbiota of the sexually transmitted infections caused by chlamydia trachomatis and trichomonas vaginalis in women with vaginitis in Taiwan},

author = {S. -F. Chiu and P. -J. Huang and W. -H. Cheng and C. -Y. Huang and L. J. Chu and C. -C. Lee and H. -C. Lin and L. -C. Chen and W. -N. Lin and C. -H. Tsao and P. Tang and Y. -M. Yeh and K. -Y. Huang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85114096837&doi=10.3390%2fmicroorganisms9091864&partnerID=40&md5=6192aaa34993c636a80a9ced6737a447},

doi = {10.3390/microorganisms9091864},

issn = {20762607},

year  = {2021},

date = {2021-01-01},

journal = {Microorganisms},

volume = {9},

number = {9},

publisher = {MDPI},

abstract = {The three most common sexually transmitted infections (STIs) are Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC) and Trichomonas vaginalis (TV). The prevalence of these STIs in Taiwan remains largely unknown and the risk of STI acquisition affected by the vaginal microbiota is also elusive. In this study, a total of 327 vaginal swabs collected from women with vaginitis were analyzed to determine the presence of STIs and the associated microorganisms by using the BD Max CT/GC/TV molecular assay, microbial cultures, and 16S rRNA sequencing. The prevalence of CT, TV, and GC was 10.8%, 2.2% and 0.6%, respectively. A culture-dependent method identified that Escherichia coli and Streptococcus agalactiae (GBS) were more likely to be associated with CT and TV infections. In CT-positive patients, the vaginal microbiota was dominated by L. iners, and the relative abundance of Gardnerella vaginalis (12.46%) was also higher than that in TV-positive patients and the non-STIs group. However, Lactobacillus spp. was significantly lower in TV-positive patients, while GBS (10.11%), Prevotella bivia (6.19%), Sneathia sanguinegens (12.75%), and Gemella asaccharolyt-ica (5.31%) were significantly enriched. Using an in vitro co-culture assay, we demonstrated that the growth of L. iners was suppressed in the initial interaction with TV, but it may adapt and survive after longer exposure to TV. Additionally, it is noteworthy that TV was able to promote GBS growth. Our study highlights the vaginal microbiota composition associated with the common STIs and the crosstalk between TV and the associated bacteria, paving the way for future development of health interventions targeting the specific vaginal bacterial taxa to reduce the risk of common STIs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.},

note = {cited By 0},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2021,

title = {Helminth egg analysis platform (HEAP): An opened platform for microscopic helminth egg identification and quantification based on the integration of deep learning architectures},

author = {C. -C. Lee and P. -J. Huang and Y. -M. Yeh and P. -H. Li and C. -H. Chiu and W. -H. Cheng and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85114697749&doi=10.1016%2fj.jmii.2021.07.014&partnerID=40&md5=8eea45753e56336c453213c4c9cc46fd},

doi = {10.1016/j.jmii.2021.07.014},

issn = {16841182},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Microbiology, Immunology and Infection},

publisher = {Elsevier Ltd},

abstract = {Background: Millions of people throughout the world suffer from parasite infections. Traditionally, technicians use manual eye inspection of microscopic specimens to perform a parasite examination. However, manual operations have limitations that hinder the ability to obtain precise egg counts and cause inefficient identification of infected parasites on co-infections. The technician requirements for handling a large number of microscopic examinations in countries that have limited medical resources are substantial. We developed the helminth egg analysis platform (HEAP) as a user-friendly microscopic helminth eggs identification and quantification platform to assist medical technicians during parasite infection examination. Methods: Multiple deep learning strategies including SSD (Single Shot MultiBox Detector), U-net, and Faster R-CNN (Faster Region-based Convolutional Neural Network) are integrated to identify the same specimen allowing users to choose the best predictions. An image binning and egg-in-edge algorithm based on pixel density detection was developed to increase the performance. Computers with different operation systems can be gathered to lower the computation time using our easy-to-deploy software architecture. Results: A user-friendly interface is provided to substantially increase the efficiency of manual validation. To adapt to low-cost computers, we architected a distributed computing structure with high flexibilities. Conclusions: HEAP serves not only as a prediction service provider but also as a parasitic egg database of microscopic helminth egg image collection, labeling data and pretrained models. All images and labeling resources are free and accessible at http://heap.cgu.edu.tw. HEAP can also be an ideal education and training resource for helminth egg examination. © 2021},

note = {cited By 0},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cheng2020,

title = {Protein cysteine S-nitrosylation provides reducing power by enhancing lactate dehydrogenase activity in Trichomonas vaginalis under iron deficiency},

author = {W. -H. Cheng and K. -Y. Huang and S. -C. Ong and F. -M. Ku and P. -J. Huang and C. -C. Lee and Y. -M. Yeh and R. Lin and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091323851&doi=10.1186%2fs13071-020-04355-0&partnerID=40&md5=59486f02fd9a3e4458bf6cb1d28de363},

doi = {10.1186/s13071-020-04355-0},

issn = {17563305},

year  = {2020},

date = {2020-01-01},

journal = {Parasites and Vectors},

volume = {13},

number = {1},

publisher = {BioMed Central Ltd},

abstract = {Background: Iron plays essential roles in the pathogenesis and proliferation of Trichomonas vaginalis, the causative agent of the most prevalent non-viral human sexually transmitted infection. We previously demonstrated that under iron deficiency, the endogenous nitric oxide (NO) is accumulated and capable of regulating the survival of T. vaginalis. Herein, we aim to explore the influence of NO on the activity of the pyruvate-reducing enzyme lactate dehydrogenase in T. vaginalis (TvLDH). Methods: Levels of lactate and pyruvate were detected for determining glycolysis activity in T. vaginalis under iron deficiency. Quantitative PCR was performed to determine the expression of TvLDH. S-nitrosylated (SNO) proteomics was conducted to identify the NO-modified proteins. The activities of glyceraldehyde-3-phosphate dehydrogenase (TvGAPDH) and TvLDH were measured after sodium nitrate treatment. The effects of protein nitrosylation on the production of cellular reducing power were examined by measuring the amount of nicotinamide adenine dinucleotide (NAD) and the ratio of the NAD redox pair (NAD+/NADH). Results: We found that although the glycolytic pathway was activated in cells under iron depletion, the level of pyruvate was decreased due to the increased level of TvLDH. By analyzing the SNO proteome of T. vaginalis upon iron deficiency, we found that TvLDH is one of the glycolytic enzymes modified by SNO. The production of pyruvate was significantly reduced after nitrate treatment, indicating that protein nitrosylation accelerated the consumption of pyruvate by increasing TvLDH activity. Nitrate treatment also induced NAD oxidation, suggesting that protein nitrosylation was the key posttranslational modification controlling cellular redox status. Conclusions: We demonstrated that NO-mediated protein nitrosylation plays pivotal roles in the regulation of glycolysis, pyruvate metabolism, and the activity of TvLDH. The recycling of oxidized NAD catalyzed by TvLDH provided the reducing power that allowed T. vaginalis to adapt to the iron-deficient environment.[Figure not available: see fulltext.] © 2020 The Author(s).},

note = {cited By 1},

keywords = {Cysteine; Glycolysis; Iron; L-Lactate Dehydrogenase; NAD; Nitric Oxide; Oxidation-Reduction; Protein Modification, Translational; Protozoan Proteins; Pyruvic Acid; Trichomonas vaginalis},

pubstate = {published},

tppubtype = {article}

}

@article{Lin2020,

title = {Proteomic signatures of metronidazole-resistant Trichomonas vaginalis reveal novel proteins associated with drug resistance},

author = {H. -C. Lin and L. J. Chu and P. -J. Huang and W. -H. Cheng and Y. -H. Zheng and C. -Y. Huang and S. -W. Hong and L. -C. Chen and H. -A. Lin and J. -Y. Wang and R. -M. Chen and W. -N. Lin and P. Tang and K. -Y. Huang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85085910154&doi=10.1186%2fs13071-020-04148-5&partnerID=40&md5=146613f2c297776c7c895d308dd2cfe0},

doi = {10.1186/s13071-020-04148-5},

issn = {17563305},

year  = {2020},

date = {2020-01-01},

journal = {Parasites and Vectors},

volume = {13},

number = {1},

publisher = {BioMed Central},

abstract = {Background: Trichomoniasis is the most common non-viral sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. Metronidazole (MTZ) is a widely used drug for the treatment of trichomoniasis; however, increased resistance of the parasite to MTZ has emerged as a highly problematic public health issue. Methods: We conducted iTRAQ-based analysis to profile the proteomes of MTZ-sensitive (MTZ-S) and MTZ-resistant (MTZ-R) parasites. STRING and gene set enrichment analysis (GESA) were utilized to explore the protein-protein interaction networks and enriched pathways of the differentially expressed proteins, respectively. Proteins potentially related to MTZ resistance were selected for functional validation. Results: A total of 3123 proteins were identified from the MTZ-S and MTZ-R proteomes in response to drug treatment. Among the identified proteins, 304 proteins were differentially expressed in the MTZ-R proteome, including 228 upregulated and 76 downregulated proteins. GSEA showed that the amino acid-related metabolism, including arginine, proline, alanine, aspartate, and glutamate are the most upregulated pathways in the MTZ-R proteome, whereas oxidative phosphorylation is the most downregulated pathway. Ten proteins categorized into the gene set of oxidative phosphorylation were ATP synthase subunit-related proteins. Drug resistance was further examined in MTZ-S parasites pretreated with the ATP synthase inhibitors oligomycin and bafilomycin A1, showing enhanced MTZ resistance and potential roles of ATP synthase in drug susceptibility. Conclusions: We provide novel insights into previously unidentified proteins associated with MTZ resistance, paving the way for future development of new drugs against MTZ-refractory trichomoniasis. © 2020 The Author(s).},

note = {cited By 1},

keywords = {alanine; arginine; aspartic acid; bafilomycin A1; glutamic acid; hydrolase; metronidazole; oligomycin; proline; proteome; proton transporting adenosine triphosphate synthase; antiprotozoal agent; metronidazole; protozoal protein, Antiprotozoal Agents; Down-Regulation; Drug Resistance; Mass Spectrometry; Metronidazole; Protein Interaction Maps; Proteomics; Protozoan Proteins; Trichomonas vaginalis; Up-Regulation},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2020,

title = {DeepVariant-on-Spark: Small-Scale Genome Analysis Using a Cloud-Based Computing Framework},

author = {P. -J. Huang and J. -H. Chang and H. -H. Lin and Y. -X. Li and C. -C. Lee and C. -T. Su and Y. -L. Li and M. -T. Chang and S. Weng and W. -H. Cheng and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091265418&doi=10.1155%2f2020%2f7231205&partnerID=40&md5=d337abe3af557ac2b86d08f201393e81},

doi = {10.1155/2020/7231205},

issn = {1748670X},

year  = {2020},

date = {2020-01-01},

journal = {Computational and Mathematical Methods in Medicine},

volume = {2020},

publisher = {Hindawi Limited},

abstract = {Although sequencing a human genome has become affordable, identifying genetic variants from whole-genome sequence data is still a hurdle for researchers without adequate computing equipment or bioinformatics support. GATK is a gold standard method for the identification of genetic variants and has been widely used in genome projects and population genetic studies for many years. This was until the Google Brain team developed a new method, DeepVariant, which utilizes deep neural networks to construct an image classification model to identify genetic variants. However, the superior accuracy of DeepVariant comes at the cost of computational intensity, largely constraining its applications. Accordingly, we present DeepVariant-on-Spark to optimize resource allocation, enable multi-GPU support, and accelerate the processing of the DeepVariant pipeline. To make DeepVariant-on-Spark more accessible to everyone, we have deployed the DeepVariant-on-Spark to the Google Cloud Platform (GCP). Users can deploy DeepVariant-on-Spark on the GCP following our instruction within 20 minutes and start to analyze at least ten whole-genome sequencing datasets using free credits provided by the GCP. DeepVaraint-on-Spark is freely available for small-scale genome analysis using a cloud-based computing framework, which is suitable for pilot testing or preliminary study, while reserving the flexibility and scalability for large-scale sequencing projects. © 2020 Po-Jung Huang et al.},

note = {cited By 1},

keywords = {Cloud Computing; Computational Biology; Cost-Benefit Analysis; Deep Learning; Genetic Variation; Genome, Computer; Software; Whole Genome Sequencing, Human; High-Throughput Nucleotide Sequencing; Humans; Neural Networks},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2019630,

title = {Metabolic reprogramming of hydrogenosomal amino acids in Trichomonas vaginalis under glucose restriction},

author = {K. -Y. Huang and S. -C. Ong and C. -C. Wu and C. -W. Hsu and H. -C. Lin and Y. -K. Fang and W. -H. Cheng and P. -J. Huang and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85035809275&doi=10.1016%2fj.jmii.2017.10.005&partnerID=40&md5=cfe415c3b7c67a7765a9191671fd655a},

doi = {10.1016/j.jmii.2017.10.005},

issn = {16841182},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Microbiology, Immunology and Infection},

volume = {52},

number = {4},

pages = {630-637},

publisher = {Elsevier Ltd},

abstract = {Background: Glucose is the major energy source that is converted to pyruvate for ATP generation in the trichomonad hydrogenosome. Under glucose restriction (GR), the regulation of amino acids metabolism is crucial for trichomonad growth and survival. RNA-sequencing (RNA-seq) analysis has been used to identify differentially expressed genes in Trichomonas vaginalis under GR, leading to significant advances in understanding adaptive responses of amino acid metabolism to GR. However, the levels of amino acid metabolites modulated by GR are unknown in T. vaginalis. Methods: Herein, we describe a comprehensive metabolomic analysis of amino acid metabolites in the hydrogenosome using liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry (LC-FT MS). The relative abundance of 17 hydrogenosomal amino acids was analyzed under GR and high-glucose (HG) conditions. Results: Levels of most amino acids were higher in GR culture. Arginine was not detectable in either HG or GR cultures; however, its metabolic end-product proline was slightly increased under GR, suggesting that the arginine dihydrolase pathway was more activated by GR. Additionally, methionine catabolism was less stimulated under GR because of greater methionine accumulation. Furthermore, branched chain amino acids (BCAA), including leucine, isoleucine and valine, as well as phenylalanine and alanine, markedly accumulated under GR, indicating that glutamate-related metabolic pathways were remarkably enhanced in this setting. Our metabolomic analysis combined with previous RNA-seq data confirm the existence of several amino acid metabolic pathways in the hydrogenosome and highlight their potentially important roles in T. vaginalis under glucose deprivation. © 2017},

note = {cited By 4},

keywords = {alanine; amino acid; arginine; arginine deiminase; branched chain amino acid; glucose; glutamic acid; isoleucine; lactate dehydrogenase; leucine; malate dehydrogenase (decarboxylating); methionine; phenylalanine; valine; amino acid; glucose; hydrolase; protozoal protein, Amino Acids; Biochemical Phenomena; Chromatography, Liquid; Energy Metabolism; Enzyme Assays; Glucose; Hydrolases; Mass Spectrometry; Metabolic Networks and Pathways; Protozoan Proteins; Sequence Analysis, RNA; Trichomonas vaginalis},

pubstate = {published},

tppubtype = {article}

}

@article{Lee2019,

title = {Pathogenic Protist Transmembranome database (PPTdb): A web-based platform for searching and analysis of protist transmembrane proteins},

author = {C. -C. Lee and P. -J. Huang and Y. -M. Yeh and S. -Y. Chen and C. -H. Chiu and W. -H. Cheng and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85069785098&doi=10.1186%2fs12859-019-2857-7&partnerID=40&md5=a8d0bc61439150c3b7d52174c56420c4},

doi = {10.1186/s12859-019-2857-7},

issn = {14712105},

year  = {2019},

date = {2019-01-01},

journal = {BMC Bioinformatics},

volume = {20},

publisher = {BioMed Central Ltd.},

abstract = {Background: Pathogenic protist membrane transporter proteins play important roles not only in exchanging molecules into and out of cells but also in acquiring nutrients and biosynthetic compounds from their hosts. Currently, there is no centralized protist membrane transporter database published, which makes system-wide comparisons and studies of host-pathogen membranomes difficult to achieve. Results: We analyzed over one million protein sequences from 139 protists with full or partial genome sequences. Putative transmembrane proteins were annotated by primary sequence alignments, conserved secondary structural elements, and functional domains. We have constructed the PPTdb (Pathogenic Protist Transmembranome database), a comprehensive membrane transporter protein portal for pathogenic protists and their human hosts. The PPTdb is a web-based database with a user-friendly searching and data querying interface, including hierarchical transporter classification (TC) numbers, protein sequences, functional annotations, conserved functional domains, batch sequence retrieving and downloads. The PPTdb also serves as an analytical platform to provide useful comparison/mining tools, including transmembrane ability evaluation, annotation of unknown proteins, informative visualization charts, and iterative functional mining of host-pathogen transporter proteins. Conclusions: The PPTdb collected putative protist transporter proteins and offers a user-friendly data retrieving interface. Moreover, a pairwise functional comparison ability can provide useful information for identifying functional uniqueness of each protist. Finally, the host and non-host protein similarity search can fulfill the needs of comprehensive studies of protists and their hosts. The PPTdb is freely accessible at http://pptdb.cgu.edu.tw. © 2019 The Author(s).},

note = {cited By 0},

keywords = {Ability evaluation; Functional annotation; Functional domains; Secondary structural elements; Trans-membrane proteins; Transporter proteins; Web based platform; WEB-BASED database, amino acid sequence; article; genome; human; infectious agent; membrane; mining; nonhuman; protein domain; protist; sequence alignment; structure activity relation; computer interface; factual database; fungus; genetics; metabolism; plant, carrier protein, Classification (of information); Database systems; Query processing; Websites, Databases, Factual; Fungi; Humans; Membrane Transport Proteins; Plants; User-Computer Interface, Proteins},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2019,

title = {CoMutPlotter: A web tool for visual summary of mutations in cancer cohorts},

author = {P. -J. Huang and H. -H. Lin and C. -C. Lee and L. -Y. Chiu and S. -M. Wu and Y. -M. Yeh and P. Tang and C. -H. Chiu and P. -C. Lyu and P. -C. Tsai},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85069492276&doi=10.1186%2fs12920-019-0510-y&partnerID=40&md5=67d7a1a9297413695b8d1b5cf820c44b},

doi = {10.1186/s12920-019-0510-y},

issn = {17558794},

year  = {2019},

date = {2019-01-01},

journal = {BMC Medical Genomics},

volume = {12},

publisher = {BioMed Central Ltd.},

abstract = {Background: CoMut plot is widely used in cancer research publications as a visual summary of mutational landscapes in cancer cohorts. This summary plot can inspect gene mutation rate and sample mutation burden with their relevant clinical details, which is a common first step for analyzing the recurrence and co-occurrence of gene mutations across samples. The cBioPortal and iCoMut are two web-based tools that allow users to create intricate visualizations from pre-loaded TCGA and ICGC data. For custom data analysis, only limited command-line packages are available now, making the production of CoMut plots difficult to achieve, especially for researchers without advanced bioinformatics skills. To address the needs for custom data and TCGA/ICGC data comparison, we have created CoMutPlotter, a web-based tool for the production of publication-quality graphs in an easy-of-use and automatic manner. Results: We introduce a web-based tool named CoMutPlotter to lower the barriers between complex cancer genomic data and researchers, providing intuitive access to mutational profiles from TCGA/ICGC projects as well as custom cohort studies. A wide variety of file formats are supported by CoMutPlotter to translate cancer mutation profiles into biological insights and clinical applications, which include Mutation Annotation Format (MAF), Tab-separated values (TSV) and Variant Call Format (VCF) files. Conclusions: In summary, CoMutPlotter is the first tool of its kind that supports VCF file, the most widely used file format, as its input material. CoMutPlotter also provides the most-wanted function for comparing mutation patterns between custom cohort and TCGA/ICGC project. Contributions of COSMIC mutational signatures in individual samples are also included in the summary plot, which is a unique feature of our tool. CoMutPlotter is freely available at http://tardis.cgu.edu.tw/comutplotter. © 2019 The Author(s).},

note = {cited By 2},

keywords = {Cohort Studies; Computational Biology; Computer Graphics; Humans; Internet; Mutation; Neoplasms},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2019336,

title = {Potential role of autophagy in proteolysis in Trichomonas vaginalis},

author = {K. -Y. Huang and R. -M. Chen and H. -C. Lin and W. -H. Cheng and H. -A. Lin and W. -N. Lin and P. -J. Huang and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057359194&doi=10.1016%2fj.jmii.2018.11.002&partnerID=40&md5=ca3517ee44fdd3527809a5caa9cef9a6},

doi = {10.1016/j.jmii.2018.11.002},

issn = {16841182},

year  = {2019},

date = {2019-01-01},

journal = {Journal of Microbiology, Immunology and Infection},

volume = {52},

number = {2},

pages = {336-344},

publisher = {Elsevier Ltd},

abstract = {Background: Autophagy has been shown to be involved in the pathogenesis of several protists, offering prospects for the developments of new drugs targeting autophagy. However, there is no evidence illustrating functional autophagy in the deep-branching trichomonads. The human parasitic protist Trichomonas vaginalis has been predicted to possess reduced autophagic machinery, with only autophagy-related protein 8 (Atg8) conjugation system required for autophagosome formation. Methods: The recombinant protein of TvAtg8 (rTvAtg8) and the polyclonal antibody against rTvAtg8 were generated. The expression and localization of TvAtg8 was monitored upon autophagy induction by glucose restriction (GR) compared with glucose-rich cultivation. The role of TvAtg8 in proteolysis was clarified. Results: Here, we report that T. vaginalis Atg8 (TvAtg8) is upregulated and conjugated to autophagosome-like vesicles upon autophagy induction by GR. Moreover, we investigate, for the first time, the role of autophagy in T. vaginalis. Proteasome inhibition (PI)-induced autophagy compensates for the removal of polyubiquitinated proteins under glucose-rich condition. GR-induced autophagy is a major proteolytic system in T. vaginalis. These results suggest that autophagy is vital for proteolysis in T. vaginalis with an impaired ubiquitin-proteasome system or under glucose-limited environment. Conclusion: Our findings unveiled previously unidentified functions of autophagy in proteostasis in trichomonads, advancing our understanding of this highly conserved process in the ancient eukaryote. © 2018},

note = {cited By 5},

keywords = {Autophagosomes; Autophagy; Autophagy-Related Protein 8 Family; Glucose; Humans; Leupeptins; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Proteolysis; Proteostasis; Recombinant Proteins; Trichomonas vaginalis; Ubiquitination},

pubstate = {published},

tppubtype = {article}

}

@article{Lu2018721,

title = {The cholesterol-hydroxyecdysone-vitellogenin pathway is involved in the longevity of trophocytes and oenocytes of queen honey bees (Apis mellifera)},

author = {C. -Y. Lu and P. -J. Huang and C. -Y. Hsu},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85058863640&doi=10.1007%2fs13592-018-0596-9&partnerID=40&md5=fc64b00f4f8ba77ed3296ced22ccdc9a},

doi = {10.1007/s13592-018-0596-9},

issn = {00448435},

year  = {2018},

date = {2018-01-01},

journal = {Apidologie},

volume = {49},

number = {6},

pages = {721-733},

publisher = {Springer-Verlag France},

abstract = {Trophocytes and oenocytes in the abdomen of honey bees do not divide after eclosion; however, trophocytes and oenocytes of queen bees have a longer lifespan and maintain better cellular function than those of worker bees. To explore this phenomenon, we assayed the molecules involved in the cholesterol-hydroxyecdysone-vitellogenin (Vg) pathway in the trophocytes and oenocytes of young and old worker and queen bees. The results showed that Vg and cholesterol levels in hemolymph and cholesterol levels, 20-hydroxyecdysone (20E) levels, and the messenger RNA levels of cytochrome P450 314A1 20-hydroxylase (Cyp314A1), ecdysone receptor isoform A (EcR-A), ecdysone receptor isoform B1 (EcR-B1), ultraspiracle (USP), ecdysone-induced protein 74 (E74), ecdysone-induced protein 75 (E75), broad-complex (BR-C), Vg, and Vg receptor (VgR) in trophocytes and oenocytes were increased in queen bees compared with worker bees. These findings indicated that queen bees have higher expression of molecules in the cholesterol-hydroxyecdysone-Vg pathway than worker bees. © 2018, INRA, DIB and Springer-Verlag France SAS, part of Springer Nature.},

note = {cited By 3},

keywords = {Apis mellifera; Apoidea, cell; cytochrome; gene expression; honeybee; longevity; molecular analysis; protein; queen},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2018,

title = {VAReporter: Variant reporter for cancer research of massive parallel sequencing},

author = {P. -J. Huang and C. -C. Lee and L. -Y. Chiu and K. -Y. Huang and Y. -M. Yeh and C. -Y. Yang and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046673650&doi=10.1186%2fs12864-018-4468-5&partnerID=40&md5=9000ef84b6c658f3b994ff25a3b7ce63},

doi = {10.1186/s12864-018-4468-5},

issn = {14712164},

year  = {2018},

date = {2018-01-01},

journal = {BMC Genomics},

volume = {19},

publisher = {BioMed Central Ltd.},

abstract = {Background: High throughput sequencing technologies have been an increasingly critical aspect of precision medicine owing to a better identification of disease targets, which contributes to improved health care cost and clinical outcomes. In particular, disease-oriented targeted enrichment sequencing is becoming a widely-accepted application for diagnostic purposes, which can interrogate known diagnostic variants as well as identify novel biomarkers from panels of entire human coding exome or disease-associated genes. Results: We introduce a workflow named VAReporter to facilitate the management of variant assessment in disease-targeted sequencing, the identification of pathogenic variants, the interpretation of biological effects and the prioritization of clinically actionable targets. State-of-art algorithms that account for mutation phenotypes are used to rank the importance of mutated genes through visual analytic strategies. We established an extensive annotation source by integrating a wide variety of biomedical databases and followed the American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation and reporting of sequence variations. Conclusions: In summary, VAReporter is the first web server designed to provide a "one-stop" resource for individual's diagnosis and large-scale cohort studies, and is freely available at http://rnd.cgu.edu.tw/vareporter. © 2018 The Author(s).},

note = {cited By 1},

keywords = {Algorithms; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Humans; Internet; Molecular Sequence Annotation; Mutation; Neoplasms; Precision Medicine; Whole Exome Sequencing; Workflow},

pubstate = {published},

tppubtype = {article}

}

@article{Yang2018,

title = {Oral microbiota community dynamics associated with oral squamous cell carcinoma staging},

author = {C. -Y. Yang and Y. -M. Yeh and H. -Y. Yu and C. -Y. Chin and C. -W. Hsu and H. Liu and P. -J. Huang and S. -N. Hu and C. -T. Liao and K. -P. Chang and Y. -L. Chang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046335186&doi=10.3389%2ffmicb.2018.00862&partnerID=40&md5=81c0c5f7bbdae70a407f7f0379e9a4d1},

doi = {10.3389/fmicb.2018.00862},

issn = {1664302X},

year  = {2018},

date = {2018-01-01},

journal = {Frontiers in Microbiology},

volume = {9},

number = {MAY},

publisher = {Frontiers Media S.A.},

abstract = {Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer and the fourth leading malignancy among males in Taiwan. Some pathogenic bacteria are associated with periodontitis and oral cancer. However, the comprehensive profile of the oral microbiome during the cancer's progression from the early stage to the late stage is still unclear. We profiled the oral microbiota and identified bacteria biomarkers associated with OSCC. The microbiota of an oral rinse from 51 healthy individuals and 197 OSCC patients at different stages were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. The oral microbiota communities from stage 4 patients showed significantly higher complexity than those from healthy controls. The populations also dynamically changed with the cancer's progression from stage 1 to stage 4. The predominant phyla in the oral samples showed variation in the relative abundance of Fusobacteria, Bacteroidetes, and Actinobacteria. The abundance of Fusobacteria increased significantly with the progression of oral cancer from the healthy controls (2.98%) to OSCC stage 1 (4.35%) through stage 4 (7.92%). At the genus level, the abundance of Fusobacterium increased, while the number of Streptococcus, Haemophilus, Porphyromonas, and Actinomyces decreased with cancer progression. Fusobacterium periodonticum, Parvimonas micra, Streptococcus constellatus, Haemophilus influenza, and Filifactor alocis were associated with OSCC, and they progressively increased in abundance from stage 1 to stage 4. The abundances of Streptococcus mitis, Haemophilus parainfluenzae, and Porphyromonas pasteri were inversely associated with OSCC progression. We selected a bacterial marker panel of three bacteria (upregulated F. periodonticum, down-regulated S. mitis, and P. pasteri), which had an AUC of 0.956 (95% CI = 0.925-0.986) in discriminating OSCC stage 4 from the healthy controls. Furthermore, the functional prediction of oral bacterial communities showed that genes involved in carbohydrate-related metabolism, such as methane metabolism, and energy-metabolism-related parameters, such as oxidative phosphorylation and carbon fixation in photosynthetic organisms, were enriched in late-stage OSCC, while those responsible for amino acid metabolism, such as folate biosynthesis and valine, leucine, and isoleucine biosynthesis, were significantly associated with the healthy controls. In conclusion, our results provided evidence of oral bacteria community changes during oral cancer progression and suggested the possibility of using bacteria as OSCC diagnostic markers. © 2018 Yang, Yeh, Yu, Chin, Hsu, Liu, Huang, Hu, Liao, Chang and Chang.},

note = {cited By 83},

keywords = {biological marker; phenylalanine; RNA 16S; tryptophan; tyrosine},

pubstate = {published},

tppubtype = {article}

}

@article{Wu20181,

title = {circlncRNAnet: An integrated web-based resource for mapping functional networks of long or circular forms of noncoding RNAs},

author = {S. -M. Wu and H. Liu and P. -J. Huang and I. Y. -F. Chang and C. -C. Lee and C. -Y. Yang and W. -S. Tsai and B. C. -M. Tan},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85043516778&doi=10.1093%2fgigascience%2fgix118&partnerID=40&md5=75661152f773bd306214b4b3c762a973},

doi = {10.1093/gigascience/gix118},

issn = {2047217X},

year  = {2018},

date = {2018-01-01},

journal = {GigaScience},

volume = {7},

number = {1},

pages = {1-10},

publisher = {Oxford University Press},

abstract = {Background: Despite their lack of protein-coding potential, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as key determinants in gene regulation, acting to fine-tune transcriptional and signaling output. These noncoding RNA transcripts are known to affect expression of messenger RNAs (mRNAs) via epigenetic and post-transcriptional regulation. Given their widespread target spectrum, as well as extensive modes of action, a complete understanding of their biological relevance will depend on integrative analyses of systems data at various levels. Findings: While a handful of publicly available databases have been reported, existing tools do not fully capture, from a network perspective, the functional implications of lncRNAs or circRNAs of interest. Through an integrated and streamlined design, circlncRNAnet aims to broaden the understanding of ncRNA candidates by testing in silico several hypotheses of ncRNA-based functions, on the basis of large-scale RNA-seq data. This web server is implemented with several features that represent advances in the bioinformatics of ncRNAs: (1) a flexible framework that accepts and processes user-defined next-generation sequencing-based expression data; (2) multiple analytic modules that assign and productively assess the regulatory networks of user-selected ncRNAs by cross-referencing extensively curated databases; (3) an all-purpose, information-rich workflow design that is tailored to all types of ncRNAs. Outputs on expression profiles, co-expression networks and pathways, and molecular interactomes, are dynamically and interactively displayed according to user-defined criteria. Conclusions: In short, users may apply circlncRNAnet to obtain, in real time, multiple lines of functionally relevant information on circRNAs/lncRNAs of their interest. In summary, circlncRNAnet provides a "one-stop" resource for in-depth analyses of ncRNA biology. circlncRNAnet is freely available at http://app.cgu.edu.tw/circlnc/. © The Author(s) 2017.},

note = {cited By 41},

keywords = {circular, circular RNA; long untranslated RNA; RNA binding protein; unclassified drug; untranslated RNA; messenger RNA; microRNA; RNA; RNA, Computational Biology; Databases, Genetic; Gene Regulatory Networks; High-Throughput Nucleotide Sequencing; Humans; Internet; MicroRNAs; RNA; RNA Processing, Genetic; User-Computer Interface, Long Noncoding; RNA, Messenger; Sequence Analysis, Nucleic Acid; Epigenesis, Post-Transcriptional; RNA, RNA; Transcription},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2018D964,

title = {MSignatureDB: A database for deciphering mutational signatures in human cancers},

author = {P. -J. Huang and L. -Y. Chiu and C. -C. Lee and Y. -M. Yeh and K. -Y. Huang and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85040945094&doi=10.1093%2fnar%2fgkx1133&partnerID=40&md5=8a9d6d3a1fa21c1b8ae7f7acbf870b6a},

doi = {10.1093/nar/gkx1133},

issn = {03051048},

year  = {2018},

date = {2018-01-01},

journal = {Nucleic Acids Research},

volume = {46},

number = {D1},

pages = {D964-D970},

publisher = {Oxford University Press},

abstract = {Cancer is a genetic disease caused by somatic mutations; however, the understanding of the causative biological processes generating these mutations is limited. A cancer genome bears the cumulative effects of mutational processes during tumor development. Deciphering mutational signatures in cancer is a new topic in cancer research. The Wellcome Trust Sanger Institute (WTSI) has categorized 30 reference signatures in the COSMIC database based on the analyses of ∼410 000 sequencing datasets from TCGA and ICGC. Large cohorts and bioinformatics skills are required to perform the same analysis as WTSI. The quantification of known signatures in custom cohorts is not possible under the current framework of the COSMIC database, which motivates us to construct a database for mutational signatures in cancers and make such analyses more accessible to general researchers. mSignatureDB (http://tardis.cgu.edu.tw/msignaturedb) integrates R packages and in-house scripts to determine the contributions of the published signatures in 15 780 individual tumors from 73 TCGA/ICGC cancer projects, making comparison of signature patterns within and between projects become possible. mSignatureDB also allows users to perform signature analysis on their own datasets, quantifying contributions of signatures at sample resolution, which is a unique feature of mSignatureDB not available in other related databases. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {cited By 26},

keywords = {Article; bioinformatics; cancer genetics; cancer research; gene sequence; genetic database; human; mutational analysis; priority journal; reference database; computer interface; genetics; mutation; neoplasm; nucleic acid database, Databases, Nucleic Acid; Humans; Mutation; Neoplasms; User-Computer Interface},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2017,

title = {APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism},

author = {T. -W. Chen and C. -C. Lee and H. Liu and C. -S. Wu and C. R. Pickering and P. -J. Huang and J. Wang and I. Y. -F. Chang and Y. -M. Yeh and C. -D. Chen and H. -P. Li and J. -D. Luo and B. C. -M. Tan and T. E. H. Chan and C. Hsueh and L. J. Chu and Y. -T. Chen and B. Zhang and C. -Y. Yang and C. -C. Wu and C. -W. Hsu and L. -C. See and P. Tang and J. -S. Yu and W. -C. Liao and W. -F. Chiang and H. Rodriguez and J. N. Myers and K. -P. Chang and Y. -S. Chang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85028934689&doi=10.1038%2fs41467-017-00493-9&partnerID=40&md5=2c10395e48de87bc22d79acdf9d8c6d6},

doi = {10.1038/s41467-017-00493-9},

issn = {20411723},

year  = {2017},

date = {2017-01-01},

journal = {Nature Communications},

volume = {8},

number = {1},

publisher = {Nature Publishing Group},

abstract = {Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n = 188; p = 0.004). The frequency of APOBEC3B-deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27A3B -/-:89A3B +/-:27A3B +/+), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types. © 2017 The Author(s).},

note = {cited By 52},

keywords = {Adult; Asian Continental Ancestry Group; Biomarkers, allele; biomarker; cancer; gene; gene expression; mutation; organic nitrogen compound; polymorphism; protein; survival, Genetic; Proteins; Sequence Deletion; Taiwan, human; cytidine deaminase; protein; tumor marker, Neoplastic; Germ-Line Mutation; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mouth Neoplasms; Polymorphism, Squamous Cell; Cohort Studies; Cytidine Deaminase; Female; Gene Expression Regulation, Taiwan, Tumor; Carcinoma},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2017b,

title = {FunctionAnnotator, a versatile and efficient web tool for non-model organism annotation},

author = {T. -W. Chen and R. -C. Gan and Y. -K. Fang and K. -Y. Chien and W. -C. Liao and C. -C. Chen and T. H. Wu and I. Y. -F. Chang and C. Yang and P. -J. Huang and Y. -M. Yeh and C. -H. Chiu and T. -W. Huang and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85028821290&doi=10.1038%2fs41598-017-10952-4&partnerID=40&md5=5be6a65ba55e7b9ad5ab8c1da14fbacd},

doi = {10.1038/s41598-017-10952-4},

issn = {20452322},

year  = {2017},

date = {2017-01-01},

journal = {Scientific Reports},

volume = {7},

number = {1},

publisher = {Nature Publishing Group},

abstract = {Along with the constant improvement in high-throughput sequencing technology, an increasing number of transcriptome sequencing projects are carried out in organisms without decoded genome information and even on environmental biological samples. To study the biological functions of novel transcripts, the very first task is to identify their potential functions. We present a web-based annotation tool, FunctionAnnotator, which offers comprehensive annotations, including GO term assignment, enzyme annotation, domain/motif identification and predictions for subcellular localization. To accelerate the annotation process, we have optimized the computation processes and used parallel computing for all annotation steps. Moreover, FunctionAnnotator is designed to be versatile, and it generates a variety of useful outputs for facilitating other analyses. Here, we demonstrate how FunctionAnnotator can be helpful in annotating non-model organisms. We further illustrate that FunctionAnnotator can estimate the taxonomic composition of environmental samples and assist in the identification of novel proteins by combining RNA-Seq data with proteomics technology. In summary, FunctionAnnotator can efficiently annotate transcriptomes and greatly benefits studies focusing on non-model organisms or metatranscriptomes. FunctionAnnotator, a comprehensive annotation web-service tool, is freely available online at: http://fa.cgu.edu.tw/. This new web-based annotator will shed light on field studies involving organisms without a reference genome. © 2017 The Author(s).},

note = {cited By 20},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lin2017771,

title = {RNA recombination in Hepatitis delta virus: Identification of a novel naturally occurring recombinant},

author = {C. -C. Lin and C. -C. Lee and S. -H. Lin and P. -J. Huang and H. -P. Li and Y. -S. Chang and P. Tang and M. Chao},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84952361456&doi=10.1016%2fj.jmii.2015.10.013&partnerID=40&md5=89910d5b9043f7adebf51c6da1f37a4f},

doi = {10.1016/j.jmii.2015.10.013},

issn = {16841182},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Microbiology, Immunology and Infection},

volume = {50},

number = {6},

pages = {771-780},

publisher = {Elsevier Ltd},

abstract = {Background/Purpose Hepatitis delta virus (HDV) is the only animal RNA virus that has an unbranched rod-like genome with ribozyme activity. It replicates in the nucleus by host RNA polymerase via a rolling circle mechanism. Similar to many RNA viruses encoding their own RNA-dependent RNA polymerases, homologous recombination of HDV occurs in mixed-genotype infections and in cultured cells cotransfected with two HDV sequences, as demonstrated by molecular analyses. Methods Among 237 published complete genomic sequences, 34 sequences were reported from the small and isolated Miyako Island, Japan, and belonged to the Asia-specific genotypes, HDV-2 and HDV-4 (the majority of them belonged to the known Miyako Island-specific subgroup, HDV-4M). We investigated the presence of naturally occurring HDV recombinant in Miyako Island using phylogenetic and recombination analyses. Results We identified a two-switch HDV-4/4M intersubtype recombinant with an unbranched rod-like RNA genome. Conclusion Our data suggest that RNA recombination plays an important role in the rapid evolution of HDV, allowing the production of new HDV strains with correct genomic structures. © 2015},

note = {cited By 10},

keywords = {Base Sequence; Genome, Genetic; RNA; RNA, genome; genotype; Hepatitis delta virus; Japan; RNA recombination; virus identification; virus strain; classification; delta agent hepatitis; genetic recombination; genetics; Hepatitis delta virus; human; nucleotide sequence; phylogeny; sequence analysis; Viet Nam; virology; virus genome, recombinant; virus RNA, RNA; RNA, RNA; Vietnam, Viral; Genotype; Hepatitis D; Hepatitis Delta Virus; Humans; Japan; Phylogeny; Recombination, Viral; Sequence Analysis},

pubstate = {published},

tppubtype = {article}

}

@article{Cheng2017,

title = {γ-Carboxymuconolactone decarboxylase: A novel cell cycle-related basal body protein in the early branching eukaryote Trichomonas vaginalis},

author = {W. -H. Cheng and K. -Y. Huang and P. -J. Huang and C. -C. Lee and Y. -M. Yeh and F. -M. Ku and R. Lin and M. -L. Cheng and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85029884915&doi=10.1186%2fs13071-017-2381-4&partnerID=40&md5=aa319d7d2fc95e9e5fa4b9fdbe3ae817},

doi = {10.1186/s13071-017-2381-4},

issn = {17563305},

year  = {2017},

date = {2017-01-01},

journal = {Parasites and Vectors},

volume = {10},

number = {1},

publisher = {BioMed Central Ltd.},

abstract = {Background: γ-Carboxymuconolactone decarboxylase (CMD) participates in the β-ketoadipate pathway, which catalyzes aromatic compounds to produce acetyl- or succinyl-CoA, in prokaryotes and yeast. Our previous study demonstrated that expression of a CMD homologue that contains two signatures (dualCMD) is negatively regulated by iron in Trichomonas vaginalis. However, we were not able to identify the components of the β-ketoadipate pathway in the parasite's genome. These observations prompted us to investigate the biological functions of this novel CMD homologue in T. vaginalis. Methods: The specific anti-TvCMD1 antibody was generated, and the expression of TvCMD1 in T. vaginalis cultured under iron-rich and iron-deficient were evaluated. Phylogenetic, metabolomic and substrate induction (protocatechuate and benzoate) analysis were conducted to clarify the function of dualCMD in trichomonad cells. Subcellular localization of TvCMD1 was observed by confocal microscopy. The cell cycle-related role of TvCMD1 was assessed by treating cells with G2/M inhibitor nocodazole. Results: We confirmed that T. vaginalis is not able to catabolize the aromatic compounds benzoate and protocatechuate, which are known substrates of the β-ketoadipate pathway. Using immunofluorescence microscopy, we found that TvCMD1 is spatially associated with the basal body, a part of the cytoskeletal organizing center in T. vaginalis. TvCMD1 accumulated upon treatment with the G2/M inhibitor nocodazole. Additionally, TvCMD1 was expressed and transported to/from the basal body during cytokinesis, suggesting that TvCMD1 plays a role in cell division. Conclusion: We demonstrated that TvCMD1 is unlikely to participate in the β-ketoadipate pathway and demonstrated that it is a novel basal body-localizing (associated) protein. This model sheds light on the importance of genes that are acquired laterally in the coevolution of ancient protists, which surprisingly functions in cell cycle regulation of T. vaginalis. © 2017 The Author(s).},

note = {cited By 2},

keywords = {Basal Bodies; Benzoates; Carboxy-Lyases; Cell Cycle; Iron; Protozoan Proteins; Trichomonas vaginalis, carboxylyase; gamma carboxymuconolactone decarboxylase; iron; nocodazole; unclassified drug; 4-carboxymuconolactone decarboxylase; benzoic acid derivative; carboxylyase; iron; protozoal protein},

pubstate = {published},

tppubtype = {article}

}

@article{Bradic20171658,

title = {Genetic indicators of drug resistance in the highly repetitive genome of trichomonas vaginalis},

author = {M. Bradic and S. D. Warring and G. E. Tooley and P. Scheid and W. E. Secor and K. M. Land and P. -J. Huang and T. -W. Chen and C. -C. Lee and P. Tang and S. A. Sullivan and J. M. Carlton},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032628679&doi=10.1093%2fgbe%2fevx110&partnerID=40&md5=7b2e5d90025b302b1b260ca666fd1fe1},

doi = {10.1093/gbe/evx110},

issn = {17596653},

year  = {2017},

date = {2017-01-01},

journal = {Genome Biology and Evolution},

volume = {9},

number = {6},

pages = {1658-1672},

publisher = {Oxford University Press},

abstract = {Trichomonas vaginalis, the most common nonviral sexually transmitted parasite, causes 283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance. Reduced representation genome sequencing of 100 T. vaginalis clinical isolates identified 3,923 SNP markers and presence of a bipartite population structure. Linkage disequilibrium was found to decay rapidly, suggesting genome-wide recombination and the feasibility of genetic association studies in the parasite. We identified 72 SNPs associated with metronidazole resistance, and a comparison of SNPs within several lab-derived resistant lines revealed an overlap with the clinically resistant isolates. We identified SNPs in genes for which no function has yet been assigned, as well as in functionally-characterized genes relevant to drug resistance (e.g., pyruvate:ferredoxin oxidoreductase). Transcription profiles of resistant strains showed common changes in genes involved in drug activation (e.g., flavin reductase), accumulation (e.g., multidrug resistance pump), and detoxification (e.g., nitroreductase). Finally, we identified convergent genetic changes in lab-derived resistant lines of Tritrichomonas foetus, a distantly related species that causes venereal disease in cattle. Shared genetic changes within and between T. vaginalis and Tr. foetus parasites suggest conservation of the pathways through which adaptation has occurred. These findings extend our knowledge of drug resistance in the parasite, providing a panel of markers that can be used as a diagnostic tool. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.},

note = {cited By 25},

keywords = {antiprotozoal agent; protozoal protein, Antiprotozoal Agents; Drug Resistance; Female; Genome, classification; drug effects; drug resistance; female; gene linkage disequilibrium; genetic recombination; genetics; genome; human; parasitology; phylogeny; single nucleotide polymorphism; Trichomonas vaginalis; vaginal trichomoniasis, Genetic; Trichomonas vaginalis; Trichomonas Vaginitis, Protozoan; Humans; Linkage Disequilibrium; Phylogeny; Polymorphism, Single Nucleotide; Protozoan Proteins; Recombination},

pubstate = {published},

tppubtype = {article}

}

@article{Sablok2017327,

title = {ChloroMitoCU: Codon patterns across organelle genomes for functional genomics and evolutionary applications},

author = {G. Sablok and T. -W. Chen and C. -C. Lee and C. Yang and R. -C. Gan and J. L. Wegrzyn and N. La Porta and K. C. Nayak and P. -J. Huang and C. Varotto and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021349951&doi=10.1093%2fdnares%2fdsw044&partnerID=40&md5=1319adee5d716b5947e7e72134e23f93},

doi = {10.1093/dnares/dsw044},

issn = {13402838},

year  = {2017},

date = {2017-01-01},

journal = {DNA Research},

volume = {24},

number = {3},

pages = {327-332},

publisher = {Oxford University Press},

abstract = {Organelle genomes are widely thought to have arisen from reduction events involving cyanobacterial and archaeal genomes, in the case of chloroplasts, or α-proteobacterial genomes, in the case of mitochondria. Heterogeneity in base composition and codon preference has long been the subject of investigation of topics ranging from phylogenetic distortion to the design of overexpression cassettes for transgenic expression. From the overexpression point of view, it is critical to systematically analyze the codon usage patterns of the organelle genomes. In light of the importance of codon usage patterns in the development of hyper-expression organelle transgenics, we present ChloroMitoCU, the first-ever curated, web-based reference catalog of the codon usage patterns in organelle genomes. ChloroMitoCU contains the pre-compiled codon usage patterns of 328 chloroplast genomes (29,960 CDS) and 3,502 mitochondrial genomes (49,066 CDS), enabling genome-wide exploration and comparative analysis of codon usage patterns across species. ChloroMitoCU allows the phylogenetic comparison of codon usage patterns across organelle genomes, the prediction of codon usage patterns based on user-submitted transcripts or assembled organelle genes, and comparative analysis with the pre-compiled patterns across species of interest. ChloroMitoCU can increase our understanding of the biased patterns of codon usage in organelle genomes across multiple clades. ChloroMitoCU can be accessed at: http://chloromitocu.cgu.edu.tw/ © The Author 2017. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.},

note = {cited By 1},

keywords = {Chloroplast; Genome, Chloroplasts; Codon; Eukaryota; Evolution, codon, Mitochondrial; Genomics; Mitochondria; Software, Molecular; Genome},

pubstate = {published},

tppubtype = {article}

}

@article{Gan2016,

title = {PARRoT- a homology-based strategy to quantify and compare RNA-sequencing from non-model organisms},

author = {R. -C. Gan and T. -W. Chen and T. H. Wu and P. -J. Huang and C. -C. Lee and Y. -M. Yeh and C. -H. Chiu and H. -D. Huang and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85006892898&doi=10.1186%2fs12859-016-1366-1&partnerID=40&md5=4991defff4e25eeca679425824ef6437},

doi = {10.1186/s12859-016-1366-1},

issn = {14712105},

year  = {2016},

date = {2016-01-01},

journal = {BMC Bioinformatics},

volume = {17},

publisher = {BioMed Central Ltd.},

abstract = {Background: Next-generation sequencing promises the de novo genomic and transcriptomic analysis of samples of interests. However, there are only a few organisms having reference genomic sequences and even fewer having well-defined or curated annotations. For transcriptome studies focusing on organisms lacking proper reference genomes, the common strategy is de novo assembly followed by functional annotation. However, things become even more complicated when multiple transcriptomes are compared. Results: Here, we propose a new analysis strategy and quantification methods for quantifying expression level which not only generate a virtual reference from sequencing data, but also provide comparisons between transcriptomes. First, all reads from the transcriptome datasets are pooled together for de novo assembly. The assembled contigs are searched against NCBI NR databases to find potential homolog sequences. Based on the searched result, a set of virtual transcripts are generated and served as a reference transcriptome. By using the same reference, normalized quantification values including RC (read counts), eRPKM (estimated RPKM) and eTPM (estimated TPM) can be obtained that are comparable across transcriptome datasets. In order to demonstrate the feasibility of our strategy, we implement it in the web service PARRoT. PARRoT stands for Pipeline for Analyzing RNA Reads of Transcriptomes. It analyzes gene expression profiles for two transcriptome sequencing datasets. For better understanding of the biological meaning from the comparison among transcriptomes, PARRoT further provides linkage between these virtual transcripts and their potential function through showing best hits in SwissProt, NR database, assigning GO terms. Our demo datasets showed that PARRoT can analyze two paired-end transcriptomic datasets of approximately 100 million reads within just three hours. Conclusions: In this study, we proposed and implemented a strategy to analyze transcriptomes from non-reference organisms which offers the opportunity to quantify and compare transcriptome profiles through a homolog based virtual transcriptome reference. By using the homolog based reference, our strategy effectively avoids the problems that may cause from inconsistencies among transcriptomes. This strategy will shed lights on the field of comparative genomics for non-model organism. We have implemented PARRoT as a web service which is freely available at http://parrot.cgu.edu.tw. © 2016 The Author(s).},

note = {cited By 3},

keywords = {animal; biological model; Cnidaria; comparative study; gene expression profiling; genetics; genomics; high throughput sequencing; Internet; molecular genetics; procedures; sequence analysis; software, Animals; Cnidaria; Gene Expression Profiling; Genomics; High-Throughput Nucleotide Sequencing; Internet; Models, Biological; Molecular Sequence Annotation; Sequence Analysis, Birds; Gene expression; RNA; Websites, Functional annotation; Gene expression profiles; Next-generation sequencing; Quantification methods; Transcriptome assemblies; Transcriptome profiles; Transcriptome quantifications; Transcriptomes, RNA; Software; Transcriptome, transcriptome, Web services},

pubstate = {published},

tppubtype = {article}

}

@article{Fang2016662,

title = {Responding to a Zoonotic Emergency with Multi-omics Research: Pentatrichomonas hominis Hydrogenosomal Protein Characterization with Use of RNA Sequencing and Proteomics},

author = {Y. -K. Fang and K. -Y. Chien and K. -Y. Huang and W. -H. Cheng and F. -M. Ku and R. Lin and T. -W. Chen and P. -J. Huang and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84995394532&doi=10.1089%2fomi.2016.0111&partnerID=40&md5=6f1e93c2dc11596f7e8eea989a21abb7},

doi = {10.1089/omi.2016.0111},

issn = {15362310},

year  = {2016},

date = {2016-01-01},

journal = {OMICS A Journal of Integrative Biology},

volume = {20},

number = {11},

pages = {662-669},

publisher = {Mary Ann Liebert Inc.},

abstract = {Pentatrichomonas hominis is an anaerobic flagellated protist that colonizes the large intestine of a number of mammals, including cats, dogs, nonhuman primates, and humans. The wide host range of this organism is alarming and suggests a rising zoonotic emergency. However, knowledge on in-depth biology of this protist is still limited. Similar to the human pathogen, Trichomonas vaginalis, P. hominis possesses hydrogenosomes instead of mitochondria. Studies in T. vaginalis indicated that hydrogenosome is essential for cell survival and associated with numerous pivotal biological functions, including drug resistance. To further decipher the biology of this important organelle, we undertook proteomic research in P. hominis hydrogenosomes. Lacking a decoded P. hominis genome, we utilized an RNA sequencing (RNA-seq) data set generated from P. hominis axenic culture as the reference for proteome analysis. Using this in-house reference data set and mass spectrometry (MS), we identified 442 putative hydrogenosomal proteins. Interestingly, the composition of the P. hominis hydrogenosomal proteins is very similar to that of T. vaginalis, but proteins such as Hmp36, Pam16, Pam18, and Isd11 are absent based on both MS and the RNA-seq. Our data underscore that P. hominis expresses different homologs of multiple gene families from T. vaginalis. To the best of our knowledge, we present here the first hydrogenosome proteome in a protist other than T. vaginalis that offers crucial new scholarship for global health, therapeutics, diagnostics, and veterinary medicine research. In addition, the research strategy used here using RNA sequencing and proteomics might inform future multi-omics research in other understudied organisms without decoded genomes. © 2016, Mary Ann Liebert, Inc. 2016.},

note = {cited By 8},

keywords = {Animals; Cats; Dogs; Humans; Mass Spectrometry; Organelles; Proteome; Proteomics; Protozoan Infections; Protozoan Proteins; Sequence Analysis, proteome; protozoal protein; protozoal RNA; proteome; protozoal protein, RNA; Trichomonadida; Zoonoses},

pubstate = {published},

tppubtype = {article}

}

@article{Fang2015662,

title = {Gene-expression analysis of cold-stress response in the sexually transmitted protist Trichomonas vaginalis},

author = {Y. -K. Fang and K. -Y. Huang and P. -J. Huang and R. Lin and M. Chao and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84951269543&doi=10.1016%2fj.jmii.2014.07.013&partnerID=40&md5=5acae31f59fb0e13c4dea9949e97997f},

doi = {10.1016/j.jmii.2014.07.013},

issn = {16841182},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Microbiology, Immunology and Infection},

volume = {48},

number = {6},

pages = {662-675},

publisher = {Elsevier Ltd},

abstract = {Background: Trichomonas vaginalis is the etiologic agent of trichomoniasis, the most common nonviral sexually transmitted disease in the world. This infection affects millions of individuals worldwide annually. Although direct sexual contact is the most common mode of transmission, increasing evidence indicates that T. vaginalis can survive in the external environment and can be transmitted by contaminated utensils. We found that the growth of T. vaginalis under cold conditions is greatly inhibited, but recovers after placing these stressed cells at the normal cultivation temperature of 37°C. However, the mechanisms by which T. vaginalis regulates this adaptive process are unclear. Methods: An expressed sequence tag (EST) database generated from a complementary DNA library of T. vaginalis messenger RNAs expressed under cold-culture conditions (4°C, TvC) was compared with a previously published normal-cultured EST library (37°C, TvE) to assess the cold-stress responses of T. vaginalis. Results: A total of 9780 clones were sequenced from the TvC library and were mapped to 2934 genes in the T. vaginalis genome. A total of 1254 genes were expressed in both the TvE and TvC libraries, and 1680 genes were only found in the TvC library. A functional analysis showed that cold temperature has effects on many cellular mechanisms, including increased H2O2 tolerance, activation of the ubiquitin-proteasome system, induction of iron-sulfur cluster assembly, and reduced energy metabolism and enzyme expression. Conclusion: The current study is the first large-scale transcriptomic analysis in cold-stressed T. vaginalis and the results enhance our understanding of this important protist. © 2014 Taiwan Society of Microbiology.},

note = {cited By 13},

keywords = {Base Sequence; Cold-Shock Response; DNA, development and aging; human; metabolism; microbiology; nucleotide sequence; ubiquitination; vaginal trichomoniasis, DNA; Trichomonas vaginalis; Trichomonas Vaginitis; Ubiquitination, hydrogen peroxide; iron; messenger RNA; proteasome; sulfur; ubiquitin; hydrogen peroxide; protozoal DNA, Protozoan; Energy Metabolism; Expressed Sequence Tags; Female; Gene Library; Humans; Hydrogen Peroxide; Sequence Analysis},

pubstate = {published},

tppubtype = {article}

}

@article{Huang20156891,

title = {Novel insights into the molecular events linking to cell death induced by tetracycline in the amitochondriate protozoan Trichomonas vaginalis},

author = {K. -Y. Huang and F. -M. Ku and W. -H. Cheng and C. -C. Lee and P. -J. Huang and L. J. Chu and C. -C. Cheng and Y. -K. Fang and H. -H. Wu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84946210816&doi=10.1128%2fAAC.01779-15&partnerID=40&md5=35f02395ead3757c7245e3e945183c7c},

doi = {10.1128/AAC.01779-15},

issn = {00664804},

year  = {2015},

date = {2015-01-01},

journal = {Antimicrobial Agents and Chemotherapy},

volume = {59},

number = {11},

pages = {6891-6903},

publisher = {American Society for Microbiology},

abstract = {Trichomonas vaginalis colonizes the human urogenital tract and causes trichomoniasis, the most common nonviral sexually transmitted disease. Currently, 5-nitroimidazoles are the only recommended drugs for treating trichomoniasis. However, increased resistance of the parasite to 5-nitroimidazoles has emerged as a highly problematic public health issue. Hence, it is essential to identify alternative chemotherapeutic agents against refractory trichomoniasis. Tetracycline (TET) is a broad-spectrum antibiotic with activity against several protozoan parasites, but the mode of action of TET in parasites remains poorly understood. The in vitro effect of TET on the growth of T. vaginalis was examined, and the mode of cell death was verified by various apoptosis-related assays. Next-generation sequencing-based RNA sequencing (RNA-seq) was employed to elucidate the transcriptome of T. vaginalis in response to TET. We show that TET has a cytotoxic effect on both metronidazole (MTZ)-sensitive and - resistant T. vaginalis isolates, inducing some features resembling apoptosis. RNA-seq data reveal that TET significantly alters the transcriptome via activation of specific pathways, such as aminoacyl-tRNA synthetases and carbohydrate metabolism. Functional analyses demonstrate that TET disrupts the hydrogenosomal membrane potential and antioxidant system, which concomitantly elicits a metabolic shift toward glycolysis, suggesting that the hydrogenosomal function is impaired and triggers cell death. Collectively, we provide in vitro evidence that TET is a potential alternative therapeutic choice for treating MTZ-resistant T. vaginalis. The in-depth transcriptomic signatures in T. vaginalis upon TET treatment presented here will shed light on the signaling pathways linking to cell death in amitochondriate organisms. Copyright © 2015, American Society for Microbiology. All Rights Reserved.},

note = {cited By 5},

keywords = {amino acid transfer RNA ligase; carbohydrate; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide dehydrogenase; tetracycline; transcriptome; antitrichomonal agent; tetracycline, Antitrichomonal Agents; Cell Death; Glycolysis; High-Throughput Nucleotide Sequencing; Tetracycline; Trichomonas vaginalis},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2015,

title = {Is the whole greater than the sum of its parts? De novo assembly strategies for bacterial genomes based on paired-end sequencing},

author = {T. -W. Chen and R. -C. Gan and Y. -F. Chang and W. -C. Liao and T. H. Wu and C. -C. Lee and P. -J. Huang and C. -Y. Lee and Y. -Y. M. Chen and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84940042756&doi=10.1186%2fs12864-015-1859-8&partnerID=40&md5=72532f8b41c9e5d2d2321e96806488d0},

doi = {10.1186/s12864-015-1859-8},

issn = {14712164},

year  = {2015},

date = {2015-01-01},

journal = {BMC Genomics},

volume = {16},

number = {1},

publisher = {BioMed Central Ltd.},

abstract = {Background: Whole genome sequence construction is becoming increasingly feasible because of advances in next generation sequencing (NGS), including increasing throughput and read length. By simply overlapping paired-end reads, we can obtain longer reads with higher accuracy, which can facilitate the assembly process. However, the influences of different library sizes and assembly methods on paired-end sequencing-based de novo assembly remain poorly understood. Results: We used 250 bp Illumina Miseq paired-end reads of different library sizes generated from genomic DNA from Escherichia coli DH1 and Streptococcus parasanguinis FW213 to compare the assembly results of different library sizes and assembly approaches. Our data indicate that overlapping paired-end reads can increase read accuracy but sometimes cause insertion or deletions. Regarding genome assembly, merged reads only outcompete original paired-end reads when coverage depth is low, and larger libraries tend to yield better assembly results. These results imply that distance information is the most critical factor during assembly. Our results also indicate that when depth is sufficiently high, assembly from subsets can sometimes produce better results. Conclusions: In summary, this study provides systematic evaluations of de novo assembly from paired end sequencing data. Among the assembly strategies, we find that overlapping paired-end reads is not always beneficial for bacteria genome assembly and should be avoided or used with caution especially for genomes containing high fraction of repetitive sequences. Because increasing numbers of projects aim at bacteria genome sequencing, our study provides valuable suggestions for the field of genomic sequence construction. © 2015 Chen et al.},

note = {cited By 4},

keywords = {Bacteria (microorganisms); Escherichia coli; Streptococcus parasanguinis, Bacterial; Genome, Bacterial; High-Throughput Nucleotide Sequencing; INDEL Mutation; Reference Standards; Streptococcus, Base Pair Mismatch; Base Pairing; Contig Mapping; Escherichia coli; Gene Library; Genes, genomic DNA},

pubstate = {published},

tppubtype = {article}

}

@article{Cheng2015,

title = {Nitric oxide maintains cell survival of Trichomonas vaginalis upon iron depletion},

author = {W. -H. Cheng and K. -Y. Huang and P. -J. Huang and J. -H. Hsu and Y. -K. Fang and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84937893919&doi=10.1186%2fs13071-015-1000-5&partnerID=40&md5=a00ff36da5f093c2b00748ac6135d464},

doi = {10.1186/s13071-015-1000-5},

issn = {17563305},

year  = {2015},

date = {2015-01-01},

journal = {Parasites and Vectors},

volume = {8},

number = {1},

publisher = {BioMed Central Ltd.},

abstract = {Background: Iron plays a pivotal role in the pathogenesis of Trichomonas vaginalis, the causative agent of highly prevalent human trichomoniasis. T. vaginalis resides in the vaginal region, where the iron concentration is constantly changing. Hence, T. vaginalis must adapt to variations in iron availability to establish and maintain an infection. The free radical signaling molecules reactive oxygen species (ROS) and reactive nitrogen species (RNS) have been proven to participate in iron deficiency in eukaryotes. However, little is known about the roles of these molecules in iron-deficient T. vaginalis. Methods: T. vaginalis cultured in iron-rich and-deficient conditions were collected for all experiments in this study. Next generation RNA sequencing was conducted to investigate the impact of iron on transcriptome of T. vaginalis. The cell viabilities were monitored after the trophozoites treated with the inhibitors of nitric oxide (NO) synthase (L-NG-monomethyl arginine, L-NMMA) and proteasome (MG132). Hydrogenosomal membrane potential was measured using JC-1 staining. Results: We demonstrated that NO rather than ROS accumulates in iron-deficient T. vaginalis. The level of NO was blocked by MG132 and L-NMMA, indicating that NO production is through a proteasome and arginine dependent pathway. We found that the inhibition of proteasome activity shortened the survival of iron-deficient cells compared with untreated iron-deficient cells. Surprisingly, the addition of arginine restored both NO level and the survival of proteasome-inhibited cells, suggesting that proteasome-derived NO is crucial for cell survival under iron-limited conditions. Additionally, NO maintains the hydrogenosomal membrane potential, a determinant for cell survival, emphasizing the cytoprotective effect of NO on iron-deficient T. vaginalis. Collectively, we determined that NO produced by the proteasome prolonged the survival of iron-deficient T. vaginalis via maintenance of the hydrogenosomal functions. Conclusion: The findings in this study provide a novel role of NO in adaptation to iron-deficient stress in T. vaginalis and shed light on a potential therapeutic strategy for trichomoniasis. © 2015 Cheng et al.},

note = {cited By 10},

keywords = {1', 3, 3'-tetraethylbenzimidazolocarbocyanine; benzimidazole derivative; benzyloxycarbonylleucyl-leucyl-leucine aldehyde; carbocyanine; enzyme inhibitor; iron; leupeptin; n(g) methylarginine; nitric oxide; nitric oxide synthase; protozoal protein; reactive oxygen metabolite; transcriptome, 5', 6, 6'-tetrachloro-1, Adaptation, arginine; benzyloxycarbonylleucylleucylleucinal; iron; n(g) methylarginine; nitric oxide; proteasome; reactive nitrogen species; reactive oxygen metabolite; transcriptome; 5, Biological; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Protozoan Proteins; Reactive Oxygen Species; Sequence Analysis, Physiological; Animals; Base Sequence; Benzimidazoles; Carbocyanines; Cell Survival; Enzyme Inhibitors; High-Throughput Nucleotide Sequencing; Humans; Iron; Leupeptins; Models, RNA; Transcriptome; Trichomonas Infections; Trichomonas vaginalis},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2015D849,

title = {CMPD: Cancer mutant proteome database},

author = {P. -J. Huang and C. -C. Lee and B. C. -M. Tan and Y. -M. Yeh and L. J. Chu and T. -W. Chen and K. -P. Chang and C. -Y. Lee and R. -C. Gan and H. Liu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84946093959&doi=10.1093%2fnar%2fgku1182&partnerID=40&md5=e9f054780369a9855f45e1efd21754bf},

doi = {10.1093/nar/gku1182},

issn = {03051048},

year  = {2015},

date = {2015-01-01},

journal = {Nucleic Acids Research},

volume = {43},

number = {D1},

pages = {D849-D855},

publisher = {Oxford University Press},

abstract = {Whole-exome sequencing, which centres on the protein coding regions of disease/cancer associated genes, represents the most cost-effective method to-date for deciphering the association between genetic alterations and diseases. Large-scale whole exome/genome sequencing projects have been launched by various institutions, such as NCI, Broad Institute and TCGA, to provide a comprehensive catalogue of coding variants in diverse tissue samples and cell lines. Further functional and clinical interrogation of these sequence variations must rely on extensive cross-platforms integration of sequencing information and a proteome database that explicitly and comprehensively archives the corresponding mutated peptide sequences. While such data resource is a critical for the mass spectrometrybased proteomic analysis of exomic variants, no database is currently available for the collection of mutant protein sequences that correspond to recent large-scale genomic data. To address this issue and serve as bridge to integrate genomic and proteomics datasets, CMPD (http://cgbc.cgu.edu.tw/cmpd) collected over 2 millions genetic alterations, which not only facilitates the confirmation and examination of potential cancer biomarkers but also provides an invaluable resource for translational medicine research and opportunities to identify mutated proteins encoded by mutated genes. © The Author(s) 2014.},

note = {cited By 7},

keywords = {Cell Line, mutant protein; proteome; tumor protein, Protein; Humans; Internet; Mutant Proteins; Mutation; Neoplasm Proteins; Neoplasms; Proteome, Tumor; Databases},

pubstate = {published},

tppubtype = {article}

}

@article{Chen201518066,

title = {Ultra-deep targeted sequencing of advanced oral squamous cell carcinoma identifies a mutation-based prognostic gene signature},

author = {S. -J. Chen and H. Liu and C. -T. Liao and P. -J. Huang and Y. Huang and A. Hsu and P. Tang and Y. -S. Chang and H. -C. Chenx and T. -C. Yen},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84938613758&doi=10.18632%2foncotarget.3768&partnerID=40&md5=e401b9db26d05a7c7dea4e6761bcb03b},

doi = {10.18632/oncotarget.3768},

issn = {19492553},

year  = {2015},

date = {2015-01-01},

journal = {Oncotarget},

volume = {6},

number = {20},

pages = {18066-18080},

publisher = {Impact Journals LLC},

abstract = {Background: Patients with advanced oral squamous cell carcinoma (OSCC) have heterogeneous outcomes that limit the implementation of tailored treatment options. Genetic markers for improved prognostic stratification are eagerly awaited. Methods: Herein, next-generation sequencing (NGS) was performed in 345 formalin-fixed paraffin-embedded (FFPE) samples obtained from advanced OSCC patients. Genetic mutations on the hotspot regions of 45 cancer-related genes were detected using an ultra-deep (>1000×) sequencing approach. Kaplan-Meier plots and Cox regression analyses were used to investigate the associations between the mutation status and disease-free survival (DFS). Results: We identified 1269 non-synonymous mutations in 276 OSCC samples. TP53, PIK3CA, CDKN2A, HRAS and BRAF were the most frequently mutated genes. Mutations in 14 genes were found to predict DFS. A mutation-based signature affecting ten genes (HRAS, BRAF, FGFR3, SMAD4, KIT, PTEN, NOTCH1, AKT1, CTNNB1, and PTPN11) was devised to predict DFS. Two different resampling methods were used to validate the prognostic value of the identified gene signature. Multivariate analysis demonstrated that presence of a mutated gene signature was an independent predictor of poorer DFS (P = 0.005). Conclusions: Genetic variants identified by NGS technology in FFPE samples are clinically useful to predict prognosis in advanced OSCC patients.},

note = {cited By 37},

keywords = {4, 5 trisphosphate 3 phosphatase; protein p53; protein tyrosine phosphatase SHP 2; Smad4 protein; tumor marker, Adult; Aged; Biomarkers, B Raf kinase; cyclin dependent kinase inhibitor 2A; fibroblast growth factor receptor 3; Notch1 receptor; phosphatidylinositol 3, Tumor; Carcinoma},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2015167,

title = {Vanno: A visualization-aided variant annotation tool},

author = {P. -J. Huang and C. -C. Lee and B. C. -M. Tan and Y. -M. Yeh and K. -Y. Huang and R. -C. Gan and T. -W. Chen and C. -Y. Lee and S. -T. Yang and C. -S. Liao and H. Liu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84922064553&doi=10.1002%2fhumu.22684&partnerID=40&md5=d975e35adca614c5a25415fe2b663066},

doi = {10.1002/humu.22684},

issn = {10597794},

year  = {2015},

date = {2015-01-01},

journal = {Human Mutation},

volume = {36},

number = {2},

pages = {167-174},

publisher = {John Wiley and Sons Inc.},

abstract = {Next-generation sequencing (NGS) technologies have revolutionized the field of genetics and are trending toward clinical diagnostics. Exome and targeted sequencing in a disease context represent a major NGS clinical application, considering its utility and cost-effectiveness. With the ongoing discovery of disease-associated genes, various gene panels have been launched for both basic research and diagnostic tests. However, the fundamental inconsistencies among the diverse annotation sources, software packages, and data formats have complicated the subsequent analysis. To manage disease-associated NGS data, we developed Vanno, a Web-based application for in-depth analysis and rapid evaluation of disease-causative genome sequence alterations. Vanno integrates information from biomedical databases, functional predictions from available evaluation models, and mutation landscapes from TCGA cancer types. A highly integrated framework that incorporates filtering, sorting, clustering, and visual analytic modules is provided to facilitate exploration of oncogenomics datasets at different levels, such as gene, variant, protein domain, or three-dimensional structure. Such design is crucial for the extraction of knowledge from sequence alterations and translating biological insights into clinical applications. Taken together, Vanno supports almost all disease-associated gene tests and exome sequencing panels designed for NGS, providing a complete solution for targeted and exome sequencing analysis. Vanno is freely available at http://cgts.cgu.edu.tw/vanno. © 2014 WILEY PERIODICALS, INC.},

note = {cited By 4},

keywords = {Data Curation; Exome; Genome, DNA; Software, Human; Genomics; High-Throughput Nucleotide Sequencing; Humans; Molecular Sequence Annotation; Sequence Analysis},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2014,

title = {ChIPseek, a web-based analysis tool for ChIP data},

author = {T. -W. Chen and H. -P. Li and C. -C. Lee and R. -C. Gan and P. -J. Huang and T. H. Wu and C. -Y. Lee and Y. -F. Chang and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84903342803&doi=10.1186%2f1471-2164-15-539&partnerID=40&md5=22672dd8f3a676f7e64a92ad424761a0},

doi = {10.1186/1471-2164-15-539},

issn = {14712164},

year  = {2014},

date = {2014-01-01},

journal = {BMC Genomics},

volume = {15},

number = {1},

publisher = {BioMed Central Ltd.},

abstract = {Background: Chromatin is a dynamic but highly regulated structure. DNA-binding proteins such as transcription factors, epigenetic and chromatin modifiers are responsible for regulating specific gene expression pattern and may result in different phenotypes. To reveal the identity of the proteins associated with the specific region on DNA, chromatin immunoprecipitation (ChIP) is the most widely used technique. ChIP assay followed by next generation sequencing (ChIP-seq) or microarray (ChIP-chip) is often used to study patterns of protein-binding profiles in different cell types and in cancer samples on a genome-wide scale. However, only a limited number of bioinformatics tools are available for ChIP datasets analysis.Results: We present ChIPseek, a web-based tool for ChIP data analysis providing summary statistics in graphs and offering several commonly demanded analyses. ChIPseek can provide statistical summary of the dataset including histogram of peak length distribution, histogram of distances to the nearest transcription start site (TSS), and pie chart (or bar chart) of genomic locations for users to have a comprehensive view on the dataset for further analysis. For examining the potential functions of peaks, ChIPseek provides peak annotation, visualization of peak genomic location, motif identification, sequence extraction, and comparison between datasets. Beyond that, ChIPseek also offers users the flexibility to filter peaks and re-analyze the filtered subset of peaks. ChIPseek supports 20 different genome assemblies for 12 model organisms including human, mouse, rat, worm, fly, frog, zebrafish, chicken, yeast, fission yeast, Arabidopsis, and rice. We use demo datasets to demonstrate the usage and intuitive user interface of ChIPseek.Conclusions: ChIPseek provides a user-friendly interface for biologists to analyze large-scale ChIP data without requiring any programing skills. All the results and figures produced by ChIPseek can be downloaded for further analysis. The analysis tools built into ChIPseek, especially the ones for selecting and examine a subset of peaks from ChIP data, provides invaluable helps for exploring the high through-put data from either ChIP-seq or ChIP-chip. ChIPseek is freely available at http://chipseek.cgu.edu.tw. © 2014 Chen et al.; licensee BioMed Central Ltd.},

note = {cited By 45},

keywords = {activating transcription factor 2; activating transcription factor 3; transcription factor Ets 1; transcription factor GATA 1, Animals; Chromatin Immunoprecipitation; Computational Biology; Genomics; High-Throughput Nucleotide Sequencing; Humans; Software; Web Browser, Arabidopsis; Danio rerio; Rattus; Rhacophorus; Schizosaccharomycetaceae},

pubstate = {published},

tppubtype = {article}

}

@article{Huang20131340,

title = {CPAP: Cancer panel analysis pipeline},

author = {P. -J. Huang and Y. -M. Yeh and R. -C. Gan and C. -C. Lee and T. -W. Chen and C. -Y. Lee and H. Liu and S. -J. Chen and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84884532707&doi=10.1002%2fhumu.22386&partnerID=40&md5=76fe590e5c4e08ac19172d34d42dabba},

doi = {10.1002/humu.22386},

issn = {10597794},

year  = {2013},

date = {2013-01-01},

journal = {Human Mutation},

volume = {34},

number = {10},

pages = {1340-1346},

abstract = {Targeted sequencing using next-generation sequencing technologies is currently being rapidly adopted for clinical sequencing and cancer marker tests. However, no existing bioinformatics tool is available for the analysis and visualization of multiple targeted sequencing datasets. In the present study, we use cancer panel targeted sequencing datasets generated by the Life Technologies Ion Personal Genome Machine Sequencer as an example to illustrate how to develop an automated pipeline for the comparative analyses of multiple datasets. Cancer Panel Analysis Pipeline (CPAP) uses standard output files from variant calling software to generate a distribution map of SNPs among all of the samples in a circular diagram generated by Circos. The diagram is hyperlinked to a dynamic HTML table that allows the users to identify target SNPs by using different filters. CPAP also integrates additional information about the identified SNPs by linking to an integrated SQL database compiled from SNP-related databases, including dbSNP, 1000 Genomes Project, COSMIC, and dbNSFP. CPAP only takes 17 min to complete a comparative analysis of 500 datasets. CPAP not only provides an automated platform for the analysis of multiple cancer panel datasets but can also serve as a model for any customized targeted sequencing project. © 2013 Wiley Periodicals, Inc.},

note = {cited By 3},

keywords = {Biological; Web Browser, cancer panel; Circos; ion torrent; target sequencing, Computational Biology; Databases, Genetic; Humans; Neoplasms; Software; Tumor Markers},

pubstate = {published},

tppubtype = {article}

}

@article{Hackenberg2013109,

title = {A Comprehensive expression profile of micrornas and other classes of non-coding small RNAs in barley under phosphorous-deficient and-sufficient conditions},

author = {M. Hackenberg and P. -J. Huang and C. -Y. Huang and B. -J. Shi and P. Gustafson and P. Langridge},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84879176878&doi=10.1093%2fdnares%2fdss037&partnerID=40&md5=b40fd11b3793b389141fecaaf1bc7e6c},

doi = {10.1093/dnares/dss037},

issn = {13402838},

year  = {2013},

date = {2013-01-01},

journal = {DNA Research},

volume = {20},

number = {2},

pages = {109-125},

abstract = {Phosphorus (P) is essential for plant growth. MicroRNAs (miRNAs) play a key role in phosphate homeostasis. However, little is known about P effect on miRNA expression in barley (Hordeum vulgare L.). In this study, we used Illumina's next-generation sequencing technology to sequence small RNAs (sRNAs) in barley grown under P-deficient and P-sufficient conditions. We identified 221 conserved miRNAs and 12 novel miRNAs, of which 55 were only present in P-deficient treatment while 32 only existed in P-sufficient treatment. Total 47 miRNAs were significantly differentially expressed between the two P treatments (jlog2j > 1). We also identified many other classes of sRNAs, including sense and antisense sRNAs, repeat-associated sRNAs, transfer RNA (tRNA)-derived sRNAs and chloroplast-derived sRNAs, and some of which were also significantly differentially expressed between the two P treatments. Of all the sRNAs identified, antisense sRNAs were the most abundant sRNA class in both P treatments. Surprisingly, about one-fourth of sRNAs were derived from the chloroplast genome, and a chloroplastencoded tRNA-derived sRNA was the most abundant sRNA of all the sRNAs sequenced. Our data provide valuable clues for understanding the properties of sRNAs and new insights into the potential roles of miRNAs and other classes of sRNAs in the control of phosphate homeostasis. © The Author 2012.},

note = {cited By 67},

keywords = {Base Sequence; Gene Expression Regulation, Chloroplast; Hordeum; MicroRNAs; Phosphorus; RNA, Hordeum; Hordeum vulgare subsp. vulgare, microRNA; phosphorus; RNA induced silencing complex; small interfering RNA; transfer RNA, Plant; Genome, Plant; RNA, RNA; Transcriptome, Small Untranslated; Sequence Analysis},

pubstate = {published},

tppubtype = {article}

}

@article{Huang201360,

title = {Functional profiling of the Tritrichomonas foetus transcriptome and proteome},

author = {K. -Y. Huang and J. -W. Shin and P. -J. Huang and F. -M. Ku and W. -C. Lin and R. Lin and W. -M. Hsu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84873300752&doi=10.1016%2fj.molbiopara.2012.12.001&partnerID=40&md5=3d7c67beac54bc68da0563a156eb09ea},

doi = {10.1016/j.molbiopara.2012.12.001},

issn = {01666851},

year  = {2013},

date = {2013-01-01},

journal = {Molecular and Biochemical Parasitology},

volume = {187},

number = {1},

pages = {60-71},

abstract = {Tritrichomonas foetus is a potent veterinary pathogen, causing bovine and feline trichomoniasis. The principal clinical manifestation of infection in cattle is inflammation of the genital tract and infertility. In feline, the parasite causes large-bowel disease resulting in chronic diarrhea. In contrast to other well-studied protozoan, genetic data regarding the molecular characterization and expression in T. foetus is far less understood. In this study, the first large-scale T. foetus expressed sequence tag (TfEST) project was conducted on 5064 randomly selected EST clones from a non-normalized unidirectional Tf30924 cDNA library. Assembling of 5064 single-pass sequences from the 5′ end resulted in 713 contigs and 1961 singlets. BLAST search revealed that 53.52% of the unigenes showed significant similarity to known sequences or protein motifs/domains. Functional classifications indicated that most of the unigenes are involved in translation, ribosomal structure and ribosome biogenesis. The average GC content of the T. foetus transcriptome is 40.93%. Intriguingly, only 31.29% of the unigenes contain the classical AAUAAA polyadenylation signal sequence at the 3′-UTR region. Furthermore, a panel of potential chemotherapeutic targets was also identified for the first time in T. foetus. The protein expression levels were verified by using two-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. A total of 68 highly abundant protein spots were successfully identified in the reference 2-DE map based on our T. foetus-specific protein database. The EST dataset and the reference 2-DE map established in the present study will provide a foundation for future whole genome sequencing project and comparative transcriptomic/proteomic analyses to provide potential drug targets against T. foetus infection. © 2012 Elsevier B.V.},

note = {cited By 12},

keywords = {article; expressed sequence tag; matrix assisted laser desorption ionization time of flight mass spectrometry; nonhuman; priority journal; protein domain; protein expression; protein motif; ribosome; Tritrichomonas foetus; two dimensional electrophoresis, complementary DNA; proteome; transcriptome, Electrophoresis, Gel, Mass, Matrix-Assisted Laser Desorption-Ionization; Transcriptome; Tritrichomonas foetus, Two-Dimensional; Expressed Sequence Tags; Proteome; Protozoan Proteins; Spectrometry},

pubstate = {published},

tppubtype = {article}

}

@article{Huang20123900,

title = {Comparative transcriptomic and proteomic analyses of Trichomonas vaginalis following adherence to fibronectin},

author = {K-Y. Huang and P. -J. Huang and F. -M. Ku and R. Lin and J. F. Alderete and P. Tanga},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84867615951&doi=10.1128%2fIAI.00611-12&partnerID=40&md5=9ea1cc7a4bea8c489b9183b798b74289},

doi = {10.1128/IAI.00611-12},

issn = {00199567},

year  = {2012},

date = {2012-01-01},

journal = {Infection and Immunity},

volume = {80},

number = {11},

pages = {3900-3911},

abstract = {The morphological transformation of Trichomonas vaginalis from an ellipsoid form in batch culture to an adherent amoeboid form results from the contact of parasites with vaginal epithelial cells and with immobilized fibronectin (FN), a basement membrane component. This suggests host signaling of the parasite. We applied integrated transcriptomic and proteomic approaches to investigate the molecular responses of T. vaginalis upon binding to FN. A transcriptome analysis was performed by using large-scale expressed-sequence-tag (EST) sequencing. A total of 20,704 ESTs generated from batch culture (trophozoite-EST) versus FN-amoeboid trichomonad (FN-EST) cDNA libraries were analyzed. The FN-EST library revealed decreased amounts of transcripts that were of lower abundance in the trophozoite-EST library. There was a shift by FN-bound organisms to the expression of transcripts encoding essential proteins, possibly indicating the expression of genes for adaptation to the morphological changes needed for the FN-adhesive processes. In addition, we identified 43 differentially expressed proteins in the proteomes of FN-bound and unbound trichomonads. Among these proteins, cysteine peptidase, glyceraldehyde-3-phosphate dehydrogenase (an FN-binding protein), and stress-related proteins were upregulated in the FN-adherent cells. Stress-related genes and proteins were highly expressed in both the transcriptome and proteome of FN-bound organisms, implying that these genes and proteins may play critical roles in the response to adherence. This is the first report of a comparative proteomic and transcriptomic analysis after the binding of T. vaginalis to FN. This approach may lead to the discovery of novel virulence genes and affirm the role of genes involved in disease pathogenesis. This knowledge will permit a greater understanding of the complex host-parasite interplay. © 2012, American Society for Microbiology.},

note = {cited By 27},

keywords = {article; cell adhesion; gene expression profiling; gene library; nonhuman; priority journal; protein binding; protein expression; proteomics; sequence analysis; transcriptomics; Trichomonas vaginalis; trophozoite; upregulation, Cell Adhesion; Electrophoresis, complementary DNA; cysteine proteinase; fibronectin; glyceraldehyde 3 phosphate; glyceraldehyde 3 phosphate dehydrogenase; heat shock protein, Gel, Messenger; Signal Transduction; Transcriptome; Trichomonas vaginalis, Two-Dimensional; Fibronectins; Gene Expression Profiling; Mass Spectrometry; Proteome; Proteomics; Protozoan Proteins; Real-Time Polymerase Chain Reaction; RNA},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2012101,

title = {Identification of putative miRNAs from the deep-branching unicellular flagellates},

author = {P. -J. Huang and W. -C. Lin and S. -C. Chen and Y. -H. Lin and C. -H. Sun and P. -C. Lyu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84856467364&doi=10.1016%2fj.ygeno.2011.11.002&partnerID=40&md5=5d802d8ceb2c5f478016ce37e4b904e1},

doi = {10.1016/j.ygeno.2011.11.002},

issn = {08887543},

year  = {2012},

date = {2012-01-01},

journal = {Genomics},

volume = {99},

number = {2},

pages = {101-107},

abstract = {MicroRNAs (miRNAs) are a class of extensively studied RNAi-associated small RNAs that play a critical role in eukaryotic gene regulation. However, knowledge on the miRNA and its regulation in unicellular eukaryotes is very limited. In order to obtain a better understanding on the origin of miRNA regulation system, we used deep-sequencing technology to investigate the miRNA expression pattern in four deep-branching unicellular flagellates: Giardia lamblia, Trichomonas vaginalis, Tritrichomonas foetus, and Pentatrichomonas hominis. In addition to the known miRNAs that have been described in G. lamblia and T. vaginalis, we identified 14 ancient animal miRNA families and 13 plant-specific families. Bioinformatics analysis also identified four novel miRNA candidates with reliable precursor structures derived from mature tRNAs. Our results indicated that miRNAs are likely to be a general feature for gene regulation throughout unicellular and multicellular eukaryotes and some of them may derive from unconventional ncRNAs such as snoRNA and tRNA. © 2011 Elsevier Inc.},

note = {cited By 29},

keywords = {Animalia; Eukaryota; Giardia intestinalis; Mastigophora (flagellates); Pentatrichomonas hominis; Protista; Trichomonas vaginalis; Tritrichomonas foetus, article; bioinformatics; controlled study; flagellate; gene control; gene expression profiling; Giardia lamblia; high throughput sequencing; nonhuman; priority journal; reverse transcription polymerase chain reaction; trichomonas hominis; Trichomonas vaginalis; Tritrichomonas foetus; trophozoite, Chromosome Mapping; Gene Expression Profiling; Giardia lamblia; High-Throughput Nucleotide Sequencing; MicroRNAs; Real-Time Polymerase Chain Reaction; RNA, DNA; Trichomonadida, microRNA, Protozoan; Sequence Analysis},

pubstate = {published},

tppubtype = {article}

}

@article{Chen2012,

title = {FastAnnotator--an efficient transcript annotation web tool.},

author = {T. W. Chen and R. C. Gan and T. H. Wu and P. J. Huang and C. Y. Lee and Y. Y. Chen and C. C. Chen and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84878804125&partnerID=40&md5=bcb1de3116f33ddc53ca741a32d393e9},

issn = {14712164},

year  = {2012},

date = {2012-01-01},

journal = {BMC genomics},

volume = {13 Suppl 7},

abstract = {Recent developments in high-throughput sequencing (HTS) technologies have made it feasible to sequence the complete transcriptomes of non-model organisms or metatranscriptomes from environmental samples. The challenge after generating hundreds of millions of sequences is to annotate these transcripts and classify the transcripts based on their putative functions. Because many biological scientists lack the knowledge to install Linux-based software packages or maintain databases used for transcript annotation, we developed an automatic annotation tool with an easy-to-use interface. To elucidate the potential functions of gene transcripts, we integrated well-established annotation tools: Blast2GO, PRIAM and RPS BLAST in a web-based service, FastAnnotator, which can assign Gene Ontology (GO) terms, Enzyme Commission numbers (EC numbers) and functional domains to query sequences. Using six transcriptome sequence datasets as examples, we demonstrated the ability of FastAnnotator to assign functional annotations. FastAnnotator annotated 88.1% and 81.3% of the transcripts from the well-studied organisms Caenorhabditis elegans and Streptococcus parasanguinis, respectively. Furthermore, FastAnnotator annotated 62.9%, 20.4%, 53.1% and 42.0% of the sequences from the transcriptomes of sweet potato, clam, amoeba, and Trichomonas vaginalis, respectively, which lack reference genomes. We demonstrated that FastAnnotator can complete the annotation process in a reasonable amount of time and is suitable for the annotation of transcriptomes from model organisms or organisms for which annotated reference genomes are not avaiable. The sequencing process no longer represents the bottleneck in the study of genomics, and automatic annotation tools have become invaluable as the annotation procedure has become the limiting step. We present FastAnnotator, which was an automated annotation web tool designed to efficiently annotate sequences with their gene functions, enzyme functions or domains. FastAnnotator is useful in transcriptome studies and especially for those focusing on non-model organisms or metatranscriptomes. FastAnnotator does not require local installation and is freely available at http://fastannotator.cgu.edu.tw.},

note = {cited By 48},

keywords = {animal; article; bacterial genome; Caenorhabditis elegans; computer interface; computer program; genetic database; genetics; genome; Internet; nucleotide sequence; Streptococcus, Animals; Base Sequence; Caenorhabditis elegans; Databases, Bacterial; Internet; Software; Streptococcus; Transcriptome; User-Computer Interface, Genetic; Genome; Genome, transcriptome},

pubstate = {published},

tppubtype = {article}

}

@article{Horváthová20121017,

title = {Transcriptomic identification of iron-regulated and iron-independent gene copies within the heavily duplicated trichomonas vaginalis genome},

author = {L. Horváthová and L. Šafaříková and M. Basler and I. Hrdý and N. B. Campo and J. -W. Shin and K. -Y. Huang and P. -J. Huang and R. Lin and P. Tang and J. Tachezy},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84875084049&doi=10.1093%2fgbe%2fevs078&partnerID=40&md5=99662b4e39519260c2c537530e9c6be3},

doi = {10.1093/gbe/evs078},

issn = {17596653},

year  = {2012},

date = {2012-01-01},

journal = {Genome Biology and Evolution},

volume = {4},

number = {10},

pages = {1017-1029},

publisher = {Oxford University Press},

abstract = {Gene duplication is an important evolutionary mechanism and no eukaryote has more duplicated gene families than the parasitic protist Trichomonas vaginalis. Iron is an essential nutrient for Trichomonas and plays a pivotal role in the establishment of infection, proliferation, and virulence. To gain insight into the role of iron in T. vaginalis gene expression and genome evolution, we screened iron-regulated genes using an oligonucleotide microarray for T. vaginalis and by comparative EST (expressed sequence tag) sequencing of cDNA libraries derived from trichomonads cultivated under iron-rich (+Fe) and iron-restricted (-Fe) conditions. Among 19,000 ESTs from both libraries, we identified 336 iron-regulated genes, of which 165 were upregulated under +Fe conditions and 171 under -Fe conditions. The microarray analysis revealed that 195 of 4,950 unique genes were differentially expressed. Of these, 117 genes were upregulated under +Fe conditions and 78 were upregulated under -Fe conditions. The results of both methods were congruent concerning the regulatory trends and the representation of gene categories. Under +Fe conditions, the expression of proteins involved in carbohydrate metabolism, particularly in the energy metabolism of hydrogenosomes, and in methionine catabolism was increased. The iron-sulfur cluster assembly machinery and certain cysteine proteases are of particular importance among the proteins upregulated under -Fe conditions. A unique feature of the T. vaginalis genome is the retention during evolution of multiple paralogous copies for a majority of all genes. Although the origins and reasons for this gene expansion remain unclear, the retention of multiple gene copies could provide an opportunity to evolve differential expression during growth in variable environmental conditions. For genes whose expression was affected by iron, we found that iron influenced the expression of only some of the paralogous copies, whereas the expression of the other paralogs was iron independent. This finding indicates a very stringent regulation of the differentially expressed paralogous genes in response to changes in the availability of exogenous nutrients and provides insight into the evolutionary rationale underlying massive paralog retention in the Trichomonas genome. © 2012 The Author(s).},

note = {cited By 45},

keywords = {article; DNA microarray; expressed sequence tag; gene; gene dosage; gene duplication; gene expression regulation; gene library; genetics; genome; glycolysis; metabolism; molecular evolution; Trichomonas vaginalis, Cysteine Proteases; Evolution, cysteine proteinase; iron; iron sulfur protein; transcriptome, Eukaryota; Protista; Trichomonadida; Trichomonas; Trichomonas vaginalis, Molecular; Expressed Sequence Tags; Gene Dosage; Gene Duplication; Gene Expression Regulation; Gene Library; Genes, Protozoan; Genome, Protozoan; Glycolysis; Iron; Iron-Sulfur Proteins; Oligonucleotide Array Sequence Analysis; Transcriptome; Trichomonas vaginalis},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2010,

title = {DSAP: Deep-sequencing small RNA analysis pipeline},

author = {P. -J. Huang and Y. -C. Liu and C. -C. Lee and W. -C. Lin and R. R. -C. Gan and P. -C. Lyu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77954304695&doi=10.1093%2fnar%2fgkq392&partnerID=40&md5=611eab287d6ef4cd8eaf15e7a371405b},

doi = {10.1093/nar/gkq392},

issn = {03051048},

year  = {2010},

date = {2010-01-01},

journal = {Nucleic Acids Research},

volume = {38},

number = {SUPPL. 2},

pages = {W385-W391},

abstract = {DSAP is an automated multiple-task web service designed to provide a total solution to analyzing deep-sequencing small RNA datasets generated by next-generation sequencing technology. DSAP uses a tab-delimited file as an input format, which holds the unique sequence reads (tags) and their corresponding number of copies generated by the Solexa sequencing platform. The input data will go through four analysis steps in DSAP: (i) cleanup: removal of adaptors and poly-A/T/C/G/N nucleotides; (ii) clustering: grouping of cleaned sequence tags into unique sequence clusters; (iii) non-coding RNA (ncRNA) matching: sequence homology mapping against a transcribed sequence library from the ncRNA database Rfam (http://rfam.sanger.ac.uk/); and (iv) known miRNA matching: detection of known miRNAs in miRBase (http://www.mirbase.org/) based on sequence homology. The expression levels corresponding to matched ncRNAs and miRNAs are summarized in multi-color clickable bar charts linked to external databases. DSAP is also capable of displaying miRNA expression levels from different jobs using a log2-scaled color matrix. Furthermore, a cross-species comparative function is also provided to show the distribution of identified miRNAs in different species as deposited in miRBase. DSAP is available at http://dsap.cgu.edu.tw. © The Author(s) 2010. Published by Oxford University Press.},

note = {cited By 77},

keywords = {article; automation; bioinformatics; chicken; client server application; gene expression; nonhuman; nucleotide sequence; priority journal; RNA analysis; RNA sequence; sequence database; sequence homology; species comparison; chemistry; computer program; Internet; metabolism; sequence analysis, Internet; MicroRNAs; RNA, microRNA; RNA; untranslated RNA, RNA; Software, Untranslated; Sequence Analysis},

pubstate = {published},

tppubtype = {article}

}

@article{Lin20091683,

title = {Malate dehydrogenase is negatively regulated by miR-1 in Trichomonas vaginalis},

author = {W. -C. Lin and K. -Y. Huang and S. -C. Chen and T. -Y. Huang and S. -J. Chen and P. -J. Huang and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-70350228364&doi=10.1007%2fs00436-009-1616-5&partnerID=40&md5=b8fc13f71ebfc0dae3ff035018be71c2},

doi = {10.1007/s00436-009-1616-5},

issn = {09320113},

year  = {2009},

date = {2009-01-01},

journal = {Parasitology Research},

volume = {105},

number = {6},

pages = {1683-1689},

abstract = {MicroRNAs are highly conserved small noncoding RNAs that can suppress protein translation through complementary binding to target mRNAs. We used a novel approach to identify miRNA targets in the protist Trichomonas vaginalis by comparing the levels of differentially expressed proteins and genes in the trophozoite and amoeboid stages. We observed that the T. vaginalis malate dehydrogenase (Tv-MDH) gene was upregulated 20-fold in the amoeboid stage, but the protein level was reduced by 4.5-fold. Bioinformatics analysis revealed that the Tv-MDH mRNA contains putative target sites of the miR-1 family. The expression level of endogenous tva-miR-1 in the amoeboid stage was 50-fold higher than in the trophozoite stage. Transfection of trophozoites with tva-miR-1 mimics reduced Tv-MDH protein expression by 60%. Based on these experimental data, we conclude that Tv-MDH is negatively regulated by tva-miR-1. The results of this study demonstrate that a combination of proteomic and transcriptomic approaches is a powerful tool for identifying miRNA targets. © 2009 Springer-Verlag.},

note = {cited By 16},

keywords = {Animals; Base Sequence; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation; Malate Dehydrogenase; MicroRNAs; Molecular Sequence Data; Proteome; Trichomonas vaginalis, article; bioinformatics; controlled study; enzyme regulation; gene; gene control; genetic transfection; miR 1 gene; nonhuman; nucleotide sequence; priority journal; protein targeting; proteomics; protozoal genetics; transcriptomics; Trichomonas vaginalis; trophozoite; tv mdh gene, malate dehydrogenase; microRNA, Protista; Trichomonas vaginalis},

pubstate = {published},

tppubtype = {article}

}

@article{Lin2009487,

title = {Identification of microRNA in the protist Trichomonas vaginalis},

author = {W. -C. Lin and S. -C. Li and W. -C. Lin and J. -W. Shin and S. -N. Hu and X. -M. Yu and T. -Y. Huang and S. -C. Chen and H. -C. Chen and S. -J. Chen and P. -J. Huang and R. Ruei-Chi Gan and C. -H. Chiu and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-64149117818&doi=10.1016%2fj.ygeno.2009.01.004&partnerID=40&md5=6502fda9f21e04ea203a95b955cef341},

doi = {10.1016/j.ygeno.2009.01.004},

issn = {08887543},

year  = {2009},

date = {2009-01-01},

journal = {Genomics},

volume = {93},

number = {5},

pages = {487-493},

abstract = {MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. However, miRNA has never been identified experimentally in protist. Direct cloning of 438 expressed miRNA tags by microRNA serial analysis of gene expression from the parasitic protist Trichomonas vaginalis identified nine candidate miRNAs. Bioinformatics analysis of the corresponding genomic region revealed that these miRNA candidates contain a classical stem-loop-stem structure of pre-microRNAs. Analysis of the 20 nt long mature tva-miR-001 showed that it is an intergenic miRNA located at the scaffold DS113596. Tva-miR-001 was differentially expressed in the trophozoite, pseudocyst and amoeboid stages. Based on the experimental results of the present study, we provided solid evidence that protist possesses a miRNA regulating network comparable with multicellular organisms for the first time. © 2009 Elsevier Inc. All rights reserved.},

note = {cited By 59},

keywords = {Amino Acid Sequence; Animals; Base Sequence; Chromosome Mapping; Cloning, article; bioinformatics; gene expression; gene identification; molecular cloning; nonhuman; nucleotide sequence; parasite cultivation; priority journal; protist life cycle stage; real time polymerase chain reaction; sequence homology; serial analysis of gene expression; Trichomonas vaginalis, microRNA, Molecular; Gene Expression Regulation; Genome, Protista; Trichomonas vaginalis, Protozoan; MicroRNAs; Molecular Sequence Data; Nucleic Acid Conformation; Trichomonas vaginalis},

pubstate = {published},

tppubtype = {article}

}

@article{Huang2009927,

title = {A proteome reference map of Trichomonas vaginalis},

author = {K. -Y. Huang and K. -Y. Chien and Y. -C. Lin and W. -M. Hsu and I. -K. Fong and P. -J. Huang and Y. -M. Yueh and R. R. -C. Gan and P. Tang},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-65549127214&doi=10.1007%2fs00436-008-1274-z&partnerID=40&md5=7ac1b50bbb56ff86abf4050baf72eb44},

doi = {10.1007/s00436-008-1274-z},

issn = {09320113},

year  = {2009},

date = {2009-01-01},

journal = {Parasitology Research},

volume = {104},

number = {4},

pages = {927-933},

abstract = {Trichomoniasis caused by Trichomonas vaginalis is the most common sexual transmitted infection in the world. The 170-MB genome of this protozoan contains 60,000 genes, the largest number of genes ever identified in protozoan. High-throughput expression sequenced tag analysis showed that at least 4,000 genes were expressed in the trophozoite stage. In the present study, we use two-dimensional electrophoresis combined with matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis to profile, identify, and characterize proteins expressed in the trophozoite stage of T. vaginalis. A total of 247 spots representing 164 different proteins were identified. The identified proteins with known sequence or motif/domain homologies were further classified into groups according to their biological functions. Among them, proteins related to carbohydrate metabolism represented the most abundant category in the T. vaginalis proteome. This study presented the most extensive proteomic analysis of T. vaginalis to date and provided a reference proteome database for future comparative proteomic studies. © 2008 Springer-Verlag.},

note = {cited By 32},

keywords = {Animals; Databases, Computer-Assisted; Proteome; Proteomics; Protozoan Proteins; Reference Standards; Spectrometry, cysteine proteinase; cytoskeleton protein; proteome; proteome; protozoal protein, development and aging; human; image processing; mass spectrometry; metabolism; protein database; proteomics; standard; trophozoite; two dimensional gel electrophoresis, Gel, Mass, Matrix-Assisted Laser Desorption-Ionization; Trichomonas vaginalis; Trophozoites, Protein; Electrophoresis, Protozoa; Trichomonas vaginalis, Two-Dimensional; Female; Gene Expression Profiling; Humans; Image Processing},

pubstate = {published},

tppubtype = {article}

}

@article{Lo2007,

title = {Protein structural similarity search by Ramachandran codes},

author = {W. -C. Lo and P. -J. Huang and C. -H. Chang and P. -C. Lyu},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-38049165999&doi=10.1186%2f1471-2105-8-307&partnerID=40&md5=5fdeb7f56944fdecd0837c22cb720914},

doi = {10.1186/1471-2105-8-307},

issn = {14712105},

year  = {2007},

date = {2007-01-01},

journal = {BMC Bioinformatics},

volume = {8},

abstract = {Background: Protein structural data has increased exponentially, such that fast and accurate tools are necessary to access structure similarity search. To improve the search speed, several methods have been designed to reduce three-dimensional protein structures to one-dimensional text strings that are then analyzed by traditional sequence alignment methods; however, the accuracy is usually sacrificed and the speed is still unable to match sequence similarity search tools. Here, we aimed to improve the linear encoding methodology and develop efficient search tools that can rapidly retrieve structural homologs from large protein databases. Results: We propose a new linear encoding method, SARST (Structural similarity search Aided by Ramachandran Sequential Transformation). SARST transforms protein structures into text strings through a Ramachandran map organized by nearest-neighbor clustering and uses a regenerative approach to produce substitution matrices. Then, classical sequence similarity search methods can be applied to the structural similarity search. Its accuracy is similar to Combinatorial Extension (CE) and works over 243,000 times faster, searching 34,000 proteins in 0.34 sec with a 3.2-GHz CPU. SARST provides statistically meaningful expectation values to assess the retrieved information. It has been implemented into a web service and a stand-alone Java program that is able to run on many different platforms. Conclusion: As a database search method, SARST can rapidly distinguish high from low similarities and efficiently retrieve homologous structures. It demonstrates that the easily accessible linear encoding methodology has the potential to serve as a foundation for efficient protein structural similarity search tools. These search tools are supposed applicable to automated and high-throughput functional annotations or predictions for the ever increasing number of published protein structures in this post-genomic era. © 2007 Lo et al; licensee BioMed Central Ltd.},

note = {cited By 42},

keywords = {Algorithms; Amino Acid Sequence; Database Management Systems; Databases, Amino Acid, Database searches; Expectation values; Functional annotation; Homologous structures; Protein structures; Sequence Alignment Methods; Sequence similarity; Structural similarity, Java programming language; Search engines; Tools; Web services, protein, Protein; Information Storage and Retrieval; Molecular Sequence Data; Proteins; Sequence Alignment; Sequence Analysis, Protein; Sequence Homology, Proteins},

pubstate = {published},

tppubtype = {article}

}