10 results on '"Yen, Ju-Chen"'
Search Results
2. Whole genome and RNA sequencing analyses for 254 Taiwanese hepatocellular carcinomas.
- Author
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Chang, Ya-Sian, Tu, Siang-Jyun, Chen, Hong-Da, Chung, Chin-Chun, Hsu, Ming-Hon, Chou, Yu-Pao, Lee, Ya-Ting, Yen, Ju-Chen, Jeng, Long-Bin, and Chang, Jan-Gowth
- Subjects
RNA sequencing ,WHOLE genome sequencing ,NUCLEOTIDE sequencing ,HEPATOCELLULAR carcinoma ,ALTERNATIVE RNA splicing ,GENE expression - Abstract
Background: Comprehensive and integrative analysis of hepatocellular carcinoma (HCC) is important. In this study, we explored Taiwanese HCCs using multi-omics analyses. Methods: We analyzed 254 HCCs by whole genome sequencing and total RNA sequencing, and then used bioinformatic tools to analyze genomic and transcriptomic alterations in coding and non-coding sequences to explore the clinical importance of each sequence. Results: The frequencies of the five most commonly mutated cancer-related genes were TERT, TP53, CTNNB1, RB1, and ARID1A. Genetic alteration frequencies influenced the etiology of HCC; some alterations were also correlated with clinicopathological conditions. Many cancer-related genes had copy number alterations (CNAs) and structure variants (SVs) that changed according to etiology and exhibited potential associations with survival. We also identified several alterations in histone-related genes, HCC-related long non-coding RNAs, and non-coding driver genes that may contribute to the onset and progression of HCC. Transcriptomic analysis revealed that 229 differentially expressed and 148 novel alternative splicing (AS) genes, as well as the presence of fusion genes, were associated with patient survival. Moreover, somatic mutations, CNAs, and SVs were associated with immune checkpoint gene expression and tumor microenvironment. Finally, we identified relationships among AS, immune checkpoint gene expression and tumor microenvironment. Conclusions: This study shows that genomic alterations are associated with survival, including DNA-based and RNA-based data. Moreover, genomic alterations and their associations with immune checkpoint genes and the tumor microenvironment may provide novel insights for the diagnosis and treatment of HCC. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Machine learning approaches for the genomic prediction of rheumatoid arthritis and systemic lupus erythematosus
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Chih-Wei Chung, Tzu-Hung Hsiao, Chih-Jen Huang, Yen-Ju Chen, Hsin-Hua Chen, Ching-Heng Lin, Seng-Cho Chou, Tzer-Shyong Chen, Yu-Fang Chung, Hwai-I Yang, and Yi-Ming Chen
- Subjects
QA299.6-433 ,Human leukocyte antigen imputation ,Genomic prediction ,Research ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Biochemistry ,Genome-wide association studies ,Computer Science Applications ,Single nucleotide polymorphism ,Computational Mathematics ,Systemic lupus erythematosus ,Computational Theory and Mathematics ,Machine learning ,Genetics ,Rheumatoid arthritis ,skin and connective tissue diseases ,Molecular Biology ,Analysis - Abstract
Background Rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) are autoimmune rheumatic diseases that share a complex genetic background and common clinical features. This study’s purpose was to construct machine learning (ML) models for the genomic prediction of RA and SLE. Methods A total of 2,094 patients with RA and 2,190 patients with SLE were enrolled from the Taichung Veterans General Hospital cohort of the Taiwan Precision Medicine Initiative. Genome-wide single nucleotide polymorphism (SNP) data were obtained using Taiwan Biobank version 2 array. The ML methods used were logistic regression (LR), random forest (RF), support vector machine (SVM), gradient tree boosting (GTB), and extreme gradient boosting (XGB). SHapley Additive exPlanation (SHAP) values were calculated to clarify the contribution of each SNPs. Human leukocyte antigen (HLA) imputation was performed using the HLA Genotype Imputation with Attribute Bagging package. Results Compared with LR (area under the curve [AUC] = 0.8247), the RF approach (AUC = 0.9844), SVM (AUC = 0.9828), GTB (AUC = 0.9932), and XGB (AUC = 0.9919) exhibited significantly better prediction performance. The top 20 genes by feature importance and SHAP values included HLA class II alleles. We found that imputed HLA-DQA1*05:01, DQB1*0201 and DRB1*0301 were associated with SLE; HLA-DQA1*03:03, DQB1*0401, DRB1*0405 were more frequently observed in patients with RA. Conclusions We established ML methods for genomic prediction of RA and SLE. Genetic variations at HLA-DQA1, HLA-DQB1, and HLA-DRB1 were crucial for differentiating RA from SLE. Future studies are required to verify our results and explore their mechanistic explanation.
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- 2021
4. Outcome of hearing preservation related to tumor morphologic analysis in acoustic neuromas treated by gamma knife radiosurgery.
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Szu-Yen Pan, Shih-An Liu, Ming-Hsi Sun, Hsi-Kai Tsou, Shinh-Dung Lee, Yen-Ju Chen, Sheehan, Jason, Meei-Ling Sheu, Hung-Chuan Pan, Pan, Szu-Yen, Liu, Shih-An, Sun, Ming-Hsi, Tsou, Hsi-Kai, Lee, Shinh-Dung, Chen, Yen-Ju, Sheu, Meei-Ling, and Pan, Hung-Chuan
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ACOUSTIC neuroma ,ACOUSTIC tumors ,RADIOSURGERY ,RADIOTHERAPY ,NEUROSURGERY ,HEARING ,THERAPEUTICS ,LONGITUDINAL method ,TREATMENT effectiveness - Abstract
Background: Gamma Knife radiosurgery (GKRS) is an important part of the neurosurgical armamentarium in the treatment of acoustic neuromas. However, the treatment outcome related to the morphology of the tumor has not been rigorously studied. In this cohort, we evaluated the morphological features of the tumor in the tumor response and neurological outcomes after GKRS.Material and Methods: From July 2003 to December 2008, there were 93 cases of acoustic neuromas treated upfront with GKRS with 64 cases with serviceable hearing and 29 cases without serviceable hearing to fulfill the margin dose of 12Gy with at least follow up 5 years.Results: The duration of symptom before GKRS in serviceable /no serviceable hearing was 7.9 ± 1.2 and 15.3 ± 3.1 months (p < 0.001) and associated no-hearing symptom was 70% and 35%, respectively (p < 0.001). There was 81.2% of hearing preservation after GKRS in serviceable hearing group including 27 cases of pear type (84%), 14 of linear type (70%), and 9 cases of sphere type (90%) (p < 0.01); however, there was no case of hearing improvement in the no-serviceable hearing group (0 of 29). There were 85% of patients with decreased tinnitus in serviceable hearing groups as compared to 61.5% of patients in no serviceable hearing group (p < 0.05). In multivariate analysis, the tumor morphology was highly correlated to hearing preservation rate (p < 0.01).Conclusion: In the limited case of this cohort, we found that the tumor morphology and timing of treatment was highly correlated to the rate of hearing preservation. The sphere type of tumor morphology was associated with the best chance of hearing preservation. [ABSTRACT FROM AUTHOR]- Published
- 2017
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5. Long noncoding RNA TUG1 is downregulated in non-small cell lung cancer and can regulate CELF1 on binding to PRC2.
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Pei-Chin Lin, Hsien-Da Huang, Chun-Chi Chang, Ya-Sian Chang, Ju-Chen Yen, Chien-Chih Lee, Wen-Hsin Chang, Ta-Chih Liu, Jan-Gowth Chang, Lin, Pei-Chin, Huang, Hsien-Da, Chang, Chun-Chi, Chang, Ya-Sian, Yen, Ju-Chen, Lee, Chien-Chih, Chang, Wen-Hsin, Liu, Ta-Chih, and Chang, Jan-Gowth
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CANCER treatment ,NON-small-cell lung carcinoma ,NON-coding RNA ,NUCLEOTIDE sequencing ,DOWNREGULATION ,NEOPLASTIC cell transformation ,RNA metabolism ,BIOCHEMISTRY ,CELL lines ,CELL physiology ,GENES ,LUNG cancer ,LUNG tumors ,PHENOMENOLOGY ,RNA ,SURVIVAL analysis (Biometry) ,SEQUENCE analysis - Abstract
Background: Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, and lncRNA taurine-upregulated gene 1 (TUG1) has been proven to be associated with several human cancers. However, the mechanisms of TUG1-involved regulation remain largely unknown.Methods: We examined the expressions of TUG1 in a cohort of 89 patients with non-small cell lung cancer (NSCLC) to determine the association between TUG1 expression and clinical parameters. We used circular chromosome conformation capture (4C) coupled with next-generation sequencing to explore the genome regions that interact with TUG1 and the TUG1-mediated regulation.Results: TUG1 was significantly downregulated, and the TUG1 downregulation correlated with sex (p = 0.006), smoking status (p = 0.016), and tumor differentiation grade (p = 0.001). Knockdown of TUG1 significantly promoted the proliferation of NSCLC cells. According to the bioinformatic analysis result of TUG1 4C sequencing data, 83 candidate genes and their interaction regions were identified. Among these candidate genes, CUGBP and Elav-like family member 1 (CELF1) are potential targets of TUG1 in-trans regulation. To confirm the interaction between TUG1 and CELF1, relative expressions of CELF1 were examined in TUG1 knockdown H520 cells; results showed that CELF1 was significantly upregulated in TUG1 knockdown H520 cells. RNA immunoprecipitation was then performed to examine whether TUG1 RNA was bound to PRC2, a TUG1-involved regulation mechanism reported in previous studies. The results demonstrated that TUG1 RNA was bound to enhancer of zeste protein 2/embryonic ectoderm development (EZH2/EED), which is essential for PRC2. Finally, our designed ChIP assay revealed that the EZH2/EED was bound to the promotor region of CELF1 within 992 bp upstream of the transcript start site.Conclusion: TUG1 is downregulated in NSCLC. Using TUG1 4C sequencing and bioinformatic analysis, we found CELF1 to be a potential target of TUG1 RNA in in-trans regulation. Moreover, subsequent experiments showed that TUG1 RNA could bind to PRC2 in the promotor region of CELF1 and negatively regulate CELF1 expressions in H520 cells. Our results may facilitate developing new treatment modalities targeting TUG1/PRC2/CELF1 interactions in patients with NSCLC. [ABSTRACT FROM AUTHOR]- Published
- 2016
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6. Long noncoding RNA TUG1 is downregulated in non-small cell lung cancer and can regulate CELF1 on binding to PRC2.
- Author
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Lin PC, Huang HD, Chang CC, Chang YS, Yen JC, Lee CC, Chang WH, Liu TC, and Chang JG
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- CELF1 Protein metabolism, Carcinoma, Non-Small-Cell Lung pathology, Cell Line, Tumor, Cell Proliferation, Chromatin Immunoprecipitation, Female, Gene Expression Regulation, Neoplastic, High-Throughput Nucleotide Sequencing methods, Humans, Lung Neoplasms pathology, Male, Promoter Regions, Genetic, RNA, Long Noncoding metabolism, Survival Analysis, Transcriptional Activation, CELF1 Protein genetics, Carcinoma, Non-Small-Cell Lung genetics, Down-Regulation, Lung Neoplasms genetics, Polycomb Repressive Complex 2 metabolism, RNA, Long Noncoding genetics
- Abstract
Background: Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, and lncRNA taurine-upregulated gene 1 (TUG1) has been proven to be associated with several human cancers. However, the mechanisms of TUG1-involved regulation remain largely unknown., Methods: We examined the expressions of TUG1 in a cohort of 89 patients with non-small cell lung cancer (NSCLC) to determine the association between TUG1 expression and clinical parameters. We used circular chromosome conformation capture (4C) coupled with next-generation sequencing to explore the genome regions that interact with TUG1 and the TUG1-mediated regulation., Results: TUG1 was significantly downregulated, and the TUG1 downregulation correlated with sex (p = 0.006), smoking status (p = 0.016), and tumor differentiation grade (p = 0.001). Knockdown of TUG1 significantly promoted the proliferation of NSCLC cells. According to the bioinformatic analysis result of TUG1 4C sequencing data, 83 candidate genes and their interaction regions were identified. Among these candidate genes, CUGBP and Elav-like family member 1 (CELF1) are potential targets of TUG1 in-trans regulation. To confirm the interaction between TUG1 and CELF1, relative expressions of CELF1 were examined in TUG1 knockdown H520 cells; results showed that CELF1 was significantly upregulated in TUG1 knockdown H520 cells. RNA immunoprecipitation was then performed to examine whether TUG1 RNA was bound to PRC2, a TUG1-involved regulation mechanism reported in previous studies. The results demonstrated that TUG1 RNA was bound to enhancer of zeste protein 2/embryonic ectoderm development (EZH2/EED), which is essential for PRC2. Finally, our designed ChIP assay revealed that the EZH2/EED was bound to the promotor region of CELF1 within 992 bp upstream of the transcript start site., Conclusion: TUG1 is downregulated in NSCLC. Using TUG1 4C sequencing and bioinformatic analysis, we found CELF1 to be a potential target of TUG1 RNA in in-trans regulation. Moreover, subsequent experiments showed that TUG1 RNA could bind to PRC2 in the promotor region of CELF1 and negatively regulate CELF1 expressions in H520 cells. Our results may facilitate developing new treatment modalities targeting TUG1/PRC2/CELF1 interactions in patients with NSCLC.
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- 2016
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7. Taiwan Y-chromosomal DNA variation and its relationship with Island Southeast Asia.
- Author
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Trejaut JA, Poloni ES, Yen JC, Lai YH, Loo JH, Lee CL, He CL, and Lin M
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- Asia, Southeastern, Genetic Drift, Genetic Loci, Human Migration, Humans, Male, Microsatellite Repeats, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Taiwan, Chromosomes, Human, Y genetics, Genetics, Population, Haplotypes
- Abstract
Background: Much of the data resolution of the haploid non-recombining Y chromosome (NRY) haplogroup O in East Asia are still rudimentary and could be an explanatory factor for current debates on the settlement history of Island Southeast Asia (ISEA). Here, 81 slowly evolving markers (mostly SNPs) and 17 Y-chromosomal short tandem repeats were used to achieve higher level molecular resolution. Our aim is to investigate if the distribution of NRY DNA variation in Taiwan and ISEA is consistent with a single pre-Neolithic expansion scenario from Southeast China to all ISEA, or if it better fits an expansion model from Taiwan (the OOT model), or whether a more complex history of settlement and dispersals throughout ISEA should be envisioned., Results: We examined DNA samples from 1658 individuals from Vietnam, Thailand, Fujian, Taiwan (Han, plain tribes and 14 indigenous groups), the Philippines and Indonesia. While haplogroups O1a*-M119, O1a1*-P203, O1a2-M50 and O3a2-P201 follow a decreasing cline from Taiwan towards Western Indonesia, O2a1-M95/M88, O3a*-M324, O3a1c-IMS-JST002611 and O3a2c1a-M133 decline northward from Western Indonesia towards Taiwan. Compared to the Taiwan plain tribe minority groups the Taiwanese Austronesian speaking groups show little genetic paternal contribution from Han. They are also characterized by low Y-chromosome diversity, thus testifying for fast drift in these populations. However, in contrast to data provided from other regions of the genome, Y-chromosome gene diversity in Taiwan mountain tribes significantly increases from North to South., Conclusion: The geographic distribution and the diversity accumulated in the O1a*-M119, O1a1*-P203, O1a2-M50 and O3a2-P201 haplogroups on one hand, and in the O2a1-M95/M88, O3a*-M324, O3a1c-IMS-JST002611 and O3a2c1a-M133 haplogroups on the other, support a pincer model of dispersals and gene flow from the mainland to the islands which likely started during the late upper Paleolithic, 18,000 to 15,000 years ago. The branches of the pincer contributed separately to the paternal gene pool of the Philippines and conjointly to the gene pools of Madagascar and the Solomon Islands. The North to South increase in diversity found for Taiwanese Austronesian speaking groups contrasts with observations based on mitochondrial DNA, thus hinting to a differentiated demographic history of men and women in these populations.
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- 2014
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8. Mitochondrial DNA association study of type 2 diabetes with or without ischemic stroke in Taiwan.
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Loo JH, Trejaut JA, Yen JC, Chen ZS, Ng WM, Huang CY, Hsu KN, Hung KH, Hsiao Y, Wei YH, and Lin M
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- Age Factors, Aged, Base Sequence, Brain Ischemia complications, Brain Ischemia pathology, Case-Control Studies, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 pathology, Female, Haplotypes, Humans, Male, Middle Aged, Molecular Sequence Data, Sequence Analysis, DNA, Sex Factors, Stroke complications, Stroke pathology, Taiwan, Brain Ischemia genetics, DNA, Mitochondrial genetics, Diabetes Mellitus, Type 2 genetics, Genetic Association Studies, Polymorphism, Single Nucleotide, Stroke genetics
- Abstract
Background: The importance of mitochondrial DNA (mtDNA) polymorphism in the prediction of type 2 diabetes (T2D) in men and women is not well understood. We questioned whether mtDNA polymorphism, mitochondrial functions, age and gender influenced the occurrence of T2D with or without ischemic stroke (IS)., Methods: We first designed a matched case-control study of 373 T2D patients and 327 healthy unrelated individuals without history of IS. MtDNA haplogroups were determined on all participants using sequencing of the control region and relevant SNPs from the coding region. Mitochondria functional tests, systemic biochemical measurements and complete genomic mtDNA sequencing were further determined on 239 participants (73 healthy controls, 33 T2D with IS, 70 T2D only and 63 IS patients without T2D)., Results: MtDNA haplogroups B4a1a, and E2b1 showed significant association with T2D (P <0.05), and haplogroup D4 indicated resistance (P <0.05). Mitochondrial and systemic functional tests showed significantly less variance within groups bearing the same mtDNA haplotypes. There was a pronounced male excess among all T2D patients and prevalence of IS was seen only in the older population. Finally, nucleotide variant np 15746, a determinant of haplogroup G3 seen in Japanese and of B4a1a prevalent in Taiwanese was associated with T2D in both populations., Conclusions: Men appeared more susceptible to T2D than women. Although the significant association of B4a1a and E2b1 with T2D ceased when corrected for multiple testings, these haplogroups are seen only among Taiwan Aborigines, Southeast Asian and the Pacific Ocean islanders where T2D is predominant. The data further suggested that physiological and biochemical measurements were influenced by the mtDNA genetic profile of the individual. More understanding of the function of the mitochondrion in the development of T2D might indicate ways of influencing the early course of the disease.
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- 2014
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9. Ancient migration routes of Austronesian-speaking populations in oceanic Southeast Asia and Melanesia might mimic the spread of nasopharyngeal carcinoma.
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Trejaut J, Lee CL, Yen JC, Loo JH, and Lin M
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- Asia, Southeastern epidemiology, Base Sequence, Genetics, Population, Haplotypes genetics, Humans, Melanesia epidemiology, Microsatellite Repeats, Nasopharyngeal Neoplasms epidemiology, Native Hawaiian or Other Pacific Islander genetics, Phylogeny, Polymorphism, Single Nucleotide, Taiwan epidemiology, Asian People genetics, Chromosomes, Human, Y genetics, DNA, Mitochondrial genetics, Emigration and Immigration, Nasopharyngeal Neoplasms genetics
- Abstract
Mitochondrial DNA (mtDNA) and non-recombining Y chromosome (NRY) are inherited uni-parentally from mother to daughter or from father to son respectively. Their polymorphism has initially been studied throughout populations of the world to demonstrate the "Out of Africa" hypothesis. Here, to correlate the distribution of nasopharyngeal carcinoma (NPC) in different populations of insular Asia, we analyze the mtDNA information (lineages) obtained from genotyping of the hyper variable region (HVS I & II) among 1400 individuals from island Southeast Asia (ISEA), Taiwan and Fujian and supplemented with the analysis of relevant coding region polymorphisms. Lineages that best represented a clade (a branch of the genetic tree) in the phylogeny were further analyzed using complete genomic mtDNA sequencing. Finally, these complete mtDNA sequences were used to construct a most parsimonious tree which now constitutes the most up-to-date mtDNA dataset available on ISEA and Taiwan. This analysis has exposed new insights of the evolutionary history of insular Asia and has strong implications in assessing possible correlations with linguistic, archaeology, demography and the NPC distribution in populations within these regions. To obtain a more objective and balanced genetic point of view, slowly evolving biallelic Y single nucleotide polymorphism (Y-SNP) was also analyzed. As in the first step above, the technique was first applied to determine affinities (macro analysis) between populations of insular Asia. Secondly, sixteen Y short tandem repeats (Y-STR) were used as they allow deeper insight (micro analysis) into the relationship between individuals of a same region. Together, mtDNA and NRY allowed a better definition of the relational, demographic, cultural and genetic components that constitute the make up of the present day peoples of ISEA. Outstanding findings were obtained on the routes of migration that occurred along with the spread of NPC during the settlement of insular Asia. The results of this analysis will be discussed using a conceptual approach.
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- 2011
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10. Genetic affinities between the Yami tribe people of Orchid Island and the Philippine Islanders of the Batanes archipelago.
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Loo JH, Trejaut JA, Yen JC, Chen ZS, Lee CL, and Lin M
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- DNA, Mitochondrial, Asia, Eastern, Female, Genealogy and Heraldry, Humans, Male, Native Hawaiian or Other Pacific Islander, Philippines ethnology, Phylogeny, Polymorphism, Genetic, Taiwan ethnology, Asian People genetics
- Abstract
Background: Yami and Ivatan islanders are Austronesian speakers from Orchid Island and the Batanes archipelago that are located between Taiwan and the Philippines. The paternal genealogies of the Yami tribe from 1962 monograph of Wei and Liu were compared with our dataset of non-recombining Y (NRY) chromosomes from the corresponding families. Then mitochondrial DNA polymorphism was also analyzed to determine the matrilineal relationships between Yami, Ivatan, and other East Asian populations., Results: The family relationships inferred from the NRY Phylogeny suggested a low number of paternal founders and agreed with the genealogy of Wei and Liu (P < 0.01). Except for one Y short tandem repeat lineage (Y-STR), seen in two unrelated Yami families, no other Y-STR lineages were shared between villages, whereas mtDNA haplotypes were indiscriminately distributed throughout Orchid Island. The genetic affinity seen between Yami and Taiwanese aborigines or between Ivatan and the Philippine people was closer than that between Yami and Ivatan, suggesting that the Orchid islanders were colonized separately by their nearest neighbors and bred in isolation. However a northward gene flow to Orchid Island from the Philippines was suspected as Yami and Ivatan peoples both speak Western Malayo-Polynesian languages which are not spoken in Taiwan. Actually, only very little gene flow was observed between Yami and Ivatan or between Yami and the Philippines as indicated by the sharing of mtDNA haplogroup B4a1a4 and one O1a1* Y-STR lineage., Conclusions: The NRY and mtDNA genetic information among Yami tribe peoples fitted well the patrilocal society model proposed by Wei and Liu. In this proposal, there were likely few genetic exchanges among Yami and the Philippine people. Trading activities may have contributed to the diffusion of Malayo-Polynesian languages among them. Finally, artifacts dating 4,000 YBP, found on Orchid Island and indicating association with the Out of Taiwan hypothesis might be related to a pioneering stage of settlement, as most dating estimates inferred from DNA variation in our data set ranged between 100-3,000 YBP.
- Published
- 2011
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