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  4. 陳柏仰

陳柏仰 (Chen, Pao-Yang)

副研究員

  • 美國加州大學洛杉磯分校分子細胞與分子生物系 助理研究員 （2012）
  • 英國牛津大學統計系博士（2008）
  • +886-2-2787-1139(Lab)
  • paoyang@gate.sinica.edu.tw
  • 基因體DNA甲基化、次世代高通量基因定序與分析、表觀遺傳學以及生物資訊學
  • Lab Website

我們是一個結合實驗及生物資訊的實驗室，研究著力於分析基因體學 (genomic) 和表觀基因體學 (epigenomic) 的資料。我們同時發展新的實驗技術及統計分析方法，來探討基因與調控的問題，研究的對象包括真菌、植物、動物以及人類。

次時代高通量基因定序
     次世代DNA定序技術對於現代基因學研究有重大的影響。我們實驗室利用DNA-seq重現全基因體序列，了解各個物種的基因特徵、RNA-seq的轉錄組學研究上，分析 基因表達程度；Bisulfite seuqencing （WGBS and RRBS）利用次世代定序建立全基因組的DNA甲基化圖譜，用以研究表觀基因的調控機制。我們針對次世代DNA定序設計並建立最新的樣品資料 (library) 進行實驗，同時針對產生的龐大資料，研究統計方法，並發展計算工具，以解讀生物學上相關的問題。

植物中的DNA甲基化 
     DNA甲基化是表觀遺傳調控上的重要機制，通常用於穩定以及抑制基因表現。我們會以植物做為研究主軸，因為植物採樣便利，容易進行遺傳工程的操作; 此外，模式植物的註解也很清楚。 植物的表觀基因組可以幫助釐清的DNA甲基轉移酶的作用機制，以及有助於了解基因啟動子和基因序列調控的演化，探討植物如何快速適應環境則變化。 

植物，動物和人類的DNA甲基化 
     動物和植物的基因組DNA甲基化的遺傳標記隱藏著很重要的生物學意義。我們的實驗室與國內外多個實驗室有合作計畫，共同研究各樣植物和動物的DNA甲基化模式。例如，我們希望對基因改良的水稻基因體及表觀基因體進行詳細的研究分析。這個結果將增進水稻基因改良的品質以及轉殖的效率。還有，我們將藉由收集臍帶血和胎盤檢體，研究試管嬰兒的全基因體DNA甲基化 (methylome) 的分布，來釐清試管胚胎植入對胚胎的表關遺傳圖譜的影響力。我們也和加州大學洛杉磯分校合作，研究人類生殖細胞早期發育時期的表觀遺傳重置（epigenetic reprogramming）的變化。新的定序技術讓我們可以分析全基因體的DNA甲基化模式，初步的結果令人振奮。

研究貢獻:
  • 包含了前一代BS-Seeker2中所有的比對特色及優點。
  • 可同時達到高精確度與高配對率，以進行超高速比對，其效能比其它相似程式多上至少兩倍。
  • 可與本實驗室研發出的下游分析程式MethGo 順暢地連結，進行高達9種的基因體以及表觀基因體分析。

    • BS-Seeker3 演算過程及分析結果

    1. (A)優化的演算過程包括新的索引方法、資料處理、超高速定位及後續資料處理。
    2. (B)使用者可上傳一般或自訂的基因體特徵（如基因、跳躍基因）繪製其相對位置前後的平均甲基化程度。
    3. (C)在模擬資料下的平均比對10M序列的時間。
    4. (D)利用模擬資料估計定位10M序列來自不同的序列複雜度的正確率。
    5. (E)平均定位一人類資料的時間。
    All publication list

    Selected publication list

    • Pei-Yu Lin *, Ya-Ting Sabrina Chang *, Yu-Chun Huang and Pao-Yang Chen (2023) Estimating genome-wide DNA methylation heterogeneity with methylation patterns. Epigenetics & Chromatin 16(1): 44.
    • HueyTyng Lee, Pei-Yu Lin and Pao-Yang Chen (2023) There’s more to it: uncovering genomewide DNA methylation heterogeneity. Epigenomics 15(13):687-691.
    • Jo-Wei Allison Hsieh, Pearl Chang, Lin-Yun Kuang, Yue-Ie Hsing, Pao-Yang Chen (2023) Rice transformation treatments leave specific epigenome changes beyond tissue culture. Plant Physiology 193(2), 1297-1312.
    • Rita Jui-Hsien Lu*, Pei-Yu Lin*, Ming-Ren Yen*, Bing-Heng Wu and Pao-Yang Chen (2023) MethylC-analyzer: a comprehensive downstream pipeline for the analysis of genome-wide DNA methylation. Botanical Studies 64(1):1.
    • Pierre Bourguet, Ramesh Yelagandula, Taiko Kim To, Akihisa Osakabe, Archana Alishe, Rita Jui-Hsien Lu, Tetsuji Kakutani, Pao-Yang Chen and Frédéric Berger (2022) The histone variant H2A.W cooperates with chromatin modifications and linker histone H1 to maintain transcriptional silencing of transposons in Arabidopsis. bioRxiv https://doi.org/10.1101/2022.05.31.493688
    • Yi-Tsung Tu, Chia-Yang Chen, Yi-Sui Huang, Chung-Han Chang, Ming-Ren Yen, Jo-Wei Allison Hsieh, Pao-Yang Chen and Keqiang Wu (2022) HISTONE DEACETYLASE 15 and MOS4-associated complex subunits 3A/3B coregulate intron retention of ABA-responsive genes. Plant Physiology 190(1): 882-897.
    • Matthew Lowe, Ming-Ren Yen, Fei-Man Hsu, Linzi Hosohama, Zhongxun Hu, Tsotne Chitiashvili, Timothy Hunt, Isaac Gorgy, Matthew Bernard, S Wamaitha, Pao-Yang Chen and Amander T Clark (2022) EED is required for Mouse Primordial Germ Cell Differentiation in the Embryonic Gonad. Developmental Cell 57(12): 1482-1495.e5.
    • Yu-Wen Liu, Shin-Huei Fu, Ming-Wei Chien, Chao-Yuan Hsu, Ming-Hong Lin, Jia-Ling Dong, Rita Jui-Hsien Lu, Yi-Jing Lee, Pao-Yang Chen, Chih-Hung Wang, and Huey-Kang Sytwu (2022) Blimp-1 moulds the epigenetic architecture of IL-21-mediated autoimmune diseases through an autoregulatory circuit. JCI Insight https://doi.org/10.1172/jci.insight.151614.
    • Feng-Chih Kuo, Yu-Chun Huang, Ming-Ren Yen, Chien-Hsing Lee, Kuo-Feng Hsu, Hsiang-Yu Yang, Li-Wei Wu, Chieh-Hua Lu, Yu-Juei Hsu and Pao-Yang Chen (2022) Aberrant overexpression of HOTAIR inhibits abdominal adipogenesis through remodelling of genome-wide DNA methylation and transcription. Molecular Metabolism https://doi.org/10.1016/j.molmet.2022.101473.
    • Ya-Ting Sabrina Chang, Ming-Ren Yen and Pao-Yang Chen (2022) BSImp: imputing partially observed methylation patterns for evaluating methylation heterogeneity. Frontiers in Bioinformatics https://doi.org/10.3389/fbinf.2022.815289.
    • Chih-Yi Yang*, Jui-Hsien Lu*, Ming-Kang Lee*, Shih-Hsiang Felix Hsiao, Ya-Ping Yen, Chun-Chun Cheng, Pu-Sheng Hsu, Yi-Tzang Tsai, Shih-Kuo Chen, I-Hsuan Liu, Pao-Yang Chen and Shau-Ping Lin (2021) Transcriptome Analysis of Dnmt3l Knock-Out Mice Derived Multipotent Mesenchymal Stem/Stromal Cells During Osteogenic Differentiation. Frontiers in Cell and Developmental Biology, section Stem Cell Research 9: 615098.
    • Yu-Shin Nai*, Yu-Chun Huang*, Ming-Ren Yen and Pao-Yang Chen (2021) Diversity of fungal DNA methyltransferases and their association with DNA methylation patterns. Frontiers in Microbiology, section Evolutionary and Genomic Microbiology 11: 616922.
    • Rita Jui-Hsein Lu*, Yen-Ting Liu*, Chih Wei Huang*, Ming-Ren Yen, Chung-Yen Lin and Pao-Yang Chen (2021) ATACgraph: profiling genome wide chromatin accessibility from ATAC-seq. Frontiers in Genetics 11: 618478.
    • Huei-Mien Ke, Hsin-Han Lee, Chan-Yi Ivy Lin, Yu-Ching Liu, Min R. Lu, Jo-Wei Allison Hsieh, Chiung-Chih Chang, Pei-Hsuan Wu, Meiyeh Jade Lu, Jeng-Yi Li, Gaus Shang, Rita Jui-Hsien Lu, László G. Nagy, Pao-Yang Chen, Hsiao-Wei Kao and Isheng Jason Tsai (2020) Mycenagenomes resolve the evolution of fungal bioluminescence. Proceedings of the National Academy of Sciences 117(49): 31267-31277.
    • Fu-Yu Hung, Chen Chen, Ming-Ren Yen, Jo-Wei Hsieh, Chenlong Li, Yuan-Hsin Shih, Fang-Fang Chen, Pao-Yang Chen, Yuhai Cui and Keqiang Wu (2020) The expression of long noncoding RNAs is associated with H3Ac and H3K4me2 changes regulated by the HDA6-LDL1/2 histone modification complex in Arabidopsis. NAR Genomics and Bioinformatics 2(3): lqaa066.
    • Hong Zhu, Pao-Yang Chen, Silin Zhong, Christopher Dardick, Ann Callahan, Yong-Qiang An, Steve van Nocker, Yingzhen Yang, Gan-Yuan Zhong, Albert Abbott and Zongrang Liu (2020) Thermal-responsive genetic and epigenetic regulation of DAM cluster controlling dormancy and chilling requirement in peach floral buds. Horticulture Research 7: 114.
    • Jo-Wei Allison Hsieh, Ming-Ren Yen and Pao-Yang Chen (2020) Epigenomic regulation of OTU5 in Arabidopsis thaliana. Genomics S0888-7543(20)30008-2.
    • Chin-Sheng Teng, Bing-Heng Wu, Ming-Ren Yen and Pao-Yang Chen (2020) MethGET: web-based bioinformatics software for correlating genome-wide DNA methylation and gene expression. BMC Genomics 21(1): 375.
    • Sheng-Yao Su, I-Hsuan Lu, Wen-Chih Cheng, Wei-Chun Chung, Pao-Yang Chen, Jan-Ming Ho, Shu-Hwa Chen and Chung-Yen Lin (2020) EpiMOLAS: an intuitive web-based framework for genome-wide DNA methylation analysis. BMC Genomics 21(Suppl 3): 163.
    • Emilie debladis, Tzuu-Fen Lee, Yan-Jiun Huang, Jui-Hsien Lu, Sandra Mathioni, Marie-Christine Carpentier, Christel Llauro, Davy Pierron, Delphine Mieulet, Emmanuel Guiderdoni, Pao-Yang Chen, Blake Meyers, Olivier Panaud and Eric Lasserre (2020) Construction and characterization of a knock-down RNA interference line of OsNRPD1 in rice (Oryza sativa ssp. Japonica cv. Nipponbare). Philosophical Transactions of the Royal Society B 375: 20190338.
    • Jie Yang*, Lianyu Yuan*, Ming-Ren Yen*, Tao Peng, Dachuan Gu, Rujun Ji, Songguang Yang, Yuhai Cui, Pao-Yang Chen, Keqiang Wu and Xuncheng Liu (2020) SWI3B and HDA6 interact and are required for transposon silencing in Arabidopsis. The Plant Journal 102(4): 809-822.
    • You-Yuan Pang*, Jui-Hsien Lu* and Pao-Yang Chen (2019) Behavioral epigenetics: perspectives based on experience-dependent epigenetic inheritance. Epigenomes 3(3): 18.
    • Phuong Nguyen Tran, Ming-Ren Yen, Chen-Yu Chiang, Hsiao-Ching Lin and Pao-Yang Chen (2019) Detecting and prioritizing biosynthetic gene clusters for bioactive compounds in bacteria and fungi. Applied Microbiology and Biotechnology (103) 8: 3277-3287.
    • Ta-Ching Chen, Pin-Yi She, Dong-Feng Chen, Jui-Hsien Lu, Chang-Hao Yang, Ding-Siang Huang, Pao-Yang Chen, Chen-Yu Lu, Kin-Sang Cho, Hsin-Fu Chen and Wei-Fang Su (2019) Polybenzyl glutamate biocompatible scaffold promotes the efficiency of retinal differentiation toward retinal ganglion cell lineage from human induced pluripotent stem cells. International Journal of Molecular Sciences 20(1): 178.
    • Jie Hou*, Xiaowen Shi*, Chen Chen*, Md. Soliman Islam*, Adam F. Johnson*, Tatsuo Kanno, Bruno Huettel, Ming-Ren Yen, Fei-Man Hsu, Tieming Ji, Pao-Yang Chen, Marjori Matzke, Antonius J.M. Matzke, Jianlin Cheng and James A. Birchler (2018) Global impacts of chromosomal imbalance on gene expression in Arabidopsis and other taxa. Proceedings of the National Academy of Sciences 115(48): E11321-E11330.
    • Fei-Man Hsu*, Moloya Gohain*, Archana Allishe, Yan-Jiun Huang, Jo-Ling Liao, Lin-Yun Kuang and Pao-Yang Chen(2018) Dynamics of the methylome and transcriptome during the regeneration of rice. Epigenomes 2(3): 14.
    • Yu-Yuan Huang, Yan-Jiun Huang and Pao-Yang Chen (2018) BS-Seeker3: ultrafast pipeline for bisulfite sequencing. BMC Bioinformatics 19: 111.
    • Fei-Man Hsu, Chung-Ju Rachel Wang and Pao-Yang Chen (2018) Reduced representation bisulfite sequencing in maize. Bio-protocol 8(6): e2778.
    • Pearl Chang, Yu-Fang Tseng, Pao-Yang Chen and Chung-Ju Rachel Wang (2018) Using flow cytometry to isolate maize meiocytes for next generation sequencing: a time and labor efficient method. Current Protocols in Plant Biology 3(2): e20068.
    • Fei-Man Hsu, Moloya Gohain, Pearl Chang, Jui-Hsien Lu and Pao-Yang Chen (2018) Bioinformatics of epigenetic data generated from next-generation sequencing. Epigenetics in Human Disease, 2nd edition, Elsevier6 in Translational Epigenetics 65-106.
    • Pearl Chang, Moloya Gohain, Ming-Ren Yen and Pao-Yang Chen (2018) Computational methods for assessing chromatin hierarchy. Computational and Structural Biotechnology Journal 16: 43-53.
    • Yu Tao*, Ming-Ren Yen*, Tsotne Chitiashvili, Haruko Nakano, Rachel Kim, Linzi Hosohama, Yao-Chang Tan, Atsushi Nakano, Pao-Yang Chen and Amander T. Clark (2017) TRIM28-regulated transposon repression is required for human germline competency and not primed or naïve human pluripotency. Stem Cell Reports 10(1): 243-256.
    • Jer-Young Lin*, Brandon H. Le*, Min Chen*, Kelli F. Henry, Jungim Hur, Tzung-Fu Hsieh, Pao-Yang Chen, Julie M. Pelletier, Matteo Pellegrini, Robert L. Fischer, John J. Harada and Robert B. Goldberg (2017) Similarity between soybean and Arabidopsis seed methylomes and loss of non-CG methylation does not affect seed development. Proceedings of the National Academy of Sciences 114(45): E9730-E9739.
    • Ming-Ren Yen, Der-Fen Suen, Fei-Man Hsu, Yi-Hsiu Tsai, Hong-Yong Fu, Wolfgang Schmidt and Pao-Yang Chen (2017) Deubiquitinating enzyme OTU5 contributes to DNA methylation patterns and is critical for phosphate nutrition signals. Plant Physiology 175 (4): 1826-1838.
    • Ta-Ching Chen*, Chao-Yuan Yeh*, Chao-Wen Lin, Chung-May Yang, Chang-Hao Yang, I-Hung Lin, Pao-Yang Chen, Jung-Yu Cheng and Fung-Rong Hu (2017) Vascular hypoperfusion in acute optic neuritis is a potentially new neurovascular model for demyelinating diseases. PLoS ONE 12(9): e0184927.
    • Huei-Mei Hsieh, Mei-Chu Chung, Pao-Yang Chen, Fei-Man Hsu, Wen-Wei Liao, Ai-Ning Sung, Chun-Ru Lin, Chung-Ju Wang, Yu-Hsin Kao, Mei-Jane Fang, Chi-Yung Lai, Chieh-Chen Huang, Jyh-Ching Chou, Wen-Neng Chou, Bill Chia-Han Chang and Yu-Ming Ju (2017) A termite symbiotic mushroom maximizing sexual activity at growing tips of vegetative hyphae. Botanical Studies 58: 39.
    • Fei-Man Hsu, Ming-Ren Yen, Chi-Ting Wang, Chien-Yu Lin, Chung-Ju Rachel Wang and Pao-Yang Chen (2017) Optimized reduced representation bisulfite sequencing reveals tissue-specific mCHH islands in maize. Epigenetics & Chromatin 10 (1): 42.
    • Pao-Yang Chen*, Alison Chu*, Wen-Wei Liao, Liudmilla Rubbi, Carla Janzen, Fei-Man Hsu, Amit Ganguly, Shanthie Thamotharan, Matteo Pelligrini and Sherin Devaskar (2017) Prenatal growth patterns and birthweight are associated with differential DNA methylation and gene expression of cardiometabolic risk genes in human placentas. Reproductive Sciences 25(4): 523-539. 

    • Meng-Ying Wu, Chia-Yeh Lin, Hsin-Yi Tseng, Fei-Man Hsu, Pao-Yang Chen and Cheng-Fu Kao (2017) H2B ubiquitylation and the histone chaperone Asf1 cooperatively mediate the formation and maintenance of heterochromatin silencing. Nucleic Acids Research 45(14): 8225-8238.
    • Fei-Man Hsu and Pao-Yang Chen (2017) Game theory in epigenetic reprogramming: Comment on: Epigenetic game theory: How to compute the epigenetic control of maternal-to-zygotic transition by Qian Wang et al. Physics of Life Reviews 20: 143 (Invited commentary).
    • Sheng-Yao Su, Shu-Hwa Chen, I-Hsuan Lu, Yih-Shien Chiang, Yu-Bin Wang, Pao-Yang Chen and Chung-Yen Lin (2016) TEA: the epigenome platform for Arabidopsis methylome study. BMC Genomics 17(13): 3326. 

    • Joseph Hargan-Calvopina, Sara Taylor, Helene Cook, Zhongxun Hu, Serena A. Lee, Ming-Ren Yen, Yih-Shien Chiang, Pao-Yang Chen and Amander T. Clark (2016) Stage-specific demethylation in primordial germ cells safeguards against precocious differentiation. Developmental Cell 39(1): 75-86. 

    • Wai-Shin Yong, Fei-Man Hsu and Pao-Yang Chen (2016) Profiling genome-wide DNA methylation. Epigenetics & Chromatin 9: 26.
    • Colin Flinders, Larry Lam, Liudmilla Rubbi, Roberto Ferrari, Sorel Fitz-Gibbon, Pao-Yang Chen, Michael Thompson, Heather Christofk, David B Agus, Daniel Ruderman, Parag Mallick and Matteo Pellegrini (2016) Epigenetic changes mediated by polycomb repressive complex 2 and E2a are associated with drug resistance in a mouse model of lymphoma. Genome Medicine 8(1): 54. 

    • Fei-Man Hsu, Wai-Shin Yong and Pao-Yang Chen (2016) Views on profiling genomewide DNA methylation and crop methylomes Crop, Environment & Bioinformatics (in Chinese), 作物、環境與生物資訊 13: 39–51.
    • Wen-Wei Liao, Ming-Ren Yen, Evaline Ju, Fei-Man Hsu, Larry Lam and Pao-Yang Chen (2015) MethGO: a comprehensive tool for analyzing whole genome bisulfite sequencing data. BMC Genomics 16(Suppl 12): S11. 

    • Fei-Man Hsu, Amander T Clark and Pao-Yang Chen (2015) Epigenetic reprogramming in the mammalian germline. Oncotarget 6 (34): 35151 (Invited review)
    • Sofia Gkountela, Kelvin Zhang, Tiasha Shafiq, Joseph Hargan-Calvopina, Pao-Yang Chen and Amander T Clark (2015) DNA demethylation dynamics in the human prenatal germline. Cell 161: 1425–1436. 

    • Taku Sasaki, Tatsuo Kanno, Shih-Chieh Liang, Pao-Yang Chen, Wen-Wei Liao, Wen-Dar Lin, Antonius J.M. Matzke and Marjori Matzke (2015) An Rtf2 domain-containing protein influences pre-mRNA splicing and is essential for embryonic development in Arabidopsis thaliana. Genetics 200(2): 523. 

    • Pao-Yang Chen*, Barbara Montanini*, Wen-Wei Liao, Marco Morselli, Artur Jaroszewicz, David Lopez, Simone Ottonello and Matteo Pellegrini (2014) A comprehensive resource of genomic, epigenomic and transcriptomic sequencing data for the black truffle Tuber melanosporum. GigaScience 3(1): 25. 

    • Barbara Montanini*, Pao-Yang Chen*, Marco Morselli, Artur Jaroszewicz, David Lopez, Francis Martin, Simone Ottonello and Matteo Pellegrini (2014) Non-exhaustive DNA methylation-mediated transposon silencing in the black truffle genome, a complex fungal genome with massive repeat element content. Genome Biology 15(8): 411. 

    • Negar M Ghahramani, Tuck C Ngun, Pao-Yang Chen, Yuan Tian, Sangitha Krishnan, Stephanie Muir, Liudmilla Rubbi, Arthur P Arnold, Geert J de Vries, Nancy G Forger, Matteo Pellegrini and Eric Vilain (2014) The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging. Biology of Sex Differences 5(1): 8. 

    • Taku Sasaki, Tzuu-fen Lee, Wen-Wei Liao, Ulf Naumann, Jo-Ling Liao, Changho Eun, Ya-Yi Huang, Jason L. Fu, Pao-Yang Chen, Blake C. Meyers, Antonius J.M. Matzke and Marjori Matzke (2014) Distinct and concurrent pathways of Pol II and Pol IV-dependent siRNA biogenesis at a repetitive trans-silencer locus in Arabidopsis thaliana. The Plant Journal 79(1): 127-138.
    • Weilong Guo, Petko Fiziev, Weihong Yan, Shawn Cokus, Xueguang Sun, Michael Q Zhang, Pao-Yang Chen and Matteo Pellegrini (2013) BS-Seeker2: a versatile aligning pipeline for bisulfite sequencing data. BMC Genomics 14(1): 774 (co-corresponding authors) 

    • Pao-Yang Chen, Amit Ganguly, Liudmilla Rubbi, Luz D. Orozco, Marco Morselli, Davin Ashraf, Artur Jaroszewicz, Suhua Feng, Steve E. Jacobsen, Atsushi Nakano, Sherin U. Devaskar and Matteo Pellegrini (2013) Intra-uterine calorie restriction affects placental DNA methylation and gene expression. Physiological Genomics 45(14): 565-576.

    • John J. Vincent, Yun Huang, Pao-Yang Chen, Suhua Feng, Joseph H. Calvopin, Kevin Nee, Serena A. Lee, Thuc Le, Alexander J. Yoon, Kym Faull, Guoping Fan, Anjana Rao, Steven E. Jacobsen, Matteo Pellegrini, and Amander T. Clark (2013) Stage-specific roles for Tet1 and Tet2 in DNA demethylation in primordial germ cells. Cell Stem Cell 12(4): 470-8.

    博士後研究 Postdoctoral Researcher
    李卉婷 Jenny Huey Tyng Lee

    生物資訊研究助理 Bioinformatics Research Assistant
    林蓓郁 Pei-Yu Lin
    陳冠霖 Kuan-Lin Chen

    博士班學生 PhD Student
    謝若微 Jo-Wei Hsieh
    黃郁珺 Yu-Chun Huang
    林冠均 Guan-Jun Lin

    大學生 Undergraduate Researcher
    黃湘芹 Siang-Cin Huang

    行政助理 Lab Manager
    楊念蓁 Nien-Chen Yang