The investigation of genome and epigenomes

Pao-Yang Chen's Laboratory

陳柏仰實驗室

Next generation genetics

Next-generation or massively parallel DNA sequencing technologies have the potential to markedly accelerate genetics research. In our lab we perform DNA-seq for whole genome assembly, mRNA-seq for transcriptome studies, ChIP-seq for protein-DNA binding and histone marks, ATAC-seq for chromatin accessibility, and BS-seq for DNA methylation profiling (WGBS and RRBS). Our goal is to integrate both experiments and statistical methods and bioinformatic software to address biologically relevant questions.

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、ChIP-seq 分析蛋白質與DNA的的交互作用位點、ATAC-seq可揭露染色質上的開放位置、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。

我們的研究

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。

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,我們將藉由收集老鼠胎兒檢體,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。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。近期我們在人類生殖細胞的表觀基因體研究,發表了人類第一個表觀基因體重置的圖譜,是近期研究上的重大突破,我們並展開一連串的相關研究,探討此一遺傳上獨特且重要的細胞。

People

2012- Assistant Research Fellow, IPMB, Academia Sinica
2012- Assistant Researcher, UCLA
2008-2012 Postdoctoral Fellow, UCLA
2008 D.Phil, Statistics, Oxford University

Pao-Yang Chen 陳柏仰

Principal Investigator

paoyang@gate.sinica.edu.tw
PhD Molecular Biology
National Chung Hsing University

Ming-Ren Yen 嚴明仁

Postdoctoral Researcher

yenmr@sinica.edu.tw
PhD Biology
University of Waterloo

Pearl Chang 張珮君

Postdoctoral Researcher (joint supervision with Rachel Wang)

pearlchang@gate.sinica.edu.tw
MS. Parasitology, National Yang Ming University

Yijing Lee 李怡靜

Lab Manager

yijinglee@gate.sinica.edu.tw TEL: 02-27871139
MS. Life Science, Tunghai University

Elina 謝佳蓉

Research Assistant

scj0716@gate.sinica.edu.tw
MS. School of Forestry and Resource Conservation, National Taiwan University

Rita 陸芮嫻

Research Assistant

ritalu@gate.sinica.edu.tw
MS. Forestry, National Taiwan University

Tim 劉彥廷

Research Assistant

timliu@gate.sinica.edu.tw
Department of Agronomy, National Taiwan University

Jason 鄧景升

Undergraduate Researcher

faf046059@gmail.com>

Publications

Google Scholar

Journal Articles

2018


Fei-Man Hsu, Moloya Gohain, Pearl Chang, Jui-Hsien Lu, Pao-Yang Chen* (2018) Bioinformatics of Epigenetic Data Generated from Next-Generation Sequencing Epigenetics in Human Disease, 2nd edition, Elsevier Invited chapter in production

2017


Jer-Young Lin, Brandon 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, 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 doi: 10.1073/pnas.1716758114

Ming-Ren Yen, Der-Fen Suen, Fei-Man Hsu, Yi-Hsiu Tsai, Hongyong 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 DOI: https://doi.org/10.1104/pp.17.01188

Ta-Ching Chen, Chao-Yuan Yeh, Chao-Wen Lin, Chung-May Yang, Chang-Hao Yang, I-Hung Lin, Pao-Yang Chen, Jung-Yu Cheng, 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 10:42 Gitlab

Pao-Yang Chen☨, Alison Chu☨, Wen-Wei Liao, Liudmilla Rubbi, Carla Janzen, Fei-Man Hsu, Amit Ganguly, Shanthie Thamotharan, Matteo Pelligrini, 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 1-17

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 doi: 10.1093/nar/gkx422

Fei-Man Hsu, 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 20:143-145

2016


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 17:3326 Website

Joseph Hargan-Calvopina, Sara Taylor, Helene Cook, Zhongxun Hu, Serena A. Lee, Ming-Ren Yen, Yih-Shien Chiang, Pao-Yang Chen, Amander T. Clark (2016) Stage-Specific Demethylation in Primordial Germ Cells Safeguards against Precocious Differentiation. Developmental Cell 39 1:12

Wai-Shin Yong☨, Fei-Man Hsu☨, 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 8:54

Fei-Man Hsu☨, Wai-Shin Yong☨, Pao-Yang Chen (2016) Views on Profiling Genomewide DNA Methylation and Crop Methylomes. Crop, Environment & Bioinformatics 13:39-51

2015


Fei-Man Hsu, Amander T Clark, Pao-Yang Chen (2015) Epigenetic reprogramming in the mammalian germline.Oncotarget DOI: 10.18632/oncotarget.6206

Wen-Wei Liao☨, Ming-Ren Yen☨, Evaline Ju, Fei-Man Hsu, Larry Lam, Pao-Yang Chen (2015) MethGO: a comprehensive tool for analyzing whole genome bisulte sequencing data. BMC Genomics 16(Suppl 12):S11 Software

Gkountela, Kelvin Zhang, Tiasha Shaq, Wen-Wei Liao, Joseph Hargan-Calvopina, Pao-Yang Chen*, Amander T Clark* (2015) DNA Demethylation Dynamics in the Human Prenatal Germline. Cell 161:1-12 (co-corresponding authors)

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 doi: 10.1534/genetics.115.176438

2014


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 truffe Tuber melanosporum. GigaScience 3:25

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 15:411

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, Eric Vilain (2014) The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging. Biol Sex Differ 5:8

Sasaki T, Lee TF, Liao, Wen-Wei, Naumann U, Liao Joling, Eun CH, Huang YY, Fu JL, Pao-Yang Chen, Meyers BC, Matzke AJM, and Matzke M. (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 doi: 10.1111/tpj.12545

2013


Guo W, Fiziev P, Yan W, Cokus S, Sun X, Zhang MQ, Pao-Yang Chen* & Pellegrini M.* (2013) BS-Seeker2: a versatile aligning pipeline for bisulfite sequencing data. BMC Genomics 14(1): 774 (co-corresponding authors) Github

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, Physiol. Genomics doi:10.1152

J. Vincent, Y. Huang, Pao-Yang Chen, S. Feng, J.. Calvopia, K. Nee, S. Lee, T. Le, A. Yoon, K. Faull, G. Fan, A. Rao, S. Jacobsen, M. Pellegrini, and A. Clark (2013) Stage-Specific Roles for Tet1 and Tet2 in DNA Demethylation in Primordial Germ Cells, Cell Stem Cell 12(4):470-8

Before 2013


Pao-Yang Chen, M. Pellegrini (2012) Methylomes, Epigenetic Regulation and Epigenomics from the Encyclopedia of Molecular Cell Biology and Molecular Medicine, pp. 815-837, UK: John Wiley & Sons, Inc. (invited review)

Pao-Yang Chen, S. Feng, J. Joo, S. Jacobsen, M. Pellegrini (2011) A comparative analysis of DNA methylation across human embryonic stem cell lines, Genome Biology 12:R62 (highly accessed)

Shota Atsumi, Tung-Yun Wu, I. Machado, W. Huang, Pao-Yang Chen, Matteo Pellegrini, James C Liao (2010) Evolution, genomic analysis, and reconstruction of isobutanol tolerance in Escherichia coli. Nature-EMBO Molecular Systems Biology 6: 499

R. Chodavarapu, S. Feng, Y. Bernatavichute, Pao-Yang Chen, H. Stroud, Y. Yu, J. Hetzel, F. Kuo, J. Kim, S. Cokus, D. Casero, M. Bernal, P. Huijser, A. Clark, U. Krmer, S. Merchant, X. Zhang, S. Jacobsen, M. Pellegrini (2010) Relationship between nucleosome positioning and DNA methylation. Nature 466, 388-392

S. Feng, S. Cokus, X. Zhang, Pao-Yang Chen, M. Bostick, M. Goll, J. Hetzel, J. Jain, S. Strauss, M. Halpern, C. Ukomadu, K. Sadler, M. Pellegrini, S. Jacobsen (2010) Conservation and divergence of plant and animal methylation patterning. Proceedings of the National Academy of Sciences, 11;107(19):8689-94

Pao-Yang Chen, S. Cokus, M. Pellegrini, (2010) BS Seeker: precise mapping for bisulfite sequencing. BMC Bioinformatics 11: 203 (highly accessed)

R. Hamer*, Pao-Yang Chen*, J. Armitage, G. Reinert, C. Deane (2010) Deciphering chemotaxis pathways using cross species comparisons. BMC Systems Biology, 4: 3 (co-furst authors)

Pao-Yang Chen, C. Deane, G. Reinert (2008) Predicting and validating protein interactions using network structure. PLoS Computational Biology 4(7): e1000118

Pao-Yang Chen, C. Deane, G. Reinert (2007) A statistical approach using network structure in the prediction of protein characteristics. Bioinformatic 23 (17): 2314-2321

C. Lin, S. Chen, C. Cho, C. Chen, F. Lin, C. Lin, Pao-Yang Chen, C. Lo, C. Hsiung, (2006) Fly-DPI: database of protein interactomes for D. melanogaster in the approach of systems biology.BMC Bioinformatics 7 (5) S18

C. Chen, C. Lin, C. Cho, L. Wang, C. Chang, Pao-Yang Chen, C. Lo, C. Hsiung, (2005) HP-DPI: Helicobacter Pylori Database of Protein Interactomes, a combined experimental and inferring interactions. Bioinformatics, 21(7):1288-1290

Y. Chen, J. Chen, K. Richard, Pao-Yang Chen, D. Christiani, (2004) Lung adenocarcinoma and human papillomavirus infection. Cancer15;101(6):1428-36

C. Hwu, C. Hsiao, S. Kuo, K. Wu, C. Ting, T. Quertermous, B, Rodriguez, I. Chen, J. Grove, Pao-Yang Chen, L. Ho, (2004) Physical inactivity is an important lifestyle determinant of insulin resistance in hypertensive patients. Blood Pressure 13 (6): 355-361 (Selected in the Outstanding Thesis Collection by Ministry of National Defense, Taiwan)

Ching Liu and Pao-Yang Chen (1999) Mapping and analysis of Quantitative Trait Loci (QTL) for Poisson distributed data. Chinese Agronomy Journal 9(3):127-141


Popular Science


Fei-Man Hsu, Pao-Yang Chen (2017) 表觀遺傳重置 – 胚胎如何抹除父母的記憶並保留細胞的全能性? 中研院週報知識天地 1604

7分之1機率不孕,下一代更嚴重?5大因素解析 聯合報 (2015)
不孕症 可能天注定 聯合報 (2015)
中研院跨國研究 助了解不孕症 蘋果日報 (2015)
禍延三代!懷孕初期吸菸、飲酒 恐導致子孫不孕 自由時報 (2015)

Call Lab

+886 2 27871139

地址

台北市南港區 11529 研究院路二段128號
中央研究院植物暨微生物學研究所 陳柏仰研究室 R315

Address

R315, Institute of Plant and Microbial Biology,
128 Sec 2, Academia Rd, Nankang, Taipei City, Taiwan