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Article: The sequence and de novo assembly of the giant panda genome
Title | The sequence and de novo assembly of the giant panda genome | ||||||||||||||
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Authors | Li, RFan, WTian, GZhu, HHe, LCai, JHuang, QCai, QLi, BBai, YZhang, ZXu, ARen, YZhang, GBruford, MWLi, QMa, LGuo, YAn, NHu, YZheng, YWang, YShi, YLi, ZLiu, QChen, YZhao, JQu, NZhao, STian, FWang, XWang, HLam, TWXu, LLiu, XVinar, TYiu, SMLiu, SZhang, HLi, DHuang, YWang, XYang, GJiang, ZZhang, YWang, JQin, NLi, LLi, JBolund, LKristiansen, KWong, GKSOlson, MZhang, XLi, SWang, WYang, HWang, JWang, JLi, JWei, FLi, HJian, MLi, JZhang, ZNielsen, RLi, DGu, WYang, ZXuan, ZRyder, OALeung, FCCZhou, YCao, JSun, XFu, YFang, XGuo, XWang, BHou, RShen, FMu, BNi, PLin, RQian, WWang, GYu, CNie, WWang, JWu, ZLiang, HMin, JWu, QCheng, SRuan, JWang, MShi, ZWen, MLiu, BRen, XZheng, HDong, DCook, KShan, GZhang, HKosiol, CXie, XLu, ZZheng, HLi, YSteiner, CCLam, TTYLin, SZhang, QLi, GTian, JGong, TLiu, HZhang, DFang, LYe, CZhang, JHu, W | ||||||||||||||
Issue Date | 2010 | ||||||||||||||
Publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/nature | ||||||||||||||
Citation | Nature, 2010, v. 463 n. 7279, p. 311-317 How to Cite? | ||||||||||||||
Abstract | Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. © 2010 Macmillan Publishers Limited. All rights reserved. | ||||||||||||||
Persistent Identifier | http://hdl.handle.net/10722/89279 | ||||||||||||||
ISSN | 2023 Impact Factor: 50.5 2023 SCImago Journal Rankings: 18.509 | ||||||||||||||
PubMed Central ID | |||||||||||||||
ISI Accession Number ID |
Funding Information: We are indebted to the faculty and staff of Beijing Genomics Institute at Shenzhen, whose names were not included in the author list, but who contributed to this team work. This project is funded by the Shenzhen Municipal Government and the Yantian District local government of Shenzhen. This project is supported by the National Natural Science Foundation of China (30725008), Ole Romer grant from the Danish Natural Science Research Council, the Solexa project (272-07-0196), and Danish Strategic Research Council (2106-07-0021). We thank C. Wang, X. Huang and L. Luo for their assistance in collecting the blood sample. We thank D. D. Pollock for repeat content estimation. We thank M. Shi, Y. Wang and M. Ting Wong for analysis of the reproduction related genes. We also thank L. Goodman for editing the manuscript. | ||||||||||||||
References | |||||||||||||||
Errata |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Li, R | en_HK |
dc.contributor.author | Fan, W | en_HK |
dc.contributor.author | Tian, G | en_HK |
dc.contributor.author | Zhu, H | en_HK |
dc.contributor.author | He, L | en_HK |
dc.contributor.author | Cai, J | en_HK |
dc.contributor.author | Huang, Q | en_HK |
dc.contributor.author | Cai, Q | en_HK |
dc.contributor.author | Li, B | en_HK |
dc.contributor.author | Bai, Y | en_HK |
dc.contributor.author | Zhang, Z | en_HK |
dc.contributor.author | Xu, A | en_HK |
dc.contributor.author | Ren, Y | en_HK |
dc.contributor.author | Zhang, G | en_HK |
dc.contributor.author | Bruford, MW | en_HK |
dc.contributor.author | Li, Q | en_HK |
dc.contributor.author | Ma, L | en_HK |
dc.contributor.author | Guo, Y | en_HK |
dc.contributor.author | An, N | en_HK |
dc.contributor.author | Hu, Y | en_HK |
dc.contributor.author | Zheng, Y | en_HK |
dc.contributor.author | Wang, Y | en_HK |
dc.contributor.author | Shi, Y | en_HK |
dc.contributor.author | Li, Z | en_HK |
dc.contributor.author | Liu, Q | en_HK |
dc.contributor.author | Chen, Y | en_HK |
dc.contributor.author | Zhao, J | en_HK |
dc.contributor.author | Qu, N | en_HK |
dc.contributor.author | Zhao, S | en_HK |
dc.contributor.author | Tian, F | en_HK |
dc.contributor.author | Wang, X | en_HK |
dc.contributor.author | Wang, H | en_HK |
dc.contributor.author | Lam, TW | en_HK |
dc.contributor.author | Xu, L | en_HK |
dc.contributor.author | Liu, X | en_HK |
dc.contributor.author | Vinar, T | en_HK |
dc.contributor.author | Yiu, SM | en_HK |
dc.contributor.author | Liu, S | en_HK |
dc.contributor.author | Zhang, H | en_HK |
dc.contributor.author | Li, D | en_HK |
dc.contributor.author | Huang, Y | en_HK |
dc.contributor.author | Wang, X | en_HK |
dc.contributor.author | Yang, G | en_HK |
dc.contributor.author | Jiang, Z | en_HK |
dc.contributor.author | Zhang, Y | en_HK |
dc.contributor.author | Wang, J | en_HK |
dc.contributor.author | Qin, N | en_HK |
dc.contributor.author | Li, L | en_HK |
dc.contributor.author | Li, J | en_HK |
dc.contributor.author | Bolund, L | en_HK |
dc.contributor.author | Kristiansen, K | en_HK |
dc.contributor.author | Wong, GKS | en_HK |
dc.contributor.author | Olson, M | en_HK |
dc.contributor.author | Zhang, X | en_HK |
dc.contributor.author | Li, S | en_HK |
dc.contributor.author | Wang, W | en_HK |
dc.contributor.author | Yang, H | en_HK |
dc.contributor.author | Wang, J | en_HK |
dc.contributor.author | Wang, J | en_HK |
dc.contributor.author | Li, J | en_HK |
dc.contributor.author | Wei, F | en_HK |
dc.contributor.author | Li, H | en_HK |
dc.contributor.author | Jian, M | en_HK |
dc.contributor.author | Li, J | en_HK |
dc.contributor.author | Zhang, Z | en_HK |
dc.contributor.author | Nielsen, R | en_HK |
dc.contributor.author | Li, D | en_HK |
dc.contributor.author | Gu, W | en_HK |
dc.contributor.author | Yang, Z | en_HK |
dc.contributor.author | Xuan, Z | en_HK |
dc.contributor.author | Ryder, OA | en_HK |
dc.contributor.author | Leung, FCC | en_HK |
dc.contributor.author | Zhou, Y | en_HK |
dc.contributor.author | Cao, J | en_HK |
dc.contributor.author | Sun, X | en_HK |
dc.contributor.author | Fu, Y | en_HK |
dc.contributor.author | Fang, X | en_HK |
dc.contributor.author | Guo, X | en_HK |
dc.contributor.author | Wang, B | en_HK |
dc.contributor.author | Hou, R | en_HK |
dc.contributor.author | Shen, F | en_HK |
dc.contributor.author | Mu, B | en_HK |
dc.contributor.author | Ni, P | en_HK |
dc.contributor.author | Lin, R | en_HK |
dc.contributor.author | Qian, W | en_HK |
dc.contributor.author | Wang, G | en_HK |
dc.contributor.author | Yu, C | en_HK |
dc.contributor.author | Nie, W | en_HK |
dc.contributor.author | Wang, J | en_HK |
dc.contributor.author | Wu, Z | en_HK |
dc.contributor.author | Liang, H | en_HK |
dc.contributor.author | Min, J | en_HK |
dc.contributor.author | Wu, Q | en_HK |
dc.contributor.author | Cheng, S | en_HK |
dc.contributor.author | Ruan, J | en_HK |
dc.contributor.author | Wang, M | en_HK |
dc.contributor.author | Shi, Z | en_HK |
dc.contributor.author | Wen, M | en_HK |
dc.contributor.author | Liu, B | en_HK |
dc.contributor.author | Ren, X | en_HK |
dc.contributor.author | Zheng, H | en_HK |
dc.contributor.author | Dong, D | en_HK |
dc.contributor.author | Cook, K | en_HK |
dc.contributor.author | Shan, G | en_HK |
dc.contributor.author | Zhang, H | en_HK |
dc.contributor.author | Kosiol, C | en_HK |
dc.contributor.author | Xie, X | en_HK |
dc.contributor.author | Lu, Z | en_HK |
dc.contributor.author | Zheng, H | en_HK |
dc.contributor.author | Li, Y | en_HK |
dc.contributor.author | Steiner, CC | en_HK |
dc.contributor.author | Lam, TTY | en_HK |
dc.contributor.author | Lin, S | en_HK |
dc.contributor.author | Zhang, Q | en_HK |
dc.contributor.author | Li, G | en_HK |
dc.contributor.author | Tian, J | en_HK |
dc.contributor.author | Gong, T | en_HK |
dc.contributor.author | Liu, H | en_HK |
dc.contributor.author | Zhang, D | en_HK |
dc.contributor.author | Fang, L | en_HK |
dc.contributor.author | Ye, C | en_HK |
dc.contributor.author | Zhang, J | en_HK |
dc.contributor.author | Hu, W | en_HK |
dc.date.accessioned | 2010-09-06T09:54:51Z | - |
dc.date.available | 2010-09-06T09:54:51Z | - |
dc.date.issued | 2010 | en_HK |
dc.identifier.citation | Nature, 2010, v. 463 n. 7279, p. 311-317 | en_HK |
dc.identifier.issn | 0028-0836 | en_HK |
dc.identifier.uri | http://hdl.handle.net/10722/89279 | - |
dc.description.abstract | Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. © 2010 Macmillan Publishers Limited. All rights reserved. | en_HK |
dc.language | eng | en_HK |
dc.publisher | Nature Publishing Group. The Journal's web site is located at http://www.nature.com/nature | en_HK |
dc.relation.ispartof | Nature | en_HK |
dc.subject.mesh | Algorithms | en_HK |
dc.subject.mesh | Animals | en_HK |
dc.subject.mesh | China | en_HK |
dc.subject.mesh | Conserved Sequence - genetics | en_HK |
dc.subject.mesh | Contig Mapping | en_HK |
dc.subject.mesh | Diet - veterinary | en_HK |
dc.subject.mesh | Dogs | en_HK |
dc.subject.mesh | Evolution, Molecular | en_HK |
dc.subject.mesh | Female | en_HK |
dc.subject.mesh | Fertility - genetics - physiology | en_HK |
dc.subject.mesh | Genome - genetics | en_HK |
dc.subject.mesh | Genomics | en_HK |
dc.subject.mesh | Heterozygote | en_HK |
dc.subject.mesh | Humans | en_HK |
dc.subject.mesh | Multigene Family - genetics | en_HK |
dc.subject.mesh | Polymorphism, Single Nucleotide - genetics | en_HK |
dc.subject.mesh | Receptors, G-Protein-Coupled - genetics | en_HK |
dc.subject.mesh | Sequence Alignment | en_HK |
dc.subject.mesh | Sequence Analysis, DNA | en_HK |
dc.subject.mesh | Synteny - genetics | en_HK |
dc.subject.mesh | Ursidae - classification - genetics - physiology | en_HK |
dc.title | The sequence and de novo assembly of the giant panda genome | en_HK |
dc.type | Article | en_HK |
dc.identifier.openurl | http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0028-0836&volume=463 &issue=7279&spage=311&epage=317&date=2009&atitle=The+sequence+and+de+novo+assembly+of+the+giant+panda+genome | en_HK |
dc.identifier.email | Leung, FCC: fcleung@hkucc.hku.hk | en_HK |
dc.identifier.email | Lam, TW: hresltk@hkucc.hku.hk | en_HK |
dc.identifier.email | Yiu, SM: smyiu@cs.hku.hk | en_HK |
dc.identifier.authority | Leung, FCC=rp00731 | en_HK |
dc.identifier.authority | Lam, TW=rp00135 | en_HK |
dc.identifier.authority | Yiu, SM=rp00207 | en_HK |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1038/nature08696 | en_HK |
dc.identifier.pmid | 20010809 | - |
dc.identifier.pmcid | PMC3951497 | - |
dc.identifier.scopus | eid_2-s2.0-75149155568 | en_HK |
dc.identifier.hkuros | 168618 | en_HK |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-75149155568&selection=ref&src=s&origin=recordpage | en_HK |
dc.identifier.volume | 463 | en_HK |
dc.identifier.issue | 7279 | en_HK |
dc.identifier.spage | 311 | en_HK |
dc.identifier.epage | 317 | en_HK |
dc.identifier.isi | WOS:000273748100035 | - |
dc.publisher.place | United Kingdom | en_HK |
dc.relation.erratum | doi:10.1038/nature08846 | - |
dc.identifier.f1000 | 2367956 | - |
dc.identifier.scopusauthorid | Li, R=34975581600 | en_HK |
dc.identifier.scopusauthorid | Fan, W=34770075500 | en_HK |
dc.identifier.scopusauthorid | Tian, G=51864819500 | en_HK |
dc.identifier.scopusauthorid | Zhu, H=12759538000 | en_HK |
dc.identifier.scopusauthorid | He, L=36080215400 | en_HK |
dc.identifier.scopusauthorid | Cai, J=37014359400 | en_HK |
dc.identifier.scopusauthorid | Huang, Q=35248207300 | en_HK |
dc.identifier.scopusauthorid | Cai, Q=35247710600 | en_HK |
dc.identifier.scopusauthorid | Li, B=36071920200 | en_HK |
dc.identifier.scopusauthorid | Bai, Y=35247469200 | en_HK |
dc.identifier.scopusauthorid | Zhang, Z=8976202700 | en_HK |
dc.identifier.scopusauthorid | Fang, L=7402470131 | en_HK |
dc.identifier.scopusauthorid | Ren, Y=36239279100 | en_HK |
dc.identifier.scopusauthorid | Ye, C=54943580400 | en_HK |
dc.identifier.scopusauthorid | Zhang, J=24734245900 | en_HK |
dc.identifier.scopusauthorid | Hu, W=55222730400 | en_HK |
dc.identifier.scopusauthorid | Zhang, G=8406672400 | en_HK |
dc.identifier.scopusauthorid | Bruford, MW=7003469332 | en_HK |
dc.identifier.scopusauthorid | Li, Q=24734042200 | en_HK |
dc.identifier.scopusauthorid | Ma, L=15760435100 | en_HK |
dc.identifier.scopusauthorid | Guo, Y=35208385500 | en_HK |
dc.identifier.scopusauthorid | Wang, H=8389375800 | en_HK |
dc.identifier.scopusauthorid | An, N=36983772000 | en_HK |
dc.identifier.scopusauthorid | Hu, Y=10141048500 | en_HK |
dc.identifier.scopusauthorid | Zheng, Y=35077992100 | en_HK |
dc.identifier.scopusauthorid | Wang, Y=8717399400 | en_HK |
dc.identifier.scopusauthorid | Shi, Y=35243243900 | en_HK |
dc.identifier.scopusauthorid | Li, Z=24921695300 | en_HK |
dc.identifier.scopusauthorid | Liu, Q=36063708000 | en_HK |
dc.identifier.scopusauthorid | Chen, Y=35766350100 | en_HK |
dc.identifier.scopusauthorid | Zhao, J=7410312624 | en_HK |
dc.identifier.scopusauthorid | Qu, N=55229025400 | en_HK |
dc.identifier.scopusauthorid | Lam, TW=7202523165 | en_HK |
dc.identifier.scopusauthorid | Zhao, S=35768633100 | en_HK |
dc.identifier.scopusauthorid | Tian, F=36554995700 | en_HK |
dc.identifier.scopusauthorid | Wang, X=11639883200 | en_HK |
dc.identifier.scopusauthorid | Xu, L=16178437400 | en_HK |
dc.identifier.scopusauthorid | Liu, X=36062545900 | en_HK |
dc.identifier.scopusauthorid | Vinar, T=6507894445 | en_HK |
dc.identifier.scopusauthorid | Yiu, SM=7003282240 | en_HK |
dc.identifier.scopusauthorid | Liu, S=9249830600 | en_HK |
dc.identifier.scopusauthorid | Zhang, H=7409190854 | en_HK |
dc.identifier.scopusauthorid | Li, D=7405322473 | en_HK |
dc.identifier.scopusauthorid | Huang, Y=55168765200 | en_HK |
dc.identifier.scopusauthorid | Li, S=7409241896 | en_HK |
dc.identifier.scopusauthorid | Wang, X=35265408100 | en_HK |
dc.identifier.scopusauthorid | Yang, G=37027479000 | en_HK |
dc.identifier.scopusauthorid | Jiang, Z=55202698200 | en_HK |
dc.identifier.scopusauthorid | Zhang, Y=7601308574 | en_HK |
dc.identifier.scopusauthorid | Wang, J=34870954400 | en_HK |
dc.identifier.scopusauthorid | Qin, N=35249244900 | en_HK |
dc.identifier.scopusauthorid | Li, L=36064664900 | en_HK |
dc.identifier.scopusauthorid | Li, J=8644253500 | en_HK |
dc.identifier.scopusauthorid | Bolund, L=7005871141 | en_HK |
dc.identifier.scopusauthorid | Kristiansen, K=7102589497 | en_HK |
dc.identifier.scopusauthorid | Wang, W=7501758370 | en_HK |
dc.identifier.scopusauthorid | Wong, GKS=7402527066 | en_HK |
dc.identifier.scopusauthorid | Olson, M=7402052919 | en_HK |
dc.identifier.scopusauthorid | Zhang, X=35249930300 | en_HK |
dc.identifier.scopusauthorid | Yang, H=7406555861 | en_HK |
dc.identifier.scopusauthorid | Wang, J=24371445200 | en_HK |
dc.identifier.scopusauthorid | Wang, J=36068781200 | en_HK |
dc.identifier.scopusauthorid | Li, J=26643260400 | en_HK |
dc.identifier.scopusauthorid | Wei, F=7202452762 | en_HK |
dc.identifier.scopusauthorid | Li, H=12777127000 | en_HK |
dc.identifier.scopusauthorid | Jian, M=35248126500 | en_HK |
dc.identifier.scopusauthorid | Li, J=35093030000 | en_HK |
dc.identifier.scopusauthorid | Guo, X=35810537100 | en_HK |
dc.identifier.scopusauthorid | Zhang, Z=8909939900 | en_HK |
dc.identifier.scopusauthorid | Nielsen, R=7202360651 | en_HK |
dc.identifier.scopusauthorid | Li, D=8236324800 | en_HK |
dc.identifier.scopusauthorid | Gu, W=7202449029 | en_HK |
dc.identifier.scopusauthorid | Yang, Z=8659403100 | en_HK |
dc.identifier.scopusauthorid | Xuan, Z=35204311500 | en_HK |
dc.identifier.scopusauthorid | Ryder, OA=7005467638 | en_HK |
dc.identifier.scopusauthorid | Leung, FCC=7103078633 | en_HK |
dc.identifier.scopusauthorid | Zhou, Y=7405369308 | en_HK |
dc.identifier.scopusauthorid | Cao, J=55182826600 | en_HK |
dc.identifier.scopusauthorid | Wang, B=7405921467 | en_HK |
dc.identifier.scopusauthorid | Sun, X=55356849900 | en_HK |
dc.identifier.scopusauthorid | Fu, Y=8296800500 | en_HK |
dc.identifier.scopusauthorid | Fang, X=23097261800 | en_HK |
dc.identifier.scopusauthorid | Hou, R=34769868300 | en_HK |
dc.identifier.scopusauthorid | Shen, F=8976202900 | en_HK |
dc.identifier.scopusauthorid | Mu, B=35768297500 | en_HK |
dc.identifier.scopusauthorid | Ni, P=7006804524 | en_HK |
dc.identifier.scopusauthorid | Lin, R=35767969900 | en_HK |
dc.identifier.scopusauthorid | Qian, W=23092294100 | en_HK |
dc.identifier.scopusauthorid | Wang, G=36044698300 | en_HK |
dc.identifier.scopusauthorid | Yu, C=7404977556 | en_HK |
dc.identifier.scopusauthorid | Zheng, H=35204266400 | en_HK |
dc.identifier.scopusauthorid | Nie, W=7005801548 | en_HK |
dc.identifier.scopusauthorid | Wang, J=7701326092 | en_HK |
dc.identifier.scopusauthorid | Wu, Z=36706700800 | en_HK |
dc.identifier.scopusauthorid | Liang, H=25637737600 | en_HK |
dc.identifier.scopusauthorid | Min, J=35484995100 | en_HK |
dc.identifier.scopusauthorid | Wu, Q=36722904400 | en_HK |
dc.identifier.scopusauthorid | Cheng, S=35767383000 | en_HK |
dc.identifier.scopusauthorid | Ruan, J=12777197200 | en_HK |
dc.identifier.scopusauthorid | Wang, M=9247026700 | en_HK |
dc.identifier.scopusauthorid | Shi, Z=35332988200 | en_HK |
dc.identifier.scopusauthorid | Dong, D=55276205200 | en_HK |
dc.identifier.scopusauthorid | Wen, M=46361899700 | en_HK |
dc.identifier.scopusauthorid | Liu, B=35768059000 | en_HK |
dc.identifier.scopusauthorid | Ren, X=35332827700 | en_HK |
dc.identifier.scopusauthorid | Cook, K=35483249200 | en_HK |
dc.identifier.scopusauthorid | Shan, G=35768479800 | en_HK |
dc.identifier.scopusauthorid | Zhang, H=34871205900 | en_HK |
dc.identifier.scopusauthorid | Kosiol, C=16239349000 | en_HK |
dc.identifier.scopusauthorid | Xie, X=36543376100 | en_HK |
dc.identifier.scopusauthorid | Lu, Z=35512315500 | en_HK |
dc.identifier.scopusauthorid | Zheng, H=25637991300 | en_HK |
dc.identifier.scopusauthorid | Li, Y=23766780600 | en_HK |
dc.identifier.scopusauthorid | Xu, A=7202655144 | en_HK |
dc.identifier.scopusauthorid | Steiner, CC=35485967700 | en_HK |
dc.identifier.scopusauthorid | Lam, TTY=35484442900 | en_HK |
dc.identifier.scopusauthorid | Lin, S=35767958400 | en_HK |
dc.identifier.scopusauthorid | Zhang, Q=7406721863 | en_HK |
dc.identifier.scopusauthorid | Li, G=8692805500 | en_HK |
dc.identifier.scopusauthorid | Tian, J=55244123800 | en_HK |
dc.identifier.scopusauthorid | Gong, T=35767682400 | en_HK |
dc.identifier.scopusauthorid | Liu, H=36072691900 | en_HK |
dc.identifier.scopusauthorid | Zhang, D=35933836300 | en_HK |
dc.identifier.citeulike | 6372380 | - |
dc.identifier.issnl | 0028-0836 | - |