Prof. Dong Zi Rui, Elvis

Prof. Dong Zi Rui, Elvis Assistant Professor

(852) 3505 3099

elvisdong@cuhk.edu.hk

Qualifications

BEng (SCUT); MSc (CUHK); PhD (CUHK)

ORCID

0000-0002-3626-6500

Research Interests

I am a clinical bioinformatician with strong interests in (1) development and implementation of the analytical algorithms for detecting novel and cryptic human genomics structural variants (SVs) with low-pass genome sequencing (low-pass GS) based on the second- or third-generation sequencing platforms; (2) investigation on SVs’ impact (gene disruption or dysregulation) to human diseases (particularly for human infertility) with multi-omics including Hi-C (chromatin conformation capture), ChIP-seq (histone modification) and single-cell RNA-seq and ATAC-seq; and (3) study on SVs’ potential formation/repair mechanism (such as insertion).

We developed robust analytical algorithms and sequencing approaches, and through that, we identified a significant number of previously unknown structural variants in prenatal or postnatal patients, couples with recurrent miscarriages, and male and female infertility. Low-pass GS has been recommended for germline structural variants detection by the American College of Medical Genetics and Genomics. In addition, we also established TEDD database (https://tedd.obg.cuhk.edu.hk/) by curating single-cell RNA-seq and ATAC-seq datasets from over 5 million cells originated from human and model organisms to help scientists identify where & when your critical genes are expressed, & how they interact with each other during development, providing potential pathomechanism to diseases. With that, we demonstrated the pathogenicity of SVs by induction of RNA aberrations (gene disruption or dysregulation by the structural variants) as well as the impacts on cell proliferation/apoptosis through cell/animal model validation. These studies led to 33 publications including Nucleic Acids Research, American Journal of Human genetics, Genetics in Medicine and Human Genetics, and 10 external grants (Dr. Dong serves as the Principal Investigator) including GRF (#14117524), HMRF (#07186576, 8190226 and 09200236), ITF (#PRP/042/22FX), NSFC (#31801042 and 32270678). I am also serving as an Associate Editor in Science China-Life Sciences, a Guest Editor in Genes and an Editorial Board Member in BMC Genomics.

Currently, our team focuses on investigation of the underlying mechanism(s) of how novel structural variants were formed, the pathogenicity to male (non-obstructive azoospermia) and female infertility (premature ovarian insufficiency), and the impact on the clinical management.

Grants

He serves as a PI of 14 competitive grants including GRF (#14117524), HMRF (07186576, 8190226 and 09200236), ITF (PRP/042/22FX), NSFC (31801042 and 32270678) and NSFGD (2023A1515030220), and a Co-PI of a CRF (C4062-21GF)

Patents

US Non-Provisional Patent (Application #17/005,569), PCT (Application # PCT/CN2020/111016) and US Provisional Patent (Application #63/504,845)

Postgraduate Students

Graduated: Yanyan ZHANG (PhD); Jicheng QIAN (PhD);

Ongoing: Ziheng ZHOU (PhD); Lin CHEN (PhD)

Editorships

Associate editor: Science China Life Sciences
Editorial board member: BMC Genomics
Guest editor: Genes (Research Topics: Novel Insights into Prenatal Genetic Testing, and Genetics and Etiology for Human Infertility)
Topic: Chromosome Structural Variants: Epidemiology, Identification and Contribution to Human Diseases)

Mate-pair Sequencing Enables Identification and Delineation of Balanced and Unbalanced Structural Variants in Prenatal Cytogenomic Diagnostics Qian J, Wang H, Liang H, Zheng Y, Yu M, Tse WT, Kwan AHW, Wong L, Wong NKL, Wah IYM, Lau SL, Hui ASY, Chau MHK, Chen X, Zhang R, Poon L C, Leung TY, Liu P, Choy KW, Dong Z Clin Chem. 2025 Jan 3;71(1):155-168

Detection of genomic variants by genome sequencing in foetuses with central nervous system abnormalities Wang Y, Liu M, Gao Z, Hua C, Jiang J, Zheng Y, Dong Z, Cao Y, Choy KW, Zhu X, Kong X Ann Med. 2024 Dec;56(1):2399317

Contribution of Genomic Imbalance in Prenatal Congenital Anomalies of the Kidney and Urinary Tract: A Multi-Center Cohort Study Li K, Wang H, Chau MHK, Dong Z, Cao Y, Zheng Y, Leung TY, Choy KW, Zhu Y Prenat Diagn. 2024 Nov;44(12):1451-1461

Genome sequencing in the prenatal diagnosis of structural malformations in the fetus Chau MHK, Choolani M, Dong Z, Cao Y, Choy KW Best Pract Res Clin Obstet Gynaecol. 2024 Sep 13:102539

Identification of cryptic balanced translocations in couples with unexplained recurrent pregnancy loss based upon embryonic PGT-A results Li S, Li H, Gao Y, Zou Y, Yin X, Chen ZJ, Choy KW, Dong Z, Yan J Journal of Assist Reprod Genet. 2024 Jan;41(1):171- 184

Incremental yield of whole genome sequencing over chromosome microarray and exome sequencing for congenital anomalies in prenatal period and infancy: systematic review and meta-analysis Shreeve N, Sproule C, Choy KW, Dong Z, Gajewska-Knapik K, Kilby MD, Mone F Ultrasound Obstet Gynecol. 2024 Jan;63(1):15-23

Prenatal diagnosis of polycystic kidney caused by biallelic hypomorphic variants in the PKD1 gene Zheng Y, Wong L, Kwan AHW, Dong Z, Kwok KY, Choy KW, Dai H, Cao Y Prenat Diagn. 2024 Feb;44(2):247-250

Single-cell analysis reveals specific neuronal transition during mouse corticogenesis Zhou Z., Pan Y., Zhou S., Wang S., Zhang D., Cao Y., Jiang X., Li J., Zhu L., Zhao L., Gu S., Lin G., Dong Z., Sun H.X. Front Cell Dev Biol. 2023 Nov 6:11:1209320

A Pilot Investigation of Low-pass Genome Sequencing Identifying Site-Specific Variation in Chromosomal Mosaicisms by a Multiple Site Sampling Approach in First-trimester Miscarriages Li Y, Chau MHK, Zhang YX, Zhao YL, Xue SW, Li TC, Cao Y, Dong Z, Choy KW, Chung JPW Hum Reprod. 2023 Aug 1;38(8):1628-1642

Low-pass genome sequencing-based detection of paternity: validation in clinical cytogenetics Li K, Zhao Y, Chau MHK, Cao Y, Leung TY, Kwok YK, Choy KW, Dong Z Genes 2023 Jul; 14(7):1357

Mate-pair genome sequencing reveals structural variants for idiopathic male infertility Dong Z, Qian J, Law TSM, Chau MHK, Cao Y, Xue S, Tong S, Zhao Y, Kwok YK, Ng K, Chan DYL, Chiu PKF, Ng CF, Chung CHS, Mak JSZM, Leung TY, Chung JPW, Morton CC, Choy KW Hum Genet. 2023 Mar;142(3):363-377

TEDD: a database of temporal gene expression patterns during multiple developmental periods in human and model organisms Zhou Z, Tan C, Chau MHK, Jiang X, Ke Z, Chen X, Cao Y, Kwok YK, Bellgard M, Leung TY, Choy KW, Dong Z Nucleic Acids Res. 2023 Jan 6;51(D1):D1168-D1178

Molecular cytogenomics of human genetic disorders Dong Z, Choy KW, Morton CC In: Human Reproductive and Prenatal Genetics (Second Edition), Academic Press. 2023, Chapter 28, pp 721-741

Editorial: Chromosome structural variants: Epidemiology, identification and contribution to human diseases Dong Z, David D, Gonzaga-Jauregui C, Morton CC, Zepeda-Mendoza CJ Front Genet. 2022 Sep 9;13:1022918

Exploring the diagnostic utility of genome sequencing for fetal congenital heart defects Cao Y, Chau MHK, Zheng Y, Zhao Y, Kwan AHW, Hui SYA, Lam YH, Tan TYT, Tse WT, Wong L, Leung TY, Dong Z, Choy KW Prenat Diagn. 2022 Jun;42(7):862-872. (Impact factor (2022): 3.0, citations: 6

Investigation of the genetic etiology in male infertility with apparently balanced chromosomal structural rearrangements by genome sequencing Chau MHK, Li Y, Dai P, Shi M, Zhu X, Chung JPW, Kwok YK, Choy KW, Kong X, Dong Z Asian J Androl. May-Jun 2022;24(3):248-254

The Burden and Benefits of Knowledge: Ethical Considerations Surrounding Population-Based Newborn Genome Screening for Hearing Mitchell CO, Rivera-Cruz G, Chau MHK, Dong Z, Choy KW, Shen J, Amr S, Giersch ABS, Morton CC Int J Neonatal Screen. 2022 May 27;8(2):36

Investigation of chromosomal structural abnormalities in patients with undiagnosed neurodevelopmental disorders Cao Y, Luk HM, Zhang YY, Chau MHK, Xue S, Cheng SSW, Li AM, Chong JSC, Leung TY, Dong Z, Choy KW, Lo IFM Front Genet. 2022 Apr 14;13:803088

International Urogynaecology Consultation chapter 1 committee 4: patients’ perception of disease burden of pelvic organ prolapse Robinson D, Prodigalidad LT, Chan S, Serati M, Lozo S, Lowder J, Ghetti C, Hullfish K, Hagen S, Dumoulin C Int Urogynecol J. 2022 Feb;33(2):189-210

SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants Fino J, Marques B, Dong Z, David D Front Genet. 2021 Dec 1;12:757170

Trio-Based Low-Pass Genome Sequencing Reveals Characteristics and Significance of Rare Copy Number Variants in Prenatal Diagnosis Chau MHK, Qian J, Chen Z, Li Y, Zheng Y, Tse WT, Kwok YK, Leung TY, Dong Z, Choy KW Front Genet. 2021 Sep 20;12:742325

Low-pass genome sequencing-based detection of absence of heterozygosity: validation in clinical cytogenetics Dong Z, Chau MHK, Zhang Y, Yang Z, Shi M, Wah YMI, Kwok YK, Leung TY, Morton C, Choy KW Genet Med. 2021 Jul;23(7):1225-1233

Performance of Cell-Free DNA Screening for Fetal Common Aneuploidies and Sex Chromosomal Abnormalities: A Prospective Study from a Less Developed Autonomous Region in Mainland China Lai Y, Zhu X, He S, Dong Z, Tang Y, Xu F, Chen Y, Meng L, Tao Y, Yi S, Su J, Huang H, Luo J, Leung TY, Wei H Genes 2021 Mar;12(4):12040478

Deciphering the complexity of simple chromosomal insertions by genome sequencing Dong Z, Chau MHK, Zhang Y, Dai P, Zhu X, Leung TY, Kong X, Kwok YK, Stankiewicz P, Cheung SW, Choy KW Hum Genet. 2021 Feb;140(2):361-380

Low-pass genome sequencing: a validated method in clinical cytogenetics. Chau MHK, Wang H, Lai Y, Zhang Y, Xu F, Tang Y, Wang Y, Chen Z, Leung TY, Chung JPW, Kwok YK, Chong SC, Choy KW, Zhu Y, Xiong L, Wei W, Dong Z Hum Genet. 2020 Nov;139(11):1403-1415

Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis Wang H, Dong Z, Zhang R, Chau MHK, Yang Z, Tsang K, Wong HK, Gui B, Meng Z, Xiao K, Zhu X, Wang Y, Chen S, Leung TY, Cheung SW, Kwok YK, Morton CC, Zhu Y, Choy KW Genet Med, 2020 Mar;22(3):500-510

Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage. Dong Z, Yan J, Xu F, Yuan J, Jiang H, Wang H, Chen H, Zhang L, Ye L, Xu J, Shi Y, Yang Z, Cao Y, Chen L, Li Q, Zhao X, Li J, Chen A, Zhang W, Wong HG, Qin Y, Zhao H, Chen Y, Li P, Ma T, Wang WJ, Kwok YK, Jiang Y, Pursley AN, Chung JPW, Hong Y, Kristiansen K, Yang H, Piña-Aguilar RE, Leung TY, Cheung SW, Morton CC, Choy KW, Chen ZJ. Am J Hum Genet. 2019 Dec 5;105(6):1102-1111.

Development of Coupling Controlled Polymerizations by Adapter-ligation in Mate-pair Sequencing for Detection of Various Genomic Variants in One Single Assay Dong Z, Zhao X, Li Q, Yang Z, Xi Y, Alexeev A, Shen H, Wang O, Ruan J, Ren H, Wei H, Qi X, Li J, Zhu X, Zhang Y, Dai P, Kong X, Kirkconnell K, Alferov O, Giles S, Yamtich J, Kermani B, Dong C, Liu P, Mi Z, Zhang W, Xu X, Drmanac R, Choy KW, Jiang Y DNA Res. 2019 Aug 1;26(4):313-325

Prenatal Diagnosis of Fetuses with Increased Nuchal Translucency by Genome Sequencing Analysis Choy KW, Wang H, Shi M, Chen J, Yang Z, Zhang R, Yan H, Wang Y, Chen S, Chau MHK, Cao Y, Chan OYM, Kwok YKY, Zhu Y, Chen M, Leung TY, Dong Z Front Genet. 2019 Aug; volume 10:761 (14 pages)

Chronic inflammatory lesions of the placenta are associated with an up-regulation of amniotic fluid CXCR3: A marker of allograft rejection Maymon E, Romero R, Bhatti G, Chaemsaithong P, Gomez-Lopez N, Panaitescu B, Chaiyasit N, Pacora P, Dong Z, Hassan SS, Erez O J Perinat Med. 2018 Feb 23;46(2):123-137

Identification of balanced chromosomal rearrangements previously unknown among participants in the 1000 Genomes Project: implications for interpretation of structural variation in genomes and the future of clinical cytogenetics Dong Z, Wang H, Chen H, Jiang H, Yuan J, Yang Z, Wang WJ, Xu F, Guo X, Cao Y, Zhu Z, Geng C, Cheung CWC, Kwok YKY, Yang H, Leung TY, Morton CC, Cheung SW, Choy KW Genet Med. 2018 Jul;20(7):697-707

Balanced Chromosomal Rearrangement Detection by Low-Pass Whole-Genome Sequencing Dong Z, Ye L, Yang Z, Chen H, Yuan J, Wang H, Guo X, Li Y, Wang J, Chen F, Cheung SW, Morton CC, Jiang H, Choy KW Curr Protoc Hum Genet. 2018 Jan 24;96:8.18.1-8.18

Copy-Number Variants Detection by Low-Pass Whole-Genome Sequencing Dong Z, Xie, W, Chen, H, Xu, J, Wang, H, Li, Y, Wang, J, Chen, F, Choy KW, Jiang H Curr Protoc Hum Genet 2017 Jul 11;94:8 17 1-8 17 16

Low-pass Whole-genome Sequencing in Clinical Cytogenetics: A Validated Approach Dong Z, Zhang J, Hu P, Chen H, Xu J, Tian Q, Meng L, Ye Y, Wang J, Zhang M, Li Y, Wang HL, Yu S, Chen F, Xie J, Jiang H, Wang W, Choy KW, Xu Z Genet Med Sep 2016;18(9): 940 - 948

A Robust Approach for Blind Detection of Balanced Chromosomal Rearrangements with Whole-Genome Low-Coverage Sequencing. Dong Z, Jiang LP, Yang CC, Hu H, Wang XH, Chen HX, Choy KW, Hu HM, Dong YL, Hu B, Xu JC, Long Y, Cao SJ, Chen H, Wang WJ, Jiang H, Xu FP, Yao H, Xu X, Liang ZQ Hum Mutat 2014;35(5): 625 - 636