Lab of Combinatorial Genetics & Synthetic Biology @ HKU

Publications

Selected articles

(For a full list see below)

Accurate top protein variant discovery via low-N pick-and-validate machine learning

Chu HY, Fong JHC, Thean DGL, Zhou P, Fung FKC, Huang Y, Wong ASL.

Cell Systems (2023) 15(2),193-203

  2024



preview

High-throughput screening of genetic and cellular drivers of syncytium formation induced by the spike protein of SARS-CoV-2

Chan CWF, Wang B, Nan L, Huang X, Mao T, Chu HY, Luo C, Chu H, Choi GCG, Shum AHC, Wong ASL.

Nature Biomedical Engineering (2023) 8,91–309

  2023



Nature portfolio blog post
Nature biomedical engineering editorial

Parallel engineering and activity profiling of a base editor system

Fong JHC, Chu HY, Zhou P, Wong ASL.

Cell Systems (2023) 14(5),392-403

  2023



What are the current bottlenecks in developing and applying CRISPR technologies?

Kellogg EH, Gootenberg J, Abudayyeh O, Wong ASL, Dahlman JE, Lapinaite A, Myhrvold C, Liu CC, Hsu PD, Mali P, Qi LS.

Cell Systems (2022) 13(8),589-593

  2022



Machine learning-coupled combinatorial mutagenesis enables resource-efficient engineering of CRISPR-Cas9 genome editor activities

Thean DGL, Chu HY, Fong JHC, Chan BKC, Zhou P, Kwok CSC, Chan YM ,Mak S, Choi GCG, Ho JWK, Zheng Z, Wong ASL.

Nature Communications 13, 2219 (2022)

  2022



Nature portfolio blog post
HKUMed press release

High-fidelity KKH variant of Staphylococcus aureus Cas9 nucleases with improved base mismatch discrimination

Yuen C, Thean DG, Chan BKC, Zhou P, Kwok CSC, Chu HY, Cheung M, Wang B, Chan YM ,Mak S,Leung A, Choi GCG, Zheng Z, Wong ASL.

Nucleic Acids Research: gkab1291 (2022)

  2022



HKUMed News
Ta Kung Pao news

A Combinatorial CRISPR–Cas9 Screen Identifies Ifenprodil as an Adjunct to Sorafenib for Liver Cancer Treatment

Xu F, Tong M, Tong CSW, Chan BKC, Chu HY, Wong TL, Fong J, Cheung M, Mak KH, Pardeshi L, Huang Y, Wong KH, Choi, GCG, Ma S, Wong ASL.

Cancer Research 81:6219–32 (2021)

  2021



Featured in Headline Daily, Sing Tao Daily and Hong Kong Economic Journal.

A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets.

Zhou, P., Chan, K.C.B., Wan, Y K, Yuen, C.T.L., Choi, C.G.G. , Li, X., Tong, S.W.C, Zhong, S.W.S., Sun, J., Bao, Y. , Mak, S.Y.L., Chow, Z.Y.M., Khaw, J.V., Leung, S.Y., Zheng, Z., Cheung, W.T.L., Tan, K., Wong, K.H., Chan, H.Y.E., Wong, S.L.A.

Cell Reports, Volume 32, Issue 6, 108020

  2020



Combinatorial mutagenesis en masse optimizes SpCas9's genome-editing activities.

Choi, C.G.G., Zhou, P., Yuen, T.L.C., Chan, K.C.B., Xu, F., Bao, S., Chu, H.Y., Thean, D., Tan, K., Wong, K.H., Zheng, Z., Wong, S.L.A.

Nature Methods 16,722–730

  2019



Awarded the Faculty Outstanding Research Output Award 2020, Faculty of Medicine, HKU
–Nature Methods’ Blog post (also mentioned on Twitter)
–BioWorld Science Editor’s Choice on July 2019
–Featured in Singpao newspaper

Deciphering combinatorial genetics.

Wong, S.L.A., Choi, C.G.G., Lu, T.K.

Annual Reviews of Genetics 50, 515-538

  2016



Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM.

Wong, S.L.A., Choi, C.G.G., Cui, C.H.*, Pregernig, G., Milani, P., Adam, M., Perli, S.D., Kazer, S.W., Gaillard, A., Hermann, M., Shalek, A.K., Fraenkel, E., Lu, T.K.

Proceedings of National Academy of Sciences 113(9), 2544-2549

  2016



–Research Highlights of Nature Reviews Genetics as a “creative combination”
–Research Highlights of Proceedings of National Academy of Sciences
–Research Highlights in Cell Systems
–Highlighted by Addgene blog

Massively parallel high-order combinatorial genetics in human cells.

Wong, S.L.A., Choi, C.G.G., Cheng, A.A., Purcell, O., Lu, T.K.

Nature Biotechnology 33(9), 952-961

  2015



–Research Highlights of Nature Reviews Genetics

 

Full List

Accurate top protein variant discovery via low-N pick-and-validate machine learning

Chu HY, Fong JHC, Thean DGL, Zhou P, Fung FKC, Huang Y, Wong ASL.
Cell Systems (2023) 15(2),193-203
2024

preview


Discovery of regulatory motifs in 5′ untranslated regions using interpretable multi-task learning models

Zheng W, Fong JHC, Wan YK, Chu HY, Huang Y, Wong ASL, Ho JWK.
Cell Systems (2023) 14(12),1103-1112
2023


High-throughput screening of genetic and cellular drivers of syncytium formation induced by the spike protein of SARS-CoV-2

Chan CWF, Wang B, Nan L, Huang X, Mao T, Chu HY, Luo C, Chu H, Choi GCG, Shum AHC, Wong ASL.
Nature Biomedical Engineering (2023) 8,91–309
2023

Nature portfolio blog post
Nature biomedical engineering editorial


Advancing CRISPR/Cas gene editing with machine learning

Fong JHC, Wong ASL.
Current Opinion in Biomedical Engineering (2023), 28:100477
2023


Parallel engineering and activity profiling of a base editor system

Fong JHC, Chu HY, Zhou P, Wong ASL.
Cell Systems (2023) 14(5),392-403
2023


What are the current bottlenecks in developing and applying CRISPR technologies?

Kellogg EH, Gootenberg J, Abudayyeh O, Wong ASL, Dahlman JE, Lapinaite A, Myhrvold C, Liu CC, Hsu PD, Mali P, Qi LS.
Cell Systems (2022) 13(8),589-593
2022


CRISPR screening in cancer stem cells

Wang B, Wong ASL.
Essays Biochem (2022) EBC20220009.
2022


Machine learning-coupled combinatorial mutagenesis enables resource-efficient engineering of CRISPR-Cas9 genome editor activities

Thean DGL, Chu HY, Fong JHC, Chan BKC, Zhou P, Kwok CSC, Chan YM ,Mak S, Choi GCG, Ho JWK, Zheng Z, Wong ASL.
Nature Communications 13, 2219 (2022)
2022

Nature portfolio blog post
HKUMed press release


High-fidelity KKH variant of Staphylococcus aureus Cas9 nucleases with improved base mismatch discrimination

Yuen C, Thean DG, Chan BKC, Zhou P, Kwok CSC, Chu HY, Cheung M, Wang B, Chan YM ,Mak S,Leung A, Choi GCG, Zheng Z, Wong ASL.
Nucleic Acids Research: gkab1291 (2022)
2022

HKUMed News
Ta Kung Pao news


Optochemical Control of mTOR Signaling and mTOR-Dependent Autophagy

Wang T, Long K, Zhou Y, Jiang X, Liu J, Fong JHC, Wong ASL, Ng WL, Wang W
ACS Pharmacology & Translational Science 5(3), 149–155 (2022)
2022


Facilitating Machine Learning-Guided Protein Engineering with Smart Library Design and Massively Parallel Assays

Chu HY, Wong ASL.
Advanced Genetics 2100038 (2021)
2021


A Combinatorial CRISPR–Cas9 Screen Identifies Ifenprodil as an Adjunct to Sorafenib for Liver Cancer Treatment

Xu F, Tong M, Tong CSW, Chan BKC, Chu HY, Wong TL, Fong J, Cheung M, Mak KH, Pardeshi L, Huang Y, Wong KH, Choi, GCG, Ma S, Wong ASL.
Cancer Research 81:6219–32 (2021)
2021

Featured in Headline Daily, Sing Tao Daily and Hong Kong Economic Journal.


High-throughput 5′ UTR engineering for enhanced protein production in non-viral gene therapies.

Cao J, Novoa EM, Zhang Z, Chen WCW, Liu D, Choi GCG, Wong ASL, Wehrspaun C, Kellis M, Lu TK.
Nat Communications 12, 4138 (2021)
2021


Combinatorial genetics methods for discovering high-order regulatory combinations and engineering genetic drivers for neural differentiation

Thean DG, Wong AS.
Neural Regen Res 2021 Apr 30;16:2403-4.
2021


Extensible combinatorial CRISPR screening in mammalian cells.

Zhou P., Wan Y.K., Chan B.K.C., Choi C.G.G., Wong S.L.A
STAR Protoc. 2021;2(1):100255
2021

CombiPIPE github link


High-Throughput Protein Engineering by Massively Parallel Combinatorial Mutagenesis.

Wan Y.K., Choi C.G.G., Wong S.L.A
Methods Mol Biol. 2021;2199:3-12.
2021


Single cell RNA-Seq reveals that CD9 is a negative marker of glucose-responsive pancreatic beta-like cells derived from human pluripotent stem cells.

Li X., Yang K.Y., Chan V., Leung K.T., Zhang X.B., Wong S..LA., Chong C., Wang C.C., Ku M., Lui K.O.
Stem Cell Reports, Volume 15, 1-16
2020


A Three-Way Combinatorial CRISPR Screen for Analyzing Interactions among Druggable Targets.

Zhou, P., Chan, K.C.B., Wan, Y K, Yuen, C.T.L., Choi, C.G.G. , Li, X., Tong, S.W.C, Zhong, S.W.S., Sun, J., Bao, Y. , Mak, S.Y.L., Chow, Z.Y.M., Khaw, J.V., Leung, S.Y., Zheng, Z., Cheung, W.T.L., Tan, K., Wong, K.H., Chan, H.Y.E., Wong, S.L.A.
Cell Reports, Volume 32, Issue 6, 108020
2020


Combinatorial mutagenesis en masse optimizes SpCas9's genome-editing activities.

Choi, C.G.G., Zhou, P., Yuen, T.L.C., Chan, K.C.B., Xu, F., Bao, S., Chu, H.Y., Thean, D., Tan, K., Wong, K.H., Zheng, Z., Wong, S.L.A.
Nature Methods 16,722–730
2019

Awarded the Faculty Outstanding Research Output Award 2020, Faculty of Medicine, HKU
–Nature Methods’ Blog post (also mentioned on Twitter)
–BioWorld Science Editor’s Choice on July 2019
–Featured in Singpao newspaper


Ectopic expression of recipient CD47 inhibits mouse macrophage-mediated immune rejection against human stem cell transplants.

Leung, C.S., Li ,J., Xu, F., Wong, S.L.A., Lui, K.O.
FASEB J. 33(1): 484-493
2018


Deciphering combinatorial genetics.

Wong, S.L.A., Choi, C.G.G., Lu, T.K.
Annual Reviews of Genetics 50, 515-538
2016


Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM.

Wong, S.L.A., Choi, C.G.G., Cui, C.H.*, Pregernig, G., Milani, P., Adam, M., Perli, S.D., Kazer, S.W., Gaillard, A., Hermann, M., Shalek, A.K., Fraenkel, E., Lu, T.K.
Proceedings of National Academy of Sciences 113(9), 2544-2549
2016

–Research Highlights of Nature Reviews Genetics as a “creative combination”
–Research Highlights of Proceedings of National Academy of Sciences
–Research Highlights in Cell Systems
–Highlighted by Addgene blog


Massively parallel high-order combinatorial genetics in human cells.

Wong, S.L.A., Choi, C.G.G., Cheng, A.A., Purcell, O., Lu, T.K.
Nature Biotechnology 33(9), 952-961
2015

–Research Highlights of Nature Reviews Genetics


TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory.

Lai, K.O., Wong, S.L.A., Cheung, M.C., Xu, P., Liang, Z., Lok, K.C., Xie, H., Palkos, M.E., Yung, W.H., Tessarollo, L., Cheung, Z.H., Ip, N.Y.
Nature Neuroscience 15(11), 1506-1515
2012

–Highlighted by News and Views of Nature Neuroscience
–Editor’s choice of Science Signaling


Cdk5-mediated phosphorylation of endophilin B1 is required for induced autophagy in models of Parkinson's disease.

Wong, S.L.A., Lee, R.H.K., Cheung, A.Y., Yeung, P.K., Chung, S.K., Cheung, Z.H. and Ip, N.Y.
Nature Cell Biology 13(5), 568-579
2011

–Research Highlights of Nature Asia-Pacific International Molecular Biology Network
–Research Highlights of Nature China


Molecular machinery of macroautophagy and its deregulation in diseases.

Wong, S.L.A., Cheung, Z.H. and Ip, N.Y.
Biochimica et Biophysica Acta Molecular Basis of Disease 1812(11), 1490-1479
2011


Sodium dodecyl sulfate-insoluble oligomers are involved in polyglutamine degeneration.

Wong, S.L.A., Chan, W. M. and Chan, H.Y.E.
FASEB J. 22(9), 3348-3357
2008


Transcriptional malfunctioning of heat shock protein gene expression in spinocerebeller ataxias.

Huen, N.Y.M., Wong, S.L.A. and Chan, H.Y.E.
The Cerebellum 6(2), 111-117
2006


In vivo functional characterization of the SARS Coronavirus 3a protein in Drosophila.

Wong, S.L.A., Chen, Y.W., Chan, C.M., Chan, C.S.M., Chan, P.K.S., Chui, Y.L., Fung, K.P., Waye, M.M.Y., Tsui, S.K.W. and Chan, H.Y.E.
Biochem. Biophy. Res. Comm. 337, 720-729
2005

–Featured on Cover of the issue