LIM Weng Khong

RESEARCH

Our work focuses on developing tools and workflows that improve clinical variant interpretation. We are particularly interested in the development of improved in silico prediction tools that expand our ability to identify disease-causing variants, especially non-coding ones. Apart from that, due to our strong collaboration with clinicians, we aim to develop and validate clinical genome analytics workflows that incorporate emerging tools and sequencing technologies (e.g., machine learning, long-read sequencing, etc.). As part of Singapore’s National Precision Medicine program, we lead efforts aimed at identifying clinically significant variants present in large-scale sequencing of Singaporeans to better understand the burden of genetic disorders in our population. We are also interested in integration of electronic health records in population health studies in support of genotype-phenotype associations.

Example projects

1. Primate Conservation Sequencing Consortium - Working closely with our partners in Mandai Nature and Illumina, we are contributing whole-genome sequences of non-human primates from the Singapore Zoo to this international consortium aimed at creating a comprehensive resource of genomic data to support primate conservation and human biomedical research.
2. Population survey of genetic disease risk - By studying large-scale whole-genome sequencing datasets generated by Singapore’s precision medicine programs (e.g., SG10K, SG100K), we are identifying genetic disorders with high carrier frequencies among Singaporeans of diverse ancestries. To support this, we are developing clinical variant annotation and prioritisation workflows capable of analysing population-scale genome datasets.
3. Long-read sequencing for clinical genomics - Long-read sequencing is making inroads in the field of clinical genetics through its ability to identify variants in ‘challenging’ genomic regions, and complex structural variants. We are developing tools to prioritise such variants, separating potentially disease-causing ones from the vast numbers of candidate variants.

Selected Publications

• Bylstra Y, Lim WK, Kam S, Tham KW, Wu RR, Teo JX, Davila S, Kuan JL, Chan SH, Bertin N, Yang CX, Rozen S, Teh BT, Yeo KK, Cook SA, Jamuar SS, Ginsburg GS, Orlando LA, Tan P. Family history assessment significantly enhances delivery of precision medicine in the genomics era. Genome Medicine. 2021; 13(1):1-11. [JIF: 11:12]
• Shaw T, Chan SH, Teo JX, Chong ST, Li ST, Courtney E, Ishak D, Sankar H, Ang ZLT, Chiang J, Loh M, Zhou L, Lee SC, Yeh HY, Kolinjivadi AM, Lim WK, Ngeow J. Investigation into the origins of an ancient BRCA1 founder mutation identified among Chinese families in Singapore. International Journal of Cancer. 2021; 148(3): 637-645. [JIF: 7.40]
• Ma D, Tan YJ, Ng ASL, Ong HL, Sim W, Lim WK, Teo JX, Ng EYL, Lim EC, Lim EW, Chan LL, Tan LCS, Yi Z, Tan EK. Association of NOTCH2NLC repeat expansions with Parkinson disease. JAMA Neurology. 2020; 77(12): 1559-1563. [JIF: 13.30]
• Teo JX, Davila S, Yang C, Hii AA, Pua CJ, Yap J, Tan SY, Sahlen A, Chin CWL, Teh BT, Rozen SG, Cook SA, Yeo KK†, Tan P†, Lim WK†. Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging. Communications Biology. 2019; 2(1). [JIF: NA] († = corresponding author)
• Lim WK*†, Davila S*, Teo JX, Yang C, Pua CJ, Blöcker C, Lim JQ, Ching J, Yap JJL, Tan SY, Sahlén A, Chin CWL, Teh BT, Rozen SG, Cook SA†, Yeo KK†, Tan P†. Beyond fitness tracking: The use of consumer-grade wearable data from normal volunteers in cardiovascular and lipidomics research. PLOS Biology. 2018; 16(2). [JIF: 9.80] (* = lead author) († = corresponding author)
• Chan SH*, Lim WK*, Ishak ND, Li ST, Goh WL, Tan GS, Lim KH, Teo M, Ng CCY, Malik S, Tan MH, Teh JYH, Chin FKC, Kesavan S, Selvarajan S, Tan P, Teh BT, Soo KC, Farid M, Quek R, Ngeow J. Germline mutations in cancer predisposition genes are frequent in sporadic sarcomas. Scientific Reports. 2017; 7(1): 10660. [JIF: 4.26] (* = lead author)
• Chan SH*, Lim WK*, Michalski ST, Lim JQ, Ishak ND, Met-Domestici M, Ng CCY, Vikstrom K, Esplin ED, Fulbright J, Ang MK, Wee J, Sittampalam K, Mohamad F, Lincoln SE, Itahana K, Abdullah S, Teh BT, Ngeow J. Germline hemizygous deletion of CDKN2A–CDKN2B locus in a patient presenting with Li–Fraumeni syndrome. npj Genomic Medicine. 2016; 1: 16015. [JIF: 4.42] (* = lead author)
• Tan J*, Ong CK*, Lim WK*, Ng CCY, Thike AA, Ng LM, Rajasegaran V, Myint SS, Nagarajan S, Thangaraju S, Dey S, Nasir ND, Wijaya GC, Lim JQ, Huang D, Li Z, Wong BH, Chan JYS, McPherson JR, Cutcutache I, Poore G, Tay ST, Tan WJ, Putti TC, Ahmad BS, Iau P, Chan CW, Tang APT, Yong WS, Madhukumar P, Ho GH, Tan VK, Wong CY, Hartman M, Ong KW, Tan BK, Rozen SG, Tan P, Tan PH, Teh BT. Genomic landscapes of breast fibroepithelial tumors. Nature Genetics. 2015; 47(11): 1341-1345. [JIF: 27.96] (* = lead author)
• Lim WK*, Ong CK*, Tan J*, Thike AA, Ng CC, Rajasegaran V, Myint SS, Nagarajan S, Nasir ND, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VK, Hartman M, Ong KW, Tan BK, Rozen SG, Tan PH, Tan P, Teh BT. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nature Genetics. 2014; 46(8): 877–880. [JIF: 27.96] (* = lead author)
• Chan-On W*, Nairismägi ML*, Ong CK*, Lim WK*, Dima S, Pairojkul C, Lim KH, McPherson JR, Cutcutache I, Heng HL, Ooi L, Chung A, Chow P, Cheow PC, Lee SY, Choo SP, Tan IB, Duda D, Nastase A, Myint SS, Wong BH, Gan A, Rajasegaran V, Ng CC, Nagarajan S, Jusakul A, Zhang S, Vohra P, Yu W, Huang D, Sithithaworn P, Yongvanit P, Wongkham S, Khuntikeo N, Bhudhisawasdi V, Popescu I, Rozen SG, Tan P, Teh BT. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nature Genetics. 2013; 45(12): 1474–1478. [JIF: 27.96] (* = lead author)