Protein Sequence Analysis



Our group expertise is in computational protein sequence and structure analysis to predict various aspects of molecular and cellular functions (enzymatic activities, posttranslational modifications, cleavage, translocation signals, 3D structures, effects of mutations, phylogenetic relationships, cellular pathways etc.) for discovering the molecular mechanisms of biological and clinical phenotypes and experimental validation together with collaborators. Our repertoire of computational analysis methods is applicable and useful in multiple research areas but our main focus currently is on infectious diseases, human mutations, allergy and enzyme function prediction.

Infectious Diseases

One of our traditional strongholds since the swine flu in 2009 is infectious disease research. Our FluSurver ( is the most complete one-stop influenza mutation analysis tool being used by researchers and surveillance experts globally. We have several published and ongoing projects with the WHO CC in Australia and National Influenza Centres relating to influenza drug resistance, viral fitness, host specificity and antigenic changes. The FluSurver is also a primary analysis tool for the global data science initiative GISAID, the most complete influenza database used by WHO flu surveillance networks. BII/A*STAR has been a technical and scientific partner to GISAID for several years providing analysis tools.

When the new coronavirus was discovered by Chinese colleagues, the sequences were shared using GISAID’s platform on January 10th 2020 ( Since it was a new virus, this required a new database system to be designed and built, as well as a new workflow to curate and release sequences. GISAID called on the Singapore team to help. In addition to the expert advice contributing to build the new system and annotation tools like the CoVsurver (, the Singapore team has been critical in processing the incoming genomes with quality checks and analysis reports since the beginning and was reinforced soon by more international colleagues. This has enabled global genome sharing from the first day to over 16 million genomes from 215 countries and territories by 2023, earning the WHO Chief Scientist’s commendation of GISAID as a “game changer”. (Swaminathan, Nature 2020). This had significant impact for Singapore and the world. Diagnostics, drugs, and vaccine development were started based on sequences in GISAID and are constantly checked with new incoming data if they are still working well and help to identify new variants. In Singapore, BII has become a hub for multiple institutions and agencies to access and benefit from the GISAID work, from other A*STAR colleagues to NPHL/NCID, MOH, Duke-NUS, hospitals and DSO.

Because we can quickly go from genomes to protein structures through modelling in our computers often only requiring the new sequences as input, our group offers powerful support in infectious disease surveillance and rapid outbreak investigations to get a quick handle on bugs here and around the world. Besides Influenza and hCoV-19, we also helped characterizing MERS, Ebola, HIV, Noro, Adeno, RSV, Hepatitis C, West Nile, Dengue and Zika viruses. Through close collaboration with the National Public Health Laboratory at the National Centre for Infectious Diseases of the Ministry of Health we contribute our knowledge and computational expertise at the national frontline for infectious disease surveillance.

Human Mutations, Allergy and Enzyme Function Prediction

We aim at bridging the gap from nucleotide variation to protein structures to interpret effects of human mutations. For example, we have helped clinical collaborators to analyze variants found in patients and tried to mechanistically explain their possible role in a range of diseases like cancer, myopia, leprosy or atopic dermatitis. We are participating in the National Precision Medicine Programme to help mapping mutations into 3D protein structures relative to drug binding sites supporting our colleagues at GIS, LKC and PRECISE.

Multinational Procter & Gamble and BII have jointly developed animal-testing-free Bioinformatics techniques for assessing the allergy potential of proteins using their amino acid sequence and tertiary structure ( with AllerCatPro ( Our team, together with the Singapore Institute of Food and Biotechnology Innovation (SIFBI), NTU FRESH and James Cook University, apply AllerCatPro to the safety assessment of proteins found in novel foods, such as those replacing meat with alternative protein sources including as advisor to the Singapore Food Authority. In other notable projects with SIFBI and other institutes often including industry collaborations, we are applying our sequence function and pathway analysis capabilities to support the Natural Product Library, Biotransformation and Synthetic Biology programmes as well as the Pharma Innovation Programme Singapore.

BII - Protein Sequence Analysis Figure 1
Figure 1. Our Emerging Variant tools at GISAID –tracking of emerging new constellations of mutations with interpretation of relevant amino acid changes


 Executive Director MAURER-STROH Sebastian   |    [View Bio]  
 Principal Scientist I  LIMVIPHUVADH Vachiranee
 Senior Scientist II KENANOV Dimitar 
 Senior Scientist I HO Wei-Hao Joses
 Senior Scientist I MAK Tze Minn Sandy
 Senior Scientist I TIRUVAYIPATI Suma
 Scientist  CHONG Cheng Shoong Ken
 Principal Research Officer I LEE Tze Chuan Raphael
 Lead Research Officer II XU Yani Angela
 Senior Research Officer I MIYAJIMA Jhoann
 Senior Research Officer I CHEW Yi Hong
 Senior Research Officer I NG Ting Ting
 Research Officer MAKHEJA Meera
 PhD Student ATTIQUE Syed Awais


Selected Publications

  • Tay MZ, Goh YS, Fong SW, Chang ZW, Rouers A, Wong N, Torres-Ruesta A, Huang Y, Selvam SK, Hor PX, Loh CY, Wang B, Mohd Salleh SN, Ngoh EZX, Lee RTC, Neo V, Kam IKJ, Poh XY, Rao S, Chia PY, Ong SWX, Lee TH, Lim C, Teo J; NCID Study Group; PRIBIVAC Cohort Study Group; Maurer-Stroh S, Wang CI, Leo YS, Lin RTP, Lye DC, Young BE, Ng LFP, Renia L. Heterologous mRNA vaccine boosters induce a stronger and longer-lasting antibody response against Omicron XBB variant. Lancet Reg Health West Pac. 2023 Apr;33:100732. doi: 10.1016/j.lanwpc.2023.100732. Epub 2023 Mar 7. PMID: 37125085; PMCID: PMC9988436.

  • Gangavarapu K, Latif AA, Mullen JL, Alkuzweny M, Hufbauer E, Tsueng G, Haag E, Zeller M, Aceves CM, Zaiets K, Cano M, Zhou X, Qian Z, Sattler R, Matteson NL, Levy JI, Lee RTC, Freitas L, Maurer-Stroh S; GISAID Core and Curation Team; Suchard MA, Wu C, Su AI, Andersen KG, Hughes LD. genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations. Nature Methods. 2023 Apr;20(4):512-522. doi: 10.1038/s41592-023-01769-3. Epub 2023 Feb 23. PMID: 36823332.

  • Wong E, Bertin N, Hebrard M, Tirado-Magallanes R, Bellis C, Lim WK, Chua CY, Tong PML, Chua R, Mak K, Lim TM, Cheong WY, Thien KE, Goh KT, Chai JF, Lee J, Sung JJ, Wong TY, Chin CWL, Gluckman PD, Goh LL, Ban KHK, Tan TW; SG10K_Health Consortium; Sim X, Cheng CY, Davila S, Karnani N, Leong KP, Liu J, Prabhakar S, Maurer-Stroh S, Verma CS, Krishnaswamy P, Goh RSM, Chia I, Ho C, Low D, Virabhak S, Yong J, Zheng W, Seow SW, Seck YK, Koh M, Chambers JC, Tai ES, Tan P. The Singapore National Precision Medicine Strategy. Nature Genet. 2023 Feb;55(2):178-186. doi: 10.1038/s41588-022-01274-x. Epub 2023 Jan 19. PMID: 36658435.

  • Brito AF, Semenova E, Dudas G, Hassler GW, Kalinich CC, Kraemer MUG, Ho J, Tegally H, Githinji G, Agoti CN, Matkin LE, Whittaker C; Bulgarian SARS-CoV-2 sequencing group; Communicable Diseases Genomics Network (Australia and New Zealand); COVID-19 Impact Project; Danish Covid-19 Genome Consortium; Fiocruz COVID-19 Genomic Surveillance Network; GISAID core curation team; Network for Genomic Surveillance in South Africa (NGS-SA); Swiss SARS-CoV-2 Sequencing Consortium; Howden BP, Sintchenko V, Zuckerman NS, Mor O, Blankenship HM, de Oliveira T, Lin RTP, Siqueira MM, Resende PC, Vasconcelos ATR, Spilki FR, Aguiar RS, Alexiev I, Ivanov IN, Philipova I, Carrington CVF, Sahadeo NSD, Branda B, Gurry C, Maurer-Stroh S, Naidoo D, von Eije KJ, Perkins MD, van Kerkhove M, Hill SC, Sabino EC, Pybus OG, Dye C, Bhatt S, Flaxman S, Suchard MA, Grubaugh ND, Baele G, Faria NR. Global disparities in SARS-CoV-2 genomic surveillance. Nature Commun. 2022 Nov 16;13(1):7003. doi: 10.1038/s41467-022-33713-y. PMID: 36385137; PMCID: PMC9667854.

  • Chan SH, Bylstra Y, Teo JX, Kuan JL, Bertin N, Gonzalez-Porta M, Hebrard M, Tirado-Magallanes R, Tan JHJ, Jeyakani J, Li Z, Chai JF, Chong YS, Davila S, Goh LL, Lee ES, Wong E, Wong TY; SG10K_Health Consortium; Prabhakar S, Liu J, Cheng CY, Eisenhaber B, Karnani N, Leong KP, Sim X, Yeo KK, Chambers JC, Tai ES, Tan P, Jamuar SS, Ngeow J, Lim WK. Analysis of clinically relevant variants from ancestrally diverse Asian genomes. Nature Commun. 2022 Nov 5;13(1):6694. doi: 10.1038/s41467-022-34116-9. PMID: 36335097; PMCID: PMC9637116.

  • Happi C, Adetifa I, Mbala P, Njouom R, Nakoune E, Happi A, Ndodo N, Ayansola O, Mboowa G, Bedford T, Neher RA, Roemer C, Hodcroft E, Tegally H, O'Toole Á, Rambaut A, Pybus O, Kraemer MUG, Wilkinson E, Isidro J, Borges V, Pinto M, Gomes JP, Freitas L, Resende PC, Lee RTC, Maurer-Stroh S, Baxter C, Lessells R, Ogwell AE, Kebede Y, Tessema SK, de Oliveira T. Urgent need for a non-discriminatory and non-stigmatizing nomenclature for monkeypox virus. PLoS Biol. 2022 Aug 23;20(8):e3001769. doi: 10.1371/journal.pbio.3001769. PMID: 35998195; PMCID: PMC9451062.

  • Nguyen MN, Krutz NL, Limviphuvadh V, Lopata AL, Gerberick GF, Maurer-Stroh S. AllerCatPro 2.0: a web server for predicting protein allergenicity potential. Nucleic Acids Res. 2022 Jul 5;50(W1):W36-W43. doi: 10.1093/nar/gkac446. PMID: 35640594; PMCID: PMC9252832.

  • GISAID's Role in Pandemic Response. Khare S, Gurry C, Freitas L, Schultz MB, Bach G, Diallo A, Akite N, Ho J, Lee RT, Yeo W, Curation Team GC, Maurer-Stroh S. China CDC Wkly. 2021 Dec 3;3(49):1049-1051. doi: 10.46234/ccdcw2021.255.

  • Clinical and virological features of SARS-CoV-2 variants of concern: a retrospective cohort study comparing B.1.1.7 (Alpha), B.1.315 (Beta), and B.1.617.2 (Delta). Ong SWX, Chiew CJ, Ang LW, Mak TM, Cui L, Toh MPHS, Lim YD, Lee PH, Lee TH, Chia PY, Maurer-Stroh S, Lin RTP, Leo YS, Lee VJ, Lye DC, Young BE. Clin Infect Dis. 2021 Aug 23:ciab721. doi: 10.1093/cid/ciab721. Online ahead of print.

  • Plasmodium vivax binds host CD98hc (SLC3A2) to enter immature red blood cells. Malleret B, El Sahili A, Tay MZ, Carissimo G, Ong ASM, Novera W, Lin J, Suwanarusk R, Kosaisavee V, Chu TTT, Sinha A, Howland SW, Fan Y, Gruszczyk J, Tham WH, Colin Y, Maurer-Stroh S, Snounou G, Ng LFP, Chan JKY, Chacko AM, Lescar J, Chandramohanadas R, Nosten F, Russell B, Rénia L. Nat Microbiol. 2021 Aug;6(8):991-999. doi: 10.1038/s41564-021-00939-3. Epub 2021 Jul 22.
  • Global spectrum of population-specific common missense variation in cytochrome P450 pharmacogenes. Chong CS, Limviphuvadh V, Maurer-Stroh S. Hum Mutat. 2021 Sep;42(9):1107-1123. doi: 10.1002/humu.24243. Epub 2021 Jun 29.

  • SARS-CoV-2 Variants of Interest and Concern naming scheme conducive for global discourse. Konings F, Perkins MD, Kuhn JH, Pallen MJ, Alm EJ, Archer BN, Barakat A, Bedford T, Bhiman JN, Caly L, Carter LL, Cullinane A, de Oliveira T, Druce J, El Masry I, Evans R, Gao GF, Gorbalenya AE, Hamblion E, Herring BL, Hodcroft E, Holmes EC, Kakkar M, Khare S, Koopmans MPG, Korber B, Leite J, MacCannell D, Marklewitz M, Maurer-Stroh S, Rico JAM, Munster VJ, Neher R, Munnink BO, Pavlin BI, Peiris M, Poon L, Pybus O, Rambaut A, Resende P, Subissi L, Thiel V, Tong S, van der Werf S, von Gottberg A, Ziebuhr J, Van Kerkhove MD. Nat Microbiol. 2021 Jul;6(7):821-823. doi: 10.1038/s41564-021-00932-w.

  • Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy. Wong HH, Seet SH, Maier M, Gurel A, Traspas RM, Lee C, Zhang S, Talim B, Loh AYT, Chia CY, Teoh TS, Sng D, Rensvold J, Unal S, Shishkova E, Cepni E, Nathan FM, Sirota FL, Liang C, Yarali N, Simsek-Kiper PO, Mitani T, Ceylaner S, Arman-Bilir O, Mbarek H, Gumruk F, Efthymiou S, Uğurlu Çi Men D, Georgiadou D, Sotiropoulou K, Houlden H, Paul F, Pehlivan D, Lainé C, Chai G, Ali NA, Choo SC, Keng SS, Boisson B, Yılmaz E, Xue S, Coon JJ, Ly TTN, Gilani N, Hasbini D, Kayserili H, Zaki MS, Isfort RJ, Ordonez N, Tripolszki K, Bauer P, Rezaei N, Seyedpour S, Khotaei GT, Bascom CC, Maroofian R, Chaabouni M, Alsubhi A, Eyaid W, Işıkay S, Gleeson JG, Lupski JR, Casanova JL, Pagliarini DJ, Akarsu NA, Maurer-Stroh S, Cetinkaya A, Bertoli-Avella A, Mathuru AS, Ho L, Bard FA, Reversade B. Am J Hum Genet. 2021 Jul 1;108(7):1301-1317. doi: 10.1016/j.ajhg.2021.05.003. Epub 2021 May 25.

  • Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia. Asarnow D, Wang B, Lee WH, Hu Y, Huang CW, Faust B, Ng PML, Ngoh EZX, Bohn M, Bulkley D, Pizzorno A, Ary B, Tan HC, Lee CY, Minhat RA, Terrier O, Soh MK, Teo FJ, Yeap YYC, Seah SGK, Chan CEZ, Connelly E, Young NJ, Maurer-Stroh S, Renia L, Hanson BJ, Rosa-Calatrava M, Manglik A, Cheng Y, Craik CS, Wang CI. Cell. 2021 Jun 10;184(12):3192-3204.e16. doi: 10.1016/j.cell.2021.04.033. Epub 2021 Apr 24.

  • An engineered CRISPR-Cas12a variant and DNA-RNA hybrid guides enable robust and rapid COVID-19 testing. Ooi KH, Liu MM, Tay JWD, Teo SY, Kaewsapsak P, Jin S, Lee CK, Hou J, Maurer-Stroh S, Lin W, Yan B, Yan G, Gao YG, Tan MH. Nat Commun. 2021 Mar 19;12(1):1739. doi: 10.1038/s41467-021-21996-6.

  • How the lessons of previous epidemics helped successful countries fight covid-19. Chua AQ, Al Knawy B, Grant B, Legido-Quigley H, Lee WC, Leung GM, Looi MK, Maurer-Stroh S. BMJ. 2021 Mar 11;372:n486. doi: 10.1136/bmj.n486.

  • Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study. Young BE, Fong SW, Chan YH, Mak TM, Ang LW, Anderson DE, Lee CY, Amrun SN, Lee B, Goh YS, Su YCF, Wei WE, Kalimuddin S, Chai LYA, Pada S, Tan SY, Sun L, Parthasarathy P, Chen YYC, Barkham T, Lin RTP, Maurer-Stroh S, Leo YS, Wang LF, Renia L, Lee VJ, Smith GJD, Lye DC, Ng LFP. Lancet. 2020 Aug 29;396(10251):603-611. doi: 10.1016/S0140-6736(20)31757-8. Epub 2020 Aug 18.

  • Investigation of three clusters of COVID-19 in Singapore: implications for surveillance and response measures. Pung R, Chiew CJ, Young BE, Chin S, Chen MI, Clapham HE, Cook AR, Maurer-Stroh S, Toh MPHS, Poh C, Low M, Lum J, Koh VTJ, Mak TM, Cui L, Lin RVTP, Heng D, Leo YS, Lye DC, Lee VJM; Singapore 2019 Novel Coronavirus Outbreak Research Team. Lancet. 2020 Mar 28;395(10229):1039-1046. doi: 10.1016/S0140-6736(20)30528-6. Epub 2020 Mar 17.

  • Early transmission patterns of coronavirus disease 2019 (COVID-19) in travellers from Wuhan to Thailand, January 2020Okada P, Buathong R, Phuygun S, Thanadachakul T, Parnmen S, Wongboot W, Waicharoen S, Wacharapluesadee S, Uttayamakul S, Vachiraphan A, Chittaganpitch M, Mekha N, Janejai N, Iamsirithaworn S, Lee RT, Maurer-Stroh S. Euro Surveill. 2020 Feb;25(8):2000097. doi: 10.2807/1560-7917.ES.2020.25.8.2000097.