Displaying publications 1 - 20 of 56 in total

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  1. A collective statement in support of saving pangolins
    Choo SW, Chong JL, Gaubert P, Hughes AC, O'Brien S, Chaber AL, et al.
    Sci Total Environ, 2022 Feb 14.
    PMID: 35176378 DOI: 10.1016/j.scitotenv.2022.153666
  2. Pangolin genomes and the evolution of mammalian scales and immunity
    Choo SW, Rayko M, Tan TK, Hari R, Komissarov A, Wee WY, et al.
    Genome Res, 2016 10;26(10):1312-1322.
    PMID: 27510566
    Pangolins, unique mammals with scales over most of their body, no teeth, poor vision, and an acute olfactory system, comprise the only placental order (Pholidota) without a whole-genome map. To investigate pangolin biology and evolution, we developed genome assemblies of the Malayan (Manis javanica) and Chinese (M. pentadactyla) pangolins. Strikingly, we found that interferon epsilon (IFNE), exclusively expressed in epithelial cells and important in skin and mucosal immunity, is pseudogenized in all African and Asian pangolin species that we examined, perhaps impacting resistance to infection. We propose that scale development was an innovation that provided protection against injuries or stress and reduced pangolin vulnerability to infection. Further evidence of specialized adaptations was evident from positively selected genes involving immunity-related pathways, inflammation, energy storage and metabolism, muscular and nervous systems, and scale/hair development. Olfactory receptor gene families are significantly expanded in pangolins, reflecting their well-developed olfaction system. This study provides insights into mammalian adaptation and functional diversification, new research tools and questions, and perhaps a new natural IFNE-deficient animal model for studying mammalian immunity.
  3. Fulltext Comparing the genomes of Helicobacter pylori clinical strain UM032 and Mice-adapted derivatives
    Khosravi Y, Rehvathy V, Wee WY, Wang S, Baybayan P, Singh S, et al.
    Gut Pathog, 2013;5:25.
    PMID: 23957912 DOI: 10.1186/1757-4749-5-25
    Helicobacter pylori is a Gram-negative bacterium that persistently infects the human stomach inducing chronic inflammation. The exact mechanisms of pathogenesis are still not completely understood. Although not a natural host for H. pylori, mouse infection models play an important role in establishing the immunology and pathogenicity of H. pylori. In this study, for the first time, the genome sequences of clinical H. pylori strain UM032 and mice-adapted derivatives, 298 and 299, were sequenced using the PacBio Single Molecule, Real-Time (SMRT) technology.
  4. Fulltext PGD: a pangolin genome hub for the research community
    Tan TK, Tan KY, Hari R, Mohamed Yusoff A, Wong GJ, Siow CC, et al.
    Database (Oxford), 2016;2016.
    PMID: 27616775 DOI: 10.1093/database/baw063
    Pangolins (order Pholidota) are the only mammals covered by scales. We have recently sequenced and analyzed the genomes of two critically endangered Asian pangolin species, namely the Malayan pangolin (Manis javanica) and the Chinese pangolin (Manis pentadactyla). These complete genome sequences will serve as reference sequences for future research to address issues of species conservation and to advance knowledge in mammalian biology and evolution. To further facilitate the global research effort in pangolin biology, we developed the Pangolin Genome Database (PGD), as a future hub for hosting pangolin genomic and transcriptomic data and annotations, and with useful analysis tools for the research community. Currently, the PGD provides the reference pangolin genome and transcriptome data, gene sequences and functional information, expressed transcripts, pseudogenes, genomic variations, organ-specific expression data and other useful annotations. We anticipate that the PGD will be an invaluable platform for researchers who are interested in pangolin and mammalian research. We will continue updating this hub by including more data, annotation and analysis tools particularly from our research consortium.Database URL: http://pangolin-genome.um.edu.my.
  5. Fulltext De novo sequencing, assembly and analysis of eight different transcriptomes from the Malayan pangolin
    Mohamed Yusoff A, Tan TK, Hari R, Koepfli KP, Wee WY, Antunes A, et al.
    Sci Rep, 2016 09 13;6:28199.
    PMID: 27618997 DOI: 10.1038/srep28199
    Pangolins are scale-covered mammals, containing eight endangered species. Maintaining pangolins in captivity is a significant challenge, in part because little is known about their genetics. Here we provide the first large-scale sequencing of the critically endangered Manis javanica transcriptomes from eight different organs using Illumina HiSeq technology, yielding ~75 Giga bases and 89,754 unigenes. We found some unigenes involved in the insect hormone biosynthesis pathway and also 747 lipids metabolism-related unigenes that may be insightful to understand the lipid metabolism system in pangolins. Comparative analysis between M. javanica and other mammals revealed many pangolin-specific genes significantly over-represented in stress-related processes, cell proliferation and external stimulus, probably reflecting the traits and adaptations of the analyzed pregnant female M. javanica. Our study provides an invaluable resource for future functional works that may be highly relevant for the conservation of pangolins.
  6. Fulltext Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma
    Chow YP, Tan LP, Chai SJ, Abdul Aziz N, Choo SW, Lim PV, et al.
    Sci Rep, 2017 03 03;7:42980.
    PMID: 28256603 DOI: 10.1038/srep42980
    In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.
  7. Fulltext HelicoBase: a Helicobacter genomic resource and analysis platform
    Choo SW, Ang MY, Fouladi H, Tan SY, Siow CC, Mutha NV, et al.
    BMC Genomics, 2014;15:600.
    PMID: 25030426 DOI: 10.1186/1471-2164-15-600
    Helicobacter is a genus of Gram-negative bacteria, possessing a characteristic helical shape that has been associated with a wide spectrum of human diseases. Although much research has been done on Helicobacter and many genomes have been sequenced, currently there is no specialized Helicobacter genomic resource and analysis platform to facilitate analysis of these genomes. With the increasing number of Helicobacter genomes being sequenced, comparative genomic analysis on members of this species will provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of diseases caused by Helicobacter pathogens.
  8. Fulltext VibrioBase: a model for next-generation genome and annotation database development
    Choo SW, Heydari H, Tan TK, Siow CC, Beh CY, Wee WY, et al.
    ScientificWorldJournal, 2014;2014:569324.
    PMID: 25243218 DOI: 10.1155/2014/569324
    To facilitate the ongoing research of Vibrio spp., a dedicated platform for the Vibrio research community is needed to host the fast-growing amount of genomic data and facilitate the analysis of these data. We present VibrioBase, a useful resource platform, providing all basic features of a sequence database with the addition of unique analysis tools which could be valuable for the Vibrio research community. VibrioBase currently houses a total of 252 Vibrio genomes developed in a user-friendly manner and useful to enable the analysis of these genomic data, particularly in the field of comparative genomics. Besides general data browsing features, VibrioBase offers analysis tools such as BLAST interfaces and JBrowse genome browser. Other important features of this platform include our newly developed in-house tools, the pairwise genome comparison (PGC) tool, and pathogenomics profiling tool (PathoProT). The PGC tool is useful in the identification and comparative analysis of two genomes, whereas PathoProT is designed for comparative pathogenomics analysis of Vibrio strains. Both of these tools will enable researchers with little experience in bioinformatics to get meaningful information from Vibrio genomes with ease. We have tested the validity and suitability of these tools and features for use in the next-generation database development.
  9. Fulltext FusoBase: an online Fusobacterium comparative genomic analysis platform
    Ang MY, Heydari H, Jakubovics NS, Mahmud MI, Dutta A, Wee WY, et al.
    Database (Oxford), 2014;2014.
    PMID: 25149689 DOI: 10.1093/database/bau082
    Fusobacterium are anaerobic gram-negative bacteria that have been associated with a wide spectrum of human infections and diseases. As the biology of Fusobacterium is still not well understood, comparative genomic analysis on members of this species will provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of infections and diseases. To facilitate the ongoing genomic research on Fusobacterium, a specialized database with easy-to-use analysis tools is necessary. Here we present FusoBase, an online database providing access to genome-wide annotated sequences of Fusobacterium strains as well as bioinformatics tools, to support the expanding scientific community. Using our custom-developed Pairwise Genome Comparison tool, we demonstrate how differences between two user-defined genomes and how insertion of putative prophages can be identified. In addition, Pathogenomics Profiling Tool is capable of clustering predicted genes across Fusobacterium strains and visualizing the results in the form of a heat map with dendrogram.
  10. Fulltext CoryneBase: Corynebacterium genomic resources and analysis tools at your fingertips
    Heydari H, Siow CC, Tan MF, Jakubovics NS, Wee WY, Mutha NV, et al.
    PLoS One, 2014;9(1):e86318.
    PMID: 24466021 DOI: 10.1371/journal.pone.0086318
    Corynebacteria are used for a wide variety of industrial purposes but some species are associated with human diseases. With increasing number of corynebacterial genomes having been sequenced, comparative analysis of these strains may provide better understanding of their biology, phylogeny, virulence and taxonomy that may lead to the discoveries of beneficial industrial strains or contribute to better management of diseases. To facilitate the ongoing research of corynebacteria, a specialized central repository and analysis platform for the corynebacterial research community is needed to host the fast-growing amount of genomic data and facilitate the analysis of these data. Here we present CoryneBase, a genomic database for Corynebacterium with diverse functionality for the analysis of genomes aimed to provide: (1) annotated genome sequences of Corynebacterium where 165,918 coding sequences and 4,180 RNAs can be found in 27 species; (2) access to comprehensive Corynebacterium data through the use of advanced web technologies for interactive web interfaces; and (3) advanced bioinformatic analysis tools consisting of standard BLAST for homology search, VFDB BLAST for sequence homology search against the Virulence Factor Database (VFDB), Pairwise Genome Comparison (PGC) tool for comparative genomic analysis, and a newly designed Pathogenomics Profiling Tool (PathoProT) for comparative pathogenomic analysis. CoryneBase offers the access of a range of Corynebacterium genomic resources as well as analysis tools for comparative genomics and pathogenomics. It is publicly available at http://corynebacterium.um.edu.my/.
  11. Fulltext MabsBase: a Mycobacterium abscessus genome and annotation database
    Heydari H, Wee WY, Lokanathan N, Hari R, Mohamed Yusoff A, Beh CY, et al.
    PLoS One, 2013;8(4):e62443.
    PMID: 23658631 DOI: 10.1371/journal.pone.0062443
    Mycobacterium abscessus is a rapidly growing non-tuberculous mycobacterial species that has been associated with a wide spectrum of human infections. As the classification and biology of this organism is still not well understood, comparative genomic analysis on members of this species may provide further insights on their taxonomy, phylogeny, pathogenicity and other information that may contribute to better management of infections. The MabsBase described in this paper is a user-friendly database providing access to whole-genome sequences of newly discovered M. abscessus strains as well as resources for whole-genome annotations and computational predictions, to support the expanding scientific community interested in M. abscessus research. The MabsBase is freely available at http://mabscessus.um.edu.my.
  12. Fulltext Development of ListeriaBase and comparative analysis of Listeria monocytogenes
    Tan MF, Siow CC, Dutta A, Mutha NV, Wee WY, Heydari H, et al.
    BMC Genomics, 2015;16:755.
    PMID: 26444974 DOI: 10.1186/s12864-015-1959-5
    Listeria consists of both pathogenic and non-pathogenic species. Reports of similarities between the genomic content between some pathogenic and non-pathogenic species necessitates the investigation of these species at the genomic level to understand the evolution of virulence-associated genes. With Listeria genome data growing exponentially, comparative genomic analysis may give better insights into evolution, genetics and phylogeny of Listeria spp., leading to better management of the diseases caused by them.
  13. Fulltext NeisseriaBase: a specialised Neisseria genomic resource and analysis platform
    Zheng W, Mutha NV, Heydari H, Dutta A, Siow CC, Jakubovics NS, et al.
    PeerJ, 2016;4:e1698.
    PMID: 27017950 DOI: 10.7717/peerj.1698
    Background. The gram-negative Neisseria is associated with two of the most potent human epidemic diseases: meningococcal meningitis and gonorrhoea. In both cases, disease is caused by bacteria colonizing human mucosal membrane surfaces. Overall, the genus shows great diversity and genetic variation mainly due to its ability to acquire and incorporate genetic material from a diverse range of sources through horizontal gene transfer. Although a number of databases exist for the Neisseria genomes, they are mostly focused on the pathogenic species. In this present study we present the freely available NeisseriaBase, a database dedicated to the genus Neisseria encompassing the complete and draft genomes of 15 pathogenic and commensal Neisseria species. Methods. The genomic data were retrieved from National Center for Biotechnology Information (NCBI) and annotated using the RAST server which were then stored into the MySQL database. The protein-coding genes were further analyzed to obtain information such as calculation of GC content (%), predicted hydrophobicity and molecular weight (Da) using in-house Perl scripts. The web application was developed following the secure four-tier web application architecture: (1) client workstation, (2) web server, (3) application server, and (4) database server. The web interface was constructed using PHP, JavaScript, jQuery, AJAX and CSS, utilizing the model-view-controller (MVC) framework. The in-house developed bioinformatics tools implemented in NeisseraBase were developed using Python, Perl, BioPerl and R languages. Results. Currently, NeisseriaBase houses 603,500 Coding Sequences (CDSs), 16,071 RNAs and 13,119 tRNA genes from 227 Neisseria genomes. The database is equipped with interactive web interfaces. Incorporation of the JBrowse genome browser in the database enables fast and smooth browsing of Neisseria genomes. NeisseriaBase includes the standard BLAST program to facilitate homology searching, and for Virulence Factor Database (VFDB) specific homology searches, the VFDB BLAST is also incorporated into the database. In addition, NeisseriaBase is equipped with in-house designed tools such as the Pairwise Genome Comparison tool (PGC) for comparative genomic analysis and the Pathogenomics Profiling Tool (PathoProT) for the comparative pathogenomics analysis of Neisseria strains. Discussion. This user-friendly database not only provides access to a host of genomic resources on Neisseria but also enables high-quality comparative genome analysis, which is crucial for the expanding scientific community interested in Neisseria research. This database is freely available at http://neisseria.um.edu.my.
  14. Whole-transcriptome analysis reveals mechanisms underlying antibacterial activity and biofilm inhibition by a malic acid combination (MAC) in Pseudomonas aeruginosa
    Song K, Chen L, Suo N, Kong X, Li J, Wang T, et al.
    PeerJ, 2023;11:e16476.
    PMID: 38084141 DOI: 10.7717/peerj.16476
    BACKGROUND: Pseudomonas aeruginosa is a highly prevalent bacterial species known for its ability to cause various infections and its remarkable adaptability and biofilm-forming capabilities. In earlier work, we conducted research involving the screening of 33 metabolites obtained from a commercial source against two prevalent bacterial strains, Escherichia coli and Staphylococcus aureus. Through screening assays, we discovered a novel malic acid combination (MAC) consisting of malic acid, citric acid, glycine, and hippuric acid, which displayed significant inhibitory effects. However, the precise underlying mechanism and the potential impact of the MAC on bacterial biofilm formation remain unknown and warrant further investigation.

    METHODS: To determine the antibacterial effectiveness of the MAC against Pseudomonas aeruginosa, we conducted minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques were employed to observe bacterial morphology and biofilm formation. We further performed a biofilm inhibition assay to assess the effect of the MAC on biofilm formation. Whole-transcriptome sequencing and bioinformatics analysis were employed to elucidate the antibacterial mechanism of the MAC. Additionally, the expression levels of differentially expressed genes were validated using the real-time PCR approach.

    RESULTS: Our findings demonstrated the antibacterial activity of the MAC against P. aeruginosa. SEM analysis revealed that the MAC can induce morphological changes in bacterial cells. The biofilm assay showed that the MAC could reduce biofilm formation. Whole-transcriptome analysis revealed 1093 differentially expressed genes consisting of 659 upregulated genes and 434 downregulated genes, in response to the MAC treatment. Mechanistically, the MAC inhibited P. aeruginosa growth by targeting metabolic processes, secretion system, signal transduction, and cell membrane functions, thereby potentially compromising the survival of this human pathogen. This study provides valuable insights into the antibacterial and antibiofilm activities of the MAC, a synergistic and cost-effective malic acid combination, which holds promise as a potential therapeutic drug cocktail for treating human infectious diseases in the future.

  15. Fulltext YersiniaBase: a genomic resource and analysis platform for comparative analysis of Yersinia
    Tan SY, Dutta A, Jakubovics NS, Ang MY, Siow CC, Mutha NV, et al.
    BMC Bioinformatics, 2015;16:9.
    PMID: 25591325 DOI: 10.1186/s12859-014-0422-y
    Yersinia is a Gram-negative bacteria that includes serious pathogens such as the Yersinia pestis, which causes plague, Yersinia pseudotuberculosis, Yersinia enterocolitica. The remaining species are generally considered non-pathogenic to humans, although there is evidence that at least some of these species can cause occasional infections using distinct mechanisms from the more pathogenic species. With the advances in sequencing technologies, many genomes of Yersinia have been sequenced. However, there is currently no specialized platform to hold the rapidly-growing Yersinia genomic data and to provide analysis tools particularly for comparative analyses, which are required to provide improved insights into their biology, evolution and pathogenicity.
  16. Fulltext MycoCAP - Mycobacterium Comparative Analysis Platform
    Choo SW, Ang MY, Dutta A, Tan SY, Siow CC, Heydari H, et al.
    Sci Rep, 2015 Dec 15;5:18227.
    PMID: 26666970 DOI: 10.1038/srep18227
    Mycobacterium spp. are renowned for being the causative agent of diseases like leprosy, Buruli ulcer and tuberculosis in human beings. With more and more mycobacterial genomes being sequenced, any knowledge generated from comparative genomic analysis would provide better insights into the biology, evolution, phylogeny and pathogenicity of this genus, thus helping in better management of diseases caused by Mycobacterium spp.With this motivation, we constructed MycoCAP, a new comparative analysis platform dedicated to the important genus Mycobacterium. This platform currently provides information of 2108 genome sequences of at least 55 Mycobacterium spp. A number of intuitive web-based tools have been integrated in MycoCAP particularly for comparative analysis including the PGC tool for comparison between two genomes, PathoProT for comparing the virulence genes among the Mycobacterium strains and the SuperClassification tool for the phylogenic classification of the Mycobacterium strains and a specialized classification system for strains of Mycobacterium abscessus. We hope the broad range of functions and easy-to-use tools provided in MycoCAP makes it an invaluable analysis platform to speed up the research discovery on mycobacteria for researchers. Database URL: http://mycobacterium.um.edu.my.
  17. Fulltext StaphyloBase: a specialized genomic resource for the staphylococcal research community
    Heydari H, Mutha NV, Mahmud MI, Siow CC, Wee WY, Wong GJ, et al.
    Database (Oxford), 2014;2014:bau010.
    PMID: 24578355 DOI: 10.1093/database/bau010
    With the advent of high-throughput sequencing technologies, many staphylococcal genomes have been sequenced. Comparative analysis of these strains will provide better understanding of their biology, phylogeny, virulence and taxonomy, which may contribute to better management of diseases caused by staphylococcal pathogens. We developed StaphyloBase with the goal of having a one-stop genomic resource platform for the scientific community to access, retrieve, download, browse, search, visualize and analyse the staphylococcal genomic data and annotations. We anticipate this resource platform will facilitate the analysis of staphylococcal genomic data, particularly in comparative analyses. StaphyloBase currently has a collection of 754 032 protein-coding sequences (CDSs), 19 258 rRNAs and 15 965 tRNAs from 292 genomes of different staphylococcal species. Information about these features is also included, such as putative functions, subcellular localizations and gene/protein sequences. Our web implementation supports diverse query types and the exploration of CDS- and RNA-type information in detail using an AJAX-based real-time search system. JBrowse has also been incorporated to allow rapid and seamless browsing of staphylococcal genomes. The Pairwise Genome Comparison tool is designed for comparative genomic analysis, for example, to reveal the relationships between two user-defined staphylococcal genomes. A newly designed Pathogenomics Profiling Tool (PathoProT) is also included in this platform to facilitate comparative pathogenomics analysis of staphylococcal strains. In conclusion, StaphyloBase offers access to a range of staphylococcal genomic resources as well as analysis tools for comparative analyses. Database URL: http://staphylococcus.um.edu.my/.
  18. Fulltext Genome Sequence of Parvimonas micra Strain A293, Isolated from an Abdominal Abscess from a Patient in the United Kingdom
    Ang MY, Dymock D, Tan JL, Thong MH, Tan QK, Wong GJ, et al.
    Genome Announc, 2013;1(6).
    PMID: 24309744 DOI: 10.1128/genomeA.01025-13
    Parvimonas micra is an important oral microbe that has the ability to grow and proliferate within oral biofilms and is involved in periodontal disease, leading to gingival bleeding, gingival recession, alveolar bone loss, and tooth mobility. However, occasionally these normally oral pathogens can cause infections at other sites in the body. We present the genome sequence of Parvimonas micra strain A293, a smooth Parvimonas micra strain isolated from an abdominal abscess from a patient at Barts Hospital, London, United Kingdom.
  19. Fulltext Genome Sequence of Fusobacterium nucleatum Strain W1481, a Possible New Subspecies Isolated from a Periodontal Pocket
    Ang MY, Dymock D, Tan JL, Thong MH, Tan QK, Wong GJ, et al.
    Genome Announc, 2014;2(1).
    PMID: 24526626 DOI: 10.1128/genomeA.00009-14
    Fusobacterium nucleatum is a bacterial species commonly detected in dental plaque within the human oral cavity, with some strains associated with periodontal disease, one of the most common clinical bacterial infections in the human body. The exact mechanisms of its pathogenesis are still not completely understood. In this study, we present the genome sequence and annotation of F. nucleatum strain W1481, isolated from a periodontal pocket of a dental patient at the University of Bristol, United Kingdom, the 16S rRNA gene sequencing of which showed it to be markedly different from the five previously named subspecies.
  20. Fulltext Genomic reconnaissance of clinical isolates of emerging human pathogen Mycobacterium abscessus reveals high evolutionary potential
    Choo SW, Wee WY, Ngeow YF, Mitchell W, Tan JL, Wong GJ, et al.
    Sci Rep, 2014;4:4061.
    PMID: 24515248 DOI: 10.1038/srep04061
    Mycobacterium abscessus (Ma) is an emerging human pathogen that causes both soft tissue infections and systemic disease. We present the first comparative whole-genome study of Ma strains isolated from patients of wide geographical origin. We found a high proportion of accessory strain-specific genes indicating an open, non-conservative pan-genome structure, and clear evidence of rapid phage-mediated evolution. Although we found fewer virulence factors in Ma compared to M. tuberculosis, our data indicated that Ma evolves rapidly and therefore should be monitored closely for the acquisition of more pathogenic traits. This comparative study provides a better understanding of Ma and forms the basis for future functional work on this important pathogen.
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