GERMS platform for Microbial Genomics

Principle Investigator

  • Swaine Chen
  • GERMS wants to be your genomics partner for the investigation of microbial diseases in Singapore.

GERMS is a GIS platform that provides comprehensive genomics solutions for studying the role of microbes in human health and diseases. The GERMS platform integrates GIS’ extensive experimental and analytical expertise in the study of viruses, bacteria, fungi, parasites and microbiomes. The platform supports everything from small to large studies involving genome sequencing, transcriptomics, functional genomics, metagenomics as well as custom applications. We partner with research and clinical groups around the world to study health and infection in single patients to whole hospitals, communities and beyond. Some recent examples of GERMS-enabled projects include:

GAS outbreak in a hospital
with Tan Tock Seng Hospital (TTSH), Singapore & the Institute of Mental Health, Singapore

We combined genomics with traditional epidemiology during a Group A Streptococcus outbreak in a local hospital. Together these identified that there was a single strain causing an outbreak in a particular ward but not throughout the hospital. In the absence of genomics, the infection control team was considering hospital-wide antibiotic prophylaxis. However, the higher resolution of whole genome sequencing enabled a targeted intervention to control the outbreak, saving the hospital money and saving many patients from unnecessary antibiotic treatment. Importantly, we helped perform the genome sequencing and analysis on a time scale fast enough to impact infection control interventions.
PMID: 29739475
Metagenomics: Can skin microbes predispose you to eczema?
with A*STAR’s Institute of Medical Biology, Singapore

Eczema or Atopic Dermatitis (AD) is a common, recurrent, inflammatory skin disease affecting nearly 1 in 5 individuals globally. The skin microbiome of eczema patients with apparently normal, inter-flare skin was dominated by a host of opportunistic pathogens. We showed that many of these opportunistic pathogens were inhibited S. aureus colonization, suggesting that there was bacterial competition and that S. aureus was in effect “keeping the peace” in the non-flare state. On the flip side, depleted bacteria had metabolic, antibiotic and anti-inflammatory properties that suggest that they may have a protective role in normal individuals. Immune challenge assays with keratinocytes and dendritic cells further confirmed that these AD-associated bacteria have distinct functional roles.
PMID: 27562258

Macromolecular therapeutics for drug resistant superbugs
with A*STAR’s Institute of Bioengineering and Nanotechnology, Singapore & the International Business Machine, USA, University of North Dakota’s School of Medicine and Health Sciences, USA and the First Affiliated Hospital of Zhejiang University’s College of Medicine, China

Superbugs that are resistant to antibiotics are a serious health threat. The research community is trying to develop alternatives to antibiotics using synthetic polymers. These biodegradable synthetic macromolecules have broad-spectrum antimicrobial activity in mice, a unique killing mechanism and no toxicity in animal models. To determine whether the bacteria will develop any resistance to the polymer, the team collaborated with GERMS to perform genomic analysis. We found that the bacteria did not show any resistance development even after multiple treatments with the polymer. Their new polymer material holds promise to be developed into an antimicrobial drug to treat patients with antibiotic-resistant infections.
PMID: 29500445
Outbreak of Zika in Singapore
with Singaporean Ministry of Health, TTSH, Environmental Health Institute, Duke-National University of Singapore, A*STAR Bioinformatics Institute and Oxford University Clinical Research Unit, Vietnam & many more collaborators from Singaporean hospitals & agencies

There was a Zika outbreak in Singapore in 2016. The major concern was whether this outbreak was imported from Brazil or elsewhere in the Americas, because that was where Zika was associated with birth defects (microcephaly) after mothers became infected. To answer this question, we used genomics, or sequencing of the viral RNA for Zika virus. We adapted expertise we had in doing genomics on Dengue to study Zika samples from Singapore. We found that the Zika outbreak in Singapore was due to a strain of Zika that was from Southeast Asia - and not from Brazil or elsewhere in the Americas. This helped to provide information to the public health agencies for communicating the risks of Zika infection as well as to target mosquito control in Singapore, a key measure important for both Dengue and Zika control.
PMID: 28527892

16S: Microbiome development in childhood diarrhea
with Oxford University Clinical Research Unit in Vietnam

We are becoming increasingly aware of the importance of the role of the gut microbiome on the effects on health and disease later in life. We collaborated with the Oxford University Clinical Research Unit in Vietnam to investigate the effect of viral or bacterial diarrhea on young children in this region, to further our understanding of bacteria in the gut and how these bacteria influence health.
PMID: 28767339

Other publications from GERMS members, since 2016:

Chen Lab
  • A Sub-population of Group A Streptococcus Elicits a Population-wide Production of Bacteriocins to Establish Dominance in the Host. Cell Host Microbe. 2018 PMID: 29544095
  • Purification of Intracellular Bacterial Communities during Experimental Urinary Tract Infection Reveals an Abundant and Viable Bacterial Reservoir. Infect Immun. 2018 PMID: 29378794
  • Draft Genome Sequence of Singapore Klebsiella pneumoniae subsp. pneumoniae Isolate DS32358_14, Which Contains the Carbapenemase Gene blaVIM-1. Genome Announc. 2018 PMID: 29301903
  • Complete genome sequence of Photobacterium leiognathi strain JS01. Genome Announc. 2018 PMID:29301879
  • Group B Streptococcus Infections Caused by Improper Sourcing and Handling of Fish for Raw Consumption, Singapore, 2015-2016. Emerg Infect Dis. 2017 PMID: 29148967
  • Putative Integrative Mobile Elements That Exploit the Xer Recombination Machinery Carrying blaIMI-Type Carbapenemase Genes in Enterobacter cloacae Complex Isolates in Singapore. Antimicrob Agents Chemother. 2017 PMID:29038281
  • Direct and convenient measurement of plasmid stability in lab and clinical isolates of E. coli. Sci Rep. 2017 PMID:29643388
  • Deep Sequencing in Infectious Diseases: Immune and Pathogen Repertoires for the Improvement of Patient Outcomes. Front Immunol. 2017 PMID:28620372
  • 2015 Epidemic of Severe Streptococcus agalactiae Sequence Type 283 Infections in Singapore Associated With the Consumption of Raw Freshwater Fish: A Detailed Analysis of Clinical, Epidemiological, and Bacterial Sequencing Data. Clin Infect Dis. 2017 PMID: 28475781
  • Complete Genome Sequence of the Uropathogenic Escherichia coli Strain NU14. Genome Announc. 2017 PMID: 28473396
  • Complete Genome Sequence of the Original Escherichia coli Isolate, Strain NCTC86. Genome Announc. 2017 PMID: 28428314
  • Complete genome sequence of Streptococcus pyogenes emm14 JS95, a necrotizing fasciitis strain isolated in Israel. Genome Announc. 2017 PMID:28302774
  • Point mutations in the major outer membrane protein drive hypervirulence of a rapidly expanding clone of Campylobacter jejuni. Proc Natl Acad Sci U S A. 2016 PMID:27601641
  • Comprehensive mutagenesis of the fimS promoter regulatory switch reveals novel regulation of type 1 pili in uropathogenic Escherichia coli. Proc Natl Acad Sci U S A. 2016 PMID: 27035967
  • Complete Genome Sequence of Streptococcus agalactiae Serotype III, Multilocus Sequence Type 283 Strain SG-M1. Genome Announc. 2015 PMID: 26494662

Florez de Sessions’ platform
  • Methicillin-resistant Staphylococcus aureus colonisation: epidemiological and molecular characteristics in an acute-care tertiary hospital in Singapore. Epidemiol Infect. 2018. PMID:30019657 [GERMS WGS pipeline]
  • Addressing drug resistance in cancer with macromolecular chemotherapeutic agents. J Am Chem Soc. 2018. PMID:29504396 [RNAseq pipeline]
  • Establishment of the Nasal Microbiota in the first 18 Months of Life - Correlation with Early Onset Rhinitis and Wheezing. J of Aller and Clin Immuno. 2018 PMID:29452199 [16S pipeline].
  • Methylation in Mycobacterium tuberculosis is lineage specific with associated mutations present globally. Sci Rep. 2018 PMID:29317751 [custom PacBio pipeline]
  • Single-virion sequencing of lamivudine-treated HBV populations reveal population evolution dynamics and demographic history. BMC Gen. 2017 PMID:29078745 [viral pipeline]
  • Analysis of nuclear and organellar genomes of Plasmodium knowlesi in humans reveals ancient population structure and recent recombination among host-specific subpopulations. PLoS Genet. 2017 PMID:28922357 [custom PacBio pipeline]
  • The epidemiology and transmission of methicillin-resistant Staphylococcus aureus in the community in Singapore: study protocol for a longitudinal household study. BMC Infect Dis. 2017 PMID:29020940 [study protocol]
  • Transcriptional Profiling of Mycobacterium tuberculosis Exposed to In Vitro Lysosomal Stress. Infect Immun. 2016 PMID:27324481 [RNAseq pipeline]
  • Extended Evaluation of Virological, Immunological and Pharmacokinetic Endpoints of CELADEN: A Randomized, Placebo-Controlled Trial of Celgosivir in Dengue Fever Patients. PLoS Negl Trop Dis. 2016 PMID:27509020 [viral pipeline]

Nagarajan Lab
  • A MinION-based pipeline for fast and cost-effective DNA barcoding. Mol Ecol Resour. 2018 PMID:29673082
  • Genome-wide identification of natural RNA aptamers in prokaryotes and eukaryotes. Nat Commun. 2018 PMID:29599443
  • Critical Assessment of Metagenome Interpretation-a benchmark of metagenomics software. Nat Methods. 2017 PMID:28967888
  • Comparative genomics of Cryptococcus neoformans var. grubii associated with meningitis in HIV infected and uninfected patients in Vietnam. PLoS Negl Trop Dis. 2017 PMID:28614360
  • Mapping RNA-RNA Interactions Globally Using Biotinylated Psoralen. J Vis Exp. 2017 PMID:28570509
  • Transcriptomics Analysis Reveals Putative Genes Involved in Biofilm Formation and Biofilm-associated Drug Resistance of Enterococcus faecalis. J Endod. 2017 PMID:28457636
  • Development of a genetically programed vanillin-sensing bacterium for high-throughput screening of lignin-degrading enzyme libraries. Biotechnol Biofuels. 2017 PMID:28174601
  • Fast and accurate de novo genome assembly from long uncorrected reads. Genome Res. 2017 PMID:28100585
  • INC-Seq: accurate single molecule reads using nanopore sequencing. Gigascience. 2016 PMID:27485345
  • Tissue Microbiome Profiling Identifies an Enrichment of Specific Enteric Bacteria in Opisthorchis viverrini Associated Cholangiocarcinoma. EBioMedicine. 2016 PMID:27428430
  • OPERA-LG: efficient and exact scaffolding of large, repeat-rich eukaryotic genomes with performance guarantees. Genome Biol. 2016 PMID:27169502
  • Fast and sensitive mapping of nanopore sequencing reads with GraphMap. Nat Commun. 2016 PMID:27079541
  • Predicting microbial interactions through computational approaches. Methods. 2016 PMID:27025964

GERMS fellows (Zhu Y.O. & Png E.)
  • Extremely Rare Polymorphisms in Saccharomyces cerevisiae Allow Inference of the Mutational Spectrum. PLoS Genet. 2017 PMID:28046117
  • Whole Genome Analysis of 132 Clinical Saccharomyces cerevisiae Strains Reveals Extensive Ploidy Variation.G3 (Bethesda). 2016 PMID:27317778
  • PRINCESS: Privacy-protecting Rare disease International Network Collaboration via Encryption through Software guard extensionS. Bioinformatics. 2017 PMID:28065902
  • Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies.Sci Rep. 2016 PMID:27805046
  • Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. Nat Genet. 2016. PMID: 27064256
  • Chronic Infection With Camelid Hepatitis E Virus in a Liver Transplant Recipient Who Regularly Consumes Camel Meat and Milk. Gastroenterology 2015. PMID: 26551551

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