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Explore Some of our Student's  Research Projects and Publications 

Led, Mentored and Guided by Our Team of Expert 

METAGENOMICS

Title: Exploring Antibiotic resistance genes, mobile Gene elements, and virulence gene factors in an urban freshwater sample using metagenomic analysis
Abstract: 

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Antibiotic resistance genes (ARGs) and antimicrobial resistance elements (AMR) are novel environmental contaminants that pose a significant risk to human health globally. Freshwater contains a variety of microorganisms that might affect human health; its quality must be assessed before use. However, the dynamics of mobile genetic elements (MGEs) and ARG propagation in freshwater have rarely been studied in Singapore. Therefore, this study used metagenomics to compare diversity, virulence factor composition, and ARG and MGE co-occurrence with bacterial communities in paired (n = 8) environmental freshwater samples. KneadData, FMAP, and Kraken2 were used for bioinformatics analysis and R (v4.1.1) for statistical analysis. Sequence reads with a total of 9043 species were taxonomically classified into 66 phyla, 130 classes, 261 orders, 584 families, and 2477 genera. Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes were found the Phyla in all samples. Analysis of QIIME output by PICRUSt and ß-diversity showed unique clusters and functional microbial community structures. A total of 2961 ARGs were found that conferred resistance to multidrug, aminoglycosides, tetracyclines, elfamycins, and more. The classified ARG mechanism revealed significant distribution of virulence factors in bacterial cells. Transposes and transposon were highly correlated to ARG gene transfer. Co-occurrence network analysis showed several MGEs appear to use the same ARGs (intI and rho) and were dominant in all samples. Furthermore, ARGs are also highly correlated with bacteria like Campylobacter and Escherichia. This study enhances the understanding of antibiotic risk assessment and provides a new perspective on bacterial assembly contamination and the functional prevalence of ARGs and MGEs with antibiotic resistance bacteria. Moreover, it raises public awareness because these contaminants put people’s lives at risk of acquiring bacterial infections. In addition, it can also help propose hybrid water treatment approaches.

CLINICAL GENOMICS

Title: GLOBAL ANALYSIS OF NON-SYNONYMOUS SNPs IN MONKEYPOX VIRUS
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In May of 2022, it was determined that a virus known as monkeypox (MPX) had spread over the world. The MPXV strain responsible for 87000 illnesses and 112 fatalities has been identified. This strain had a global average of 38.35 mutations per virus sample, with the 2022 epidemic seeing the highest MPXV mutation rate. Our aim was to use publicly accessible NCBI (National Center for Biotechnology Information) data to explore the genetic diversity and evolutionary history of monkeypox viruses (MPXVs). In-depth comparisons of the genomic characteristics of 376 publicly available complete MPXV genome sequences were performed. Nucleotide sequence variation, gene order, mapping, alignment, and mapping accuracy were among these features. A large amount of sequence conservation was discovered in the MPXV genomes by the meta-analysis, with only a few minor changes between isolates. Multiple genomic regions were discovered to be highly conserved among all MPXV strains, suggesting an essential function in viral replication and persistence. The use of phylogenetic analyses to trace the evolutionary relationships of MPXV strains revealed that the virus has diverged into several subgroups with distinct genetic makeups.

PROBIO-GENOMICS 

Title: Complete Genome Sequence and Comparative Analysis of Bifidobacterium bifidum Strains Reveal Insight into Probiotic Properties
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Despite the widespread use of probiotic supplements for their beneficial health effects, there have recently been some concerns expressed over the absorption and potential colonization of the intestinal tract by the bacteria that these products contain. One of the bacterial species of the genus Bifidobacterium is the strain Bifidobacterium bifidum. One of the most prevalent probiotic bacteria in the bodies of mammals, including humans, is called Bifidobacterium bifidum. Recently, probiotics like Bifidobacterium bifidum have become more and more well-liked. However, it has been the focus of a few studies that demonstrate its efficacy in treating a number of ailments, including dyspepsia and malnutrition. The Bifidobacterium bifidum strain has genes that let the organism tolerate and be resistant to hazardous toxins and some medications, which helps with their capacity to cling to the host. Specialty genes, such as those encoding for vitamins, DNA repair, stress response, amino acids, bacteriocins, phages, and antibiotic tolerance and resistance, are responsible for certain bodily processes in hosts. In our study, eight sequencing datasets produced from Bifidobacterium bifidum sample were subjected to bioinformatic analysis. A particular number of ARGs were connected to integrated mobile genomic elements or prophages that assisted the HGT. In this study, we identified the genes that code for fundamental and significant properties of probiotics in the host, such as the production of bacteriocin and vitamins.

PROBIO-GENOMICS 2

Title: Probiotics, their action modality and the use of multi-omics in metamorphosis of commensal microbiota into target-based probiotics
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This review article addresses the strategic formulation of human probiotics and allows the reader to walk along the journey that metamorphoses commensal microbiota into target-based probiotics. It recapitulates what are probiotics, their history, and the main mechanisms through which probiotics exert beneficial effects on the host. It articulates how a given probiotic preparation could not be all-encompassing and how each probiotic strain has its unique repertoire of functional genes. It answers what criteria should be met to formulate probiotics intended for human use, and why certain probiotics meet ill-fate in pre-clinical and clinical trials? It communicates the reasons that taint the reputation of probiotics and cause discord between the industry, medical and scientific communities. It revisits the notion of host-adapted strains carrying niche-specific genetic modifications. Lastly, this paper emphasizes the strategic development of target-based probiotics using host-adapted microbial isolates with known molecular effectors that would serve as better candidates for bioprophylactic and biotherapeutic interventions in disease-susceptible individuals.

DRUG DESIGN & DISC0VERY

Title: Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes Mellitus
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Diabetes mellitus is a chronic hormonal and metabolic disorder in which our body cannot generate necessary insulin or does not act in response to it, accordingly, ensuing in discordantly high blood sugar (glucose) levels. Diabetes mellitus can lead to systemic dysfunction in the multiorgan system, including cardiac dysfunction, severe kidney disease, lowered quality of life, and increased mortality risk from diabetic complications. To uncover possible therapeutic targets to treat diabetes mellitus, the in silico drug design technique is widely used, which connects the ligand molecules with target proteins to construct a protein-ligand network. To identify new therapeutic targets for type 2 diabetes mellitus, Azadirachta indica is subjected to phytochemical screening using in silico molecular docking, pharmacokinetic behavior analysis, and simulation-based molecular dynamic analysis. This study has analyzed around 63 phytochemical compounds, and the initial selection of the compounds was made by analyzing their pharmacokinetic properties by comparing them with Lipinski’s rule of 5. The selected compounds were subjected to molecular docking. The top four ligand compounds were reported along with the control drug nateglinide based on their highest negative molecular binding affinity. The protein-ligand interaction of selected compounds has been analyzed to understand better how compounds interact with the targeted protein structure. The results of the in silico analysis revealed that 7-Deacetyl-7-oxogedunin had the highest negative docking score of −8.9 Kcal/mol and also demonstrated standard stability in a 100 ns molecular dynamic simulation performed with insulin receptor ectodomain. It has been found that these substances may rank among the essential supplementary antidiabetic drugs for treating type 2 diabetes mellitus. It is suggested that more in vivo and in vitro research studies be carried out to support the conclusions drawn from this in silico research strategy.

PLANT GENOMICS

Title: Phylogenetic Analysis of Blast Resistant RMG7 (Resistance to Magnaporthe Grisea 7) Gene in Cereals (Wheat and Rice)
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Understanding the emergence and evolution of plant pathogens has benefited greatly from phylogenetic approaches. Phylogenetic analysis of the Blast Resistant RMG7 (Resistance to Magnaporthe grisea 7) gene would involve the study of its evolutionary relationships with related genes across different species. This study aimed to understand the gene's origin, divergence, and evolutionary history, which can provide insights into its function and potential applications in crop improvement. The study obtained the total of 36 DNA sequences of the RMG7 gene from different organisms (wheat and rice) from publicly available NCBI(https://www.ncbi.nlm.nih.gov) database on 20 May 2023 to investigate its evolution. The Sequences were selected based on the representation of a diverse range of species, including those known to have blast resistance or related traits. Using the generic time reversible model and the maximum likelihood method, evolutionary history was determined. These methods used statistical algorithms to estimate the evolutionary relationships between the sequences, forming a tree that represents their common ancestry. An evolutionary tree evolved using the aligned RMG7 sequences to determine the common ancestor of each strain. The Geneious software, for which purpose (sequence alignment), which tool (such as muscle, geneious aligner, cluster) was used to carry sequence alignment, including parameters (in Geneious: local alignment or global, and at which identity value (65% identical) used in doing the alignment. The phylogenetic analysis showed that the resulting tree to interpret the evolutionary relationships among the RMG7 gene sequences. The Intensified clusters or branches that group sequences with similar blast resistance characteristics or closely related species. Overall, this research provides valuable insights into the evolutionary history, genetic diversity, and relatedness of the RMG7 gene in cereals, particularly in wheat and rice. The findings have implications for understanding the mechanisms of blast resistance and for enhancing crop protection strategies against Magnaporthe grisea.

YEAST GENOMICS

Title: Snapshot of the Probiotic Potential of Kluveromyces marxianus DMKU-1042 Using a Comparative Probiogenomics Approach
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Kluyveromyces marxianus is a rapidly growing thermotolerant yeast that secretes a variety of lytic enzymes, utilizes different sugars, and produces ethanol. The probiotic potential of this yeast has not been well explored. To evaluate its probiotic potential, the yeast strain Kluyveromyces marxianus DMKU3-1042 was analyzed using next-generation sequencing technology. Analysis of the genomes showed that the yeast isolates had a GC content of 40.10–40.59%. The isolates had many genes related to glycerol and mannose metabolism, as well as genes for acetoin and butanediol metabolism, acetolactate synthase subunits, and lactic acid fermentation. The strain isolates were also found to possess genes for the synthesis of different vitamins and Coenzyme A. Genes related to heat and hyperosmotic shock tolerance, as well as protection against reactive oxygen species were also found. Additionally, the isolates contained genes for the synthesis of lysine, threonine, methionine, and cysteine, as well as genes with anticoagulation and anti-inflammatory properties. Based on our analysis, we concluded that the strain DMKU3-1042 possesses probiotic properties that make it suitable for use in food and feed supplementation.

HUMAN GUT-MICROBIOME

Title: Draft genome sequence of Lactiplantibacillus plantarum subsp. plantarum strain HF43, a human gut-associated potential probiotic
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Lactiplantibacillus plantarum adapts to a wide range of ecological niches, including the human gut. Numerous health-promoting benefits have been associated with L. plantarum strains. Motivated for the development of human-origin target-based probiotics with known genetic markers, we report the draft genome sequence of human gut-associated Lactiplantibacillus plantarum subsp. plantarum HF43.

CANCER RESEARCH

Title: Bioinformatic challenge on prostate cancer and urinary microbiome
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The Bioinformatics Resource Center (BRC) program was developed by the National Institute of Allergy and Infectious Diseases (NIAID) to assist researchers in analyzing the increasing amount of genomic sequences and other omics-related data. In this work, whole-genome sequences of prostate cancer and genitourinary diseases (WGS) were examined for genes utilizing the BV-BRC Bioinformatics Resource Center. using the Usegalaxy program to combine the plasma and gut microbiome sequences from prostate cancer patients. Following that, chromosomes, plasmids, and unclassified sequences were subjected to ARG analysis. As a result of comprehensive genomic analysis of all samples, the S2 sequences were of good quality compared to the other sequences. As for virulence factors, intracellular survival is one of the important virulence factors, a common gene of Salmonella, which was represented in the prostate cancer samples but not in the urine microbiome samples.

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