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1.
J Hum Genet ; 68(12): 823-833, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37620670

ABSTRACT

OBJECTIVES: Genome-wide association studies (GWAS) have successfully revealed numerous susceptibility loci for obesity. However, identifying the causal genes, pathways, and tissues/cell types responsible for these associations remains a challenge, and standardized analysis workflows are lacking. Additionally, due to limited treatment options for obesity, there is a need for the development of new pharmacological therapies. This study aimed to address these issues by performing step-wise utilization of knowledgebase for gene prioritization and assessing the potential relevance of key obesity genes as therapeutic targets. METHODS AND RESULTS: First, we generated a list of 28,787 obesity-associated SNPs from the publicly available GWAS dataset (approximately 800,000 individuals in the GIANT meta-analysis). Then, we prioritized 1372 genes with significant in silico evidence against genomic and transcriptomic data, including transcriptionally regulated genes in the brain from transcriptome-wide association studies. In further narrowing down the gene list, we selected key genes, which we found to be useful for the discovery of potential drug seeds as demonstrated in lipid GWAS separately. We thus identified 74 key genes for obesity, which are highly interconnected and enriched in several biological processes that contribute to obesity, including energy expenditure and homeostasis. Of 74 key genes, 37 had not been reported for the pathophysiology of obesity. Finally, by drug-gene interaction analysis, we detected 23 (of 74) key genes that are potential targets for 78 approved and marketed drugs. CONCLUSIONS: Our results provide valuable insights into new treatment options for obesity through a data-driven approach that integrates multiple up-to-date knowledgebases.


Subject(s)
Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Genome-Wide Association Study/methods , Obesity/genetics , Gene Expression Profiling , Transcriptome , Polymorphism, Single Nucleotide
2.
Life Sci Alliance ; 6(10)2023 10.
Article in English | MEDLINE | ID: mdl-37491046

ABSTRACT

We investigated the progression of nonalcoholic fatty liver disease from fatty liver to steatohepatitis using single-nucleus and bulk ATAC-seq on the livers of rats fed a high-fat diet (HFD). Rats fed HFD for 4 wk developed fatty liver, and those fed HFD for 8 wk further progressed to steatohepatitis. We observed an increase in the proportion of inflammatory macrophages, consistent with the pathological progression. Utilizing machine learning, we divided global gene regulation into modules, wherein transcription factors within a module could regulate genes within the same module, reaffirming known regulatory relationships between transcription factors and biological processes. We identified core genes-central to co-expression and protein-protein interaction-for the biological processes discovered. Notably, a large part of the core genes overlapped with genes previously implicated in nonalcoholic fatty liver disease. Single-nucleus ATAC-seq, combined with data-driven statistical analysis, offers insight into in vivo global gene regulation as a combination of modules and assists in identifying core genes of relevant biological processes.


Subject(s)
Non-alcoholic Fatty Liver Disease , Rats , Animals , Non-alcoholic Fatty Liver Disease/genetics , Chromatin Immunoprecipitation Sequencing , Gene Expression Regulation/genetics , Transcription Factors/genetics
3.
Trop Med Infect Dis ; 7(12)2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36548693

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is a successful pathogen that has achieved global dissemination, with high prevalence rates in Southeast Asia. A huge diversity of clones has been reported in this region, with MRSA ST239 being the most successful lineage. Nonetheless, description of MRSA genotypes circulating in the Southeast Asia region has, until now, remained poorly compiled. In this review, we aim to provide a better understanding of the molecular epidemiology and distribution of MRSA clones in 11 Southeast Asian countries: Singapore, Malaysia, Thailand, Vietnam, Cambodia, Lao People's Democratic Republic (PDR), Myanmar, Philippines, Indonesia, Brunei Darussalam, and Timor-Leste. Notably, while archaic multidrug-resistant hospital-associated (HA) MRSAs, such as the ST239-III and ST241-III, were prominent in the region during earlier observations, these were then largely replaced by the more antibiotic-susceptible community-acquired (CA) MRSAs, such as ST22-IV and PVL-positive ST30-IV, in recent years after the turn of the century. Nonetheless, reports of livestock-associated (LA) MRSAs remain few in the region.

4.
Microbiol Resour Announc ; 11(12): e0086722, 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36413024

ABSTRACT

Draft genome sequences were obtained for four methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from various wards of the Hospital Canselor Tuanku Muhriz (HCTM), Kuala Lumpur, Malaysia, in 2017. Using different bioinformatics tools, we annotated the draft genomes and identified multiple antimicrobial resistance genes.

6.
Hypertension ; 79(2): 413-423, 2022 02.
Article in English | MEDLINE | ID: mdl-34879704

ABSTRACT

Certain classes of antihypertensive drug may exert specific, blood pressure (BP)-independent protective effects on end-organ damages such as left ventricular hypertrophy, although the overall evidence has not been definitive in clinical trials. To unravel antihypertensive drug-induced gene expression changes that are potentially related to the amelioration of end-organ damages, we performed in vivo phenotypic evaluation and transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred strains (ie, hypertensive and normotensive) of rats. We chose 6 antihypertensive classes: enalapril (angiotensin-converting enzyme inhibitor), candesartan (angiotensin receptor blocker), hydrochlorothiazide (diuretics), amlodipine (calcium-channel blocker), carvedilol (vasodilating ß-blocker), and hydralazine. In the tested rat strains, 4 of 6 drugs, including 2 renin-angiotensin system inhibitors, were effective for BP lowering, whereas the remaining 2 drugs were not. Besides BP lowering, there appeared to be some interdrug heterogeneity in phenotypic changes, such as suppressed body weight gain and body weight-adjusted heart weight reduction. For the transcriptomic response, a considerable number of genes showed prominent mRNA expression changes either in a BP-dependent or BP-independent manner with substantial diversity between the target organs. Noticeable changes of mRNA expression were induced particularly by renin-angiotensin system blockade, for example, for genes in the natriuretic peptide system (Nppb and Corin) in the heart and for those in the renin-angiotensin system/kallikrein-kinin system (Ren and rat Klk1 paralogs) and those related to calcium ion binding (Calb1 and Slc8a1) in the kidney. The research resources constructed here will help corroborate occasionally inconclusive evidence in clinical settings.


Subject(s)
Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Heart/drug effects , Kidney/drug effects , Myocardium/metabolism , Transcriptome/drug effects , Amlodipine/pharmacology , Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Benzimidazoles/pharmacology , Biphenyl Compounds/pharmacology , Calcium Channel Blockers/pharmacology , Carvedilol/pharmacology , Diuretics/pharmacology , Enalapril/pharmacology , Hydralazine/pharmacology , Hydrochlorothiazide/pharmacology , Kidney/metabolism , Male , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Renin-Angiotensin System/drug effects , Tetrazoles/pharmacology
7.
Sci Rep ; 11(1): 2925, 2021 02 03.
Article in English | MEDLINE | ID: mdl-33536501

ABSTRACT

Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.


Subject(s)
Colorectal Neoplasms/diagnosis , Dysbiosis/diagnosis , Gastrointestinal Microbiome , Aged , Akkermansia/isolation & purification , Case-Control Studies , Cohort Studies , Colorectal Neoplasms/microbiology , DNA, Bacterial/isolation & purification , Dysbiosis/complications , Dysbiosis/microbiology , Feces/microbiology , Female , Firmicutes/isolation & purification , Fusobacterium nucleatum/isolation & purification , Humans , Malaysia , Male , Middle Aged , Peptostreptococcus/isolation & purification , RNA, Ribosomal, 16S/genetics
8.
Clin Chim Acta ; 498: 38-46, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31421119

ABSTRACT

One of the best-established area within multi-omics is proteogenomics, whereby the underpinning technologies are next-generation sequencing (NGS) and mass spectrometry (MS). Proteogenomics has contributed significantly to genome (re)-annotation, whereby novel coding sequences (CDS) are identified and confirmed. By incorporating in-silico translated genome variants in protein database, single amino acid variants (SAAV) and splice proteoforms can be identified and quantified at peptide level. The application of proteogenomics in cancer research potentially enables the identification of patient-specific proteoforms, as well as the association of the efficacy or resistance of cancer therapy to different mutations. Here, we discuss how NGS/TGS data are analyzed and incorporated into the proteogenomic framework. These sequence data mainly originate from whole genome sequencing (WGS), whole exome sequencing (WES) and RNA-Seq. We explain two major strategies for sequence analysis i.e., de novo assembly and reads mapping, followed by construction of customized protein databases using such data. Besides, we also elaborate on the procedures of spectrum to peptide sequence matching in proteogenomics, and the relationship between database size on the false discovery rate (FDR). Finally, we discuss the latest development in proteogenomics-assisted precision oncology and also challenges and opportunities in proteogenomics research.


Subject(s)
Precision Medicine/methods , Proteogenomics/methods , Animals , High-Throughput Nucleotide Sequencing/methods , High-Throughput Nucleotide Sequencing/trends , Humans , Mass Spectrometry , Proteogenomics/trends , Proteomics/methods
9.
Proteomics ; 19(10): e1800235, 2019 05.
Article in English | MEDLINE | ID: mdl-30431238

ABSTRACT

Understanding the relationship between genotypes and phenotypes is essential to disentangle biological mechanisms and to unravel the molecular basis of diseases. Genes and proteins are closely linked in biological systems. However, genomics and proteomics have developed separately into two distinct disciplines whereby crosstalk among scientists from the two domains is limited and this constrains the integration of both fields into a single data modality of useful information. The emerging field of proteogenomics attempts to address this by building bridges between the two disciplines. In this review, how genomics and transcriptomics data in different formats can be utilized to assist proteogenomics application is briefly discussed. Subsequently, a much larger part of this review focuses on proteogenomics research articles that are published in the last five years that answer two important questions. First, how proteogenomics can be applied to tackle biological problems is discussed, covering genome annotation and precision medicine. Second, the latest developments in analytical technologies for data acquisition and the bioinformatics tools to interpret and visualize proteogenomics data are covered.


Subject(s)
Computational Biology , High-Throughput Nucleotide Sequencing/trends , Precision Medicine/trends , Proteogenomics/trends , Algorithms , Animals , Big Data , Genome , Humans , Open Reading Frames , Proteome/metabolism , Sequence Analysis, RNA , Software , Tandem Mass Spectrometry , Transcriptome
10.
Genome Biol Evol ; 8(9): 2928-2938, 2016 10 05.
Article in English | MEDLINE | ID: mdl-27540086

ABSTRACT

Fusobacterium nucleatum is considered to be a key oral bacterium in recruiting periodontal pathogens into subgingival dental plaque. Currently F. nucleatum can be subdivided into five subspecies. Our previous genome analysis of F. nucleatum W1481 (referred to hereafter as W1481), isolated from an 8-mm periodontal pocket in a patient with chronic periodontitis, suggested the possibility of a new subspecies. To further investigate the biology and relationships of this possible subspecies with other known subspecies, we performed comparative analysis between W1481 and 35 genome sequences represented by the five known Fusobacterium subspecies. Our analyses suggest that W1481 is most likely a new F. nucleatum subspecies, supported by evidence from phylogenetic analyses and maximal unique match indices (MUMi). Interestingly, we found a horizontally transferred W1481-specific genomic island harboring the tripartite ATP-independent (TRAP)-like transporter genes, suggesting this bacterium might have a high-affinity transport system for the C4-dicarboxylates malate, succinate, and fumarate. Moreover, we found virulence genes in the W1481 genome that may provide a strong defense mechanism which might enable it to colonize and survive within the host by evading immune surveillance. This comparative study provides better understanding of F. nucleatum and the basis for future functional work on this important pathogen.


Subject(s)
Fusobacterium nucleatum/genetics , Genome, Bacterial , Fusobacterium nucleatum/classification , Gene Transfer, Horizontal , Genomic Islands , Phylogeny
11.
PLoS One ; 11(4): e0150413, 2016.
Article in English | MEDLINE | ID: mdl-27035710

ABSTRACT

Mycobacteria have been reported to cause a wide range of human diseases. We present the first whole-genome study of a Non-Tuberculous Mycobacterium, Mycobacterium sp. UM_CSW (referred to hereafter as UM_CSW), isolated from a patient diagnosed with bronchiectasis. Our data suggest that this clinical isolate is likely a novel mycobacterial species, supported by clear evidence from molecular phylogenetic, comparative genomic, ANI and AAI analyses. UM_CSW is closely related to the Mycobacterium avium complex. While it has characteristic features of an environmental bacterium, it also shows a high pathogenic potential with the presence of a wide variety of putative genes related to bacterial virulence and shares very similar pathogenomic profiles with the known pathogenic mycobacterial species. Thus, we conclude that this possible novel Mycobacterium species should be tightly monitored for its possible causative role in human infections.


Subject(s)
Bronchiectasis/microbiology , Genome, Bacterial , Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/genetics , Nontuberculous Mycobacteria/isolation & purification , Bacterial Proteins/genetics , Bronchiectasis/diagnosis , Comparative Genomic Hybridization , Genomics , Humans , Mycobacterium Infections, Nontuberculous/diagnosis , Nontuberculous Mycobacteria/pathogenicity , Phylogeny , Virulence Factors/genetics
12.
PeerJ ; 4: e1698, 2016.
Article in English | MEDLINE | ID: mdl-27017950

ABSTRACT

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.

13.
Sci Rep ; 5: 18227, 2015 Dec 15.
Article in English | MEDLINE | ID: mdl-26666970

ABSTRACT

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.


Subject(s)
Computational Biology/methods , Genome, Bacterial , Genomics/methods , Mycobacterium/genetics , Software , Databases, Genetic , Humans , Mycobacterium/classification , Search Engine , Web Browser
14.
BMC Genomics ; 16: 755, 2015 Oct 06.
Article in English | MEDLINE | ID: mdl-26444974

ABSTRACT

BACKGROUND: 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. DESCRIPTION: With this motivation, we have developed ListeriaBase, a web Listeria genomic resource and analysis platform to facilitate comparative analysis of Listeria spp. ListeriaBase currently houses 850,402 protein-coding genes, 18,113 RNAs and 15,576 tRNAs from 285 genome sequences of different Listeria strains. An AJAX-based real time search system implemented in ListeriaBase facilitates searching of this huge genomic data. Our in-house designed comparative analysis tools such as Pairwise Genome Comparison (PGC) tool allowing comparison between two genomes, Pathogenomics Profiling Tool (PathoProT) for comparing the virulence genes, and ListeriaTree for phylogenic classification, were customized and incorporated in ListeriaBase facilitating comparative genomic analysis of Listeria spp. Interestingly, we identified a unique genomic feature in the L. monocytogenes genomes in our analysis. The Auto protein sequences of the serotype 4 and the non-serotype 4 strains of L. monocytogenes possessed unique sequence signatures that can differentiate the two groups. We propose that the aut gene may be a potential gene marker for differentiating the serotype 4 strains from other serotypes of L. monocytogenes. CONCLUSIONS: ListeriaBase is a useful resource and analysis platform that can facilitate comparative analysis of Listeria for the scientific communities. We have successfully demonstrated some key utilities of ListeriaBase. The knowledge that we obtained in the analyses of L. monocytogenes may be important for functional works of this human pathogen in future. ListeriaBase is currently available at http://listeria.um.edu.my .


Subject(s)
Genome, Bacterial , Listeria monocytogenes/genetics , Listeriosis/genetics , Phylogeny , Chromosome Mapping , Evolution, Molecular , Genetic Markers , Humans , Listeria monocytogenes/pathogenicity , Listeriosis/microbiology
15.
BMC Bioinformatics ; 16: 9, 2015 Jan 16.
Article in English | MEDLINE | ID: mdl-25591325

ABSTRACT

BACKGROUND: 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. DESCRIPTION: To facilitate the ongoing and future research of Yersinia, especially those generally considered non-pathogenic species, a well-defined repository and analysis platform is needed to hold the Yersinia genomic data and analysis tools for the Yersinia research community. Hence, we have developed the YersiniaBase, a robust and user-friendly Yersinia resource and analysis platform for the analysis of Yersinia genomic data. YersiniaBase has a total of twelve species and 232 genome sequences, of which the majority are Yersinia pestis. In order to smooth the process of searching genomic data in a large database, we implemented an Asynchronous JavaScript and XML (AJAX)-based real-time searching system in YersiniaBase. Besides incorporating existing tools, which include JavaScript-based genome browser (JBrowse) and Basic Local Alignment Search Tool (BLAST), YersiniaBase also has in-house developed tools: (1) Pairwise Genome Comparison tool (PGC) for comparing two user-selected genomes; (2) Pathogenomics Profiling Tool (PathoProT) for comparative pathogenomics analysis of Yersinia genomes; (3) YersiniaTree for constructing phylogenetic tree of Yersinia. We ran analyses based on the tools and genomic data in YersiniaBase and the preliminary results showed differences in virulence genes found in Yersinia pestis and Yersinia pseudotuberculosis compared to other Yersinia species, and differences between Yersinia enterocolitica subsp. enterocolitica and Yersinia enterocolitica subsp. palearctica. CONCLUSIONS: YersiniaBase offers free access to wide range of genomic data and analysis tools for the analysis of Yersinia. YersiniaBase can be accessed at http://yersinia.um.edu.my .


Subject(s)
Databases, Genetic , Genome, Bacterial , Genomics/methods , Software , Virulence/genetics , Yersinia/genetics , Chromosome Mapping , Humans , Internet , Phylogeny , Search Engine , User-Computer Interface , Yersinia/classification , Yersinia/pathogenicity , Yersinia Infections/microbiology
16.
ScientificWorldJournal ; 2014: 569324, 2014.
Article in English | MEDLINE | ID: mdl-25243218

ABSTRACT

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.


Subject(s)
Data Curation/trends , Databases, Genetic/trends , Genome, Bacterial/genetics , Vibrio/genetics , Data Curation/methods , Phylogeny
17.
Article in English | MEDLINE | ID: mdl-25149689

ABSTRACT

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. DATABASE URL: http://fusobacterium.um.edu.my.


Subject(s)
Databases, Genetic , Fusobacterium , Genome, Bacterial , Genomics/methods , Internet , Cluster Analysis , Software , User-Computer Interface
18.
BMC Genomics ; 15: 600, 2014 Jul 16.
Article in English | MEDLINE | ID: mdl-25030426

ABSTRACT

BACKGROUND: 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. DESCRIPTION: To facilitate the ongoing research on Helicobacter, a specialized central repository and analysis platform for the Helicobacter research community is needed to host the fast-growing amount of genomic data and facilitate the analysis of these data, particularly comparative analysis. Here we present HelicoBase, a user-friendly Helicobacter resource platform with diverse functionality for the analysis of Helicobacter genomic data for the Helicobacter research communities. HelicoBase hosts a total of 13 species and 166 genome sequences of Helicobacter spp. Genome annotations such as gene/protein sequences, protein function and sub-cellular localisation are also included. Our web implementation supports diverse query types and seamless searching of annotations using an AJAX-based real-time searching system. JBrowse is also incorporated to allow rapid and seamless browsing of Helicobacter genomes and annotations. Advanced bioinformatics analysis tools consisting of standard BLAST for similarity search, VFDB BLAST for sequence similarity 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 are also included to facilitate the analysis of Helicobacter genomic data. CONCLUSIONS: HelicoBase offers access to a range of genomic resources as well as tools for the analysis of Helicobacter genome data. HelicoBase can be accessed at http://helicobacter.um.edu.my.


Subject(s)
Databases, Genetic , Genome, Bacterial , Helicobacter/genetics , Computational Biology , Internet , Open Reading Frames , Search Engine
19.
Database (Oxford) ; 2014: bau010, 2014.
Article in English | MEDLINE | ID: mdl-24578355

ABSTRACT

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/.


Subject(s)
Databases, Genetic , Genomics/methods , Research , Software , Staphylococcus/genetics , Genome, Bacterial/genetics , Internet , Search Engine , Sequence Homology, Nucleic Acid
20.
Genome Announc ; 2(1)2014 Feb 13.
Article in English | MEDLINE | ID: mdl-24526626

ABSTRACT

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.

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