Displaying publications 1 - 20 of 56 in total

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  1. Fulltext A Meta-Analysis of Quantitative Trait Loci Associated with Multiple Disease Resistance in Rice (Oryza sativa L.)
    Kumar IS, Nadarajah K
    Plants (Basel), 2020 Nov 05;9(11).
    PMID: 33167299 DOI: 10.3390/plants9111491
    Rice blast, sheath blight and bacterial leaf blight are major rice diseases found worldwide. The development of resistant cultivars is generally perceived as the most effective way to combat these diseases. Plant disease resistance is a polygenic trait where a combinatorial effect of major and minor genes affects this trait. To locate the source of this trait, various quantitative trait loci (QTL) mapping studies have been performed in the past two decades. However, investigating the congruency between the reported QTL is a daunting task due to the heterogeneity amongst the QTLs studied. Hence, the aim of our study is to integrate the reported QTLs for resistance against rice blast, sheath blight and bacterial leaf blight and objectively analyze and consolidate the location of QTL clusters in the chromosomes, reducing the QTL intervals and thus identifying candidate genes within the selected meta-QTL. A total of twenty-seven studies for resistance QTLs to rice blast (8), sheath blight (15) and bacterial leaf blight (4) was compiled for QTL projection and analyses. Cumulatively, 333 QTLs associated with rice blast (114), sheath blight (151) and bacterial leaf blight (68) resistance were compiled, where 303 QTLs could be projected onto a consensus map saturated with 7633 loci. Meta-QTL analysis on 294 QTLs yielded 48 meta-QTLs, where QTLs with membership probability lower than 60% were excluded, reducing the number of QTLs within the meta-QTL to 274. Further, three meta-QTL regions (MQTL2.5, MQTL8.1 and MQTL9.1) were selected for functional analysis on the basis that MQTL2.5 harbors the highest number of QTLs; meanwhile, MQTL8.1 and MQTL9.1 have QTLs associated with all three diseases mentioned above. The functional analysis allows for determination of enriched gene ontology and resistance gene analogs (RGAs) and other defense-related genes. To summarize, MQTL2.5, MQTL8.1 and MQTL9.1 have a considerable number of R-genes that account for 10.21%, 4.08% and 6.42% of the total genes found in these meta-QTLs, respectively. Defense genes constitute around 3.70%, 8.16% and 6.42% of the total number of genes in MQTL2.5, MQTL8.1 and MQTL9.1, respectively. This frequency is higher than the total frequency of defense genes in the rice genome, which is 0.0096% (167 defense genes/17,272 total genes). The integration of the QTLs facilitates the identification of QTL hotspots for rice blast, sheath blight and bacterial blight resistance with reduced intervals, which helps to reduce linkage drag in breeding. The candidate genes within the promising regions could be utilized for improvement through genetical engineering.
    Matched MeSH terms: Gene Ontology
  2. Fulltext Analyses of hypomethylated oil palm gene space
    Low ET, Rosli R, Jayanthi N, Mohd-Amin AH, Azizi N, Chan KL, et al.
    PLoS One, 2014;9(1):e86728.
    PMID: 24497974 DOI: 10.1371/journal.pone.0086728
    Demand for palm oil has been increasing by an average of ∼8% the past decade and currently accounts for about 59% of the world's vegetable oil market. This drives the need to increase palm oil production. Nevertheless, due to the increasing need for sustainable production, it is imperative to increase productivity rather than the area cultivated. Studies on the oil palm genome are essential to help identify genes or markers that are associated with important processes or traits, such as flowering, yield and disease resistance. To achieve this, 294,115 and 150,744 sequences from the hypomethylated or gene-rich regions of Elaeis guineensis and E. oleifera genome were sequenced and assembled into contigs. An additional 16,427 shot-gun sequences and 176 bacterial artificial chromosomes (BAC) were also generated to check the quality of libraries constructed. Comparison of these sequences revealed that although the methylation-filtered libraries were sequenced at low coverage, they still tagged at least 66% of the RefSeq supported genes in the BAC and had a filtration power of at least 2.0. A total 33,752 microsatellites and 40,820 high-quality single nucleotide polymorphism (SNP) markers were identified. These represent the most comprehensive collection of microsatellites and SNPs to date and would be an important resource for genetic mapping and association studies. The gene models predicted from the assembled contigs were mined for genes of interest, and 242, 65 and 14 oil palm transcription factors, resistance genes and miRNAs were identified respectively. Examples of the transcriptional factors tagged include those associated with floral development and tissue culture, such as homeodomain proteins, MADS, Squamosa and Apetala2. The E. guineensis and E. oleifera hypomethylated sequences provide an important resource to understand the molecular mechanisms associated with important agronomic traits in oil palm.
    Matched MeSH terms: Gene Ontology
  3. BZD9L1 sirtuin inhibitor: Identification of key molecular targets and their biological functions in HCT 116 colorectal cancer cells
    Tan YJ, Lee YT, Mancera RL, Oon CE
    Life Sci, 2021 Nov 01;284:119747.
    PMID: 34171380 DOI: 10.1016/j.lfs.2021.119747
    BZD9L1 was previously described as a SIRT1/2 inhibitor with anti-cancer activities in colorectal cancer (CRC), either as a standalone chemotherapy or in combination with 5-fluorouracil. BZD9L1 was reported to induce apoptosis in CRC cells; however, the network of intracellular pathways and crosstalk between molecular players mediated by BZD9L1 is not fully understood. This study aimed to uncover the mechanisms involved in BZD9L1-mediated cytotoxicity based on previous and new findings for the prediction and identification of related pathways and key molecular players. BZD9L1-regulated candidate targets (RCTs) were identified using a range of molecular, cell-based and biochemical techniques on the HCT 116 cell line. BZD9L1 regulated major cancer pathways including Notch, p53, cell cycle, NFκB, Myc/MAX, and MAPK/ERK signalling pathways. BZD9L1 also induced reactive oxygen species (ROS), regulated apoptosis-related proteins, and altered cell polarity and adhesion profiles. In silico analyses revealed that most RCTs were interconnected, and were involved in the modulation of catalytic activity, metabolism and transcription regulation, response to cytokines, and apoptosis signalling pathways. These RCTs were implicated in p53-dependent apoptosis pathway. This study provides the first assessment of possible associations of molecular players underlying the cytotoxic activity of BZD9L1, and establishes the links between RCTs and apoptosis through the p53 pathway.
    Matched MeSH terms: Gene Ontology
  4. Biomarkers for ischemic stroke subtypes: A protein-protein interaction analysis
    Wei LK, Quan LS
    Comput Biol Chem, 2019 Dec;83:107116.
    PMID: 31561071 DOI: 10.1016/j.compbiolchem.2019.107116
    According to the Trial of Org 10172 in Acute Stroke Treatment, ischemic stroke is classified into five subtypes. However, the predictive biomarkers of ischemic stroke subtypes are still largely unknown. The utmost objective of this study is to map, construct and analyze protein-protein interaction (PPI) networks for all subtypes of ischemic stroke, and to suggest the predominant biological pathways for each subtypes. Through 6285 protein data retrieved from PolySearch2 and STRING database, the first PPI networks for all subtypes of ischemic stroke were constructed. Notably, F2 and PLG were identified as the critical proteins for large artery atherosclerosis (LAA), lacunar, cardioembolic, stroke of other determined etiology (SOE) and stroke of undetermined etiology (SUE). Gene ontology and DAVID analysis revealed that GO:0030193 regulation of blood coagulation and GO:0051917 regulation of fibrinolysis were the important functional clusters for all the subtypes. In addition, inflammatory pathway was the key etiology for LAA and lacunar, while FOS and JAK2/STAT3 signaling pathways might contribute to cardioembolic stroke. Due to many risk factors associated with SOE and SUE, the precise etiology for these two subtypes remained to be concluded.
    Matched MeSH terms: Gene Ontology
  5. Bursal transcriptome profiling of different inbred chicken lines reveals key differentially expressed genes at 3 days post-infection with very virulent infectious bursal disease virus
    Farhanah MI, Yasmin AR, Mat Isa N, Hair-Bejo M, Ideris A, Powers C, et al.
    J Gen Virol, 2018 Jan;99(1):21-35.
    PMID: 29058656 DOI: 10.1099/jgv.0.000956
    Infectious bursal disease is a highly contagious disease in the poultry industry and causes immunosuppression in chickens. Genome-wide regulations of immune response genes of inbred chickens with different genetic backgrounds, following very virulent infectious bursal disease virus (vvIBDV) infection are poorly characterized. Therefore, this study aims to analyse the bursal tissue transcriptome of six inbred chicken lines 6, 7, 15, N, O and P following infection with vvIBDV strain UK661 using strand-specific next-generation sequencing, by highlighting important genes and pathways involved in the infected chicken during peak infection at 3 days post-infection. All infected chickens succumbed to the infection without major variations among the different lines. However, based on the viral loads and bursal lesion scoring, lines P and 6 can be considered as the most susceptible lines, while lines 15 and N were regarded as the least affected lines. Transcriptome profiling of the bursa identified 4588 genes to be differentially expressed, with 2985 upregulated and 1642 downregulated genes, in which these genes were commonly or uniquely detected in all or several infected lines. Genes that were upregulated are primarily pro-inflammatory cytokines, chemokines and IFN-related. Various genes that are associated with B-cell functions and genes related to apoptosis were downregulated, together with the genes involved in p53 signalling. In conclusion, bursal transcriptome profiles of different inbred lines showed differential expressions of pro-inflammatory cytokines and chemokines, Th1 cytokines, JAK-STAT signalling genes, MAPK signalling genes, and their related pathways following vvIBDV infection.
    Matched MeSH terms: Gene Ontology
  6. Fulltext Comparative genomic and transcriptomic analysis of selected fatty acid biosynthesis genes and CNL disease resistance genes in oil palm
    Rosli R, Amiruddin N, Ab Halim MA, Chan PL, Chan KL, Azizi N, et al.
    PLoS One, 2018;13(4):e0194792.
    PMID: 29672525 DOI: 10.1371/journal.pone.0194792
    Comparative genomics and transcriptomic analyses were performed on two agronomically important groups of genes from oil palm versus other major crop species and the model organism, Arabidopsis thaliana. The first analysis was of two gene families with key roles in regulation of oil quality and in particular the accumulation of oleic acid, namely stearoyl ACP desaturases (SAD) and acyl-acyl carrier protein (ACP) thioesterases (FAT). In both cases, these were found to be large gene families with complex expression profiles across a wide range of tissue types and developmental stages. The detailed classification of the oil palm SAD and FAT genes has enabled the updating of the latest version of the oil palm gene model. The second analysis focused on disease resistance (R) genes in order to elucidate possible candidates for breeding of pathogen tolerance/resistance. Ortholog analysis showed that 141 out of the 210 putative oil palm R genes had homologs in banana and rice. These genes formed 37 clusters with 634 orthologous genes. Classification of the 141 oil palm R genes showed that the genes belong to the Kinase (7), CNL (95), MLO-like (8), RLK (3) and Others (28) categories. The CNL R genes formed eight clusters. Expression data for selected R genes also identified potential candidates for breeding of disease resistance traits. Furthermore, these findings can provide information about the species evolution as well as the identification of agronomically important genes in oil palm and other major crops.
    Matched MeSH terms: Gene Ontology
  7. Fulltext Comparative transcriptome analysis to identify candidate genes involved in 2-methoxy-1,4-naphthoquinone (MNQ) biosynthesis in Impatiens balsamina L
    Foong LC, Chai JY, Ho ASH, Yeo BPH, Lim YM, Tam SM
    Sci Rep, 2020 09 30;10(1):16123.
    PMID: 32999341 DOI: 10.1038/s41598-020-72997-2
    Impatiens balsamina L. is a tropical ornamental and traditional medicinal herb rich in natural compounds, especially 2-methoxy-1,4-naphthoquinone (MNQ) which is a bioactive compound with tested anticancer activities. Characterization of key genes involved in the shikimate and 1,4-dihydroxy-2-naphthoate (DHNA) pathways responsible for MNQ biosynthesis and their expression profiles in I. balsamina will facilitate adoption of genetic/metabolic engineering or synthetic biology approaches to further increase production for pre-commercialization. In this study, HPLC analysis showed that MNQ was present in significantly higher quantities in the capsule pericarps throughout three developmental stages (early-, mature- and postbreaker stages) whilst its immediate precursor, 2-hydroxy-1,4-naphthoquinone (lawsone) was mainly detected in mature leaves. Transcriptomes of I. balsamina derived from leaf, flower, and three capsule developmental stages were generated, totalling 59.643 Gb of raw reads that were assembled into 94,659 unigenes (595,828 transcripts). A total of 73.96% of unigenes were functionally annotated against seven public databases and 50,786 differentially expressed genes (DEGs) were identified. Expression profiles of 20 selected genes from four major secondary metabolism pathways were studied and validated using qRT-PCR method. Majority of the DHNA pathway genes were found to be significantly upregulated in early stage capsule compared to flower and leaf, suggesting tissue-specific synthesis of MNQ. Correlation analysis identified 11 candidate unigenes related to three enzymes (NADH-quinone oxidoreductase, UDP-glycosyltransferases and S-adenosylmethionine-dependent O-methyltransferase) important in the final steps of MNQ biosynthesis based on genes expression profiles consistent with MNQ content. This study provides the first molecular insight into the dynamics of MNQ biosynthesis and accumulation across different tissues of I. balsamina and serves as a valuable resource to facilitate further manipulation to increase production of MNQ.
    Matched MeSH terms: Gene Ontology
  8. Fulltext Computational discovery and annotation of conserved small open reading frames in fungal genomes
    Mat-Sharani S, Firdaus-Raih M
    BMC Bioinformatics, 2019 Feb 04;19(Suppl 13):551.
    PMID: 30717662 DOI: 10.1186/s12859-018-2550-2
    BACKGROUND: Small open reading frames (smORF/sORFs) that encode short protein sequences are often overlooked during the standard gene prediction process thus leading to many sORFs being left undiscovered and/or misannotated. For many genomes, a second round of sORF targeted gene prediction can complement the existing annotation. In this study, we specifically targeted the identification of ORFs encoding for 80 amino acid residues or less from 31 fungal genomes. We then compared the predicted sORFs and analysed those that are highly conserved among the genomes.

    RESULTS: A first set of sORFs was identified from existing annotations that fitted the maximum of 80 residues criterion. A second set was predicted using parameters that specifically searched for ORF candidates of 80 codons or less in the exonic, intronic and intergenic sequences of the subject genomes. A total of 1986 conserved sORFs were predicted and characterized.

    CONCLUSIONS: It is evident that numerous open reading frames that could potentially encode for polypeptides consisting of 80 amino acid residues or less are overlooked during standard gene prediction and annotation. From our results, additional targeted reannotation of genomes is clearly able to complement standard genome annotation to identify sORFs. Due to the lack of, and limitations with experimental validation, we propose that a simple conservation analysis can provide an acceptable means of ensuring that the predicted sORFs are sufficiently clear of gene prediction artefacts.

    Matched MeSH terms: Gene Ontology
  9. Computational prediction of miRNAs in Nipah virus genome reveals possible interaction with human genes involved in encephalitis
    Saini S, Thakur CJ, Kumar V, Tandon S, Bhardwaj V, Maggar S, et al.
    Mol Biol Res Commun, 2018 Sep;7(3):107-118.
    PMID: 30426028 DOI: 10.22099/mbrc.2018.29577.1322
    Current re-emergence of Nipah virus (NiV) in India caused 11 deaths so far and many patients were kept in quarantine. A thorough study of previous outbreaks occurred in Malaysia, Bangladesh and India represents cases with high rate of fatality due to acute encephalitis. Our work involves genome analysis of NiV for prediction of miRNAs and their targeted genes in human in order to understand encephalitis origin. Ab-intio program-VMir was used for initial screening of genome, obtained nine pre-miRNAs was analyzed by ViralMir to check for any pseudo pre-miRNAs. Eighteen functional mature miRNAs were extracted from pre-miRNAs by using Mature-Bayes tool, which targets 669 genes in human genome as retrieved by miRDB. Gene ontology terms by PANTHER provide important pathways in which target genes were involved like Axon guidance, T cell activation, and nicotinic acetylcholine receptor signaling. Significant outcome was obtained after NCBI Gene and OMIM database mining and literature search for predicted target genes. TLR3, TJP1, NOTCH2, FHL1, and GRIA3 target genes obtained showed their involvement in host defense, blood brain barrier, neurogenesis, mental retardation and encephalitis. To conclude, we predicted significant genes in human that can be inhibited by miRNAs of NiV and results in etiology of encephalitis.
    Matched MeSH terms: Gene Ontology
  10. DNMT1 is associated with cell cycle and DNA replication gene sets in diffuse large B-cell lymphoma
    Loo SK, Ab Hamid SS, Musa M, Wong KK
    Pathol Res Pract, 2018 Jan;214(1):134-143.
    PMID: 29137822 DOI: 10.1016/j.prp.2017.10.005
    Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells. Independent gene set enrichment analysis (GSEA) performed using GEPs of shRNA-treated HT cells and primary GCB-DLBCL cases derived from two publicly-available datasets (i.e. GSE10846 and GSE31312) produced three separate lists of enriched gene sets for each gene sets collection from Molecular Signatures Database (MSigDB). Subsequent Venn analysis identified 268, 145 and six consensus gene sets from analyzing gene sets in C2 collection (curated gene sets), C5 sub-collection [gene sets from gene ontology (GO) biological process ontology] and Hallmark collection, respectively to be enriched in positive correlation with DNMT1 expression profiles in shRNA-treated HT cells, GSE10846 and GSE31312 datasets [false discovery rate (FDR) <0.05]. Cell cycle progression and DNA replication were among the significantly enriched biological processes (FDR <0.05). Expression of genes involved in the activation of cell cycle and DNA replication (e.g. CDK1, CCNA2, E2F2, PCNA, RFC5 and POLD3) were highly correlated (r>0.8) with DNMT1 expression and significantly downregulated (log fold-change
    Matched MeSH terms: Gene Ontology
  11. 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.
    Matched MeSH terms: Gene Ontology
  12. Fulltext Deep sequencing and in silico analysis of small RNA library reveals novel miRNA from leaf Persicaria minor transcriptome
    Samad AFA, Nazaruddin N, Murad AMA, Jani J, Zainal Z, Ismail I
    3 Biotech, 2018 Mar;8(3):136.
    PMID: 29479512 DOI: 10.1007/s13205-018-1164-8
    In current era, majority of microRNA (miRNA) are being discovered through computational approaches which are more confined towards model plants. Here, for the first time, we have described the identification and characterization of novel miRNA in a non-model plant, Persicaria minor (P. minor) using computational approach. Unannotated sequences from deep sequencing were analyzed based on previous well-established parameters. Around 24 putative novel miRNAs were identified from 6,417,780 reads of the unannotated sequence which represented 11 unique putative miRNA sequences. PsRobot target prediction tool was deployed to identify the target transcripts of putative novel miRNAs. Most of the predicted target transcripts (mRNAs) were known to be involved in plant development and stress responses. Gene ontology showed that majority of the putative novel miRNA targets involved in cellular component (69.07%), followed by molecular function (30.08%) and biological process (0.85%). Out of 11 unique putative miRNAs, 7 miRNAs were validated through semi-quantitative PCR. These novel miRNAs discoveries in P. minor may develop and update the current public miRNA database.
    Matched MeSH terms: Gene Ontology
  13. Differentially Expressed Genes and Their Clinical Significance in Ischaemic Stroke: An In-Silico Study
    Appunni S, Rubens M, Ramamoorthy V, Sharma H, Singh AK, Swarup V, et al.
    Malays J Med Sci, 2020 Dec;27(6):53-67.
    PMID: 33447134 DOI: 10.21315/mjms2020.27.6.6
    Background: Ischaemic stroke (IS), a multifactorial neurological disorder, is mediated by interplay between genes and the environment and, thus, blood-based IS biomarkers are of significant clinical value. Therefore, this study aimed to find global differentially expressed genes (DEGs) in-silico, to identify key enriched genes via gene set enrichment analysis (GSEA) and to determine the clinical significance of these genes in IS.

    Methods: Microarray expression dataset GSE22255 was retrieved from the Gene Expression Omnibus (GEO) database. It includes messenger ribonucleic acid (mRNA) expression data for the peripheral blood mononuclear cells of 20 controls and 20 IS patients. The bioconductor-package 'affy' was used to calculate expression and a pairwise t-test was applied to screen DEGs (P < 0.01). Further, GSEA was used to determine the enrichment of DEGs specific to gene ontology (GO) annotations.

    Results: GSEA analysis revealed 21 genes to be significantly plausible gene markers, enriched in multiple pathways among all the DEGs (n = 881). Ten gene sets were found to be core enriched in specific GO annotations. JunD, NCX3 and fibroblast growth factor receptor 4 (FGFR4) were under-represented and glycoprotein M6-B (GPM6B) was persistently over-represented.

    Conclusion: The identified genes are either associated with the pathophysiology of IS or they affect post-IS neuronal regeneration, thereby influencing clinical outcome. These genes should, therefore, be evaluated for their utility as suitable markers for predicting IS in clinical scenarios.

    Matched MeSH terms: Gene Ontology
  14. Fulltext Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative Virulence-Associated Differentially Abundant Membrane Proteins
    Ng YL, Olivos-García A, Lim TK, Noordin R, Lin Q, Othman N
    Am J Trop Med Hyg, 2018 12;99(6):1518-1529.
    PMID: 30298805 DOI: 10.4269/ajtmh.18-0415
    Entamoeba histolytica is a protozoan parasite that causes amebiasis and poses a significant health risk for populations in endemic areas. The molecular mechanisms involved in the pathogenesis and regulation of the parasite are not well characterized. We aimed to identify and quantify the differentially abundant membrane proteins by comparing the membrane proteins of virulent and avirulent variants of E. histolytica HM-1:IMSS, and to investigate the potential associations among the differentially abundant membrane proteins. We performed quantitative proteomics analysis using isobaric tags for relative and absolute quantitation labeling, in combination with two mass spectrometry instruments, that is, nano-liquid chromatography (nanoLC)-matrix-assisted laser desorption/ionization-mass spectrometry/mass spectrometry and nanoLC-electrospray ionization tandem mass spectrometry. Overall, 37 membrane proteins were found to be differentially abundant, whereby 19 and 18 membrane proteins of the virulent variant of E. histolytica increased and decreased in abundance, respectively. Proteins that were differentially abundant include Rho family GTPase, calreticulin, a 70-kDa heat shock protein, and hypothetical proteins. Analysis by Protein ANalysis THrough Evolutionary Relationships database revealed that the differentially abundant membrane proteins were mainly involved in catalytic activities (29.7%) and metabolic processes (32.4%). Differentially abundant membrane proteins that were found to be involved mainly in the catalytic activities and the metabolic processes were highlighted together with their putative roles in relation to the virulence. Further investigations should be performed to elucidate the roles of these proteins in E. histolytica pathogenesis.
    Matched MeSH terms: Gene Ontology
  15. EuDBase: An online resource for automated EST analysis pipeline (ESTFrontier) and database for red seaweed Eucheuma denticulatum
    Hussein ZA, Loke KK, Abidin RA, Othman R
    Bioinformation, 2011;7(4):157-62.
    PMID: 22102771
    Functional genomics has proven to be an efficient tool in identifying genes involved in various biological functions. However the availability of commercially important seaweed Eucheuma denticulatum functional resources is still limited. EuDBase is the first seaweed online repository that provides integrated access to ESTs of Eucheuma denticulatum generated from samples collected from Kudat and Semporna in Sabah, Malaysia. The database stored 10,031 ESTs that are clustered and assembled into 2,275 unique transcripts (UT) and 955 singletons. Raw data were automatically processed using ESTFrontier, an in-house automated EST analysis pipeline. Data was collected in MySQL database. Web interface is implemented using PHP and it allows browsing and querying EuDBase through search engine. Data is searchable via BLAST hit, domain search, Gene Ontology or KEGG Pathway. A user-friendly interface allows the identification of sequences either using a simple text query or similarity search. The development of EuDBase is initiated to store, manage and analyze the E. denticulatum ESTs and to provide accumulative digital resources for the use of global scientific community. EuDBase is freely available from http://www.inbiosis.ukm.my/eudbase/.
    Matched MeSH terms: Gene Ontology
  16. Fulltext FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures
    Wong KK, Gascoyne DM, Soilleux EJ, Lyne L, Spearman H, Roncador G, et al.
    Oncotarget, 2016 Aug 16;7(33):52940-52956.
    PMID: 27224915 DOI: 10.18632/oncotarget.9507
    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL.
    Matched MeSH terms: Gene Ontology
  17. Fulltext Flavonoid biosynthesis genes putatively identified in the aromatic plant Polygonum minus via Expressed Sequences Tag (EST) analysis
    Roslan ND, Yusop JM, Baharum SN, Othman R, Mohamed-Hussein ZA, Ismail I, et al.
    Int J Mol Sci, 2012;13(3):2692-706.
    PMID: 22489118 DOI: 10.3390/ijms13032692
    P. minus is an aromatic plant, the leaf of which is widely used as a food additive and in the perfume industry. The leaf also accumulates secondary metabolites that act as active ingredients such as flavonoid. Due to limited genomic and transcriptomic data, the biosynthetic pathway of flavonoids is currently unclear. Identification of candidate genes involved in the flavonoid biosynthetic pathway will significantly contribute to understanding the biosynthesis of active compounds. We have constructed a standard cDNA library from P. minus leaves, and two normalized full-length enriched cDNA libraries were constructed from stem and root organs in order to create a gene resource for the biosynthesis of secondary metabolites, especially flavonoid biosynthesis. Thus, large-scale sequencing of P. minus cDNA libraries identified 4196 expressed sequences tags (ESTs) which were deposited in dbEST in the National Center of Biotechnology Information (NCBI). From the three constructed cDNA libraries, 11 ESTs encoding seven genes were mapped to the flavonoid biosynthetic pathway. Finally, three flavonoid biosynthetic pathway-related ESTs chalcone synthase, CHS (JG745304), flavonol synthase, FLS (JG705819) and leucoanthocyanidin dioxygenase, LDOX (JG745247) were selected for further examination by quantitative RT-PCR (qRT-PCR) in different P. minus organs. Expression was detected in leaf, stem and root. Gene expression studies have been initiated in order to better understand the underlying physiological processes.
    Matched MeSH terms: Gene Ontology
  18. Fulltext Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa
    Riveron JM, Ibrahim SS, Mulamba C, Djouaka R, Irving H, Wondji MJ, et al.
    G3 (Bethesda), 2017 06 07;7(6):1819-1832.
    PMID: 28428243 DOI: 10.1534/g3.117.040147
    Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes (CYP6P9a and CYP6P9b) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies.
    Matched MeSH terms: Gene Ontology
  19. Fulltext Human Mesenchymal Stem Cells-mediated Transcriptomic Regulation of Leukemic Cells in Delivering Anti-tumorigenic Effects
    Sarmadi VH, Ahmadloo S, Boroojerdi MH, John CM, Al-Graitte SJR, Lawal H, et al.
    Cell Transplant, 2020 2 7;29:963689719885077.
    PMID: 32024378 DOI: 10.1177/0963689719885077
    Treatment of leukemia has become much difficult because of resistance to the existing anticancer therapies. This has thus expedited the search for alternativ therapies, and one of these is the exploitation of mesenchymal stem cells (MSCs) towards control of tumor cells. The present study investigated the effect of human umbilical cord-derived MSCs (UC-MSCs) on the proliferation of leukemic cells and gauged the transcriptomic modulation and the signaling pathways potentially affected by UC-MSCs. The inhibition of growth of leukemic tumor cell lines was assessed by proliferation assays, apoptosis and cell cycle analysis. BV173 and HL-60 cells were further analyzed using microarray gene expression profiling. The microarray results were validated by RT-qPCR and western blot assay for the corresponding expression of genes and proteins. The UC-MSCs attenuated leukemic cell viability and proliferation in a dose-dependent manner without inducing apoptosis. Cell cycle analysis revealed that the growth of tumor cells was arrested at the G0/G1 phase. The microarray results identified that HL-60 and BV173 share 35 differentially expressed genes (DEGs) (same expression direction) in the presence of UC-MSCs. In silico analysis of these selected DEGs indicated a significant influence in the cell cycle and cell cycle-related biological processes and signaling pathways. Among these, the expression of DBF4, MDM2, CCNE2, CDK6, CDKN1A, and CDKN2A was implicated in six different signaling pathways that play a pivotal role in the anti-tumorigenic activity exerted by UC-MSCs. The UC-MSCs perturbate the cell cycle process of leukemic cells via dysregulation of tumor suppressor and oncogene expression.
    Matched MeSH terms: Gene Ontology
  20. Fulltext Human non-small cell lung cancer expresses putative cancer stem cell markers and exhibits the transcriptomic profile of multipotent cells
    Zakaria N, Yusoff NM, Zakaria Z, Lim MN, Baharuddin PJ, Fakiruddin KS, et al.
    BMC Cancer, 2015;15:84.
    PMID: 25881239 DOI: 10.1186/s12885-015-1086-3
    Despite significant advances in staging and therapies, lung cancer remains a major cause of cancer-related lethality due to its high incidence and recurrence. Clearly, a novel approach is required to develop new therapies to treat this devastating disease. Recent evidence indicates that tumours contain a small population of cells known as cancer stem cells (CSCs) that are responsible for tumour maintenance, spreading and resistant to chemotherapy. The genetic composition of CSCs so far is not fully understood, but manipulation of the specific genes that maintain their integrity would be beneficial for developing strategies to combat cancer. Therefore, the goal of this study isto identify the transcriptomic composition and biological functions of CSCs from non-small cell lung cancer (NSCLC).
    Matched MeSH terms: Gene Ontology
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