Displaying publications 21 - 40 of 56 in total

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  1. 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
  2. Fulltext Mapping kras gene in colon cancer pathway using string and cytoscape software
    Sandya Menon Prabhakaran Menon, Asita Elengoe
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):15-15.
    MyJurnal
    Introduction: Colorectal cancer is one of the top three most commonly occurring cancer worldwide with more than 1.8 million cases in 2018. In Malaysia, colorectal cancer is the most common cancer in males and the second most common cancer in females. Albeit being the second most common form of cancer in Malaysia, there is a lack of a formal or structured national colorectal cancer screening programme in Malaysia and it remains a low priority in healthcare planning and expenditure in Malaysia. The risk of developing colon cancer is greatly influenced by factors such as lifestyle habits, genetic inheritance, diet, weight, and exercise. Kras, the most frequently mutated oncogene in cancer, occurs in about 50 percent of colorectal cancers. Methods: This study maps the kras gene involved in colon cancer pathway, using bioinformatics applications such as STRING version 11.0 and Cytoscape version 3.7.0 to provide a clear visualisation of all the related and involved proteins and genes that interact with this kras gene in the pathway. Results: The 3391 protein interactions were assembled and visualized in y organic form. Six spe-cific non-overlapping clusters of various sizes, which emerged from the huge network of protein-interactors using MCODE version 1.32 clustering algorithm were found. Biological Networks Gene Ontology (BiNGO) was used to determine two ontologies (molecular function and biological process) involved in the protein network. Based on the resulting protein-protein network interaction map, each interaction plays an important role in the cell cycle, meta-bolic pathways and signal transduction. Conclusion: Understanding these interactions provide insight into cellular activities and thus assist in the understanding of the aetiology of disease.
    Matched MeSH terms: Gene Ontology
  3. 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
  4. 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
  5. 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
  6. Identification and expression profiling of genes governing lignin biosynthesis in Casuarina equisetifolia L
    Vikashini B, Shanthi A, Ghosh Dasgupta M
    Gene, 2018 Nov 15;676:37-46.
    PMID: 30201104 DOI: 10.1016/j.gene.2018.07.012
    Casuarina equisetifolia L. is an important multi-purpose, fast growing and widely planted tree species native to tropical and subtropical coastlines of Australia, Southeast Asia, Malaysia, Melanesia, Polynesia and New Caledonia. It is a nitrogen-fixing tree mainly used for charcoal making, construction poles, landscaping, timber, pulp, firewood, windbreaks, shelterbelts, soil erosion and sand dune stabilization. Casuarina wood is presently used for paper and pulp production. Raw material with reduced lignin is highly preferred to increase the pulp yield. Hence, understanding the molecular regulation of wood formation in this tree species is vital for selecting industrially suitable phenotypes for breeding programs. The lignin biosynthetic pathway has been extensively studied in tree species like Eucalypts, poplars, pines, Picea, Betula and Acacia sp. However, studies on wood formation at molecular level is presently lacking in casuarinas. Hence, in the present study, the transcriptome of the developing secondary tissues of 15 years old Casuarina equiseitfolia subsp. equisetifolia was sequenced, de novo assembled, annotated and mapped to functional pathways. Transcriptome sequencing generated a total of 26,985 transcripts mapped to 31 pathways. Mining of the annotated data identified nine genes involved in lignin biosynthesis pathway and relative expression of the transcripts in four tissues including scale-like leaves, needle-like brachlets, wood and root were documented. The expression of CeCCR1 and CeF5H were found to be significantly high in wood tissues, while maximum expression of CeHCT was documented in stem. Additionally, CeTUBA and CeH2A were identified as the most stable reference transcript for normalization of qRT-PCR data in C. equisetifolia. The present study is the first wood genomic resource in C. equisetifolia, which will be valuable for functional genomics research in this genus.
    Matched MeSH terms: Gene Ontology
  7. 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
  8. Fulltext SuCComBase: a manually curated repository of plant sulfur-containing compounds
    Harun S, Abdullah-Zawawi MR, A-Rahman MRA, Muhammad NAN, Mohamed-Hussein ZA
    Database (Oxford), 2019 01 01;2019.
    PMID: 30793170 DOI: 10.1093/database/baz021
    Plants produce a wide range of secondary metabolites that play important roles in plant defense and immunity, their interaction with the environment and symbiotic associations. Sulfur-containing compounds (SCCs) are a group of important secondary metabolites produced in members of the Brassicales order. SCCs constitute various groups of phytochemicals, but not much is known about them. Findings from previous studies on SCCs were scattered in published literatures, hence SuCComBase was developed to store all molecular information related to the biosynthesis of SCCs. Information that includes genes, proteins and compounds that are involved in the SCC biosynthetic pathway was manually identified from databases and published scientific literatures. Sets of co-expression data was analyzed to search for other possible (previously unknown) genes that might be involved in the biosynthesis of SCC. These genes were named as potential SCC-related encoding genes. A total of 147 known and 92 putative Arabidopsis thaliana SCC-related genes from literatures were used to identify other potential SCC-related encoding genes. We identified 778 potential SCC-related encoding genes, 4026 homologs to the SCC-related encoding genes and 116 SCCs as shown on SuCComBase homepage. Data entries are searchable from the Main page, Search, Browse and Datasets tabs. Users can easily download all data stored in SuCComBase. All publications related to SCCs are also indexed in SuCComBase, which is currently the first and only database dedicated to plant SCCs. SuCComBase aims to become a manually curated and au fait knowledge-based repository for plant SCCs.
    Matched MeSH terms: Gene Ontology
  9. 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
  10. Fulltext RNA sequencing (RNA-Seq) of lymph node, spleen, and thymus transcriptome from wild Peninsular Malaysian cynomolgus macaque (Macaca fascicularis)
    Ee Uli J, Yong CSY, Yeap SK, Rovie-Ryan JJ, Mat Isa N, Tan SG, et al.
    PeerJ, 2017;5:e3566.
    PMID: 28828235 DOI: 10.7717/peerj.3566
    The cynomolgus macaque (Macaca fascicularis) is an extensively utilised nonhuman primate model for biomedical research due to its biological, behavioural, and genetic similarities to humans. Genomic information of cynomolgus macaque is vital for research in various fields; however, there is presently a shortage of genomic information on the Malaysian cynomolgus macaque. This study aimed to sequence, assemble, annotate, and profile the Peninsular Malaysian cynomolgus macaque transcriptome derived from three tissues (lymph node, spleen, and thymus) using RNA sequencing (RNA-Seq) technology. A total of 174,208,078 paired end 70 base pair sequencing reads were obtained from the Illumina Hi-Seq 2500 sequencer. The overall mapping percentage of the sequencing reads to the M. fascicularis reference genome ranged from 53-63%. Categorisation of expressed genes to Gene Ontology (GO) and KEGG pathway categories revealed that GO terms with the highest number of associated expressed genes include Cellular process, Catalytic activity, and Cell part, while for pathway categorisation, the majority of expressed genes in lymph node, spleen, and thymus fall under the Global overview and maps pathway category, while 266, 221, and 138 genes from lymph node, spleen, and thymus were respectively enriched in the Immune system category. Enriched Immune system pathways include Platelet activation pathway, Antigen processing and presentation, B cell receptor signalling pathway, and Intestinal immune network for IgA production. Differential gene expression analysis among the three tissues revealed 574 differentially expressed genes (DEG) between lymph and spleen, 5402 DEGs between lymph and thymus, and 7008 DEGs between spleen and thymus. Venn diagram analysis of expressed genes revealed a total of 2,630, 253, and 279 tissue-specific genes respectively for lymph node, spleen, and thymus tissues. This is the first time the lymph node, spleen, and thymus transcriptome of the Peninsular Malaysian cynomolgus macaque have been sequenced via RNA-Seq. Novel transcriptomic data will further enrich the present M. fascicularis genomic database and provide future research potentials, including novel transcript discovery, comparative studies, and molecular markers development.
    Matched MeSH terms: Gene Ontology
  11. Transcriptome-seq provides insights into sex-preference pattern of gene expression between testis and ovary of the crucifix crab ( Charybdis feriatus)
    Zhang Y, Miao G, Fazhan H, Waiho K, Zheng H, Li S, et al.
    Physiol Genomics, 2018 05 01;50(5):393-405.
    PMID: 29570432 DOI: 10.1152/physiolgenomics.00016.2018
    The crucifix crab, Charybdis feriatus, which mainly inhabits Indo-Pacific region, is regarded as one of the most high-potential species for domestication and incorporation into the aquaculture sector. However, the regulatory mechanisms of sex determination and differentiation of this species remain unclear. To identify candidate genes involved in sex determination and differentiation, high throughput sequencing of transcriptome from the testis and ovary of C. feriatus was performed by the Illumina platform. After removing adaptor primers, low-quality sequences and very short (<50 nt) reads, we obtained 80.9 million and 66.2 million clean reads from testis and ovary, respectively. A total of 86,433 unigenes were assembled, and ~43% (37,500 unigenes) were successfully annotated to the NR, NT, Swiss-Prot, KEGG, COG, GO databases. By comparing the testis and ovary libraries, we obtained 27,636 differentially expressed genes. Some candidate genes involved in the sex determination and differentiation of C. feriatus were identified, such as vasa, pgds, vgr, hsp90, dsx-f, fem-1, and gpr. In addition, 88,608 simple sequence repeats were obtained, and 61,929 and 77,473 single nucleotide polymorphisms from testis and ovary were detected, respectively. The transcriptome profiling was validated by quantitative real-time PCR in 30 selected genes, which showed a good consistency. The present study is the first high-throughput transcriptome sequencing of C. feriatus. These findings will be useful for future functional analysis of sex-associated genes and molecular marker-assisted selections in C. feriatus.
    Matched MeSH terms: Gene Ontology
  12. 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
  13. Fulltext In-depth tanscriptomic analysis on giant freshwater prawns
    Mohd-Shamsudin MI, Kang Y, Lili Z, Tan TT, Kwong QB, Liu H, et al.
    PLoS One, 2013;8(5):e60839.
    PMID: 23734171 DOI: 10.1371/journal.pone.0060839
    Gene discovery in the Malaysian giant freshwater prawn (Macrobrachium rosenbergii) has been limited to small scale data collection, despite great interest in various research fields related to the commercial significance of this species. Next generation sequencing technologies that have been developed recently and enabled whole transcriptome sequencing (RNA-seq), have allowed generation of large scale functional genomics data sets in a shorter time than was previously possible. Using this technology, transcriptome sequencing of three tissue types: hepatopancreas, gill and muscle, has been undertaken to generate functional genomics data for M. rosenbergii at a massive scale. De novo assembly of 75-bp paired end Ilumina reads has generated 102,230 unigenes. Sequence homology search and in silico prediction have identified known and novel protein coding candidate genes (∼24%), non-coding RNA, and repetitive elements in the transcriptome. Potential markers consisting of simple sequence repeats associated with known protein coding genes have been successfully identified. Using KEGG pathway enrichment, differentially expressed genes in different tissues were systematically represented. The functions of gill and hepatopancreas in the context of neuroactive regulation, metabolism, reproduction, environmental stress and disease responses are described and support relevant experimental studies conducted previously in M. rosenbergii and other crustaceans. This large scale gene discovery represents the most extensive transcriptome data for freshwater prawn. Comparison with model organisms has paved the path to address the possible conserved biological entities shared between vertebrates and crustaceans. The functional genomics resources generated from this study provide the basis for constructing hypotheses for future molecular research in the freshwater shrimp.
    Matched MeSH terms: Gene Ontology
  14. Fulltext IntFOLD: an integrated web resource for high performance protein structure and function prediction
    McGuffin LJ, Adiyaman R, Maghrabi AHA, Shuid AN, Brackenridge DA, Nealon JO, et al.
    Nucleic Acids Res, 2019 07 02;47(W1):W408-W413.
    PMID: 31045208 DOI: 10.1093/nar/gkz322
    The IntFOLD server provides a unified resource for the automated prediction of: protein tertiary structures with built-in estimates of model accuracy (EMA), protein structural domain boundaries, natively unstructured or disordered regions in proteins, and protein-ligand interactions. The component methods have been independently evaluated via the successive blind CASP experiments and the continual CAMEO benchmarking project. The IntFOLD server has established its ranking as one of the best performing publicly available servers, based on independent official evaluation metrics. Here, we describe significant updates to the server back end, where we have focused on performance improvements in tertiary structure predictions, in terms of global 3D model quality and accuracy self-estimates (ASE), which we achieve using our newly improved ModFOLD7_rank algorithm. We also report on various upgrades to the front end including: a streamlined submission process, enhanced visualization of models, new confidence scores for ranking, and links for accessing all annotated model data. Furthermore, we now include an option for users to submit selected models for further refinement via convenient push buttons. The IntFOLD server is freely available at: http://www.reading.ac.uk/bioinf/IntFOLD/.
    Matched MeSH terms: Gene Ontology
  15. 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
  16. 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
  17. Fulltext Meta-analysis of gene expression in relapsed childhood B-acute lymphoblastic leukemia
    Chow YP, Alias H, Jamal R
    BMC Cancer, 2017 02 10;17(1):120.
    PMID: 28183295 DOI: 10.1186/s12885-017-3103-1
    BACKGROUND: Relapsed pediatric B-acute lymphoblastic leukemia (B-ALL) remains as the leading cause of cancer death among children. Other than stem cell transplantation and intensified chemotherapy, no other improved treatment strategies have been approved clinically. Gene expression profiling represents a powerful approach to identify potential biomarkers and new therapeutic targets for various diseases including leukemias. However, inadequate sample size in many individual experiments has failed to provide adequate study power to yield translatable findings. With the hope of getting new insights into the biological mechanisms underpinning relapsed ALL and identifying more promising biomarkers or therapeutic targets, we conducted a meta-analysis of gene expression studies involving ALL from 3 separate studies.

    METHOD: By using the keywords "acute lymphoblastic leukemia", and "microarray", a total of 280 and 275 microarray datasets were found listed in Gene Expression Omnibus database GEO and ArrayExpress database respectively. Further manual inspection found that only three studies (GSE18497, GSE28460, GSE3910) were focused on gene expression profiling of paired diagnosis-relapsed pediatric B-ALL. These three datasets which comprised of a total of 108 matched diagnosis-relapsed pediatric B-ALL samples were then included for this meta-analysis using RankProd approach.

    RESULTS: Our analysis identified a total of 1795 upregulated probes which corresponded to 1527 genes (pfp  1), and 1493 downregulated probes which corresponded to 1214 genes (pfp gene (pfp gene ontology biological process annotation, the upregulated genes were most enriched in cell cycle processes (enrichment score = 15.3), whilst the downregulated genes were clustered in transcription regulation (enrichment score = 12.6). Elevated expression of cell cycle regulators (e.g kinesins, AURKA, CDKs) was the key genetic defect implicated in relapsed ALL, and serve as attractive targets for therapeutic intervention.

    CONCLUSION: We identified S100A8 as the most overexpressed gene, and the cell cycle pathway as the most promising biomarker and therapeutic target for relapsed childhood B-ALL. The validity of the results warrants further investigation.

    Matched MeSH terms: Gene Ontology
  18. Fulltext Rare Copy Number Variants Identified Suggest the Regulating Pathways in Hypertension-Related Left Ventricular Hypertrophy
    Boon-Peng H, Mat Jusoh JA, Marshall CR, Majid F, Danuri N, Basir F, et al.
    PLoS One, 2016;11(3):e0148755.
    PMID: 26930585 DOI: 10.1371/journal.pone.0148755
    Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality, and a powerful predictor of adverse cardiovascular outcomes in the hypertensive patients. It has complex multifactorial and polygenic basis for its pathogenesis. We hypothesized that rare copy number variants (CNVs) contribute to the LVH pathogenesis in hypertensive patients. Copy number variants (CNV) were identified in 258 hypertensive patients, 95 of whom had LVH, after genotyping with a high resolution SNP array. Following stringent filtering criteria, we identified 208 rare, or private CNVs that were only present in our patients with hypertension related LVH. Preliminary findings from Gene Ontology and pathway analysis of this study confirmed the involvement of the genes known to be functionally involved in cardiac development and phenotypes, in line with previously reported transcriptomic studies. Network enrichment analyses suggested that the gene-set was, directly or indirectly, involved in the transcription factors regulating the "foetal cardiac gene programme" which triggered the hypertrophic cascade, confirming previous reports. These findings suggest that multiple, individually rare copy number variants altering genes may contribute to the pathogenesis of hypertension-related LVH. In summary, we have provided further supporting evidence that rare CNV could potentially impact this common and complex disease susceptibility with lower heritability.
    Matched MeSH terms: Gene Ontology
  19. Fulltext Insight into different environmental niches adaptation and allergenicity from the Cladosporium sphaerospermum genome, a common human allergy-eliciting Dothideomycetes
    Yew SM, Chan CL, Ngeow YF, Toh YF, Na SL, Lee KW, et al.
    Sci Rep, 2016 05 31;6:27008.
    PMID: 27243961 DOI: 10.1038/srep27008
    Cladosporium sphaerospermum, a dematiaceous saprophytic fungus commonly found in diverse environments, has been reported to cause allergy and other occasional diseases in humans. However, its basic biology and genetic information are largely unexplored. A clinical isolate C. sphaerospermum genome, UM 843, was re-sequenced and combined with previously generated sequences to form a model 26.89 Mb genome containing 9,652 predicted genes. Functional annotation on predicted genes suggests the ability of this fungus to degrade carbohydrate and protein complexes. Several putative peptidases responsible for lung tissue hydrolysis were identified. These genes shared high similarity with the Aspergillus peptidases. The UM 843 genome encodes a wide array of proteins involved in the biosynthesis of melanin, siderophores, cladosins and survival in high salinity environment. In addition, a total of 28 genes were predicted to be associated with allergy. Orthologous gene analysis together with 22 other Dothideomycetes showed genes uniquely present in UM 843 that encode four class 1 hydrophobins which may be allergens specific to Cladosporium. The mRNA of these hydrophobins were detected by RT-PCR. The genomic analysis of UM 843 contributes to the understanding of the biology and allergenicity of this widely-prevalent species.
    Matched MeSH terms: Gene Ontology
  20. Fulltext Identification of Gene Modules Associated with Low Temperatures Response in Bambara Groundnut by Network-Based Analysis
    Bonthala VS, Mayes K, Moreton J, Blythe M, Wright V, May ST, et al.
    PLoS One, 2016;11(2):e0148771.
    PMID: 26859686 DOI: 10.1371/journal.pone.0148771
    Bambara groundnut (Vigna subterranea (L.) Verdc.) is an African legume and is a promising underutilized crop with good seed nutritional values. Low temperature stress in a number of African countries at night, such as Botswana, can effect the growth and development of bambara groundnut, leading to losses in potential crop yield. Therefore, in this study we developed a computational pipeline to identify and analyze the genes and gene modules associated with low temperature stress responses in bambara groundnut using the cross-species microarray technique (as bambara groundnut has no microarray chip) coupled with network-based analysis. Analyses of the bambara groundnut transcriptome using cross-species gene expression data resulted in the identification of 375 and 659 differentially expressed genes (p<0.01) under the sub-optimal (23°C) and very sub-optimal (18°C) temperatures, respectively, of which 110 genes are commonly shared between the two stress conditions. The construction of a Highest Reciprocal Rank-based gene co-expression network, followed by its partition using a Heuristic Cluster Chiseling Algorithm resulted in 6 and 7 gene modules in sub-optimal and very sub-optimal temperature stresses being identified, respectively. Modules of sub-optimal temperature stress are principally enriched with carbohydrate and lipid metabolic processes, while most of the modules of very sub-optimal temperature stress are significantly enriched with responses to stimuli and various metabolic processes. Several transcription factors (from MYB, NAC, WRKY, WHIRLY & GATA classes) that may regulate the downstream genes involved in response to stimulus in order for the plant to withstand very sub-optimal temperature stress were highlighted. The identified gene modules could be useful in breeding for low-temperature stress tolerant bambara groundnut varieties.
    Matched MeSH terms: Gene Ontology
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