Publications by authors named "Zeti-Azura Mohamed-Hussein"

32 Publications

Molecular characterization and enzyme inhibition studies of NADP+- farnesol dehydrogenase from diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae).

Biosci Biotechnol Biochem 2021 Apr 23. Epub 2021 Apr 23.

Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia (UKM), 43600 UKM, Bangi, Selangor, Malaysia.

Juvenile hormone III (JH III) plays an important role in insect reproduction, development, and behavior. The second branch of JH III production includes oxidation of farnesol to farnesal by farnesol dehydrogenase. This study reported the identification and characterization of Plutella xylostella farnesol dehydrogenase (PxFoLDH). Our results showed that PxFoLDH belongs to the short-chain dehydrogenase/reductase superfamily, consisting of a single domain with a structurally conserved Rossman fold, an NAD(P) (H)-binding region and a structurally diverse C- terminal region. The purified enzyme displayed maximum activity at 55 °C with pH 9.5 and was stable in the temperature below 70 °C. PxFoLDH was determined to be a monomer with a relative molecular weight of 27 kDa and highly specific for trans, trans-farnesol and NADP+. Among analog inhibitors tested, farnesyl acetate was the most effective inhibitor with the lowest Ki value of 0.02 µM. Our findings showed this purified enzyme may represent as NADP+-farnesol dehydrogenase.
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http://dx.doi.org/10.1093/bbb/zbab072DOI Listing
April 2021

Dietary polyphenols suppress chronic inflammation by modulation of multiple inflammation-associated cell signaling pathways.

J Nutr Biochem 2021 Mar 29;93:108634. Epub 2021 Mar 29.

Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia; Department of Applied Physics, Faculty of Science & Technology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor.

The high failure rate of the reductionist approach to discover effective and safe drugs to treat chronic inflammatory diseases has led scientists to seek alternative ways. Recently, targeting cell signaling pathways has been utilized as an innovative approach to discover drug leads from natural products. Cell signaling mechanisms have been identified playing key role in diverse diseases by inducing proliferation, cell survival and apoptosis. Phytochemicals are known to be able to modulate the cellular and molecular networks which are associated to chronic diseases including cancer-associated inflammation. In this review, the roles of dietary polyphenols (apigenin, kaempferol, quercetin, curcumin, genistein, isoliquiritigenin, resveratrol and gallic acid) in modulating multiple inflammation-associated cell signaling networks are deliberated. Scientific databases on suppressive effects of the polyphenols on chronic inflammation via modulation of the pathways especially in the recent five years are gathered and critically analyzed. The polyphenols are able to modulate several inflammation-associated cell signaling pathways, namely nuclear factor-kappa β, mitogen activated protein kinases, Wnt/β-catenin and phosphatidylinositol 3-kinase and protein kinase B via selective actions on various components of the networks. The suppressive effects of the polyphenols on the multiple cell signaling pathways reveal their potential use in prevention and treatment of chronic inflammatory disorders. Understanding the mechanistic effects involved in modulation of the signaling pathways by the polyphenols is necessary for lead identification and development of future functional foods for prevention and treatment of chronic inflammatory diseases.
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http://dx.doi.org/10.1016/j.jnutbio.2021.108634DOI Listing
March 2021

Construction of Protein Expression Network.

Methods Mol Biol 2021 ;2189:119-132

Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.

In this post-genomic era, protein network can be used as a complementary way to shed light on the growing amount of data generated from current high-throughput technologies. Protein network is a powerful approach to describe the molecular mechanisms of the biological events through protein-protein interactions. Here, we describe the computational methods used to construct the protein network using expression data. We provide a list of available tools and databases that can be used in constructing the network.
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http://dx.doi.org/10.1007/978-1-0716-0822-7_10DOI Listing
March 2021

Data on genome resequencing of pigmented and non-pigmented Malaysian rice varieties.

Data Brief 2020 Aug 3;31:105806. Epub 2020 Jun 3.

Biotechnology and Nanotechnology Research Centre, Malaysian Agricultural Research & Development Institute (MARDI), 43400 Serdang, Selangor, Malaysia.

The genomics and genetic data of pigmented and non-pigmented Malaysian rice varieties are still limited. Hence, we performed the genome resequencing of two black rice varieties (Bali, Pulut Hitam 9), two red rice varieties (MRM16, MRQ100) and two white rice varieties (MR297 and MRQ76) using Illumina HiSeq 4000 platform with 30x sequencing coverage. We aimed to identify and annotate single nucleotide polymorphisms (SNPs) from the genome of these four pigmented and two non-pigmented rice varieties. The potential SNPs will be used in developing the functional SNP markers related to nutritional (i.e. antioxidant, folate, amylose) and quality (i.e. aromatic) traits. Raw data of the pigmented and non-pigmented rice varieties have been deposited into the European Nucleotide Archive (ENA) database with accession number PRJEB29070 and PRJEB32344, respectively.
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http://dx.doi.org/10.1016/j.dib.2020.105806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298397PMC
August 2020

A Comprehensive Gene Inventory for Glucosinolate Biosynthetic Pathway in .

J Agric Food Chem 2020 Jul 1;68(28):7281-7297. Epub 2020 Jul 1.

Centre for Bioinformatics Research, Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.

Glucosinolates (GSLs) are plant secondary metabolites comprising sulfur and nitrogen mainly found in plants from the order of Brassicales, such as broccoli, cabbage, and . The activated forms of GSL play important roles in fighting against pathogens and have health benefits to humans. The increasing amount of data on generated from various omics technologies can be investigated more deeply in search of new genes or compounds involved in GSL biosynthesis and metabolism. This review describes a comprehensive inventory of GSLs identified from published literature and databases such as KNApSAcK, KEGG, and AraCyc. A total of 113 GSL genes encoding for 23 transcription components, 85 enzymes, and five protein transporters were experimentally characterized in the past two decades. Continuous efforts are still on going to identify all molecules related to the production of GSLs. A manually curated database known as SuCCombase (http://plant-scc.org) was developed to serve as a comprehensive GSL inventory. Realizing lack of information on the regulation of GSL biosynthesis and degradation mechanisms, this review also includes relevant information and their connections with crosstalk among various factors, such as light, sulfur metabolism, and nitrogen metabolism, not only in but also in other crucifers.
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http://dx.doi.org/10.1021/acs.jafc.0c01916DOI Listing
July 2020

In silico analysis on the functional and structural impact of Rad50 mutations involved in DNA strand break repair.

PeerJ 2020 22;8:e9197. Epub 2020 May 22.

Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.

Background: DNA double strand break repair is important to preserve the fidelity of our genetic makeup after DNA damage. Rad50 is one of the components in MRN complex important for DNA repair mechanism. Rad50 mutations can lead to microcephaly, mental retardation and growth retardation in human. However, Rad50 mutations in human and other organisms have never been gathered and heuristically compared for their deleterious effects. It is important to assess the conserved region in Rad50 and its homolog to identify vital mutations that can affect functions of the protein.

Method: In this study, Rad50 mutations were retrieved from SNPeffect 4.0 database and literature. Each of the mutations was analyzed using various bioinformatic analyses such as PredictSNP, MutPred, SNPeffect 4.0, I-Mutant and MuPro to identify its impact on molecular mechanism, biological function and protein stability, respectively.

Results: We identified 103 mostly occurred mutations in the Rad50 protein domains and motifs, which only 42 mutations were classified as most deleterious. These mutations are mainly situated at the specific motifs such as Walker A, Q-loop, Walker B, D-loop and signature motif of the Rad50 protein. Some of these mutations were predicted to negatively affect several important functional sites that play important roles in DNA repair mechanism and cell cycle signaling pathway, highlighting Rad50 crucial role in this process. Interestingly, mutations located at non-conserved regions were predicted to have neutral/non-damaging effects, in contrast with previous experimental studies that showed deleterious effects. This suggests that software used in this study may have limitations in predicting mutations in non-conserved regions, implying further improvement in their algorithm is needed. In conclusion, this study reveals the priority of acid substitution associated with the genetic disorders. This finding highlights the vital roles of certain residues such as K42E, C681A/S, CC684R/S, S1202R, E1232Q and D1238N/A located in Rad50 conserved regions, which can be considered for a more targeted future studies.
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http://dx.doi.org/10.7717/peerj.9197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247530PMC
May 2020

RNA-seq data from whole rice grains of pigmented and non-pigmented Malaysian rice varieties.

Data Brief 2020 Jun 16;30:105432. Epub 2020 Mar 16.

Malaysian Agricultural Research & Development Institute (MARDI), 43300 Serdang, Selangor, Malaysia.

Pigmented rice is enriched with antioxidants, macro- and micronutrients. A comprehensive investigation of the gene expression patterns among the pigmented rice varieties would help to understand the cellular mechanism and biological processes of rice grain pigmentation. Hence, we performed RNA sequencing and analysis on the whole grain of dehusked mature seeds of selected six Malaysian rice varieties with varying grain pigmentations. These varieties were black rice (BALI and Pulut Hitam 9), red rice (MRM16 and MRQ100) and white rice (MR297 and MRQ76). Illumina HiSeq™ 4000 sequencer was used to generate total raw nucleotides of approximately 53 Gb in size. From 353,937,212 total paired-end raw reads, 340,131,496 total clean reads were obtained. The raw reads were deposited into European Nucleotide Archive (ENA) database and can be accessed via accession number PRJEB34340. This dataset allows us to identify and profile all expressed genes with functions related to nutritional traits (i.e. antioxidants, folate and amylose content) and quality trait (i.e. aroma) across both pigmented and non-pigmented rice varieties. In addition, the transcriptome data obtained will be valuable for discovery of potential gene markers and functional SNPs related to functional traits to assist in rice breeding programme.
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http://dx.doi.org/10.1016/j.dib.2020.105432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138961PMC
June 2020

Graph cluster approach in identifying novel proteins and significant pathways involved in polycystic ovary syndrome.

Reprod Biomed Online 2020 Feb 29;40(2):319-330. Epub 2019 Nov 29.

Centre for Bioinformatics Research, Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia; Centre for Frontier Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia. Electronic address:

Research Question: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with diverse clinical implications, such as infertility, metabolic disorders, cardiovascular diseases and psychological problems among others. The heterogeneity of conditions found in PCOS contribute to its various phenotypes, leading to difficulties in identifying proteins involved in this abnormality. Several studies, however, have shown the feasibility in identifying molecular evidence underlying other diseases using graph cluster analysis. Therefore, is it possible to identify proteins and pathways related to PCOS using the same approach?

Methods: Known PCOS-related proteins (PCOSrp) from PCOSBase and DisGeNET were integrated with protein-protein interactions (PPI) information from Human Integrated Protein-Protein Interaction reference to construct a PCOS PPI network. The network was clustered with DPClusO algorithm to generate clusters, which were evaluated using Fisher's exact test. Pathway enrichment analysis using gProfileR was conducted to identify significant pathways.

Results: The statistical significance of the identified clusters has successfully predicted 138 novel PCOSrp with 61.5% reliability and, based on Cronbach's alpha, this prediction is acceptable. Androgen signalling pathway and leptin signalling pathway were among the significant PCOS-related pathways corroborating the information obtained from the clinical observation, where androgen signalling pathway is responsible in producing male hormones in women with PCOS, whereas leptin signalling pathway is involved in insulin sensitivity.

Conclusions: These results show that graph cluster analysis can provide additional insight into the pathobiology of PCOS, as the pathways identified as statistically significant correspond to earlier biological studies. Therefore, integrative analysis can reveal unknown mechanisms, which may enable the development of accurate diagnosis and effective treatment in PCOS.
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http://dx.doi.org/10.1016/j.rbmo.2019.11.012DOI Listing
February 2020

Discovery of Functional SNPs via Genome-Wide Exploration of Malaysian Pigmented Rice Varieties.

Int J Genomics 2019 10;2019:4168045. Epub 2019 Oct 10.

Centre for Bioinformatics Research, Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia (UKM), 43600 UKM Bangi, Selangor, Malaysia.

Recently, rice breeding program has shown increased interests on the pigmented rice varieties due to their benefits to human health. However, the genetic variation of pigmented rice varieties is still scarce and remains unexplored. Hence, we performed genome-wide SNP analysis from the genome resequencing of four Malaysian pigmented rice varieties, representing two black and two red rice varieties. The genome of four pigmented varieties was mapped against Nipponbare reference genome sequences, and 1.9 million SNPs were discovered. Of these, 622 SNPs with polymorphic sites were identified in 258 protein-coding genes related to metabolism, stress response, and transporter. Comparative analysis of 622 SNPs with polymorphic sites against six rice SNP datasets from the Ensembl Plants variation database was performed, and 70 SNPs were identified as novel SNPs. Analysis of SNPs in the flavonoid biosynthetic genes revealed 40 nonsynonymous SNPs, which has potential as molecular markers for rice seed colour identification. The highlighted SNPs in this study show effort in producing valuable genomic resources for application in the rice breeding program, towards the genetic improvement of new and improved pigmented rice varieties.
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http://dx.doi.org/10.1155/2019/4168045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6811786PMC
October 2019

Protein-Protein Interaction Network Analysis Reveals Several Diseases Highly Associated with Polycystic Ovarian Syndrome.

Int J Mol Sci 2019 Jun 18;20(12). Epub 2019 Jun 18.

Centre for Bioinformatics Research, Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, UKM Bangi 43600, Selangor, Malaysia.

Based on clinical observations, women with polycystic ovarian syndrome (PCOS) are prone to developing several other diseases, such as metabolic and cardiovascular diseases. However, the molecular association between PCOS and these diseases remains poorly understood. Recent studies showed that the information from protein-protein interaction (PPI) network analysis are useful in understanding the disease association in detail. This study utilized this approach to deepen the knowledge on the association between PCOS and other diseases. A PPI network for PCOS was constructed using PCOS-related proteins (PCOSrp) obtained from PCOSBase. MCODE was used to identify highly connected regions in the PCOS network, known as subnetworks. These subnetworks represent protein families, where their molecular information is used to explain the association between PCOS and other diseases. Fisher's exact test and comorbidity data were used to identify PCOS-disease subnetworks. Pathway enrichment analysis was performed on the PCOS-disease subnetworks to identify significant pathways that are highly involved in the PCOS-disease associations. Migraine, schizophrenia, depressive disorder, obesity, and hypertension, along with twelve other diseases, were identified to be highly associated with PCOS. The identification of significant pathways, such as ribosome biogenesis, antigen processing and presentation, and mitophagy, suggest their involvement in the association between PCOS and migraine, schizophrenia, and hypertension.
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http://dx.doi.org/10.3390/ijms20122959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627153PMC
June 2019

Evaluation of potential molecular interaction between quorum sensing receptor, LuxP and grouper fatty acids: in-silico screening and simulation.

PeerJ 2019 5;7:e6568. Epub 2019 Apr 5.

Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.

Pathologically relevant behaviors of , such as the expression of virulence factors, biofilm production, and swarming motility, have been shown to be controlled by quorum sensing. The autoinducer-2 quorum sensing receptor protein LuxP is one of the target proteins for drug development to suppress the virulence of . Here, we reported the potential molecular interaction of fatty acids identified in vibriosis-resistant grouper with LuxP. Fatty acid, 4-oxodocosahexaenoic acid (4R8) showed significant binding affinity toward LuxP (-6.0 kcal/mol) based on molecular docking analysis. The dynamic behavior of the protein-ligand complex was illustrated by molecular dynamic simulations. The fluctuation of the protein backbone, the stability of ligand binding, and hydrogen bond interactions were assessed, suggesting 4R8 possesses potential interaction with LuxP, which was supported by the low binding free energy (-29.144 kJ/mol) calculated using the molecular mechanics Poisson-Boltzmann surface area.
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http://dx.doi.org/10.7717/peerj.6568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452917PMC
April 2019

SuCComBase: a manually curated repository of plant sulfur-containing compounds.

Database (Oxford) 2019 01;2019

Centre for Bioinformatics Research, Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia.

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.
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http://dx.doi.org/10.1093/database/baz021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384505PMC
January 2019

RNA-seq data of the L. shoot system.

Data Brief 2018 Dec 29;21:71-74. Epub 2018 Sep 29.

School of Environmental and Natural Resource Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM, 43600 Bangi, Selangor, Malaysia.

L. or the physic nut is a monoecious shrub belonging to the family. The plant is an ideal feedstock for biodiesel production; oil-rich seed (37-42%), has a broad range of growth habitat such as arid, semi-arid and tropical and a relatively feasible process for conversion of crude oil into biodiesel. The major constraint affecting the success of large-scale plantation is seed yield inconsistency. Numerous research projects conducted on with integrated genetic, genomic and transcriptomic approaches have been applied on the leaf, apical meristem, flower, root and fruit tissues. However, to date, no genomics data of shoot system are publicly available, despite its importance in understanding flowering, fruiting and seed set qualities targeted for yield improvement. Here, we present eighteen sets of shoot and inflorescence transcriptomes generated from plants with contrasting yields. Raw reads of the RNA-seq data are found in NCBI׳s Sequence Read Archive (SRA) database with the accession number SRP090662 (https://www.ncbi.nlm.nih.gov/sra/?term=SRP090662). This transcriptomic data could be integrated with the present genomic resources for in depth understanding of reproductive system.
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http://dx.doi.org/10.1016/j.dib.2018.09.081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187019PMC
December 2018

Crystal structure and functional analysis of human C1ORF123.

PeerJ 2018 28;6:e5377. Epub 2018 Sep 28.

Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.

Proteins of the DUF866 superfamily are exclusively found in eukaryotic cells. A member of the DUF866 superfamily, C1ORF123, is a human protein found in the open reading frame 123 of chromosome 1. The physiological role of C1ORF123 is yet to be determined. The only available protein structure of the DUF866 family shares just 26% sequence similarity and does not contain a zinc binding motif. Here, we present the crystal structure of the recombinant human C1ORF123 protein (rC1ORF123). The structure has a 2-fold internal symmetry dividing the monomeric protein into two mirrored halves that comprise of distinct electrostatic potential. The N-terminal half of rC1ORF123 includes a zinc-binding domain interacting with a zinc ion near to a potential ligand binding cavity. Functional studies of human C1ORF123 and its homologue in the fission yeast (SpEss1) point to a role of DUF866 protein in mitochondrial oxidative phosphorylation.
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http://dx.doi.org/10.7717/peerj.5377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166629PMC
September 2018

An integration of phenotypic and transcriptomic data analysis reveals yield-related hub genes in Jatropha curcas inflorescence.

PLoS One 2018 21;13(9):e0203441. Epub 2018 Sep 21.

School of Environmental and Natural Resource Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM Bangi, Selangor, Malaysia.

Jatropha curcas is an oil-rich seed crop with huge potentials for bioenergy production. The inflorescence carries a number of processes that are likely to affect the overall yield potentials; floral development, male-to-female flower ratio, floral abscission and fruit set. In this study, a weighted gene co-expression network analysis which integrates the transcriptome, physical and simple sugar data of J. curcas inflorescence was performed and nine modules were identified by means of hierarchical clustering. Among them, four modules (green4, antiquewhite2, brown2 and lightskyblue4) showed significant correlation to yield factors at p≤0.01. The four modules are categorized into two clusters; cluster 1 of green4 and antiquewhite2 modules correspond to number of flowers/inflorescence, total seed weight/plant, number of seeds/plant, and number of fruits/plant, whereas cluster 2 of brown2 and lightskyblue4 modules correspond to glucose and fructose. Descriptive characterizations of cluster 1 show putative involvement in gibberellin signaling and responses, whereas cluster 2 may have been involved in sugar signaling, signal transductions and regulation of flowerings. Our findings present a list of hub genes for J. curcas yield improvement and reproductive biology enhancement strategies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203441PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150480PMC
February 2019

A gene co-expression network model identifies yield-related vicinity networks in Jatropha curcas shoot system.

Sci Rep 2018 06 15;8(1):9211. Epub 2018 Jun 15.

School of Environmental and Natural Resource Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor, Malaysia.

The plant shoot system consists of reproductive organs such as inflorescences, buds and fruits, and the vegetative leaves and stems. In this study, the reproductive part of the Jatropha curcas shoot system, which includes the aerial shoots, shoots bearing the inflorescence and inflorescence were investigated in regard to gene-to-gene interactions underpinning yield-related biological processes. An RNA-seq based sequencing of shoot tissues performed on an Illumina HiSeq. 2500 platform generated 18 transcriptomes. Using the reference genome-based mapping approach, a total of 64 361 genes was identified in all samples and the data was annotated against the non-redundant database by the BLAST2GO Pro. Suite. After removing the outlier genes and samples, a total of 12 734 genes across 17 samples were subjected to gene co-expression network construction using petal, an R library. A gene co-expression network model built with scale-free and small-world properties extracted four vicinity networks (VNs) with putative involvement in yield-related biological processes as follow; heat stress tolerance, floral and shoot meristem differentiation, biosynthesis of chlorophyll molecules and laticifers, cell wall metabolism and epigenetic regulations. Our VNs revealed putative key players that could be adapted in breeding strategies for J. curcas shoot system improvements.
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http://dx.doi.org/10.1038/s41598-018-27493-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003958PMC
June 2018

Structural and kinetic studies of a novel nerol dehydrogenase from Persicaria minor, a nerol-specific enzyme for citral biosynthesis.

Plant Physiol Biochem 2018 Feb 26;123:359-368. Epub 2017 Dec 26.

School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia; Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia. Electronic address:

Geraniol degradation pathway has long been elucidated in microorganisms through bioconversion studies, yet weakly characterised in plants; enzyme with specific nerol-oxidising activity has not been reported. A novel cDNA encodes nerol dehydrogenase (PmNeDH) was isolated from Persicaria minor. The recombinant PmNeDH (rPmNeDH) is a homodimeric enzyme that belongs to MDR (medium-chain dehydrogenases/reductases) superfamily that catalyses the first oxidative step of geraniol degradation pathway in citral biosynthesis. Kinetic analysis revealed that rPmNeDH has a high specificity for allylic primary alcohols with backbone ≤10 carbons. rPmNeDH has ∼3 fold higher affinity towards nerol (cis-3,7-dimethyl-2,6-octadien-1-ol) than its trans-isomer, geraniol. To our knowledge, this is the first alcohol dehydrogenase with higher preference towards nerol, suggesting that nerol can be effective substrate for citral biosynthesis in P. minor. The rPmNeDH crystal structure (1.54 Å) showed high similarity with enzyme structures from MDR superfamily. Structure guided mutation was conducted to describe the relationships between substrate specificity and residue substitutions in the active site. Kinetics analyses of wild-type rPmNeDH and several active site mutants demonstrated that the substrate specificity of rPmNeDH can be altered by changing any selected active site residues (Asp, Leu and Ala). Interestingly, the L294F, A303F and A303G mutants were able to revamp the substrate preference towards geraniol. Furthermore, mutant that exhibited a broader substrate range was also obtained. This study demonstrates that P. minor may have evolved to contain enzyme that optimally recognise cis-configured nerol as substrate. rPmNeDH structure provides new insights into the substrate specificity and active site plasticity in MDR superfamily.
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http://dx.doi.org/10.1016/j.plaphy.2017.12.033DOI Listing
February 2018

Transcriptome analysis of reproductive tissue differentiation in Linn.

Genom Data 2017 Sep 15;13:11-14. Epub 2017 May 15.

School of Environmental and Natural Resource Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia.

Shoot and inflorescence are central physiological and developmental tissues of plants. Flowering is one of the most important agronomic traits for improvement of crop yield. To analyze the vegetative to reproductive tissue transition in , gene expression profiles were generated from shoot and inflorescence tissues. RNA isolated from both tissues was sequenced using the Ilumina HiSeq 2500 platform. Differential gene expression analysis identified key biological processes associated with vegetative to reproductive tissue transition. The present data for may inform the design of breeding strategies particularly with respect to reproductive tissue transition. The raw data of this study has been deposited in the NCBI's Sequence Read Archive (SRA) database with the accession number SRP090662.
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http://dx.doi.org/10.1016/j.gdata.2017.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460744PMC
September 2017

Transcriptome analysis of reveals candidate genes involved in important secondary metabolic pathways of phenylpropanoids and flavonoids.

PeerJ 2017 28;5:e2938. Epub 2017 Feb 28.

Institute of Systems Biology, Universiti Kebangsaan Malaysia , Bangi , Malaysia.

Background: is an herbal plant in the Polygonaceae family which is rich in ethnomedicinal plants. The chemical composition and characteristic pungent fragrance of have been extensively studied due to its culinary and medicinal properties. There are only a few transcriptome sequences available for species from this important family of medicinal plants. The limited genetic information from the public expressed sequences tag (EST) library hinders further study on molecular mechanisms underlying secondary metabolite production.

Methods: In this study, we performed a hybrid assembly of 454 and Illumina sequencing reads from root and leaf tissues, respectively, to generate a combined transcriptome library as a reference.

Results: A total of 34.37 million filtered and normalized reads were assembled into 188,735 transcripts with a total length of 136.67 Mbp. We performed a similarity search against all the publicly available genome sequences and found similarity matches for 163,200 (86.5%) of transcripts, largely from (58.9%). Transcript abundance in the leaf and root tissues were estimated and validated through RT-qPCR of seven selected transcripts involved in the biosynthesis of phenylpropanoids and flavonoids. All the transcripts were annotated against KEGG pathways to profile transcripts related to the biosynthesis of secondary metabolites.

Discussion: This comprehensive transcriptome profile will serve as a useful sequence resource for molecular genetics and evolutionary research on secondary metabolite biosynthesis in Polygonaceae family. Transcriptome assembly of can be accessed at http://prims.researchfrontier.org/index.php/dataset/transcriptome.
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http://dx.doi.org/10.7717/peerj.2938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333554PMC
February 2017

PCOSBase: a manually curated database of polycystic ovarian syndrome.

Database (Oxford) 2017 Jan;2017

Institute of Systems Biology (INBIOSIS).

Polycystic ovarian syndrome (PCOS) is one of the main causes of infertility and affects 5-20% women of reproductive age. Despite the increased prevalence of PCOS, the mechanisms involved in its pathogenesis and pathophysiology remains unclear. The expansion of omics on studying the mechanisms of PCOS has lead into vast amounts of proteins related to PCOS resulting to a challenge in collating and depositing this deluge of data into one place. A knowledge-based repository named as PCOSBase was developed to systematically store all proteins related to PCOS. These proteins were compiled from various online databases and published expression studies. Rigorous criteria were developed to identify those that were highly related to PCOS. They were manually curated and analysed to provide additional information on gene ontologies, pathways, domains, tissue localizations and diseases that associate with PCOS. Other proteins that might interact with PCOS-related proteins identified from this study were also included. Currently, 8185 PCOS-related proteins were identified and assigned to 13 237 gene ontology vocabulary, 1004 pathways, 7936 domains, 29 disease classes, 1928 diseases, 91 tissues and 320 472 interactions. All publications related to PCOS are also indexed in PCOSBase. Data entries are searchable in the main page, search, browse and datasets tabs. Protein advanced search is provided to search for specific proteins. To date, PCOSBase has the largest collection of PCOS-related proteins. PCOSBase aims to become a self-contained database that can be used to further understand the PCOS pathogenesis and towards the identification of potential PCOS biomarkers. Database URL: http://pcosbase.org.
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http://dx.doi.org/10.1093/database/bax098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243924PMC
January 2017

Novel NAD+-Farnesal Dehydrogenase from Polygonum minus Leaves. Purification and Characterization of Enzyme in Juvenile Hormone III Biosynthetic Pathway in Plant.

PLoS One 2016 25;11(8):e0161707. Epub 2016 Aug 25.

Institute of Systems Biology, Universiti Kebangsaan Malaysia (UKM), 43600 UKM, Bangi, Selangor, Malaysia.

Juvenile Hormone III is of great concern due to negative effects on major developmental and reproductive maturation in insect pests. Thus, the elucidation of enzymes involved JH III biosynthetic pathway has become increasing important in recent years. One of the enzymes in the JH III biosynthetic pathway that remains to be isolated and characterized is farnesal dehydrogenase, an enzyme responsible to catalyze the oxidation of farnesal into farnesoic acid. A novel NAD+-farnesal dehydrogenase of Polygonum minus was purified (315-fold) to apparent homogeneity in five chromatographic steps. The purification procedures included Gigacap S-Toyopearl 650M, Gigacap Q-Toyopearl 650M, and AF-Blue Toyopearl 650ML, followed by TSK Gel G3000SW chromatographies. The enzyme, with isoelectric point of 6.6 is a monomeric enzyme with a molecular mass of 70 kDa. The enzyme was relatively active at 40°C, but was rapidly inactivated above 45°C. The optimal temperature and pH of the enzyme were found to be 35°C and 9.5, respectively. The enzyme activity was inhibited by sulfhydryl agent, chelating agent, and metal ion. The enzyme was highly specific for farnesal and NAD+. Other terpene aldehydes such as trans- cinnamaldehyde, citral and α- methyl cinnamaldehyde were also oxidized but in lower activity. The Km values for farnesal, citral, trans- cinnamaldehyde, α- methyl cinnamaldehyde and NAD+ were 0.13, 0.69, 0.86, 1.28 and 0.31 mM, respectively. The putative P. minus farnesal dehydrogenase that's highly specific towards farnesal but not to aliphatic aldehydes substrates suggested that the enzyme is significantly different from other aldehyde dehydrogenases that have been reported. The MALDI-TOF/TOF-MS/MS spectrometry further identified two peptides that share similarity to those of previously reported aldehyde dehydrogenases. In conclusion, the P. minus farnesal dehydrogenase may represent a novel plant farnesal dehydrogenase that exhibits distinctive substrate specificity towards farnesal. Thus, it was suggested that this novel enzyme may be functioning specifically to oxidize farnesal in the later steps of JH III pathway. This report provides a basic understanding for recombinant production of this particular enzyme. Other strategies such as adding His-tag to the protein makes easy the purification of the protein which is completely different to the native protein. Complete sequence, structure and functional analysis of the enzyme will be important for developing insect-resistant crop plants by deployment of transgenic plant.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161707PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999093PMC
July 2017

RNA-seq analysis for secondary metabolite pathway gene discovery in Polygonum minus.

Genom Data 2016 Mar 7;7:12-3. Epub 2015 Nov 7.

Institute of Systems Biology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia; School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia.

Polygonum minus plant is rich in secondary metabolites, especially terpenoids and flavonoids. Present study generates transcriptome resource for P. minus to decipher its secondary metabolite biosynthesis pathways. Raw reads and the transcriptome assembly project have been deposited at GenBank under the accessions SRX313492 (root) and SRX669305 (leaf) respectively.
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http://dx.doi.org/10.1016/j.gdata.2015.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778588PMC
March 2016

Cloning, expression, purification, crystallization and X-ray crystallographic analysis of recombinant human C1ORF123 protein.

Acta Crystallogr F Struct Biol Commun 2016 Mar 16;72(Pt 3):207-13. Epub 2016 Feb 16.

Institute of Systems Biology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia.

C1ORF123 is a human hypothetical protein found in open reading frame 123 of chromosome 1. The protein belongs to the DUF866 protein family comprising eukaryote-conserved proteins with unknown function. Recent proteomic and bioinformatic analyses identified the presence of C1ORF123 in brain, frontal cortex and synapses, as well as its involvement in endocrine function and polycystic ovary syndrome (PCOS), indicating the importance of its biological role. In order to provide a better understanding of the biological function of the human C1ORF123 protein, the characterization and analysis of recombinant C1ORF123 (rC1ORF123), including overexpression and purification, verification by mass spectrometry and a Western blot using anti-C1ORF123 antibodies, crystallization and X-ray diffraction analysis of the protein crystals, are reported here. The rC1ORF123 protein was crystallized by the hanging-drop vapor-diffusion method with a reservoir solution comprised of 20% PEG 3350, 0.2 M magnesium chloride hexahydrate, 0.1 M sodium citrate pH 6.5. The crystals diffracted to 1.9 Å resolution and belonged to an orthorhombic space group with unit-cell parameters a = 59.32, b = 65.35, c = 95.05 Å. The calculated Matthews coefficient (VM) value of 2.27 Å(3) Da(-1) suggests that there are two molecules per asymmetric unit, with an estimated solvent content of 45.7%.
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http://dx.doi.org/10.1107/S2053230X16002016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774879PMC
March 2016

Purification and Characterization of a Novel NAD(P)+-Farnesol Dehydrogenase from Polygonum minus Leaves.

PLoS One 2015 23;10(11):e0143310. Epub 2015 Nov 23.

Institute of Systems Biology, Universiti Kebangsaan Malaysia (UKM), 43600 UKM, Bangi, Selangor, Malaysia.

Juvenile hormones have attracted attention as safe and selective targets for the design and development of environmentally friendly and biorational insecticides. In the juvenile hormone III biosynthetic pathway, the enzyme farnesol dehydrogenase catalyzes the oxidation of farnesol to farnesal. In this study, farnesol dehydrogenase was extracted from Polygonum minus leaves and purified 204-fold to apparent homogeneity by ion-exchange chromatography using DEAE-Toyopearl, SP-Toyopearl, and Super-Q Toyopearl, followed by three successive purifications by gel filtration chromatography on a TSK-gel GS3000SW. The enzyme is a heterodimer comprised of subunits with molecular masses of 65 kDa and 70 kDa. The optimum temperature and pH were 35°C and pH 9.5, respectively. Activity was inhibited by sulfhydryl reagents, metal-chelating agents and heavy metal ions. The enzyme utilized both NAD+ and NADP+ as coenzymes with Km values of 0.74 mM and 40 mM, respectively. Trans, trans-farnesol was the preferred substrate for the P. minus farnesol dehydrogenase. Geometrical isomers of trans, trans-farnesol, cis, trans-farnesol and cis, cis-farnesol were also oxidized by the enzyme with lower activity. The Km values for trans, trans-farnesol, cis, trans-farnesol and cis, cis-farnesol appeared to be 0.17 mM, 0.33 mM and 0.42 mM, respectively. The amino acid sequences of 4 tryptic peptides of the enzyme were analyzed by MALDI-TOF/TOF-MS spectrometry, and showed no significant similarity to those of previously reported farnesol dehydrogenases. These results suggest that the purified enzyme is a novel NAD(P)+-dependent farnesol dehydrogenase. The purification and characterization established in the current study will serve as a basis to provide new information for recombinant production of the enzyme. Therefore, recombinant farnesol dehydrogenase may provide a useful molecular tool in manipulating juvenile hormone biosynthesis to generate transgenic plants for pest control.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143310PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657912PMC
June 2016

Functional characterization of sesquiterpene synthase from Polygonum minus.

ScientificWorldJournal 2014 11;2014:840592. Epub 2014 Feb 11.

School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia ; Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.

Polygonum minus is an aromatic plant, which contains high abundance of terpenoids, especially the sesquiterpenes C15H24. Sesquiterpenes were believed to contribute to the many useful biological properties in plants. This study aimed to functionally characterize a full length sesquiterpene synthase gene from P. minus. P. minus sesquiterpene synthase (PmSTS) has a complete open reading frame (ORF) of 1689 base pairs encoding a 562 amino acid protein. Similar to other sesquiterpene synthases, PmSTS has two large domains: the N-terminal domain and the C-terminal metal-binding domain. It also consists of three conserved motifs: the DDXXD, NSE/DTE, and RXR. A three-dimensional protein model for PmSTS built clearly distinguished the two main domains, where conserved motifs were highlighted. We also constructed a phylogenetic tree, which showed that PmSTS belongs to the angiosperm sesquiterpene synthase subfamily Tps-a. To examine the function of PmSTS, we expressed this gene in Arabidopsis thaliana. Two transgenic lines, designated as OE3 and OE7, were further characterized, both molecularly and functionally. The transgenic plants demonstrated smaller basal rosette leaves, shorter and fewer flowering stems, and fewer seeds compared to wild type plants. Gas chromatography-mass spectrometry analysis of the transgenic plants showed that PmSTS was responsible for the production of β -sesquiphellandrene.
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http://dx.doi.org/10.1155/2014/840592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942395PMC
October 2014

Draft Genome Sequences of Four Nosocomial Methicillin-Resistant Staphylococcus aureus (MRSA) Strains (PPUKM-261-2009, PPUKM-332-2009, PPUKM-377-2009, and PPUKM-775-2009) Representative of Dominant MRSA Pulsotypes Circulating in a Malaysian University Teaching Hospital.

Genome Announc 2013 Jan 31;1(1). Epub 2013 Jan 31.

Medical Molecular Biology Institute (UMBI).

Here, we report the draft genome sequences of four nosocomial methicillin-resistant Staphylococcus aureus strains (PPUKM-261-2009, PPUKM-332-2009, PPUKM-377-2009, and PPUKM-775-2009) isolated from a university teaching hospital in Malaysia. Three of the strains belong to sequence type 239 (ST239), which has been associated with sustained hospital epidemics worldwide.
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http://dx.doi.org/10.1128/genomeA.00103-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569319PMC
January 2013

Transcriptome profiling of genes induced by salicylic acid and methyl jasmonate in Polygonum minus.

Mol Biol Rep 2013 Mar 27;40(3):2231-41. Epub 2012 Nov 27.

School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600, UKM Bangi, Selangor, Malaysia.

The importance of plant secondary metabolites for both mankind and the plant itself has long been established. However, despite extensive research on plant secondary metabolites, plant secondary metabolism and its regulation still remained poorly characterized. In this present study, cDNA-amplified fragment length polymorphism (cDNA-AFLP) transcript profiling was applied to generate the expression profiles of Polygonum minus in response to salicylic acid (SA) and methyl jasmonate (MeJA) elicitations. This study reveals two different sets of genes induced by SA and MeJA, respectively where stress-related genes were proved to lead to the expression of genes involved in plant secondary metabolite biosynthetic pathways. A total of 98 transcript-derived fragments (TDFs) were up-regulated, including 46 from SA-treated and 52 from MeJA-treated samples. The cDNA-AFLP transcripts generated using 64 different Mse1/Taq1 primer combinations showed that treatments with SA and MeJA induced genes mostly involved in scavenging reactive oxygen species, including zeaxanthin epoxidase, cytosolic ascorbate peroxidase 1 and peroxidase. Of these stress-related genes, 15 % of other annotated TDFs are involved mainly in secondary metabolic processes where among these, two genes encoding (+)-delta cadinene synthase and cinnamoyl-CoA reductase were highlighted.
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http://dx.doi.org/10.1007/s11033-012-2286-4DOI Listing
March 2013

Flavonoid biosynthesis genes putatively identified in the aromatic plant Polygonum minus via Expressed Sequences Tag (EST) analysis.

Int J Mol Sci 2012 28;13(3):2692-706. Epub 2012 Feb 28.

Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600 Bangi Selangor, Malaysia; E-Mails: (N.D.R.); (J.M.Y.); (S.N.B.); (R.O.); (Z.-A.M.-H.); (I.I.); (N.M.N.).

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.
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http://dx.doi.org/10.3390/ijms13032692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317681PMC
July 2015

A protein short motif search tool using amino acid sequence and their secondary structure assignment.

Bioinformation 2011 20;7(6):304-6. Epub 2011 Nov 20.

Unlabelled: We present the development of a web server, a protein short motif search tool that allows users to simultaneously search for a protein sequence motif and its secondary structure assignments. The web server is able to query very short motifs searches against PDB structural data from the RCSB Protein Databank, with the users defining the type of secondary structures of the amino acids in the sequence motif. The output utilises 3D visualisation ability that highlights the position of the motif in the structure and on the corresponding sequence. Researchers can easily observe the locations and conformation of multiple motifs among the results. Protein short motif search also has an application programming interface (API) for interfacing with other bioinformatics tools.

Availability: The database is available for free at http://birg3.fbb.utm.my/proteinsms.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280500PMC
http://dx.doi.org/10.6026/007/97320630007304DOI Listing
August 2012

EuDBase: An online resource for automated EST analysis pipeline (ESTFrontier) and database for red seaweed Eucheuma denticulatum.

Bioinformation 2011 14;7(4):157-62. Epub 2011 Oct 14.

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/.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218516PMC
http://dx.doi.org/10.6026/97320630007157DOI Listing
November 2011