Search results for: tetracycline resistance genes.

Authors: M. Raissy, M. Shahrani

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The present study was done to evaluate the presence of tetracycline resistance genes in Lactococcus garvieae isolated from cultured rainbow trout, West Iran. The isolates were examined for antimicrobial resistance using disc diffusion method. Of the 49 strains tested, 19 were resistant to tetracycline (38.7%), 32 to enrofloxacin (65.3%), 21 to erythromycin (42.8%), 20 to chloramphenicol and trimetoprim-sulfamethoxazole (40.8%). The strains were then characterized for their genotypic resistance profiles. The results revealed that all 49 isolates contained at least one of the tetracycline resistance genes. Tet (A) was found in 89.4% of tetracycline resistant isolates and the frequency of other gene were as follows: tet (E) 42.1%, tet (B) 47.3%, tet (D) 15.7%, tet (L) 26.3%, tet (K) 52.6%, tet (G) 36.8%, tet (34) 21%, tet (S) 63.1%, tet (C) 57.8%, tet (M) 73.6%, tet (O) 42.1%. The results revealed high levels of antibiotic resistance in L. garvieae strains which is a potential danger for trout culture as well as for public health.

Keywords: Lactococcus garvieae, rainbow trout, tetracycline resistance genes.

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Authors: Anasheh Maridiroosi, Ali Reza Mahjoub, Hanieh Fakhri

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Heteropoly acid nanoparticles anchored on graphene oxide based on UiO-66 were synthesized via in-situ growth hydrothermal method and tested for photodegradation of a tetracycline as critical pollutant. Results showed that presence of graphene oxide and UiO-66 with high specific surface area, great electron mobility and various functional groups make an excellent support for heteropoly acid and improve photocatalytic efficiency up to 95% for tetracycline. Furthermore, total organic carbon (TOC) analysis verified 79% mineralization of this pollutant under optimum condition.

Keywords: Heteropoly acid, graphene oxide, MOF, tetracycline.

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Authors: Efendi Zaenudin, Chien-Hung Huang, Ka-Lok Ng

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Essential genes play an important role in the survival of an organism. It has been shown that cancer-associated essential genes are genes necessary for cancer cell proliferation, where these genes are potential therapeutic targets. Also, it was demonstrated that mutations of the cancer-associated essential genes give rise to the resistance of immunotherapy for patients with tumors. In the present study, we focus on studying the biological effects of the essential genes from a network perspective. We hypothesize that one can analyze a biological molecular network by decomposing it into both three-node and four-node digraphs (subgraphs). These network subgraphs encode the regulatory interaction information among the network’s genetic elements. In this study, the frequency of occurrence of the subgraph-associated essential genes in a molecular network was quantified by using the statistical parameter, odds ratio. Biological effects of subgraph-associated essential genes are discussed. In summary, the subgraph approach provides a systematic method for analyzing molecular networks and it can capture useful biological information for biomedical research.

Keywords: Biological molecular networks, essential genes, graph theory, network subgraphs.

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Authors: Igbakura I. Luga, Alex A. Adikwu

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A comparison of resistance to quinolones was carried out on isolates of Shiga toxin-producing Escherichia coliO157:H7 from cattle and mecA and nuc genes harbouring Staphylococcus aureus from pigs. The isolates were separately tested in the first and current decades of the 21^st century. The objective was to demonstrate the dissemination of resistance to this frontline class of antibiotic by bacteria from food animals and bring to the limelight the spread of antibiotic resistance in Nigeria. A total of 10 isolates of the E. coli O157:H7 and 9 of mecA and nuc genes harbouring S. aureus were obtained following isolation, biochemical testing, and serological identification using the Remel Wellcolex E. coli O157:H7 test. Shiga toxin-production screening in the E. coli O157:H7 using the verotoxin E. coli reverse passive latex agglutination (VTEC-RPLA) test; and molecular identification of the mecA and nuc genes in S. aureus. Detection of the mecA and nuc genes were carried out using the protocol by the Danish Technical University (DTU) using the following primers mecA-1:5'-GGGATCATAGCGTCATTATTC-3', mecA-2: 5'-AACGATTGTGACACGATAGCC-3', nuc-1: 5'-TCAGCAAATGCATCACAAACAG-3', nuc-2: 5'-CGTAAATGCACTTGCTTCAGG-3' for the mecA and nuc genes, respectively. The nuc genes confirm the S. aureus isolates and the mecA genes as being methicillin-resistant and so pathogenic to man. The fluoroquinolones used in the antibiotic resistance testing were norfloxacin (10 µg) and ciprofloxacin (5 µg) in the E. coli O157:H7 isolates and ciprofloxacin (5 µg) in the S. aureus isolates. Susceptibility was tested using the disk diffusion method on Muller-Hinton agar. Fluoroquinolone resistance was not detected from isolates of E. coli O157:H7 from cattle. However, 44% (4/9) of the S. aureus were resistant to ciprofloxacin. Resistance of up to 44% in isolates of mecA and nuc genes harbouring S. aureus is a compelling evidence for the rapid spread of antibiotic resistance from bacteria in food animals from Nigeria. Ciprofloxacin is the drug of choice for the treatment of Typhoid fever, therefore widespread resistance to it in pathogenic bacteria is of great public health significance. The study concludes that antibiotic resistance in bacteria from food animals is on the increase in Nigeria. The National Food and Drug Administration and Control (NAFDAC) agency in Nigeria should implement the World Health Organization (WHO) global action plan on antimicrobial resistance. A good starting point can be coordinating the WHO, Office of International Epizootics (OIE), Food and Agricultural Organization (FAO) tripartite draft antimicrobial resistance monitoring and evaluation (M&E) framework in Nigeria.

Keywords: Fluoroquinolone, Nigeria, resistance, Staphylococcus aureus.

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Authors: Jackson H. O. Onyuka, Rose Kakai, David M. Onyango, Peter F. Arama, John Gichuki, Ayub V.O. Ofulla

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A cross sectional study design and standard microbiological procedures were used to determine the prevalence and antimicrobial susceptibility patterns of Escherichia coli, Salmonella enterica serovar typhimurium and Vibrio cholerae O1 isolated from water and two fish species Rastrineobola argentea and Oreochromis niloticus collected from fish landing beaches and markets in the Lake Victoria Basin of western Kenya. Out of 162 samples analyzed, 133 (82.1%) were contaminated, with S. typhimurium as the most prevalent (49.6%), followed by E. coli (46.6%), and lastly V. cholerae (2.8%). All the bacteria isolates were sensitive to ciprofloxacin. E. coli isolates were resistant to ampicillin, tetracycline, cotrimoxazole, chloramphenical and gentamicin while S. typhimurium isolates exhibited resistance to ampicillin, tetracycline, and cotrimoxazole. The V. cholerae O1 isolates were resistant to tetracycline and ampicillin. The high prevalence of drug resistant enteric bacteria in water and fish from the study region needs public health intervention from the local government.

Keywords: Aquatic environments, Antimicrobial resistance, Enteric bacteria, Lake Victoria Basin

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Authors: Hyunjin Rho, Bongjin Shin, Okbok Lee, Yu-Hyun Choi, Jiyoung Lee, Jaerang Rho

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The increasing usage of antibiotics in the animal farming industry is an emerging worldwide problem contributing to the development of antibiotic resistance. The purpose of this work was to investigate the prevalence and antibiotic resistance profile of bacterial isolates collected from aquatic environments and meats in a peri-urban community in Daejeon, Korea. In an antibacterial susceptibility test, the bacterial isolates showed a high incidence of resistance (~ 26.04 %) to cefazolin, tetracycline, gentamycin, norfloxacin, erythromycin and vancomycin. The results from a test for multiple antibiotic resistance indicated that the isolates were displaying an approximately 5-fold increase in the incidence of multiple antibiotic resistance to combinations of two different antibiotics compared to combinations of three or more antibiotics. Most of the isolates showed multi-antibiotic resistance, and the resistance patterns were similar among the sampling groups. Sequencing data analysis of 16S rRNA showed that most of the resistant isolates appeared to be dominated by the classes Betaproteobacteria and Gammaproteobacteria in the phylum Proteobacteria.

Keywords: Antibiotics, Antibiotic resistance, Antimicrobial resistance, Multi-resistance

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Authors: U. Kairov, T. Karpenyuk, E. Ramanculov, A. Zinovyev

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The most common result of analysis of highthroughput data in molecular biology represents a global list of genes, ranked accordingly to a certain score. The score can be a measure of differential expression. Recent work proposed a new method for selecting a number of genes in a ranked gene list from microarray gene expression data such that this set forms the Optimally Functionally Enriched Network (OFTEN), formed by known physical interactions between genes or their products. Here we present calculation results of relative connectivity of genes from META-OFTEN network and tentative biological interpretation of the most reproducible signal. The relative connectivity and inbetweenness values of genes from META-OFTEN network were estimated.

Keywords: Microarray, META-OFTEN, gene network.

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Authors: Masaki Yamaguchi, Akira Ito, Noriaki Okamoto, Yoshinori Kawabe, Masamichi Kamihira

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Heat-inducible gene expression vectors are useful for hyperthermia-induced cancer gene therapy, because the combination of hyperthermia and gene therapy can considerably improve the therapeutic effects. In the present study, we developed an enhanced heat-inducible transgene expression system in which a heat-shock protein (HSP) promoter and tetracycline-responsive transactivator were combined. When the transactivator plasmid containing the tetracycline-responsive transactivator gene was co-transfected with the reporter gene expression plasmid, a high level of heat-induced gene expression was observed compared with that using the HSP promoter without the transactivator. In vitro evaluation of the therapeutic effect using HeLa cells showed that heat-induced therapeutic gene expression caused cell death in a high percentage of these cells, indicating that this strategy is promising for cancer gene therapy.

Keywords: Inducible gene expression, Gene therapy, Hyperthermia, Heat shock protein, Tetracycline transactivator.

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Authors: R. K. Agrawal, Rajni Bala

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Developing an accurate classifier for high dimensional microarray datasets is a challenging task due to availability of small sample size. Therefore, it is important to determine a set of relevant genes that classify the data well. Traditionally, gene selection method often selects the top ranked genes according to their discriminatory power. Often these genes are correlated with each other resulting in redundancy. In this paper, we have proposed a hybrid method using feature ranking and wrapper method (Genetic Algorithm with multiclass SVM) to identify a set of relevant genes that classify the data more accurately. A new fitness function for genetic algorithm is defined that focuses on selecting the smallest set of genes that provides maximum accuracy. Experiments have been carried on four well-known datasets1. The proposed method provides better results in comparison to the results found in the literature in terms of both classification accuracy and number of genes selected.

Keywords: Gene selection, genetic algorithm, microarray datasets, multi-class SVM.

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Authors: Sh. A. Yousif, M. Bhave

Abstract:

There is strong evidence that water channel proteins 'aquaporins (AQPs)' are central components in plant-water relations as well as a number of other physiological parameters. We had previously reported the isolation of 24 plasma membrane intrinsic protein (PIP) type AQPs. However, the gene numbers in rice and the polyploid nature of bread wheat indicated a high probability of further genes in the latter. The present work focused on identification of further AQP isoforms in bread wheat. With the use of altered primer design, we identified five genes homologous, designated PIP1;5b, PIP2;9b, TaPIP2;2, TaPIP2;2a, TaPIP2;2b. Sequence alignments indicate PIP1;5b, PIP2;9b are likely to be homeologues of two previously reported genes while the other three are new genes and could be homeologs of each other. The results indicate further AQP diversity in wheat and the sequence data will enable physical mapping of these genes to identify their genomes as well as genetic to determine their association with any quantitative trait loci (QTLs) associated with plant-water relation such as salinity or drought tolerance.

Keywords: Aquaporins, homeologues, PIP, wheat

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Authors: T. Chandrasekhar, K. Thangavel, E. N. Sathishkumar

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Microarrays are made it possible to simultaneously monitor the expression profiles of thousands of genes under various experimental conditions. It is used to identify the co-expressed genes in specific cells or tissues that are actively used to make proteins. This method is used to analysis the gene expression, an important task in bioinformatics research. Cluster analysis of gene expression data has proved to be a useful tool for identifying co-expressed genes, biologically relevant groupings of genes and samples. In this work K-Means algorithms has been applied for clustering of Gene Expression Data. Further, rough set based Quick reduct algorithm has been applied for each cluster in order to select the most similar genes having high correlation. Then the ACV measure is used to evaluate the refined clusters and classification is used to evaluate the proposed method. They could identify compact clusters with feature selection method used to genes are selected.

Keywords: Clustering, Feature selection, Gene expression data, Quick reduct.

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Authors: R. Haddad, K. Morris, V. Buchanan-Wollaston

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Biochemical and molecular analysis of some antioxidant enzyme genes revealed different level of gene expression on oilseed (Brassica napus). For molecular and biochemical analysis, leaf tissues were harvested from plants at eight different developmental stages, from young to senescence. The levels of total protein and chlorophyll were increased during maturity stages of plant, while these were decreased during the last stages of plant growth. Structural analysis (nucleotide and deduced amino acid sequence, and phylogenic tree) of a complementary DNA revealed a high level of similarity for a family of Catalase genes. The expression of the gene encoded by different Catalase isoforms was assessed during different plant growth phase. No significant difference between samples was observed, when Catalase activity was statistically analyzed at different developmental stages. EST analysis exhibited different transcripts levels for a number of other relevant antioxidant genes (different isoforms of SOD and glutathione). The high level of transcription of these genes at senescence stages was indicated that these genes are senescenceinduced genes.

Keywords: Biochemical analysis, Oilseed, Expression pattern, Growth phases

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Authors: Yuhong Lu

Abstract:

Graves’ Disease (GD), an autoimmune health condition caused by the over reactiveness of the thyroid, affects about 1 in 200 people worldwide. GD is not caused by one specific single nucleotide polymorphism (SNP) or gene mutation, but rather determined by multiple factors, each differing from each other. Malfunction of the genes in Human Leukocyte Antigen (HLA) family tend to play a major role in autoimmune diseases, but other genes, such as LOC101929163, have functions that still remain ambiguous. Currently, little studies were done to study GD, resulting in inconclusive results. This study serves not only to introduce background knowledge about GD, but also to organize and pinpoint the major SNPs and genes that are potentially related to the occurrence of GD in humans. Collected from multiple sources from genome-wide association studies (GWAS) Central, the potential SNPs related to the causes of GD are included in this study. This study has located the genes that are related to those SNPs and closely examines a selected sample. Using the data from this study, scientists will then be able to focus on the most expressed genes in GD patients and develop a treatment for GD.

Keywords: CTLA4, Graves’ Disease, HLA, single nucleotide polymorphism, SNP.

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Authors: Fereshteh Shacheraghi, Mohammad Reza Shakibaie, Hanieh Noveiri

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Fourty one strains of ESBL producing P.aeruginosa which were previously isolated from burn patients in Kerman University general hospital, Iran were subjected to PCR, RFLP and sequencing in order to determine the type of extended spectrum β- lactamases (ESBL), the restriction digestion pattern and possibility of mutation among detected genes. DNA extraction was carried out by phenol chloroform method. PCR for detection of bla genes was performed using specific primer for each gene. Restriction Fragment Length Polymorphism (RFLP) for ESBL genes was carried out using EcoRI, NheI, PVUII, EcoRV, DdeI, and PstI restriction enzymes. The PCR products were subjected to direct sequencing of both the strands for identification of the ESBL genes.The blaCTX-M, blaVEB-1, blaPER-1, blaGES-1, blaOXA-1, blaOXA-4 and blaOXA-10 genes were detected in the (n=1) 2.43%, (n=41)100%, (n=28) 68.3%, (n=10) 24.4%, (n=29) 70.7%, (n=7)17.1% and (n=38) 92.7% of the ESBL producing isolates respectively. The RFLP analysis showed that each ESBL gene has identical pattern of digestion among the isolated strains. Sequencing of the ESBL genes confirmed the genuinety of PCR products and revealed no mutation in the restriction sites of the above genes. From results of the present investigation it can be concluded that blaVEB-1 and blaCTX-M were the most and the least frequently isolated ESBL genes among the P.aeruginosa strains isolated from burn patients. The RFLP and sequencing analysis revealed that same clone of the bla genes were indeed existed among the antibiotic resistant strains.

Keywords: ESBL genes, PCR, RFLP, Sequencing, P.aeruginosa

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Authors: JiEun Jeong, Se-Won Kang, Hee-Ju Hwang, Sung-Hwa Chae, Sang-Haeng Choi, Hong-SeogPark, YeonSoo Han, Bok-Reul Lee, Dae-Hyun Seog, Yong Seok Lee

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Tofurther advance research on immune-related genes from T. molitor, we constructed acDNA library and analyzed expressed sequence taq (EST) sequences from 1,056 clones. After removing vector sequence and quality checkingthrough thePhred program (trim_alt 0.05 (P-score>20), 1039 sequences were generated. The average length of insert was 792 bp. In addition, we identified 162 clusters, 167 contigs and 391 contigs after clustering and assembling process using a TGICL package. EST sequences were searchedagainst NCBI nr database by local BLAST (blastx, EKeywords: EST, Innate immunity, Tenebriomolitor

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Authors: C. Gunavathi, K. Premalatha

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Microarray technology is universally used in the study of disease diagnosis using gene expression levels. The main shortcoming of gene expression data is that it includes thousands of genes and a small number of samples. Abundant methods and techniques have been proposed for tumor classification using microarray gene expression data. Feature or gene selection methods can be used to mine the genes that directly involve in the classification and to eliminate irrelevant genes. In this paper statistical measures like T-Statistics, Signal-to-Noise Ratio (SNR) and F-Statistics are used to rank the genes. The ranked genes are used for further classification. Particle Swarm Optimization (PSO) algorithm and Shuffled Frog Leaping (SFL) algorithm are used to find the significant genes from the top-m ranked genes. The Naïve Bayes Classifier (NBC) is used to classify the samples based on the significant genes. The proposed work is applied on Lung and Ovarian datasets. The experimental results show that the proposed method achieves 100% accuracy in all the three datasets and the results are compared with previous works.

Keywords: Microarray, T-Statistics, Signal-to-Noise Ratio, FStatistics, Particle Swarm Optimization, Shuffled Frog Leaping, Naïve Bayes Classifier.

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Authors: P. Chihomvu, P. Stegmann, M. Pillay

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Pollution of the Klip River has caused microorganisms inhabiting it to develop protective survival mechanisms. This study isolated and characterized the heavy metal resistant bacteria in the Klip River. Water and sediment samples were collected from six sites along the course of the river. The pH, turbidity, salinity, temperature and dissolved oxygen were measured in-situ. The concentrations of six heavy metals (Cd, Cu, Fe, Ni, Pb and Zn) of the water samples were determined by atomic absorption spectroscopy. Biochemical and antibiotic profiles of the isolates were assessed using the API 20E® and Kirby Bauer Method. Growth studies were carried out using spectrophotometric methods. The isolates were identified using 16SrDNA sequencing. The uppermost part of the Klip River with the lowest pH had the highest levels of heavy metals. Turbidity, salinity and specific conductivity increased measurably at Site 4 (Henley on Klip Weir). MIC tests showed that 16 isolates exhibited high iron and lead resistance. Antibiotic susceptibility tests revealed that the isolates exhibited multitolerances to drugs such as Tetracycline, Ampicillin, and Amoxicillin.

Keywords: Klip River, heavy metals, resistance.

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Authors: Chien-Hung Huang, Chia-Wei Weng, Chang-Chih Chiang, Shih-Hua Wu, Chih-Hsien Huang, Ka-Lok Ng

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MicroRNAs (miRNAs) are a class of non-coding RNAs that hybridize to mRNAs and induce either translation repression or mRNA cleavage. Recently, it has been reported that miRNAs could possibly play an important role in human diseases. By integrating miRNA target genes, cancer genes, miRNA and mRNA expression profiles information, a database is developed to link miRNAs to cancer target genes. The database provides experimentally verified human miRNA target genes information, including oncogenes and tumor suppressor genes. In addition, fragile sites information for miRNAs, and the strength of the correlation of miRNA and its target mRNA expression level for nine tissue types are computed, which serve as an indicator for suggesting miRNAs could play a role in human cancer. The database is freely accessible at http://ppi.bioinfo.asia.edu.tw/mirna_target/index.html.

Keywords: MicroRNA, miRNA expression profile, mRNAexpression profile, cancer genes, oncogene, tumor suppressor gene

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Authors: Frank Emmert-Streib, Matthias Dehmer, Jing Liu, Max Muhlhauser

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The major objective of this paper is to introduce a new method to select genes from DNA microarray data. As criterion to select genes we suggest to measure the local changes in the correlation graph of each gene and to select those genes whose local changes are largest. More precisely, we calculate the correlation networks from DNA microarray data of cervical cancer whereas each network represents a tissue of a certain tumor stage and each node in the network represents a gene. From these networks we extract one tree for each gene by a local decomposition of the correlation network. The interpretation of a tree is that it represents the n-nearest neighbor genes on the n-th level of a tree, measured by the Dijkstra distance, and, hence, gives the local embedding of a gene within the correlation network. For the obtained trees we measure the pairwise similarity between trees rooted by the same gene from normal to cancerous tissues. This evaluates the modification of the tree topology due to tumor progression. Finally, we rank the obtained similarity values from all tissue comparisons and select the top ranked genes. For these genes the local neighborhood in the correlation networks changes most between normal and cancerous tissues. As a result we find that the top ranked genes are candidates suspected to be involved in tumor growth. This indicates that our method captures essential information from the underlying DNA microarray data of cervical cancer.

Keywords: Graph similarity, generalized trees, graph alignment, DNA microarray data, cervical cancer.

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Authors: Khlopova N.S., Glazko V.I., Glazko T.T.

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Using DNA microarrays the comparative analysis of a gene expression profiles is carried out in a liver and kidneys of pigs. The hypothesis of a cross hybridization of one probe with different cDNA sites of the same gene or different genes is checked up, and it is shown, that cross hybridization can be a source of essential errors at revealing of a key genes in organ-specific transcriptome. It is reveald that distinctions in profiles of a gene expression are well coordinated with function, morphology, biochemistry and histology of these organs.

Keywords: Microarray, gene expression profiles, key genes.

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Authors: E. N. Sathishkumar, K. Thangavel, T. Chandrasekhar

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Feature selection is a process to select features which are more informative. It is one of the important steps in knowledge discovery. The problem is that all genes are not important in gene expression data. Some of the genes may be redundant, and others may be irrelevant and noisy. Here a novel approach is proposed Hybrid K-Mean-Quick Reduct (KMQR) algorithm for gene selection from gene expression data. In this study, the entire dataset is divided into clusters by applying K-Means algorithm. Each cluster contains similar genes. The high class discriminated genes has been selected based on their degree of dependence by applying Quick Reduct algorithm to all the clusters. Average Correlation Value (ACV) is calculated for the high class discriminated genes. The clusters which have the ACV value as 1 is determined as significant clusters, whose classification accuracy will be equal or high when comparing to the accuracy of the entire dataset. The proposed algorithm is evaluated using WEKA classifiers and compared. The proposed work shows that the high classification accuracy.

Keywords: Clustering, Gene Selection, K-Mean-Quick Reduct, Rough Sets.

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Authors: Michael Netzer, Michael Seger, Mahesh Visvanathan, Bernhard Pfeifer, Gerald H. Lushington, Christian Baumgartner

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Lung cancer accounts for the most cancer related deaths for men as well as for women. The identification of cancer associated genes and the related pathways are essential to provide an important possibility in the prevention of many types of cancer. In this work two filter approaches, namely the information gain and the biomarker identifier (BMI) are used for the identification of different types of small-cell and non-small-cell lung cancer. A new method to determine the BMI thresholds is proposed to prioritize genes (i.e., primary, secondary and tertiary) using a k-means clustering approach. Sets of key genes were identified that can be found in several pathways. It turned out that the modified BMI is well suited for microarray data and therefore BMI is proposed as a powerful tool for the search for new and so far undiscovered genes related to cancer.

Keywords: lung cancer, micro arrays, data mining, feature selection.

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Authors: Ankit Agrawal, Ankush Mittal

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A gene network gives the knowledge of the regulatory relationships among the genes. Each gene has its activators and inhibitors that regulate its expression positively and negatively respectively. Genes themselves are believed to act as activators and inhibitors of other genes. They can even activate one set of genes and inhibit another set. Identifying gene networks is one of the most crucial and challenging problems in Bioinformatics. Most work done so far either assumes that there is no time delay in gene regulation or there is a constant time delay. We here propose a Dynamic Time- Lagged Correlation Based Method (DTCBM) to learn the gene networks, which uses time-lagged correlation to find the potential gene interactions, and then uses a post-processing stage to remove false gene interactions to common parents, and finally uses dynamic correlation thresholds for each gene to construct the gene network. DTCBM finds correlation between gene expression signals shifted in time, and therefore takes into consideration the multi time delay relationships among the genes. The implementation of our method is done in MATLAB and experimental results on Saccharomyces cerevisiae gene expression data and comparison with other methods indicate that it has a better performance.

Keywords: Activators, correlation, dynamic time-lagged correlation based method, inhibitors, multi-time delay gene network.

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Authors: Shohei Maruyama, Yasuo Matsuyama, Sachiyo Aburatani

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Development of a method to estimate gene functions is an important task in bioinformatics. One of the approaches for the annotation is the identification of the metabolic pathway that genes are involved in. Since gene expression data reflect various intracellular phenomena, those data are considered to be related with genes’ functions. However, it has been difficult to estimate the gene function with high accuracy. It is considered that the low accuracy of the estimation is caused by the difficulty of accurately measuring a gene expression. Even though they are measured under the same condition, the gene expressions will vary usually. In this study, we proposed a feature extraction method focusing on the variability of gene expressions to estimate the genes' metabolic pathway accurately. First, we estimated the distribution of each gene expression from replicate data. Next, we calculated the similarity between all gene pairs by KL divergence, which is a method for calculating the similarity between distributions. Finally, we utilized the similarity vectors as feature vectors and trained the multiclass SVM for identifying the genes' metabolic pathway. To evaluate our developed method, we applied the method to budding yeast and trained the multiclass SVM for identifying the seven metabolic pathways. As a result, the accuracy that calculated by our developed method was higher than the one that calculated from the raw gene expression data. Thus, our developed method combined with KL divergence is useful for identifying the genes' metabolic pathway.

Keywords: Metabolic pathways, gene expression data, microarray, Kullback–Leibler divergence, KL divergence, support vector machines, SVM, machine learning.

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Authors: Tom Snir, Eitan Rubin

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Mendelian Disease Genes represent a collection of single points of failure for the various systems they constitute. Such genes have been shown, on average, to encode longer proteins than 'non-disease' proteins. Existing models suggest that this results from the increased likeli-hood of longer genes undergoing mutations. Here, we show that in saturated mutagenesis experiments performed on model organisms, where the likelihood of each gene mutating is one, a similar relationship between length and the probability of a gene being lethal was observed. We thus suggest an extended model demonstrating that the likelihood of a mutated gene to produce a severe phenotype is length-dependent. Using the occurrence of conserved domains, we bring evidence that this dependency results from a correlation between protein length and the number of functions it performs. We propose that protein length thus serves as a proxy for protein cardinality in different networks required for the organism's survival and well-being. We use this example to argue that the collection of Mendelian Disease Genes can, and should, be used to study the rules governing systems vulnerability in living organisms.

Keywords: Systems Biology, Protein Length

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Authors: Zeinep A. Berkimbayeva, Almagul T. Mansharipova, Elmira M. Khussainova, Leyla B. Djansugurova

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It is believed that DNA damaging toxic metabolites contributes to the development of different pathological conditions. To prevent harmful influence of toxic agents, cells developed number of protecting mechanisms, such as enzymatic reaction of detoxification of reactive metabolites and repair of DNA damage. The aim of the study was to examine the association between polymorphism of GSTT1/GSTM1 and XRCC1/3 genes and coronary artery disease (CAD) incidence. To examine a polymorphism of these genes in CAD susceptibility in patients and controls, PCR based genotyping assay was performed. For GST genes, frequency of GSTM1 null genotype among CAD affected group was significantly increased than in control group (P<0.001). Frequencies of the GSTT1 null and positive alleles are almost equal in both groups (P>0.1). We found that neither XRCC1 Arg399Gln nor XRCC3 Thr241Met were associated with CAD risk. Obtained data suggests that GSTM1 null genotype carriers are more susceptible to CAD development.

Keywords: Cardiovascular disease, DNA reparation, gene polymorphism, risk factors, xenobiotic detoxification.

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Authors: Achitphol Chookaew, Paramee Thongsukhsai, Patamarerk Engsontia, Narongwit Nakwan, Pritsana Raugrut

Abstract:

Lung cancer is one of the most common malignancies and primary cause of death due to cancer worldwide. Non-small cell lung cancer (NSCLC) is the main subtype in which majority of patients present with advanced-stage disease. Herein, we analyzed differentially expressed genes to find potential biomarkers for lung cancer diagnosis as well as prognostic markers. We used transcriptome data from our 2 NSCLC patients and public data (GSE81089) composing of 8 NSCLC and 10 normal lung tissues. Differentially expressed genes (DEGs) between NSCLC and normal tissue and between early-stage and late-stage NSCLC were analyzed by the DESeq2. Pairwise correlation was used to find the DEGs with false discovery rate (FDR) adjusted p-value £ 0.05 and |log2 fold change| ³ 4 for NSCLC versus normal and FDR adjusted p-value £ 0.05 with |log2 fold change| ³ 2 for early versus late-stage NSCLC. Bioinformatic tools were used for functional and pathway analysis. Moreover, the top ten genes in each comparison group were verified the expression and survival analysis via GEPIA. We found 150 up-regulated and 45 down-regulated genes in NSCLC compared to normal tissues. Many immnunoglobulin-related genes e.g., IGHV4-4, IGHV5-10-1, IGHV4-31, IGHV4-61, and IGHV1-69D were significantly up-regulated. 22 genes were up-regulated, and five genes were down-regulated in late-stage compared to early-stage NSCLC. The top five DEGs genes were KRT6B, SPRR1A, KRT13, KRT6A and KRT5. Keratin 6B (KRT6B) was the most significantly increased gene in the late-stage NSCLC. From GEPIA analysis, we concluded that IGHV4-31 and IGKV1-9 might be used as diagnostic biomarkers, while KRT6B and KRT6A might be used as prognostic biomarkers. However, further clinical validation is needed.

Keywords: Bioinformatics, differentially expressed genes, non-small cell lung cancer, transcriptomics.

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Authors: C. M. De Marco Muscat-Fenech, A. M. Grech La Rosa

Abstract:

Although a lot of importance has been given to resistance analysis for various vessel types, explicit guidelines applied to multihull vessels have not been clearly defined.  The purpose of this investigation is to highlight the importance of the vessel’s layout in terms of three axes, the transverse (separation), the longitudinal (stagger) and the vertical (draught) with respect to resistance analysis. When a vessel has the potential to experience less resistance at a particular range of speeds a vast selection of opportunities are made available for both the commercial and leisure market.

Keywords: Multihull, Reistance, Trimaran.

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Authors: S. Kapoor, R. Liu, X. J. Wu, M. X. Yao

Abstract:

A group of Stellite alloys are studied in consideration of temperature effects on their hardness and wear resistance. The hardness test is conducted on a micro-hardness tester with a hot stage equipped that allows heating the specimen up to 650°C. The wear resistance of each alloy is evaluated using a pin-on-disc tribometer with a heating furnace built-in that provides the temperature capacity up to 450°C. The experimental results demonstrate that the hardness and wear resistance of Stellite alloys behave differently at room temperature and at high temperatures. The wear resistance of Stellite alloys at room temperature mainly depends on their carbon content and also influenced by the tungsten content in the alloys. However, at high temperatures the wear mechanisms of Stellite alloys become more complex, involving multiple factors. The relationships between chemical composition, microstructure, hardness and wear resistance of these alloys are studied, with focus on temperature effect on these relations.

Keywords: Stellite alloy, temperature, hardness, wear resistance

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Authors: Robert Setekera, Luuk Tiemeijer, Ramses van der Toorn

Abstract:

In this paper an extensive verification of the extraction method (published earlier) that consistently accounts for self-heating and Early effect to accurately extract both base and thermal resistance of bipolar junction transistors is presented. The method verification is demonstrated on advanced RF SiGe HBTs were the extracted results for the thermal resistance are compared with those from another published method that ignores the effect of Early effect on internal base-emitter voltage and the extracted results of the base resistance are compared with those determined from noise measurements. A self-consistency of our method in the extracted base resistance and thermal resistance using compact model simulation results is also carried out in order to study the level of accuracy of the method.

Keywords: Avalanche, Base resistance, Bipolar transistor, Compact modeling, Early voltage, Thermal resistance, Self-heating, parameter extraction.

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