Search results for: key genes.
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 141

Search results for: key genes.

111 A Systems Approach to Gene Ranking from DNA Microarray Data of Cervical Cancer

Authors: Frank Emmert Streib, Matthias Dehmer, Jing Liu, Max Mühlhauser

Abstract:

In this paper we present a method for gene ranking from DNA microarray data. More precisely, we calculate the correlation networks, which are unweighted and undirected graphs, from 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 progression of the tumor. 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 and, hence, indicates that our method captures essential information from the underlying DNA microarray data of cervical cancer.

Keywords: Graph similarity, DNA microarray data, cancer.

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110 Emergence of Fluoroquinolone Resistance in Pigs, Nigeria

Authors: Igbakura I. Luga, Alex A. Adikwu

Abstract:

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 21st 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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109 VHL, PBRM1 and SETD2 Genes in Kidney Cancer: A Molecular Investigation

Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

Abstract:

Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p>0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: Kidney cancer, molecular biomarker, expression analysis, mutation screening.

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108 Reducing SAGE Data Using Genetic Algorithms

Authors: Cheng-Hong Yang, Tsung-Mu Shih, Li-Yeh Chuang

Abstract:

Serial Analysis of Gene Expression is a powerful quantification technique for generating cell or tissue gene expression data. The profile of the gene expression of cell or tissue in several different states is difficult for biologists to analyze because of the large number of genes typically involved. However, feature selection in machine learning can successfully reduce this problem. The method allows reducing the features (genes) in specific SAGE data, and determines only relevant genes. In this study, we used a genetic algorithm to implement feature selection, and evaluate the classification accuracy of the selected features with the K-nearest neighbor method. In order to validate the proposed method, we used two SAGE data sets for testing. The results of this study conclusively prove that the number of features of the original SAGE data set can be significantly reduced and higher classification accuracy can be achieved.

Keywords: Serial Analysis of Gene Expression, Feature selection, Genetic Algorithm, K-nearest neighbor method.

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107 Attribute Selection Methods Comparison for Classification of Diffuse Large B-Cell Lymphoma

Authors: Helyane Bronoski Borges, Júlio Cesar Nievola

Abstract:

The most important subtype of non-Hodgkin-s lymphoma is the Diffuse Large B-Cell Lymphoma. Approximately 40% of the patients suffering from it respond well to therapy, whereas the remainder needs a more aggressive treatment, in order to better their chances of survival. Data Mining techniques have helped to identify the class of the lymphoma in an efficient manner. Despite that, thousands of genes should be processed to obtain the results. This paper presents a comparison of the use of various attribute selection methods aiming to reduce the number of genes to be searched, looking for a more effective procedure as a whole.

Keywords: Attribute selection, data mining.

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106 Apoptosis Pathway Targeted by Thymoquinone in MCF7 Breast Cancer Cell Line

Authors: M. Marjaneh, M. Y. Narazah, H. Shahrul

Abstract:

Array-based gene expression analysis is a powerful tool to profile expression of genes and to generate information on therapeutic effects of new anti-cancer compounds. Anti-apoptotic effect of thymoquinone was studied in MCF7 breast cancer cell line using gene expression profiling with cDNA microarray. The purity and yield of RNA samples were determined using RNeasyPlus Mini kit. The Agilent RNA 6000 NanoLabChip kit evaluated the quantity of the RNA samples. AffinityScript RT oligo-dT promoter primer was used to generate cDNA strands. T7 RNA polymerase was used to convert cDNA to cRNA. The cRNA samples and human universal reference RNA were labelled with Cy-3-CTP and Cy-5-CTP, respectively. Feature Extraction and GeneSpring softwares analysed the data. The single experiment analysis revealed involvement of 64 pathways with up-regulated genes and 78 pathways with downregulated genes. The MAPK and p38-MAPK pathways were inhibited due to the up-regulation of PTPRR gene. The inhibition of p38-MAPK suggested up-regulation of TGF-ß pathway. Inhibition of p38-MAPK caused up-regulation of TP53 and down-regulation of Bcl2 genes indicating involvement of intrinsic apoptotic pathway. Down-regulation of CARD16 gene as an adaptor molecule regulated CASP1 and suggested necrosis-like programmed cell death and involvement of caspase in apoptosis. Furthermore, down-regulation of GPCR, EGF-EGFR signalling pathways suggested reduction of ER. Involvement of AhR pathway which control cytochrome P450 and glucuronidation pathways showed metabolism of Thymoquinone. The findings showed differential expression of several genes in apoptosis pathways with thymoquinone treatment in estrogen receptor-positive breast cancer cells.

Keywords: CARD16, CASP10, cDNA microarray, PTPRR, Thymoquinone.

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105 Characterization of Screening Staphylococcus aureus Isolates Harboring mecA Genes among Intensive Care Unit Patients from Tertiary Care Hospital in Jakarta, Indonesia

Authors: Delly C. Lestari, Linosefa, Ardiana Kusumaningrum, Andi Yasmon, Anis Karuniawati

Abstract:

The objective of this study is to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) harboring mecA genes from screening isolates among intensive care unit (ICU) patients. All MRSA screening isolates from ICU’s patients of Cipto Mangunkusumo Hospital during 2011 and 2014 were included in this study. Identification and susceptibility test was performed using Vitek2 system (Biomereux®). PCR was conducted to characterize the SCCmec of S. aureus harboring the mecA gene on each isolate. Patient’s history of illness was traced through medical record. 24 isolates from 327 screening isolates were MRSA positive (7.3%). From PCR, we found 17 (70.8%) isolates carrying SCCmec type I, 3 (12.5%) isolates carrying SCCmec type III, and 2 (8.3%) isolates carrying SCCmec type IV. In conclusion, SCCmec type I is the most prevalent MRSA colonization among ICU patients in Cipto Mangunkusumo Hospital.

Keywords: MRSA, mecA genes, ICU, colonization.

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104 Gene Expression Signature for Classification of Metastasis Positive and Negative Oral Cancer in Homosapiens

Authors: A. Shukla, A. Tarsauliya, R. Tiwari, S. Sharma

Abstract:

Cancer classification to their corresponding cohorts has been key area of research in bioinformatics aiming better prognosis of the disease. High dimensionality of gene data has been makes it a complex task and requires significance data identification technique in order to reducing the dimensionality and identification of significant information. In this paper, we have proposed a novel approach for classification of oral cancer into metastasis positive and negative patients. We have used significance analysis of microarrays (SAM) for identifying significant genes which constitutes gene signature. 3 different gene signatures were identified using SAM from 3 different combination of training datasets and their classification accuracy was calculated on corresponding testing datasets using k-Nearest Neighbour (kNN), Fuzzy C-Means Clustering (FCM), Support Vector Machine (SVM) and Backpropagation Neural Network (BPNN). A final gene signature of only 9 genes was obtained from above 3 individual gene signatures. 9 gene signature-s classification capability was compared using same classifiers on same testing datasets. Results obtained from experimentation shows that 9 gene signature classified all samples in testing dataset accurately while individual genes could not classify all accurately.

Keywords: Cancer, Gene Signature, SAM, Classification.

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103 Biodegradation of Carbazole By a Promising Gram-Negative Bacterium

Authors: G. B. Singh, S. Srivastava, N. Gupta

Abstract:

In the present work we report a gram negative bacterial isolate, from soil of a dye industry, with promising biorefining and bioremediation potential. This isolate (GBS.5) could utilize carbazole (nitrogen containing polycyclic aromatic hydrocarbon) as the sole source of nitrogen and carbon and utilize almost 98% of 3mM carbazole in 100 hours. The specific activity of our GBS.5 isolate for carbazole degradation at 30°C and pH 7.0 was found to be 11.36 μmol/min/g dry cell weight as compared to 10.4 μmol/min/g dry cell weight, the highest reported specific activity till date. The presence of car genes (the genes involved in denitrogenation of carbazole) was confirmed through PCR amplification.

Keywords: Biodenitrogenation, Biorefining, Carbazoledegradation, Crude oil.

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102 Identification and Classification of Gliadin Genes in Iranian Diploid Wheat

Authors: Jafar Ahmadi, Alireza Pour-Aboughadareh

Abstract:

Wheat is the first and the most important grain of the world and its bakery property is due to glutenin and gliadin qualities. Wheat seed proteins were divided into four groups according to solubility including albumin, globulin, glutenin and prolamin or gliadin. Gliadins are major components of the storage proteins in wheat endosperm. It seems that little information is available about gliadin genes in Iranian wild relatives of wheat. Thus, the aim of this study was the evaluation of the wheat wild relatives collected from different origins of Zagros Mountains in Iran, in terms of coding gliadin genes using specific primers. For this, forty accessions of Triticum boeoticum and Triticum urartu were selected for this study. For each accession, genomic DNA was extracted and PCRs were performed in total volumes of 15 μl. The amplification products were separated on 1.5% agarose gels. In results, for Gli-2A locus three allelic variants were detected by Gli-2As primer pairs. The sizes of PCR products for these alleles were 210, 490 and 700 bp. Only five (13%) and two accessions (5%) produced 700 and 490 bp fragments when their DNA was amplified with the Gli.As.2 primer pairs. However, 93% of the accessions carried allele 210 bp, and only 8% did not any product for this marker. Therefore, these germplasm could be used as rich gene pool to broaden the genetic base of bread wheat.

Keywords: Diploied wheat, gliadin, Triticum boeoticum, Triticum urartu.

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101 Recognition of Gene Names from Gene Pathway Figures Using Siamese Network

Authors: Muhammad Azam, Micheal Olaolu Arowolo, Fei He, Mihail Popescu, Dong Xu

Abstract:

The number of biological papers is growing quickly, which means that the number of biological pathway figures in those papers is also increasing quickly. Each pathway figure shows extensive biological information, like the names of genes and how the genes are related. However, manually annotating pathway figures takes a lot of time and work. Even though using advanced image understanding models could speed up the process of curation, these models still need to be made more accurate. To improve gene name recognition from pathway figures, we applied a Siamese network to map image segments to a library of pictures containing known genes in a similar way to person recognition from photos in many photo applications. We used a triple loss function and a triplet spatial pyramid pooling network by combining the triplet convolution neural network and the spatial pyramid pooling (TSPP-Net). We compared VGG19 and VGG16 as the Siamese network model. VGG16 achieved better performance with an accuracy of 93%, which is much higher than Optical Character Recognition (OCR) results.

Keywords: Biological pathway, image understanding, gene name recognition, object detection, Siamese network, Visual Geometry Group.

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100 Using Genetic Programming to Evolve a Team of Data Classifiers

Authors: Gregor A. Morrison, Dominic P. Searson, Mark J. Willis

Abstract:

The purpose of this paper is to demonstrate the ability of a genetic programming (GP) algorithm to evolve a team of data classification models. The GP algorithm used in this work is “multigene" in nature, i.e. there are multiple tree structures (genes) that are used to represent team members. Each team member assigns a data sample to one of a fixed set of output classes. A majority vote, determined using the mode (highest occurrence) of classes predicted by the individual genes, is used to determine the final class prediction. The algorithm is tested on a binary classification problem. For the case study investigated, compact classification models are obtained with comparable accuracy to alternative approaches.

Keywords: classification, genetic programming.

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99 Probe Selection for Pathway-Specific Microarray Probe Design Minimizing Melting Temperature Variance

Authors: Fabian Horn, Reinhard Guthke

Abstract:

In molecular biology, microarray technology is widely and successfully utilized to efficiently measure gene activity. If working with less studied organisms, methods to design custom-made microarray probes are available. One design criterion is to select probes with minimal melting temperature variances thus ensuring similar hybridization properties. If the microarray application focuses on the investigation of metabolic pathways, it is not necessary to cover the whole genome. It is more efficient to cover each metabolic pathway with a limited number of genes. Firstly, an approach is presented which minimizes the overall melting temperature variance of selected probes for all genes of interest. Secondly, the approach is extended to include the additional constraints of covering all pathways with a limited number of genes while minimizing the overall variance. The new optimization problem is solved by a bottom-up programming approach which reduces the complexity to make it computationally feasible. The new method is exemplary applied for the selection of microarray probes in order to cover all fungal secondary metabolite gene clusters for Aspergillus terreus.

Keywords: bottom-up approach, gene clusters, melting temperature, metabolic pathway, microarray probe design, probe selection

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98 Mining Genes Relations in Microarray Data Combined with Ontology in Colon Cancer Automated Diagnosis System

Authors: A. Gruzdz, A. Ihnatowicz, J. Siddiqi, B. Akhgar

Abstract:

MATCH project [1] entitle the development of an automatic diagnosis system that aims to support treatment of colon cancer diseases by discovering mutations that occurs to tumour suppressor genes (TSGs) and contributes to the development of cancerous tumours. The constitution of the system is based on a) colon cancer clinical data and b) biological information that will be derived by data mining techniques from genomic and proteomic sources The core mining module will consist of the popular, well tested hybrid feature extraction methods, and new combined algorithms, designed especially for the project. Elements of rough sets, evolutionary computing, cluster analysis, self-organization maps and association rules will be used to discover the annotations between genes, and their influence on tumours [2]-[11]. The methods used to process the data have to address their high complexity, potential inconsistency and problems of dealing with the missing values. They must integrate all the useful information necessary to solve the expert's question. For this purpose, the system has to learn from data, or be able to interactively specify by a domain specialist, the part of the knowledge structure it needs to answer a given query. The program should also take into account the importance/rank of the particular parts of data it analyses, and adjusts the used algorithms accordingly.

Keywords: Bioinformatics, gene expression, ontology, selforganizingmaps.

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97 Gene Expressions Associated with Ultrastructural Changes in Vascular Endothelium of Atherosclerotic Lesion

Authors: M. Maimunah, G.A. Froemming, H. Nawawi, M.I. Nafeeza, O. Effat, M.R. Rohayu Izanwati, M.S. Mohamed Saifulaman

Abstract:

Attachment of the circulating monocytes to the endothelium is the earliest detectable events during formation of atherosclerosis. The adhesion molecules, chemokines and matrix proteases genes were identified to be expressed in atherogenesis. Expressions of these genes may influence structural integrity of the luminal endothelium. The aim of this study is to relate changes in the ultrastructural morphology of the aortic luminal surface and gene expressions of the endothelial surface, chemokine and MMP-12 in normal and hypercholesterolemic rabbits. Luminal endothelial surface from rabbit aortic tissue was examined by scanning electron microscopy (SEM) using low vacuum mode to ascertain ultrastructural changes in development of atherosclerotic lesion. Gene expression of adhesion molecules, MCP-1 and MMP-12 were studied by Real-time PCR. Ultrastructural observations of the aortic luminal surface exhibited changes from normal regular smooth intact endothelium to irregular luminal surface including marked globular appearance and ruptures of the membrane layer. Real-time PCR demonstrated differentially expressed of studied genes in atherosclerotic tissues. The appearance of ultrastructural changes in aortic tissue of hypercholesterolemic rabbits is suggested to have relation with underlying changes of endothelial surface molecules, chemokine and MMP-12 gene expressions.

Keywords: Ultrastructure of luminal endothelial surface, Macrophage metalloelastase (MMP-12), Real-time PCR.

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96 Novel Hybrid Method for Gene Selection and Cancer Prediction

Authors: Liping Jing, Michael K. Ng, Tieyong Zeng

Abstract:

Microarray data profiles gene expression on a whole genome scale, therefore, it provides a good way to study associations between gene expression and occurrence or progression of cancer. More and more researchers realized that microarray data is helpful to predict cancer sample. However, the high dimension of gene expressions is much larger than the sample size, which makes this task very difficult. Therefore, how to identify the significant genes causing cancer becomes emergency and also a hot and hard research topic. Many feature selection algorithms have been proposed in the past focusing on improving cancer predictive accuracy at the expense of ignoring the correlations between the features. In this work, a novel framework (named by SGS) is presented for stable gene selection and efficient cancer prediction . The proposed framework first performs clustering algorithm to find the gene groups where genes in each group have higher correlation coefficient, and then selects the significant genes in each group with Bayesian Lasso and important gene groups with group Lasso, and finally builds prediction model based on the shrinkage gene space with efficient classification algorithm (such as, SVM, 1NN, Regression and etc.). Experiment results on real world data show that the proposed framework often outperforms the existing feature selection and prediction methods, say SAM, IG and Lasso-type prediction model.

Keywords: Gene Selection, Cancer Prediction, Lasso, Clustering, Classification.

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95 Prediction of MicroRNA-Target Gene by Machine Learning Algorithms in Lung Cancer Study

Authors: Nilubon Kurubanjerdjit, Nattakarn Iam-On, Ka-Lok Ng

Abstract:

MicroRNAs are small non-coding RNA found in many different species. They play crucial roles in cancer such as biological processes of apoptosis and proliferation. The identification of microRNA-target genes can be an essential first step towards to reveal the role of microRNA in various cancer types. In this paper, we predict miRNA-target genes for lung cancer by integrating prediction scores from miRanda and PITA algorithms used as a feature vector of miRNA-target interaction. Then, machine-learning algorithms were implemented for making a final prediction. The approach developed in this study should be of value for future studies into understanding the role of miRNAs in molecular mechanisms enabling lung cancer formation.

Keywords: MicroRNA, miRNAs, lung cancer, machine learning, Naïve Bayes, SVM.

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94 Detection of Pathogenic Escherichia coli Strains Pollution in Red Deer Meat in Latvia and Determination the Compatibility of VT1, VT2, eae A Genes in their Isolate

Authors: S. Liepina, A. Jemeljanovs

Abstract:

Tasks of the work were study the possible E.coli contamination in red deer meat, identify pathogenic strains from isolated E.coli, determine their incidence in red deer meat and determine the presence of VT1, VT2 and eaeA genes for the pathogenic E.coli. 8 (10%) samples were randomly selected from 80 analysed isolates of E.coli and PCR reaction was performed on them. PCR was done both on initial materials – samples of red deer meat - and for already isolated liqueurs. Two of analysed venison samples contain verotoxin-producing strains of E. coli. It means that this meat is not safe to consumer. It was proven by the sequestration reaction of E. coli and by comparison of the obtained results with the database of microorganism genome available on the internet that the isolated culture corresponds to region 16S rDNS of E. coli thus presenting correctness of the microbiological methods.

Keywords: Deer meat, pathogenic Escherichia coli

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93 Enhanced Character Based Algorithm for Small Parsimony

Authors: Parvinder Singh Sandhu, Sumeet Kaur Sehra, Karmjit Kaur

Abstract:

Phylogenetic tree is a graphical representation of the evolutionary relationship among three or more genes or organisms. These trees show relatedness of data sets, species or genes divergence time and nature of their common ancestors. Quality of a phylogenetic tree requires parsimony criterion. Various approaches have been proposed for constructing most parsimonious trees. This paper is concerned about calculating and optimizing the changes of state that are needed called Small Parsimony Algorithms. This paper has proposed enhanced small parsimony algorithm to give better score based on number of evolutionary changes needed to produce the observed sequence changes tree and also give the ancestor of the given input.

Keywords: Phylogenetic Analysis, Small Parsimony, EnhancedFitch Algorithm, Enhanced Sakoff Algorithm.

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92 Modeling Stress-Induced Regulatory Cascades with Artificial Neural Networks

Authors: Maria E. Manioudaki, Panayiota Poirazi

Abstract:

Yeast cells live in a constantly changing environment that requires the continuous adaptation of their genomic program in order to sustain their homeostasis, survive and proliferate. Due to the advancement of high throughput technologies, there is currently a large amount of data such as gene expression, gene deletion and protein-protein interactions for S. Cerevisiae under various environmental conditions. Mining these datasets requires efficient computational methods capable of integrating different types of data, identifying inter-relations between different components and inferring functional groups or 'modules' that shape intracellular processes. This study uses computational methods to delineate some of the mechanisms used by yeast cells to respond to environmental changes. The GRAM algorithm is first used to integrate gene expression data and ChIP-chip data in order to find modules of coexpressed and co-regulated genes as well as the transcription factors (TFs) that regulate these modules. Since transcription factors are themselves transcriptionally regulated, a three-layer regulatory cascade consisting of the TF-regulators, the TFs and the regulated modules is subsequently considered. This three-layer cascade is then modeled quantitatively using artificial neural networks (ANNs) where the input layer corresponds to the expression of the up-stream transcription factors (TF-regulators) and the output layer corresponds to the expression of genes within each module. This work shows that (a) the expression of at least 33 genes over time and for different stress conditions is well predicted by the expression of the top layer transcription factors, including cases in which the effect of up-stream regulators is shifted in time and (b) identifies at least 6 novel regulatory interactions that were not previously associated with stress-induced changes in gene expression. These findings suggest that the combination of gene expression and protein-DNA interaction data with artificial neural networks can successfully model biological pathways and capture quantitative dependencies between distant regulators and downstream genes.

Keywords: gene modules, artificial neural networks, yeast, stress

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91 A Novel Microarray Biclustering Algorithm

Authors: Chieh-Yuan Tsai, Chuang-Cheng Chiu

Abstract:

Biclustering aims at identifying several biclusters that reveal potential local patterns from a microarray matrix. A bicluster is a sub-matrix of the microarray consisting of only a subset of genes co-regulates in a subset of conditions. In this study, we extend the motif of subspace clustering to present a K-biclusters clustering (KBC) algorithm for the microarray biclustering issue. Besides minimizing the dissimilarities between genes and bicluster centers within all biclusters, the objective function of the KBC algorithm additionally takes into account how to minimize the residues within all biclusters based on the mean square residue model. In addition, the objective function also maximizes the entropy of conditions to stimulate more conditions to contribute the identification of biclusters. The KBC algorithm adopts the K-means type clustering process to efficiently make the partition of K biclusters be optimized. A set of experiments on a practical microarray dataset are demonstrated to show the performance of the proposed KBC algorithm.

Keywords: Microarray, Biclustering, Subspace clustering, Meansquare residue model.

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90 Gene Selection Guided by Feature Interdependence

Authors: Hung-Ming Lai, Andreas Albrecht, Kathleen Steinhöfel

Abstract:

Cancers could normally be marked by a number of differentially expressed genes which show enormous potential as biomarkers for a certain disease. Recent years, cancer classification based on the investigation of gene expression profiles derived by high-throughput microarrays has widely been used. The selection of discriminative genes is, therefore, an essential preprocess step in carcinogenesis studies. In this paper, we have proposed a novel gene selector using information-theoretic measures for biological discovery. This multivariate filter is a four-stage framework through the analyses of feature relevance, feature interdependence, feature redundancy-dependence and subset rankings, and having been examined on the colon cancer data set. Our experimental result show that the proposed method outperformed other information theorem based filters in all aspect of classification errors and classification performance.

Keywords: Colon cancer, feature interdependence, feature subset selection, gene selection, microarray data analysis.

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89 rRNA Maturation Genes (KRR1 and PWP2) in Saccharomyces cerevisiae Inhibited by Silver Nanoparticles

Authors: Anjali Haloi, Debabrata Das

Abstract:

Silver nanoparticles inhibit a wide variety of microorganisms. The mechanism of inhibition is not entirely known although it is recognized to be concentration dependent and associated with the disruption of membrane permeability. Data on differential gene expression as a response to nanoparticles could provide insights into the mechanism of this inhibitory effect. Silver nanoparticles were synthesized in yeast growth media using a modification of the Creighton method and characterized with UV-Vis spectrophotometry, transmission electron microscopy (TEM), and X-ray diffraction (XRD). In yeasts grown in the presence of silver nanoparticles, we observed that at concentrations below the minimum inhibitory concentration (MIC) of 48.51 µg/ml, the total RNA content was steady while the cellular protein content declined rapidly. The analysis of the expression levels of KRR1 and PWP2, two important genes involved in rRNA maturation in yeasts, showed up to 258 and 42-fold decreases, respectively, compared to that of control samples. Whether silver nanoparticles have an adverse effect on ribosome assembly and function could be an area of further investigation.

Keywords: Ag NP, yeast, qRT-PCR, KRR1, PWP2.

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88 Screen of MicroRNA Targets in Zebrafish Using Heterogeneous Data Sources: A Case Study for Dre-miR-10 and Dre-miR-196

Authors: Yanju Zhang, Joost M. Woltering, Fons J. Verbeek

Abstract:

It has been established that microRNAs (miRNAs) play an important role in gene expression by post-transcriptional regulation of messengerRNAs (mRNAs). However, the precise relationships between microRNAs and their target genes in sense of numbers, types and biological relevance remain largely unclear. Dissecting the miRNA-target relationships will render more insights for miRNA targets identification and validation therefore promote the understanding of miRNA function. In miRBase, miRanda is the key algorithm used for target prediction for Zebrafish. This algorithm is high-throughput but brings lots of false positives (noise). Since validation of a large scale of targets through laboratory experiments is very time consuming, several computational methods for miRNA targets validation should be developed. In this paper, we present an integrative method to investigate several aspects of the relationships between miRNAs and their targets with the final purpose of extracting high confident targets from miRanda predicted targets pool. This is achieved by using the techniques ranging from statistical tests to clustering and association rules. Our research focuses on Zebrafish. It was found that validated targets do not necessarily associate with the highest sequence matching. Besides, for some miRNA families, the frequency of their predicted targets is significantly higher in the genomic region nearby their own physical location. Finally, in a case study of dre-miR-10 and dre-miR-196, it was found that the predicted target genes hoxd13a, hoxd11a, hoxd10a and hoxc4a of dre-miR- 10 while hoxa9a, hoxc8a and hoxa13a of dre-miR-196 have similar characteristics as validated target genes and therefore represent high confidence target candidates.

Keywords: MicroRNA targets validation, microRNA-target relationships, dre-miR-10, dre-miR-196.

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87 First Studies of the Influence of Single Gene Perturbations on the Inference of Genetic Networks

Authors: Frank Emmert-Streib, Matthias Dehmer

Abstract:

Inferring the network structure from time series data is a hard problem, especially if the time series is short and noisy. DNA microarray is a technology allowing to monitor the mRNA concentration of thousands of genes simultaneously that produces data of these characteristics. In this study we try to investigate the influence of the experimental design on the quality of the result. More precisely, we investigate the influence of two different types of random single gene perturbations on the inference of genetic networks from time series data. To obtain an objective quality measure for this influence we simulate gene expression values with a biologically plausible model of a known network structure. Within this framework we study the influence of single gene knock-outs in opposite to linearly controlled expression for single genes on the quality of the infered network structure.

Keywords: Dynamic Bayesian networks, microarray data, structure learning, Markov chain Monte Carlo.

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86 Identification of Conserved Domains and Motifs for GRF Gene Family

Authors: Jafar Ahmadi, Nafiseh Noormohammadi, Sedigheh Fabriki Ourang

Abstract:

GRF, Growth regulating factor, genes encode a novel class of plant-specific transcription factors. The GRF proteins play a role in the regulation of cell numbers in young and growing tissues and may act as transcription activations in growth and development of plants. Identification of GRF genes and their expression are important in plants to performance of the growth and development of various organs. In this study, to better understanding the structural and functional differences of GRFs family, 45 GRF proteins sequences in A. thaliana, Z. mays, O. sativa, B. napus, B. rapa, H. vulgare and S. bicolor, have been collected and analyzed through bioinformatics data mining. As a result, in secondary structure of GRFs, the number of alpha helices was more than beta sheets and in all of them QLQ domains were completely in the biggest alpha helix. In all GRFs, QLQ and WRC domains were completely protected except in AtGRF9. These proteins have no trans-membrane domain and due to have nuclear localization signals act in nuclear and they are component of unstable proteins in the test tube.

Keywords: Domain, Gene Family, GRF, Motif.

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85 Gene Network Analysis of PPAR-γ: A Bioinformatics Approach Using STRING

Authors: S. Bag, S. Ramaiah, P. Anitha, K. M. Kumar, P. Lavanya, V. Sivasakhthi, A. Anbarasu

Abstract:

Gene networks present a graphical view at the level of gene activities and genetic functions and help us to understand complex interactions in a meaningful manner. In the present study, we have analyzed the gene interaction of PPAR-γ (peroxisome proliferator-activated receptor gamma) by search tool for retrieval of interacting genes. We find PPAR-γ is highly networked by genetic interactions with 10 genes: RXRA (retinoid X receptor, alpha), PPARGC1A (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), NCOA1 (nuclear receptor coactivator 1), NR0B2 (nuclear receptor subfamily 0, group B, member 2), HDAC3 (histone deacetylase 3), MED1 (mediator complex subunit 1), INS (insulin), NCOR2 (nuclear receptor co-repressor 2), PAX8 (paired box 8), ADIPOQ (adiponectin) and it augurs well for the fact that obesity and several other metabolic disorders are inter related.

Keywords: Gene networks, NCOA1, PPARγ, PPARGC1A, RXRA.

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84 Identification of Complex Sense-antisense Gene's Module on 17q11.2 Associated with Breast Cancer Aggressiveness and Patient's Survival

Authors: O. Grinchuk, E. Motakis, V. Kuznetsov

Abstract:

Sense-antisense gene pair (SAGP) is a pair of two oppositely transcribed genes sharing a common region on a chromosome. In the mammalian genomes, SAGPs can be organized in more complex sense-antisense gene architectures (CSAGA) in which at least one gene could share loci with two or more antisense partners. Many dozens of CSAGAs can be found in the human genome. However, CSAGAs have not been systematically identified and characterized in context of their role in human diseases including cancers. In this work we characterize the structural-functional properties of a cluster of 5 genes –TMEM97, IFT20, TNFAIP1, POLDIP2 and TMEM199, termed TNFAIP1 / POLDIP2 module. This cluster is organized as CSAGA in cytoband 17q11.2. Affymetrix U133A&B expression data of two large cohorts (410 atients, in total) of breast cancer patients and patient survival data were used. For the both studied cohorts, we demonstrate (i) strong and reproducible transcriptional co-regulatory patterns of genes of TNFAIP1/POLDIP2 module in breast cancer cell subtypes and (ii) significant associations of TNFAIP1/POLDIP2 CSAGA with amplification of the CSAGA region in breast cancer, (ii) cancer aggressiveness (e.g. genetic grades) and (iv) disease free patient-s survival. Moreover, gene pairs of this module demonstrate strong synergetic effect in the prognosis of time of breast cancer relapse. We suggest that TNFAIP1/ POLDIP2 cluster can be considered as a novel type of structural-functional gene modules in the human genome.

Keywords: Sense-antisense gene pair, complex genome architecture, TMEM97, IFT20, TNFAIP1, POLDIP2, TMEM199, 17q11.2, breast cancer, transcription regulation, survival analysis, prognosis.

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83 A Cuckoo Search with Differential Evolution for Clustering Microarray Gene Expression Data

Authors: M. Pandi, K. Premalatha

Abstract:

A DNA microarray technology is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome. Elucidating the patterns hidden in gene expression data offers a tremendous opportunity for an enhanced understanding of functional genomics. However, the large number of genes and the complexity of biological networks greatly increase the challenges of comprehending and interpreting the resulting mass of data, which often consists of millions of measurements. It is handled by clustering which reveals the natural structures and identifying the interesting patterns in the underlying data. In this paper, gene based clustering in gene expression data is proposed using Cuckoo Search with Differential Evolution (CS-DE). The experiment results are analyzed with gene expression benchmark datasets. The results show that CS-DE outperforms CS in benchmark datasets. To find the validation of the clustering results, this work is tested with one internal and one external cluster validation indexes.

Keywords: DNA, Microarray, genomics, Cuckoo Search, Differential Evolution, Gene expression data, Clustering.

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82 On Figuring the City Characteristics and Landscape in Overall Urban Design: A Case Study in Xiangyang Central City, China

Authors: Guyue Zhu, Liangping Hong

Abstract:

Chinese overall urban design faces a large number of problems such as the neglect of urban characteristics, generalization of content, and difficulty in implementation. Focusing on these issues, this paper proposes the main points of shaping urban characteristics in overall urban design: focuses on core problems in city function and scale, landscape pattern, historical culture, social resources and modern city style and digs the urban characteristic genes. Then, we put forward “core problem location and characteristic gene enhancement” as a kind of overall urban design technical method. Firstly, based on the main problems in urban space as a whole, for the operability goal, the method extracts the key genes and integrates into the multi-dimension system in a targeted manner. Secondly, hierarchical management and guidance system is established which may be in line with administrative management. Finally, by converting the results, action plan is drawn up that can be dynamically implemented. Based on the above idea and method, a practical exploration has been performed in the case of Xiangyang central city.

Keywords: City characteristics, overall urban design, planning implementation, Xiangyang central city.

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