Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 385

Search results for: Gene therapy

385 A Heat-Inducible Transgene Expression System for Gene Therapy

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

Abstract:

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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384 Combining Gene and Chemo Therapy using Multifunctional Polymeric Micelles

Authors: Hong Yi Huang, Wei Ti Kuo, Yi You Huang

Abstract:

Non-viral gene carriers composed of biodegradable polymers or lipids have been considered as a safer alternative for gene carriers over viral vectors. We have developed multi-functional nano-micelles for both drug and gene delivery application. Polyethyleneimine (PEI) was modified by grafting stearic acid (SA) and formulated to polymeric micelles (PEI-SA) with positive surface charge for gene and drug delivery. Our results showed that PEI-SA micelles provided high siRNA binding efficiency. In addition, siRNA delivered by PEI-SA carriers also demonstrated significantly high cellular uptake even in the presence of serum proteins. The post-transcriptional gene silencing efficiency was greatly improved by the polyplex formulated by 10k PEI-SA/siRNA. The amphiphilic structure of PEI-SA micelles provided advantages for multifunctional tasks; where the hydrophilic shell modified with cationic charges can electrostatically interact with DNA or siRNA, and the hydrophobic core can serve as payloads for hydrophobic drugs, making it a promising multifunctional vehicle for both genetic and chemotherapy application.

Keywords: polyethyleneimine, gene delivery, micelles, siRNA

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383 A New blaVIM Gene in a Pseudomonas putida Isolated from ENT Units in Sulaimani Hospitals

Authors: Dalanya Asaad Mohammed, Dara Abdul Razaq

Abstract:

A total of twenty tensile biopsies were collected from children undergoing tonsillectomy from teaching hospital ENT department and Kurdistan private hospital in sulaimani city. All biopsies were homogenized and cultured; the obtained bacterial isolates were purified and identified by biochemical tests and VITEK 2 compact system. Among the twenty studied samples, only one Pseudomonas putida with probability of 99% was isolated. Antimicrobial susceptibility was carried out by disk diffusion method, Pseudomonas putida showed resistance to all antibiotics used except vancomycin. The isolate further subjected to PCR and DNA sequence analysis of blaVIM gene using different set of primers for different regions of VIM gene. The results were found to be PCR positive for the blaVIM gene. To determine the sequence of blaVIM gene, DNA sequencing performed. Sequence alignment of blaVIM gene with previously recorded blaVIM gene in NCBI- database showed that P. putida isolate have different blaVIM gene.

Keywords: Clinical isolates, Putida, Sulaimani, Vim gene.

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382 A Dynamic Time-Lagged Correlation based Method to Learn Multi-Time Delay Gene Networks

Authors: Ankit Agrawal, Ankush Mittal

Abstract:

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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381 Differentiation of Gene Expression Profiles Data for Liver and Kidney of Pigs

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

Abstract:

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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380 Automatic Clustering of Gene Ontology by Genetic Algorithm

Authors: Razib M. Othman, Safaai Deris, Rosli M. Illias, Zalmiyah Zakaria, Saberi M. Mohamad

Abstract:

Nowadays, Gene Ontology has been used widely by many researchers for biological data mining and information retrieval, integration of biological databases, finding genes, and incorporating knowledge in the Gene Ontology for gene clustering. However, the increase in size of the Gene Ontology has caused problems in maintaining and processing them. One way to obtain their accessibility is by clustering them into fragmented groups. Clustering the Gene Ontology is a difficult combinatorial problem and can be modeled as a graph partitioning problem. Additionally, deciding the number k of clusters to use is not easily perceived and is a hard algorithmic problem. Therefore, an approach for solving the automatic clustering of the Gene Ontology is proposed by incorporating cohesion-and-coupling metric into a hybrid algorithm consisting of a genetic algorithm and a split-and-merge algorithm. Experimental results and an example of modularized Gene Ontology in RDF/XML format are given to illustrate the effectiveness of the algorithm.

Keywords: Automatic clustering, cohesion-and-coupling metric, gene ontology; genetic algorithm, split-and-merge algorithm.

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379 Integration of Microarray Data into a Genome-Scale Metabolic Model to Study Flux Distribution after Gene Knockout

Authors: Mona Heydari, Ehsan Motamedian, Seyed Abbas Shojaosadati

Abstract:

Prediction of perturbations after genetic manipulation (especially gene knockout) is one of the important challenges in systems biology. In this paper, a new algorithm is introduced that integrates microarray data into the metabolic model. The algorithm was used to study the change in the cell phenotype after knockout of Gss gene in Escherichia coli BW25113. Algorithm implementation indicated that gene deletion resulted in more activation of the metabolic network. Growth yield was more and less regulating gene were identified for mutant in comparison with the wild-type strain.

Keywords: Metabolic network, gene knockout, flux balance analysis, microarray data, integration.

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378 Clustering Approach to Unveiling Relationships between Gene Regulatory Networks

Authors: Hiba Hasan, Khalid Raza

Abstract:

Reverse engineering of genetic regulatory network involves the modeling of the given gene expression data into a form of the network. Computationally it is possible to have the relationships between genes, so called gene regulatory networks (GRNs), that can help to find the genomics and proteomics based diagnostic approach for any disease. In this paper, clustering based method has been used to reconstruct genetic regulatory network from time series gene expression data. Supercoiled data set from Escherichia coli has been taken to demonstrate the proposed method.

Keywords: Gene expression, gene regulatory networks (GRNs), clustering, data preprocessing, network visualization.

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377 Multifunctional Cell Processing with Plasmonic Nanobubbles

Authors: Ekaterina Y. Lukianova-Hleb, Dmitri O. Lapotko

Abstract:

Cell processing techniques for gene and cell therapies use several separate procedures for gene transfer and cell separation or elimination, because no current technology can offer simultaneous multi-functional processing of specific cell sub-sets in heterogeneous cell systems. Using our novel on-demand nonstationary intracellular events instead of permanent materials, plasmonic nanobubbles, generated with a short laser pulse only in target cells, we achieved simultaneous multifunctional cell-specific processing with the rate up to 50 million cells per minute.

Keywords: Delivery, cell separation, graft, laser, plasmonic nanobubble, cell therapy, gold nanoparticle.

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376 Computational Model for Predicting Effective siRNA Sequences Using Whole Stacking Energy (% G) for Gene Silencing

Authors: Reena Murali, David Peter S.

Abstract:

The small interfering RNA (siRNA) alters the regulatory role of mRNA during gene expression by translational inhibition. Recent studies show that upregulation of mRNA because serious diseases like cancer. So designing effective siRNA with good knockdown effects plays an important role in gene silencing. Various siRNA design tools had been developed earlier. In this work, we are trying to analyze the existing good scoring second generation siRNA predicting tools and to optimize the efficiency of siRNA prediction by designing a computational model using Artificial Neural Network and whole stacking energy (%G), which may help in gene silencing and drug design in cancer therapy. Our model is trained and tested against a large data set of siRNA sequences. Validation of our results is done by finding correlation coefficient of experimental versus observed inhibition efficacy of siRNA. We achieved a correlation coefficient of 0.727 in our previous computational model and we could improve the correlation coefficient up to 0.753 when the threshold of whole tacking energy is greater than or equal to -32.5 kcal/mol.

Keywords: Artificial Neural Network, Double Stranded RNA, RNA Interference, Short Interfering RNA.

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375 An SVM based Classification Method for Cancer Data using Minimum Microarray Gene Expressions

Authors: R. Mallika, V. Saravanan

Abstract:

This paper gives a novel method for improving classification performance for cancer classification with very few microarray Gene expression data. The method employs classification with individual gene ranking and gene subset ranking. For selection and classification, the proposed method uses the same classifier. The method is applied to three publicly available cancer gene expression datasets from Lymphoma, Liver and Leukaemia datasets. Three different classifiers namely Support vector machines-one against all (SVM-OAA), K nearest neighbour (KNN) and Linear Discriminant analysis (LDA) were tested and the results indicate the improvement in performance of SVM-OAA classifier with satisfactory results on all the three datasets when compared with the other two classifiers.

Keywords: Support vector machines-one against all, cancerclassification, Linear Discriminant analysis, K nearest neighbour, microarray gene expression, gene pair ranking.

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374 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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373 UTMGO: A Tool for Searching a Group of Semantically Related Gene Ontology Terms and Application to Annotation of Anonymous Protein Sequence

Authors: Razib M. Othman, Safaai Deris, Rosli M. Illias

Abstract:

Gene Ontology terms have been actively used to annotate various protein sets. SWISS-PROT, TrEMBL, and InterPro are protein databases that are annotated according to the Gene Ontology terms. However, direct implementation of the Gene Ontology terms for annotation of anonymous protein sequences is not easy, especially for species not commonly represented in biological databases. UTMGO is developed as a tool that allows the user to quickly and easily search for a group of semantically related Gene Ontology terms. The applicability of the UTMGO is demonstrated by applying it to annotation of anonymous protein sequence. The extended UTMGO uses the Gene Ontology terms together with protein sequences associated with the terms to perform the annotation task. GOPET, GOtcha, GoFigure, and JAFA are used to compare the performance of the extended UTMGO.

Keywords: Anonymous protein sequence, Gene Ontology, Protein sequence annotation, Protein sequence alignment

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372 Dynamical Analysis of Circadian Gene Expression

Authors: Carla Layana Luis Diambra

Abstract:

Microarrays technique allows the simultaneous measurements of the expression levels of thousands of mRNAs. By mining this data one can identify the dynamics of the gene expression time series. By recourse of principal component analysis, we uncover the circadian rhythmic patterns underlying the gene expression profiles from Cyanobacterium Synechocystis. We applied PCA to reduce the dimensionality of the data set. Examination of the components also provides insight into the underlying factors measured in the experiments. Our results suggest that all rhythmic content of data can be reduced to three main components.

Keywords: circadian rhythms, clustering, gene expression, PCA.

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371 A Hybrid Gene Selection Technique Using Improved Mutual Information and Fisher Score for Cancer Classification Using Microarrays

Authors: M. Anidha, K. Premalatha

Abstract:

Feature Selection is significant in order to perform constructive classification in the area of cancer diagnosis. However, a large number of features compared to the number of samples makes the task of classification computationally very hard and prone to errors in microarray gene expression datasets. In this paper, we present an innovative method for selecting highly informative gene subsets of gene expression data that effectively classifies the cancer data into tumorous and non-tumorous. The hybrid gene selection technique comprises of combined Mutual Information and Fisher score to select informative genes. The gene selection is validated by classification using Support Vector Machine (SVM) which is a supervised learning algorithm capable of solving complex classification problems. The results obtained from improved Mutual Information and F-Score with SVM as a classifier has produced efficient results.

Keywords: Gene selection, mutual information, Fisher score, classification, SVM.

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370 A Simple Affymetrix Ratio-transformation Method Yields Comparable Expression Level Quantifications with cDNA Data

Authors: Chintanu K. Sarmah, Sandhya Samarasinghe, Don Kulasiri, Daniel Catchpoole

Abstract:

Gene expression profiling is rapidly evolving into a powerful technique for investigating tumor malignancies. The researchers are overwhelmed with the microarray-based platforms and methods that confer them the freedom to conduct large-scale gene expression profiling measurements. Simultaneously, investigations into cross-platform integration methods have started gaining momentum due to their underlying potential to help comprehend a myriad of broad biological issues in tumor diagnosis, prognosis, and therapy. However, comparing results from different platforms remains to be a challenging task as various inherent technical differences exist between the microarray platforms. In this paper, we explain a simple ratio-transformation method, which can provide some common ground for cDNA and Affymetrix platform towards cross-platform integration. The method is based on the characteristic data attributes of Affymetrix- and cDNA- platform. In the work, we considered seven childhood leukemia patients and their gene expression levels in either platform. With a dataset of 822 differentially expressed genes from both these platforms, we carried out a specific ratio-treatment to Affymetrix data, which subsequently showed an improvement in the relationship with the cDNA data.

Keywords: Gene expression profiling, microarray, cDNA, Affymetrix, childhood leukaemia.

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369 Inhibiting Gene for a Late-Heading Gene Responsible for Photoperiod Sensitivity in Rice (Oryza sativa)

Authors: Amol Dahal, Shunsuke Hori, Haruki Nakazawa, Kazumitsu Onishi, Toshio Kawano, Masayuki Murai

Abstract:

Two indica varieties, IR36 and ‘Suweon 258’ (“S”) are middle-heading in southern Japan. 36U, also middle-heading, is an isogenic line of IR36 carrying Ur1 (Undulate rachis-1) gene. However, late-heading plants segregated in the F2 population from the F1 of S × 36U, and so did in the following generations. The concerning lateness gene is designated as Ex. From the F8 generation, isogenic-line pair of early-heading and late-heading lines, denoted by “E” (ex/ex) and “L” (Ex/Ex), were developed. Genetic analyses of heading time were conducted, using F1s and F2s among L, E, S and 36U. The following inferences were drawn from the experimental results: 1) L, and both of E and 36U harbor Ex and ex, respectively; 2) Besides Ex, S harbors an inhibitor gene to it, i.e. I-Ex which is a novel finding of the present study. 3) Ex is a dominant allele at the E1 locus.

Keywords: Basic vegetative phase, heading time, lateness gene, photoperiod-sensitive phase.

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368 Application of KL Divergence for Estimation of Each Metabolic Pathway Genes

Authors: Shohei Maruyama, Yasuo Matsuyama, Sachiyo Aburatani

Abstract:

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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367 What Do Young People Seeking Professional Help Want and Expect From Therapy?

Authors: Clare Watsford, Debra Rickwood

Abstract:

Client expectations and preferences about therapy represent an important area of investigation as research shows they are linked to engagement in therapy and therapy outcomes. Studies examining young people-s expectations and preferences of therapy remain a neglected area of research. The present study explored what expectations and preferences young people seeking professional help held regarding: their role as a client, their therapist-s role, their therapeutic outcomes, and the processes of therapy. Gender and age differences were also examined. Participants included 188 young people aged 12-25 who completed a survey while attending their initial session at a youth mental health service. Data were analysed using quantitative methods. Results found the young people held significantly more pessimistic expectations around therapy when compared to what they had wanted therapy to be like. Few age and gender differences were found. Results highlight the importance of a collaborative therapy approach when working with young people.

Keywords: Client expectations, mental health services, preferences, young people

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366 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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365 A Phenomic Algorithm for Reconstruction of Gene Networks

Authors: Rio G. L. D'Souza, K. Chandra Sekaran, A. Kandasamy

Abstract:

The goal of Gene Expression Analysis is to understand the processes that underlie the regulatory networks and pathways controlling inter-cellular and intra-cellular activities. In recent times microarray datasets are extensively used for this purpose. The scope of such analysis has broadened in recent times towards reconstruction of gene networks and other holistic approaches of Systems Biology. Evolutionary methods are proving to be successful in such problems and a number of such methods have been proposed. However all these methods are based on processing of genotypic information. Towards this end, there is a need to develop evolutionary methods that address phenotypic interactions together with genotypic interactions. We present a novel evolutionary approach, called Phenomic algorithm, wherein the focus is on phenotypic interaction. We use the expression profiles of genes to model the interactions between them at the phenotypic level. We apply this algorithm to the yeast sporulation dataset and show that the algorithm can identify gene networks with relative ease.

Keywords: Evolutionary computing, gene expression analysis, gene networks, microarray data analysis, phenomic algorithms.

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364 Analysis of OPG Gene Polymorphism T245G (rs3134069) in Slovak Postmenopausal Women

Authors: I. Boroňová, J. Bernasovská, J. Kľoc, Z. Tomková, E. Petrejčíková, S. Mačeková, J. Poráčová, M. M. Blaščáková

Abstract:

Osteoporosis is a common multifactorial disease with a strong genetic component characterized by reduced bone mass and increased risk of fractures. Genetic factors play an important role in the pathogenesis of osteoporosis. The aim of our study was to identify the genotype and allele distribution of T245G polymorphism in OPG gene in Slovak postmenopausal women. A total of 200 unrelated Slovak postmenopausal women with diagnosed osteoporosis and 200 normal controls were genotyped for T245G (rs3134069) polymorphism of OPG gene. Genotyping was performed using the Custom Taqman®SNP Genotyping assays. Genotypes and alleles frequencies showed no significant differences (p=0.5551; p=0.6022). The results of the present study confirm the importance of T245G polymorphism in OPG gene in the pathogenesis of osteoporosis.

Keywords: OPG gene, osteoporosis, Real-time PCR, T245G polymorphism.

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363 Comparative Study on Swarm Intelligence Techniques for Biclustering of Microarray Gene Expression Data

Authors: R. Balamurugan, A. M. Natarajan, K. Premalatha

Abstract:

Microarray gene expression data play a vital in biological processes, gene regulation and disease mechanism. Biclustering in gene expression data is a subset of the genes indicating consistent patterns under the subset of the conditions. Finding a biclustering is an optimization problem. In recent years, swarm intelligence techniques are popular due to the fact that many real-world problems are increasingly large, complex and dynamic. By reasons of the size and complexity of the problems, it is necessary to find an optimization technique whose efficiency is measured by finding the near optimal solution within a reasonable amount of time. In this paper, the algorithmic concepts of the Particle Swarm Optimization (PSO), Shuffled Frog Leaping (SFL) and Cuckoo Search (CS) algorithms have been analyzed for the four benchmark gene expression dataset. The experiment results show that CS outperforms PSO and SFL for 3 datasets and SFL give better performance in one dataset. Also this work determines the biological relevance of the biclusters with Gene Ontology in terms of function, process and component.

Keywords: Particle swarm optimization, Shuffled frog leaping, Cuckoo search, biclustering, gene expression data.

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362 Construction of a Fusion Gene Carrying E10A and K5 with 2A Peptide-Linked by Using Overlap Extension PCR

Authors: Tiancheng Lan

Abstract:

E10A is a kind of replication-defective adenovirus which carries the human endostatin gene to inhibit the growth of tumors. Kringle 5(K5) has almost the same function as angiostatin to also inhibit the growth of tumors since they are all the byproduct of the proteolytic cleavage of plasminogen. Tumor size increasing can be suppressed because both of the endostatin and K5 can restrain the angiogenesis process. Therefore, in order to improve the treatment effect on tumor, 2A peptide is used to construct a fusion gene carrying both E10A and K5. Using 2A peptide is an ideal strategy when a fusion gene is expressed because it can avoid many problems during the expression of more than one kind of protein. The overlap extension PCR is also used to connect 2A peptide with E10A and K5. The final construction of fusion gene E10A-2A-K5 can provide a possible new method of the anti-angiogenesis treatment with a better expression performance.

Keywords: E10A, Kringle 5, 2A peptide, overlap extension PCR.

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361 Bioinformatics Profiling of Missense Mutations

Authors: I. Nassiri, B. Goliaei, M. Tavassoli

Abstract:

The ability to distinguish missense nucleotide substitutions that contribute to harmful effect from those that do not is a difficult problem usually accomplished through functional in vivo analyses. In this study, instead current biochemical methods, the effects of missense mutations upon protein structure and function were assayed by means of computational methods and information from the databases. For this order, the effects of new missense mutations in exon 5 of PTEN gene upon protein structure and function were examined. The gene coding for PTEN was identified and localized on chromosome region 10q23.3 as the tumor suppressor gene. The utilization of these methods were shown that c.319G>A and c.341T>G missense mutations that were recognized in patients with breast cancer and Cowden disease, could be pathogenic. This method could be use for analysis of missense mutation in others genes.

Keywords: Bioinformatics, missense mutations, PTEN tumorsuppressor gene.

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360 Simultaneous Clustering and Feature Selection Method for Gene Expression Data

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

Abstract:

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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359 Analysis of DNA Microarray Data using Association Rules: A Selective Study

Authors: M. Anandhavalli Gauthaman

Abstract:

DNA microarrays allow the measurement of expression levels for a large number of genes, perhaps all genes of an organism, within a number of different experimental samples. It is very much important to extract biologically meaningful information from this huge amount of expression data to know the current state of the cell because most cellular processes are regulated by changes in gene expression. Association rule mining techniques are helpful to find association relationship between genes. Numerous association rule mining algorithms have been developed to analyze and associate this huge amount of gene expression data. This paper focuses on some of the popular association rule mining algorithms developed to analyze gene expression data.

Keywords: DNA microarray, gene expression, association rule mining.

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358 Evaluation of Clustering Based on Preprocessing in Gene Expression Data

Authors: Seo Young Kim, Toshimitsu Hamasaki

Abstract:

Microarrays have become the effective, broadly used tools in biological and medical research to address a wide range of problems, including classification of disease subtypes and tumors. Many statistical methods are available for analyzing and systematizing these complex data into meaningful information, and one of the main goals in analyzing gene expression data is the detection of samples or genes with similar expression patterns. In this paper, we express and compare the performance of several clustering methods based on data preprocessing including strategies of normalization or noise clearness. We also evaluate each of these clustering methods with validation measures for both simulated data and real gene expression data. Consequently, clustering methods which are common used in microarray data analysis are affected by normalization and degree of noise and clearness for datasets.

Keywords: Gene expression, clustering, data preprocessing.

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357 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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356 ZBTB17 Gene rs10927875 Polymorphism in Slovak Patients with Dilated Cardiomyopathy

Authors: I. Boroňová, J. Bernasovská, J. Kmec, E. Petrejčíková

Abstract:

Dilated cardiomyopathy (DCM) is a severe cardiovascular disorder characterized by progressive systolic dysfunction due to cardiac chamber dilatation and inefficient myocardial contractility often leading to chronic heart failure. Recently, a genome-wide association studies (GWASs) on DCM indicate that the ZBTB17 gene rs10927875 single nucleotide polymorphism is associated with DCM. The aim of the study was to identify the distribution of ZBTB17 gene rs10927875 polymorphism in 50 Slovak patients with DCM and 80 healthy control subjects using the Custom Taqman®SNP Genotyping assays. Risk factors detected at baseline in each group included age, sex, body mass index, smoking status, diabetes and blood pressure. The mean age of patients with DCM was 52.9±6.3 years; the mean age of individuals in control group was 50.3±8.9 years. The distribution of investigated genotypes of rs10927875 polymorphism within ZBTB17 gene in the cohort of Slovak patients with DCM was as follows: CC (38.8%), CT (55.1%), TT (6.1%), in controls: CC (43.8%), CT (51.2%), TT (5.0%). The risk allele T was more common among the patients with dilated cardiomyopathy than in normal controls (33.7% versus 30.6%). The differences in genotype or allele frequencies of ZBTB17 gene rs10927875 polymorphism were not statistically significant (p=0.6908; p=0.6098). The results of this study suggest that ZBTB17 gene rs10927875 polymorphism may be a risk factor for susceptibility to DCM in Slovak patients with DCM. Studies of numerous files and additional functional investigations are needed to fully understand the roles of genetic associations.

Keywords: Dilated cardiomyopathy, SNP polymorphism, ZBTB17 gene.

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