Search results for: Gene Dosage.

Authors: Mehrdad Hashemi, Mitra Behrooz Aghdam, Reza Mahdian, Ahmad Reza Kamyab

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Cytogenetic analysis still remains the gold standard method for prenatal diagnosis of trisomy 21 (Down syndrome, DS). Nevertheless, the conventional cytogenetic analysis needs live cultured cells and is too time-consuming for clinical application. In contrast, molecular methods such as FISH, QF-PCR, MLPA and quantitative Real-time PCR are rapid assays with results available in 24h. In the present study, we have successfully used a novel MGB TaqMan probe-based real time PCR assay for rapid diagnosis of trisomy 21 status in Down syndrome samples. We have also compared the results of this molecular method with corresponding results obtained by the cytogenetic analysis. Blood samples obtained from DS patients (n=25) and normal controls (n=20) were tested by quantitative Real-time PCR in parallel to standard G-banding analysis. Genomic DNA was extracted from peripheral blood lymphocytes. A high precision TaqMan probe quantitative Real-time PCR assay was developed to determine the gene dosage of DSCAM (target gene on 21q22.2) relative to PMP22 (reference gene on 17p11.2). The DSCAM/PMP22 ratio was calculated according to the formula; ratio=2 -ΔΔCT. The quantitative Real-time PCR was able to distinguish between trisomy 21 samples and normal controls with the gene ratios of 1.49±0.13 and 1.03±0.04 respectively (p value <0.001). These results represent the presence of 3 copies of target gene in DS samples Vs 2 copies in normal controls. The results of quantitative Real-time PCR were in complete agreement with results of cytogenetic analysis. This study confirms previous reports regarding successful implementation of quantitative Real-time PCR for detection of trisomy 21. However, the assay has been improved by using MGB probes and more accurate data analysis. This assay, in particular, when performed in combination with another molecular assay such as QF-PCR or MLPA, can be used as a reliable technique for rapid prenatal diagnosis of trisomy 21.

Keywords: Trisomy 21, Real-time PCR, MGB-TaqMan Probes, Gene Dosage.

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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: Dalanya Asaad Mohammed, Dara Abdul Razaq

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

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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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Authors: Mona Heydari, Ehsan Motamedian, Seyed Abbas Shojaosadati

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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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Authors: Hiba Hasan, Khalid Raza

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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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Authors: R. Mallika, V. Saravanan

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

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

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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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Authors: Farahnaz Amini, Woo Yun Kin, Lazwani Kolandaiveloo

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Availability of different genetic tests after completion of Human Genome Project increases the physicians’ responsibility to keep themselves update on the potential implementation of these genetic tests in their daily practice. However, due to numbers of barriers, still many of physicians are not either aware of these tests or are not willing to offer or refer their patients for genetic tests. This study was conducted an anonymous, cross-sectional, mailed-based survey to develop a primary data of Malaysian physicians’ level of knowledge and perception of gene profiling. Questionnaire had 29 questions. Total scores on selected questions were used to assess the level of knowledge. The highest possible score was 11. Descriptive statistics, one way ANOVA and chi-squared test was used for statistical analysis. Sixty three completed questionnaires were returned by 27 general practitioners (GPs) and 36 medical specialists. Responders’ age ranges from 24 to 55 years old (mean 30.2 ± 6.4). About 40% of the participants rated themselves as having poor level of knowledge in genetics in general whilst 60% believed that they have fair level of knowledge; however, almost half (46%) of the respondents felt that they were not knowledgeable about available genetic tests. A majority (94%) of the responders were not aware of any lab or company which is offering gene profiling services in Malaysia. Only 4% of participants were aware of using gene profiling for detection of dosage of some drugs. Respondents perceived greater utility of gene profiling for breast cancer (38%) compared to the colorectal familial cancer (3%). The score of knowledge ranged from 2 to 8 (mean 4.38 ± 1.67). Non- significant differences between score of knowledge of GPs and specialists were observed, with score of 4.19 and 4.58 respectively. There was no significant association between any demographic factors and level of knowledge. However, those who graduated between years 2001 to 2005 had higher level of knowledge. Overall, 83% of participants showed relatively high level of perception on value of gene profiling to detect patient’s risk of disease. However, low perception was observed for both statements of using gene profiling for general population in order to alter their lifestyle (25%) as well as having the full sequence of a patient genome for the purpose of determining a patient’s best match for treatment (18%). The lack of clinical guidelines, limited provider knowledge and awareness, lack of time and resources to educate patients, lack of evidence-based clinical information and cost of tests were the most barriers of ordering gene profiling mentioned by physicians. In conclusion Malaysian physicians who participate in this study had mediocre level of knowledge and awareness in gene profiling. The low exposure to the genetic questions and problems might be a key predictor of lack of awareness and knowledge on available genetic tests. Educational and training workshop might be useful in helping Malaysian physicians incorporate genetic profiling into practice for eligible patients.

Keywords: Gene Profiling, Knowledge, Malaysia, Physician.

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Authors: Carla Layana Luis Diambra

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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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Authors: M. Anidha, K. Premalatha

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

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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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Authors: T. Holden, G. Tremberger, Jr, E. Cheung, R. Subramaniam, R. Sullivan, N. Gadura, P. Schneider, P. Marchese, A. Flamholz, T. Cheung, D. Lieberman

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A nucleotide sequence can be expressed as a numerical sequence when each nucleotide is assigned its proton number. A resulting gene numerical sequence can be investigated for its fractal dimension in terms of evolution and chemical properties for comparative studies. We have investigated such nucleotide fluctuation in the 16S rRNA gene of archaea thermophiles. The studied archaea thermophiles were archaeoglobus fulgidus, methanothermobacter thermautotrophicus, methanocaldococcus jannaschii, pyrococcus horikoshii, and thermoplasma acidophilum. The studied five archaea-euryarchaeota thermophiles have fractal dimension values ranging from 1.93 to 1.97. Computer simulation shows that random sequences would have an average of about 2 with a standard deviation about 0.015. The fractal dimension was found to correlate (negative correlation) with the thermophile-s optimal growth temperature with R2 value of 0.90 (N =5). The inclusion of two aracheae-crenarchaeota thermophiles reduces the R2 value to 0.66 (N = 7). Further inclusion of two bacterial thermophiles reduces the R2 value to 0.50 (N =9). The fractal dimension is correlated (positive) to the sequence GC content with an R2 value of 0.89 for the five archaea-euryarchaeota thermophiles (and 0.74 for the entire set of N = 9), although computer simulation shows little correlation. The highest correlation (positive) was found to be between the fractal dimension and di-nucleotide Shannon entropy. However Shannon entropy and sequence GC content were observed to correlate with optimal growth temperature having an R2 of 0.8 (negative), and 0.88 (positive), respectively, for the entire set of 9 thermophiles; thus the correlation lacks species specificity. Together with another correlation study of bacterial radiation dosage with RecA repair gene sequence fractal dimension, it is postulated that fractal dimension analysis is a sensitive tool for studying the relationship between genotype and phenotype among closely related sequences.

Keywords: Fractal dimension, archaea thermophiles, Shannon entropy, GC content

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

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

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As the quantity of biological articles rises, so does the number of biological route figures. Each route figure shows gene names and relationships. Manually annotating pathway diagrams is time-consuming. Advanced image understanding models could speed up curation, but they must be more precise. There is rich information in biological pathway figures. The first step to performing image understanding of these figures is to recognize gene names automatically. Classical optical character recognition methods have been employed for gene name recognition, but they are not optimized for literature mining data. This study devised a method to recognize an image bounding box of gene name as a photo using deep Siamese neural network models to outperform the existing methods using ResNet, DenseNet and Inception architectures, the results obtained about 84% accuracy.

Keywords: Biological pathway, gene identification, object detection, Siamese network, ResNet.

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

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

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

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

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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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Authors: Tiancheng Lan

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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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Authors: Gulten Yilmaz, A. Beril Tugrul, Mustafa Demir, Dogan Yasar, Bayram Demir, Bulent Buyuk

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A Positron Emission Tomography (PET) is a radioisotope imaging technique that illustrates the organs and the metabolisms of the human body. This technique is based on the simultaneous detection of 511 keV annihilation photons, annihilated as a result of electrons annihilating positrons that radiate from positron-emitting radioisotopes that enter biological active molecules in the body. This study was conducted on ten patients in an effort to conduct patient-related experimental studies. Dosage monitoring for the bladder, which was the organ that received the highest dose during PET applications, was conducted for 24 hours. Assessment based on measuring urination activities after injecting patients was also a part of this study. The MIRD method was used to conduct dosage calculations for results obtained from experimental studies. Results obtained experimentally and theoretically were assessed comparatively.

Keywords: PET/CT, TLD, MIRD, Dose measurement, Patient doses.

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Authors: Nafisur Rahman, Habibur Rahman, Syed Najmul Hejaz Azmi

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This paper presents a simple and sensitive kinetic spectrophotometric method for the determination of ramipril in commercial dosage forms. The method is based on the reaction of the drug with 1-chloro-2,4-dinitrobenzene (CDNB) in dimethylsulfoxide (DMSO) at 100 ± 1ºC. The reaction is followed spectrophotometrically by measuring the rate of change of the absorbance at 420 nm. Fixed-time (ΔA) and equilibrium methods are adopted for constructing the calibration curves. Both the calibration curves were found to be linear over the concentration ranges 20 - 220 μg/ml. The regression analysis of calibration data yielded the linear equations: Δ A = 6.30 × 10-4 + 1.54 × 10-3 C and A = 3.62 × 10-4 + 6.35 × 10-3 C for fixed time (Δ A) and equilibrium methods, respectively. The limits of detection (LOD) for fixed time and equilibrium methods are 1.47 and 1.05 μg/ml, respectively. The method has been successfully applied to the determination of ramipril in commercial dosage forms. Statistical comparison of the results shows that there is no significant difference between the proposed methods and Abdellatef-s spectrophotometric method.

Keywords: Equilibrium method, Fixed-time (ΔA) method, Ramipril, Spectrophotometry.

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

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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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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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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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Authors: Fatima Rasool, Mahmood Ahmad, Ghulam Murtaza, Haji M. S. Khan, Shujaat A. Khan, Sonia Khiljee, Muhammad Qamar-Uz-Zaman

Abstract:

This study describes the methodology for the development of a validated in-vitro in-vivo correlation (IVIVC) for metoprolol tartrate modified release dosage forms with distinctive release rate characteristics. Modified release dosage forms were formulated by microencapsulation of metoprolol tartrate into different amounts of ethylcellulose by non-solvent addition technique. Then in-vitro and in-vivo studies were conducted to develop and validate level A IVIVC for metoprolol tartrate. The values of regression co-efficient (R2-values) for IVIVC of T2 and T3 formulations were not significantly (p<0.05) different from 1 while the values of R2 for IVIVC of T1 and Mepressor® were significantly (p<0.05) different from 1. Internal prediction errors of IVIVC, calculated from observed Area under Curve (AUC) and predicted AUC, were less than 10%. This study successfully presents a valid level A IVIVC for metoprolol tartrate modified dosage forms.

Keywords: Metoprolol tartrate, Dissolution, Bioavailability, Validated in-vitro in-vivo correlation.

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