39 research outputs found

    An efficient platform for astrocyte differentiation from human induced pluripotent stem cells

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    Summary: Growing evidence implicates the importance of glia, particularly astrocytes, in neurological and psychiatric diseases. Here, we describe a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs), via a neural progenitor cell (NPC) intermediate. We evaluated this protocol across 42 NPC lines (derived from 30 individuals). Transcriptomic analysis demonstrated that hiPSC-astrocytes from four individuals are highly similar to primary human fetal astrocytes and characteristic of a non-reactive state. hiPSC-astrocytes respond to inflammatory stimulants, display phagocytic capacity, and enhance microglial phagocytosis. hiPSC-astrocytes also possess spontaneous calcium transient activity. Our protocol is a reproducible, straightforward (single medium), and rapid (<30 days) method to generate populations of hiPSC-astrocytes that can be used for neuron-astrocyte and microglia-astrocyte co-cultures for the study of neuropsychiatric disorders. : Brennand, Goate, and colleagues report a rapid and robust method for the differentiation of highly pure populations of replicative astrocytes from human induced pluripotent stem cells (hiPSCs) via a neural progenitor cell (NPC) intermediate. hiPSC-astrocytes resemble primary human fetal astrocytes, have a transcriptional signature consistent with a non-reactive state, respond to inflammatory stimulants, and enhance microglial phagocytosis. Keywords: human induced pluripotent stem cell, iPSC, astrocyt

    A Novel Ant based Clustering of Gene Expression Data using MapReduce Framework

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    Genes which exhibit similar patterns are often functionally related. Microarray technology provides a unique tool to examine how a cells gene expression pattern chang es under various conditions. Analyzing and interpreting these gene expression data is a challenging task. Clustering is one of the useful and popular methods to extract useful patterns from these gene expression data. In this paper multi colony ant based clustering approach is proposed. The whole processing procedure is divided into two parts: The first is the construction of Minimum spanning tree from the gene expression data using MapReduce version of ant colony optimization techniques. The second part is clustering, which is done by cutting the costlier edges from the minimum spanning tree, followed by one step k - means clustering procedure. Applied to different file sizes of gene expression data over different number of processors, the proposed approach exhibits good scalability and accuracy

    GEPAS, an experiment-oriented pipeline for the analysis of microarray gene expression data

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    The Gene Expression Profile Analysis Suite, GEPAS, has been running for more than three years. With >76 000 experiments analysed during the last year and a daily average of almost 300 analyses, GEPAS can be considered a well-established and widely used platform for gene expression microarray data analysis. GEPAS is oriented to the analysis of whole series of experiments. Its design and development have been driven by the demands of the biomedical community, probably the most active collective in the field of microarray users. Although clustering methods have obviously been implemented in GEPAS, our interest has focused more on methods for finding genes differentially expressed among distinct classes of experiments or correlated to diverse clinical outcomes, as well as on building predictors. There is also a great interest in CGH-arrays which fostered the development of the corresponding tool in GEPAS: InSilicoCGH. Much effort has been invested in GEPAS for developing and implementing efficient methods for functional annotation of experiments in the proper statistical framework. Thus, the popular FatiGO has expanded to a suite of programs for functional annotation of experiments, including information on transcription factor binding sites, chromosomal location and tissues. The web-based pipeline for microarray gene expression data, GEPAS, is available at

    Next station in microarray data analysis: GEPAS

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    The Gene Expression Profile Analysis Suite (GEPAS) has been running for more than four years. During this time it has evolved to keep pace with the new interests and trends in the still changing world of microarray data analysis. GEPAS has been designed to provide an intuitive although powerful web-based interface that offers diverse analysis options from the early step of preprocessing (normalization of Affymetrix and two-colour microarray experiments and other preprocessing options), to the final step of the functional annotation of the experiment (using Gene Ontology, pathways, PubMed abstracts etc.), and include different possibilities for clustering, gene selection, class prediction and array-comparative genomic hybridization management. GEPAS is extensively used by researchers of many countries and its records indicate an average usage rate of 400 experiments per day. The web-based pipeline for microarray gene expression data, GEPAS, is available at

    Identification of amplified and highly expressed genes in amplicons of the T-cell line huT78 detected by cDNA microarray CGH

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    BACKGROUND: Conventional Comparative Genomic Hybridization (CGH) has been widely used for detecting copy number alterations in cancer and for identifying regions containing candidate tumor responsible genes. Recently, several studies have shown the utility of cDNA microarray CGH for studing gene copy changes in various types of tumors. However, no such studies on T-cell lymphomas have been performed. To date T-cell lymphomas analyzed by the use of chromosome CGH have revealed only slight copy number alterations and not gene amplifications. RESULTS: In the present study, we describe the characterization of three amplicons of the T-cell line huT78 located at 2q34-q37, 8q23-q24 and 20p, where new amplified and overexpressed genes are found. The use of a cDNA microarray containing 7.657 transcripts allowed the identification of certain genes, such as BCLX, PCNA, FKBP1A, IGFBP2 and cMYC, that are amplified, highly expressed, and also contained in the amplicons on 20p and 2q. The expresion of these genes was analyzed in 39 T-cell lymphomas and 3 other T-cell lines. CONCLUSION: By the use of conventional CGH and CGH and expression cDNA microarrays we defined three amplicons in the T-cell line huT78 and identified several novel gene amplifications (BCLX, PCNA, FKBP1A, IGFBP2 and cMYC). We showed that overexpression of the amplified genes could be attributable to gene dosage. We speculate that deregulation of those genes could be important in the development of T-cell lymphomas and/or in the maintenance of T-cell lines

    A Pairwise Feature Selection Method For Gene Data Using Information Gain

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    The current technical practice for doing classification has limitations when using gene expression microarray data. For example, the robustness of top scoring pairs does not extend to some datasets involving small data size and the gene set with best discrimination power may not be involve a combination of genes. Hence, it is necessary to construct a discriminative and stable classifier that generates highly informative gene sets. As we know, not all the features will be active in a biological process. So a good feature selector should be robust with respect to noise and outliers; the challenge is to select the most informative genes. In this study, the top discriminating pair (TDP) approach is motivated by this issue and aims to reveal which features are highly ranked according to their discrimination power. To identify TDPS, each pair of genes is assigned a score based on their relative probability distribution. Our experiment combines the TDP methodology with information gain (ig) to achieve an effective feature set. To illustrate the effectiveness of TDP with ig, we applied this method to two breast cancer datasets (Wang et al., 2005 and Van\u27t Veer et al., 2002). The result from these experimental datasets using the TDP method is competitive with the baseline method using random forests. Information gain combined with the TDP algorithm used in this study provides a new effective method for feature selection for machine learning
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