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Trans-10, cis 12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPAR gamma Signaling and Inflammation in Murine Mammary Tissue

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JOURNAL OF LIPIDS 2013年第unknown期2013卷 890343-890343页

作者： Kadegowda, Anil K. G. Khan, M. Jawad Piperova, Liliana S. Teter, Beverly B. Rodriguez-Zas, Sandra L. Erdman, Richard A. Loor, Juan J. Univ Maryland Dept Anim & Avian Sci College Pk MD 20742 USA Univ Illinois Div Nutr Sci Dept Anim Sci Mammalian NutriPhysioGenom Urbana IL 61801 USA

Exogenous trans-10, cis-12-CLA (CLA) reduces lipid synthesis in murine adipose and mammary (MG) tissues. However, genomewide alterations in MG and liver (LIV) associated with dietary CLA during lactation remain unknown. We fed mice (n = 5/diet) control or control + trans-10, cis-12-CLA (37 mg/day) between d 6 and d 10 postpartum. The 35,302 annotated murine exonic evidence-based oligo (MEEBO) microarray and quantitative RT-PCR were used for transcript profiling. Milk fat concentration was 44% lower on d 10 versus d 6 due to CLA. The CLA diet resulted in differential expression of 1,496 genes. Bioinformatics analyses underscored that a major effect of CLA on MG encompassed alterations in cellular signaling pathways and phospholipid species biosynthesis. Dietary CLA induced genes related to ER stress (Xbp1), apoptosis (Bcl2), and inflammation (Orm1, Saa2, and Cp). It also induced marked inhibition of PPAR.. signaling, including down regulation of Pparg and Srebf1 and several lipogenic target genes (Scd, Fasn, and Gpam). In LIV, CLA induced hepatic steatosis probably through perturbations in the mitochondrial functions and induction of ER stress. Overall, results from this study underscored the role of PPAR.. signaling on mammary lipogenic target regulation. The proinflammatory effect due to CLA could be related to inhibition of PPAR gamma signaling.

关键词： LINOLEIC acid MENTAL depression CELLULAR signal transduction MICE as laboratory animals microarray technology GENE expression GENE targeting

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Embracing noise to improve cross-batch prediction accuracy

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BMC SYSTEMS BIOLOGY 2012年第2-Sup期6卷 S3-S3页

作者： Koh, Chuan Hock Wong, Limsoon NUS Grad Sch Integrat Sci & Engn Singapore 117597 Singapore Natl Univ Singapore Sch Comp Singapore 117417 Singapore

One important application of microarray in clinical settings is for constructing a diagnosis or prognosis model. Batch effects are a well-known obstacle in this type of applications. Recently, a prominent study was published on how batch effects removal techniques could potentially improve microarray prediction performance. However, the results were not very encouraging, as prediction performance did not always improve. In fact, in up to 20% of the cases, prediction accuracy was reduced. Furthermore, it was stated in the paper that the techniques studied require sufficiently large sample sizes in both batches (train and test) to be effective, which is not a realistic situation especially in clinical settings. In this paper, we propose a different approach, which is able to overcome limitations faced by conventional methods. Our approach uses ranking value of microarray data and a bagging ensemble classifier with sequential hypothesis testing to dynamically determine the number of classifiers required in the ensemble. Using similar datasets to those in the original study, we showed that in only one case (<2%) is our performance reduced (by more than -0.05 AUC) and, in >60% of cases, it is improved (by more than 0.05 AUC). In addition, our approach works even on much smaller training data sets and is independent of the sample size of the test data, making it feasible to be applied on clinical studies.

关键词： microarray technology SAMPLE size (Statistics) SAMPLING (Statistics) HYPOTHESIS LOGIC

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ENTROPY-BASED CLUSTER VALIDATION AND ESTIMATION OF THE NUMBER OF CLUSTERS IN GENE EXPRESSION DATA

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JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY 2012年第5期10卷 1250011-1250011页

作者： Novoselova, Natalia Tom, Igor United Inst Informat Problems Dept Bioinformat Minsk 220012 BELARUS

Many external and internal validity measures have been proposed in order to estimate the number of clusters in gene expression data but as a rule they do not consider the analysis of the stability of the groupings produced by a clustering algorithm. Based on the approach assessing the predictive power or stability of a partitioning, we propose the new measure of cluster validation and the selection procedure to determine the suitable number of clusters. The validity measure is based on the estimation of the "clearness" of the consensus matrix, which is the result of a resampling clustering scheme or consensus clustering. According to the proposed selection procedure the stable clustering result is determined with the reference to the validity measure for the null hypothesis encoding for the absence of clusters. The final number of clusters is selected by analyzing the distance between the validity plots for initial and permutated data sets. We applied the selection procedure to estimate the clustering results on several datasets. As a result the proposed procedure produced an accurate and robust estimate of the number of clusters, which are in agreement with the biological knowledge and gold standards of cluster quality.

关键词： microarray technology gene expression data entropy clustering

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Advances in BAC-Based Physical Mapping and Map Integration Strategies in Plants

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JOURNAL OF BIOMEDICINE AND BIOtechnology 2012年第unknown期2012卷 184854-184854页

作者： Ariyadasa, Ruvini Stein, Nils Leibniz Inst Plant Genet & Crop Plant Res IPK D-06466 Gatersleben Germany

In the advent of next-generation sequencing (NGS) platforms, map-based sequencing strategy has been recently suppressed being too expensive and laborious. The detailed studies on NGS drafts alone indicated these assemblies remain far from gold standard reference quality, especially when applied on complex genomes. In this context the conventional BAC-based physical mapping has been identified as an important intermediate layer in current hybrid sequencing strategy. BAC-based physical map construction and its integration with high-density genetic maps have benefited from NGS and high-throughput array platforms. This paper addresses the current advancements of BAC-based physical mapping and high-throughput map integration strategies to obtain densely anchored well-ordered physical maps. The resulted maps are of immediate utility while providing a template to harness the maximum benefits of the current NGS platforms.

关键词： GENE mapping CLASSIFICATION of plants CHROMOSOMES COMPUTER simulation GENES GENOMES microarray technology SEQUENCE analysis

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TP53 Mutation, Epithelial-Mesenchymal Transition, and Stemlike Features in Breast Cancer Subtypes

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JOURNAL OF BIOMEDICINE AND BIOtechnology 2012年第unknown期000卷 254085-254085页

作者： Coradini, Danila Fornili, Marco Ambrogi, Federico Boracchi, Patrizia Biganzoli, Elia Univ Milan Dept Clin & Community Hlth Sci I-20133 Milan Italy

Altered p53 protein is prevalently associated with the pathologic class of triple-negative breast cancers and loss of p53 function has recently been linked to the induction of an epithelial-mesenchymal transition (EMT) and acquisition of stemness properties. We explored the association between TP53 mutational status and expression of some genes involved in the canonical TGF-beta signaling pathway (the most potent EMT inducer) and in two early EMT associated events: loss of cell polarity and acquisition of stemness-associated features. We used a publicly accessible microarray dataset consisting of 251 p53-sequenced primary breast cancers. Statistical analysis indicated that mutant p53 tumors (especially those harboring a severe mutation) were consistent with the aggressive class of triple-negative cancers and that, differently from cell cultures, surgical tumors underexpressed some TGF-beta related transcription factors known as involved in EMT (ID1, ID4, SMAD3, SMAD4, SMAD5, ZEB1). These unexpected findings suggest an interesting relationship between p53 mutation, mammary cell dedifferentiation, and the concomitant acquisition of stemlike properties (as indicated by the overexpression of PROM1 and NOTCH1 genes), which improve tumor cells aggressiveness as indicated by the overexpression of genes associated with cell proliferation (CDK4, CDK6, MKI67) and migration (CXCR4, MMP1).

关键词： STEM cells PHYSIOLOGY BREAST tumors CLUSTER analysis (Statistics) FACTOR analysis GENE expression GENETICS MUTATION (Biology) ONCOGENES PROTEINS PHENOTYPE DATA analysis software microarray technology DESCRIPTIVE statistics NEOPLASTIC cell transformation

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ArraySearch: A Web-Based Genomic Search Engine

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COMPARATIVE AND FUNCTIONAL GENOMICS 2012年第1期000卷 1-10页

作者： Wilson, Tyler J. Ge, Steven X. S Dakota State Univ Dept Math & Stat Brookings SD 57007 USA

Recent advances in microarray technologies have resulted in a flood of genomics data. This large body of accumulated data could be used as a knowledge base to help researchers interpret new experimental data. ArraySearch finds statistical correlations between newly observed gene expression profiles and the huge source of well-characterized expression signatures deposited in the public domain. A search query of a list of genes will return experiments on which the genes are significantly up- or downregulated collectively. Searches can also be conducted using gene expression signatures from new experiments. This resource will empower biological researchers with a statistical method to explore expression data from their own research by comparing it with expression signatures from a large public archive.

关键词： WEB search engines GENE expression CORRELATION (Statistics) microarray technology GENOMICS DATA analysis

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Low Concentration of S100A8/9 Promotes Angiogenesis-Related Activity of Vascular Endothelial Cells: Bridges among Inflammation, Angiogenesis, and Tumorigenesis?

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MEDIATORS OF INFLAMMATION 2012年第1期2012卷 1-8页

作者： Li, Changyou Li, Siyuan Jia, Changkai Yang, Lingling Song, Zicheng Wang, Yiqiang Shandong Acad Med Sci Shandong Eye Inst Shandong Prov Key Lab Ophthalmol Qingdao 266071 Peoples R China

Previous studies showed that several members of the S100A family are involved in neovascularization and tumor development. This study checked whether low concentrations of S100A8 or S100A9 has any effect on the behaviour of vascular endothelial cells. A human umbilical vascular endothelial cell (HUVEC) line was used to measure vascular endothelial cell bioactivity related to angiogenesis, such as cell proliferation, migration, and vessel formation. In the low concentration range up to 10 mu g/mL, either each alone or in combination, S100A8 and S100A9 proteins promoted proliferation of HUVEC cells in a dose-dependent manner. The presence of both proteins in culture showed additive effects over each single protein. Both proteins enhanced HUVEC cells to migrate across the transwell membrane and to form tube-like structures on the Matrigel surface. When mixed in Matrigel and injected subcutaneously in Balb/c mice, both proteins increased vessel development in the gel plugs. microarray assay of HUVEC cells treated with 10 mu g/mL S100A8 revealed that ribosome pathway, pathogenic Escherichia coli infection pathway, apoptosis, and stress response genes were modulated by S100A8 treatment. We propose that S100A8 and S100A9 proteins from either infiltrating inflammatory cells or tumor cells play an important role in the interplay among inflammation, angiogenesis, and tumorigenesis.

关键词： NEOVASCULARIZATION ENDOTHELIAL cells INFLAMMATION NEOPLASTIC cell transformation microarray technology PROTEINS

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A Systems Approach and Skeletal Myogenesis

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COMPARATIVE AND FUNCTIONAL GENOMICS 2012年第1期2012卷 1-7页

作者： Ito, Yoshiaki Kayama, Tomohiro Asahara, Hiroshi Tokyo Med & Dent Univ Grad Sch Med & Dent Sci Dept Syst BioMed Tokyo 1138510 Japan Natl Res Inst Child Hlth & Dev Dept Syst BioMed Tokyo 1578535 Japan Jikei Univ Sch Med Dept Orthoped Surg Tokyo 1058461 Japan

Skeletal myogenesis depends on the strict regulation of the expression of various gene subsets. Therefore, the understanding of genome wide gene regulation is imperative for elucidation of skeletal myogenesis. In recent years, systems approach has contributed to the understanding of various biological processes. Our group recently revealed the critical genome network of skeletal myogenesis by using a novel systems approach combined with whole-mount in situ hybridization ( WISH) database, high-throughput screening, and microarray analysis. In this paper, we introduce our systems approach for understanding the myogenesis regulatory network and describe the advantages of systems approach.

关键词： MYOGENESIS GENETIC regulation GENE regulatory networks IN situ hybridization GENE expression microarray technology

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Tailored microarray Platform for the Detection of Marine Toxins

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ENVIRONMENTAL SCIENCE & technology 2011年第20期45卷 8965-8973页

作者： Bovee, T. F. H. Hendriksen, P. J. M. Portier, L. Wang, S. Elliott, C. T. van Egmond, H. P. Nielen, M. W. F. Peijnenburg, A. A. C. M. Hoogenboom, L. A. P. Wageningen UR RIKILT Inst Food Safety Business Unit Bioanal & Toxicol NL-6708 WB Wageningen Netherlands Univ Wageningen & Res Ctr Div Toxicol NL-6703 HE Wageningen Netherlands Queens Univ Sch Biol Sci Inst Agri Food & Land Use Belfast BT9 5AY Antrim North Ireland

Currently, there are no fast in vitro broad spectrum screening bioassays for the detection of marine toxins. The aim of this study was to develop such an assay. In gene expression profiling experiments 17 marker genes were provisionally selected that were differentially regulated in human intestinal Caco-2 cells upon exposure to the lipophilic shellfish poisons azaspiracid-1 (AZA1) or dinophysis toxin-1 (DTX1). These 17 genes together with two control genes were the basis for the design of a tailored microarray platform for the detection of these marine toxins and potentially others. Five out of the 17 selected marker genes on this dedicated DNA microarray gave dear signals, whereby the resulting fingerprints could be used to detect these toxins. CEACAM1, DDIT4, and TUBB3 were up-regulated by both AZA1 and DTX1, TRIB3 was up-regulated by AZA1 only, and OSR2 by DTX1 only. Analysis by singleplex qRT-PCR revealed the up- and down-regulation of the selected RGS16 and NPPB marker genes by DTX1, that were not envisioned by the new developed dedicated array. The qRT-PCR targeting the DDIT4, RSG16 and NPPB genes thus already resulted in a specific pattern for AZA1 and DTX1 indicating that for this specific case qRT-PCR might a be more suitable approach than a dedicated array.

关键词： Marine toxins In vitro toxicity testing Biological assay Gene expression profiling Genetic markers Cytochemical bioassay microarray technology Scientific development

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microarray and Proteomic Analysis of Breast Cancer Cell and Osteoblast Co-cultures ROLE OF OSTEOBLAST MATRIX METALLOPROTEINASE (MMP)-13 IN BONE METASTASIS

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JOURNAL OF BIOLOGICAL CHEMISTRY 2011年第39期286卷 34271-34285页

作者： Morrison, Charlotte Mancini, Stephanie Cipollone, Jane Kappelhoff, Reinhild Roskelley, Calvin Overall, Christopher Univ British Columbia Ctr Blood Res Vancouver BC V6T 1Z3 Canada Univ British Columbia Dept Oral Biol & Med Sci Vancouver BC V6T 1Z3 Canada Univ British Columbia Dept Biochem & Mol Biol Vancouver BC V6T 1Z3 Canada Univ British Columbia Dept Cellular & Physiol Sci Vancouver BC V6T 1Z3 Canada

Dynamic reciprocal interactions between a tumor and its microenvironment impact both the establishment and progression of metastases. These interactions are mediated, in part, through proteolytic sculpting of the microenvironment, particularly by the matrix metalloproteinases, with both tumors and stroma contributing to the proteolytic milieu. Because bone is one of the predominant sites of breast cancer metastases, we used a co-culture system in which a subpopulation of the highly invasive human breast cancer cell line MDA-MB-231, with increased propensity to metastasize to bone, was overlaid onto a monolayer of differentiated osteoblast MC3T3-E1 cells in a mineralized osteoid matrix. CLIP-CHIP (R) microarrays identified changes in the complete protease and inhibitor expression profile of the breast cancer and osteoblast cells that were induced upon co-culture. A large increase in osteoblast-derived MMP-13 mRNA and protein was observed. Affymetrix analysis and validation showed induction of MMP-13 was initiated by soluble factors produced by the breast tumor cells, including oncostatin M and the acute response apolipoprotein SAA3. Significant changes in the osteoblast secretomes upon addition of MMP-13 were identified by degradomics from which six novel MMP-13 substrates with the potential to functionally impact breast cancer metastasis to bone were identified and validated. These included inactivation of the chemokines CCL2 and CCL7, activation of platelet-derived growth factor-C, and cleavage of SAA3, osteoprotegerin, CutA, and antithrombin III. Hence, the influence of breast cancer metastases on the bone microenvironment that is executed via the induction of osteoblast MMP-13 with the potential to enhance metastases growth by generating a microenvironmental amplifying feedback loop is revealed.

关键词： Breast cancer -- Genetic aspects microarray technology Metastasis Chemokines Cancer cells

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