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Search Results: 1 - 10 of 19754 matches for " Alexander Ploner "
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Detecting differential expression in microarray data: comparison of optimal procedures
Elena Perelman, Alexander Ploner, Stefano Calza, Yudi Pawitan
BMC Bioinformatics , 2007, DOI: 10.1186/1471-2105-8-28
Abstract: Using simulated and real datasets, we compare the ODP and fdr2d procedures. We also introduce a new procedure called S2d that combines the ODP test statistic with the extended FDR assessment of fdr2d.For both simulated and real datasets, fdr2d performs better than ODP. As expected, both methods perform better than a standard t-statistic with standard local FDR. The new procedure S2d performs as well as fdr2d on simulated data, but performs better on the real data sets.The ODP can be improved by including the standard error information as in fdr2d. This means that the optimality enjoyed in theory by ODP does not hold for the estimated version that has to be used in practice. The new procedure S2d has a slight advantage over fdr2d, which has to be balanced against a significantly higher computational effort and a less intuititive test statistic.High-throughput methods in molecular biology have challenged existing data analysis methods and stimulated the development of new methods. A key example is the gene expression microarray and its use as a screening tool for detecting genes that are differentially expressed (DE) between different biological states. The need to identify a possibly very small number of regulated genes among the 10,000s of sequences found on modern microarray chips, based on tens to hundreds of biological samples, has led to a plethora of different methods. The emerging consensus in the field [1] suggests that a) despite ongoing research on p-value adjustments [2], false discovery rates (FDR, [3]) are more practical for dealing with the multiplicity problem, and b) classical test statistics requires modification to limit the influence of unrealistically small variance estimates. Nonetheless, many competing methods for detecting DE exist, and even attempts at validation on data sets with known mRNA composition [4] cannot offer definitive guidelines.In this context, the introduction of the so-called optimal discovery procedure (ODP, [5]) constitutes a
Computation of Framed Deformation Functors
Pietro Ploner
Mathematics , 2012,
Abstract: In this work we compute the universal framed deformation functor for a reducible Galois representation $\rho$ given by direct sum of 2-dimensional representations $\rho_i$ coming from p-divisible groups. We impose the local conditions of flatness in the residual characteristic prime $p$ and semistable action in a single auxiliary prime $\ell$. The main application is the case of $\rho_i$ being the representation attached to the $p$-torsion points of an elliptic curve $E_i$ over $\mathbb{Q}$ with good reduction but in $\ell$ and semistable reduction in $\ell$. This article was inspired by a series of works of Schoof about abelian varieties with bad reduction in one prime only. Our local deformation condition correspond to reduction properties of such varieties.
Constructing a Population-Based Research Database from Routine Maternal Screening Records: A Resource for Studying Alloimmunization in Pregnant Women
Brian K. Lee, Alexander Ploner, Zhongxing Zhang, Gunilla Gryfelt, Agneta Wikman, Marie Reilly
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027619
Abstract: Background Although screening for maternal red blood cell antibodies during pregnancy is a standard procedure, the prevalence and clinical consequences of non-anti-D immunization are poorly understood. The objective was to create a national database of maternal antibody screening results that can be linked with population health registers to create a research resource for investigating these issues. Study Design and Methods Each birth in the Swedish Medical Birth Register was uniquely identified and linked to the text stored in routine maternal antibody screening records in the time window from 9 months prior to 2 weeks after the delivery date. These text records were subjected to a computerized search for specific antibodies using regular expressions. To illustrate the research potential of the resulting database, selected antibody prevalence rates are presented as tables and figures, and the complete data (from more than 60 specific antibodies) presented as online moving graphical displays. Results More than one million (1,191,761) births with valid screening information from 1982–2002 constitute the study population. Computerized coverage of screening increased steadily over time and varied by region as electronic records were adopted. To ensure data quality, we restricted analysis to birth records in areas and years with a sustained coverage of at least 80%, representing 920,903 births from 572,626 mothers in 17 of the 24 counties in Sweden. During the study period, non-anti-D and anti-D antibodies occurred in 76.8/10,000 and 14.1/10,000 pregnancies respectively, with marked differences between specific antibodies over time. Conclusion This work demonstrates the feasibility of creating a nationally representative research database from the routine maternal antibody screening records from an extended calendar period. By linkage with population registers of maternal and child health, such data are a valuable resource for addressing important clinical questions, such as the etiological significance of non-anti-D antibodies.
Correlating gene and protein expression data using Correlated Factor Analysis
Chuen Tan, Agus Salim, Alexander Ploner, Janne Lehti?, Kee Chia, Yudi Pawitan
BMC Bioinformatics , 2009, DOI: 10.1186/1471-2105-10-272
Abstract: Our simulation study indicates that the CFA estimates can consistently capture the dominant patterns of correlation between two sets of measurements; in contrast, the gSVD estimates cannot do that. Applied to real cancer data, the list of co-regulated genes and proteins identified by CFA has biologically meaningful interpretation, where both the gene and protein expressions are pointing to the same processes. Among the GO terms for which the genes and proteins are most correlated, we observed blood vessel morphogenesis and development.We demonstrate that CFA is a useful tool for gene-protein data integration and modeling, where the main question is in finding which patterns of gene expression are most correlated with protein expression.Recent advancements in technology have made it possible to jointly analyze a genome-scale gene and protein expression from the same sample. The joint analysis of transcriptomic and proteomic data has potential for shedding new light on complex biological processes. However, the co-analysis of the large datasets continues to present challenges. Some immediate questions are: how does one efficiently characterize the patterns of correlation between the large number of gene and protein expressions? There are many different regulatory pathways within a cell, and many genes and proteins are likely to be co-expressed in a single biological process. How then, can we better identify genes and proteins that are co-regulated, bearing in mind their complex associations? The objective of this paper is to address the above questions.Although the central dogma of molecular biology suggests a strong correlation between gene and protein expressions, past empirical studies suggest only a modest correlation [1]. Empirical correlations could be masked due to various reasons: the analytical variability of the measurement technologies, post-transcriptional mechanisms affecting mRNA stability and protein degradation, as well as timing differences between ge
Correlation test to assess low-level processing of high-density oligonucleotide microarray data
Alexander Ploner, Lance D Miller, Per Hall, Jonas Bergh, Yudi Pawitan
BMC Bioinformatics , 2005, DOI: 10.1186/1471-2105-6-80
Abstract: We analyzed coregulation between genes in order to detect insufficient normalization between arrays, where coregulation is measured in terms of statistical correlation. In a large collection of genes, a random pair of genes should have on average zero correlation, hence allowing a correlation test. For all data sets that we evaluated, and the three most commonly used low-level processing procedures including MAS5, RMA and MBEI, the housekeeping-gene normalization failed the test. For a real clinical data set, RMA and MBEI showed significant correlation for absent genes. We also found that a second round of normalization on the probe set level improved normalization significantly throughout.Previous evaluation of low-level processing in the literature has been limited to artificial spike-in and mixture data sets. In the absence of a known gold-standard, the correlation criterion allows us to assess the appropriateness of low-level processing of a specific data set and the success of normalization for subsets of genes.The spread of microarray technology has made possible the routine and simultaneous measurement of expression profiles for tens of thousands of genes. In the case of photolithographically synthesized high-density oligonucleotide arrays as described in [1], the technology for hybridizing RNA on chips and quantitating fluoresence-intensity data has been highly standardized and automated. The results are then related to the biology of interest, both through exploratory methods (e.g. [2]) and a large and growing number of sophisticated prediction and classification algorithms (e.g. [3]). Yet the very first step on which these procedures rely is still open to discussion: the derivation of a numerical summary value that is both representative of a gene's relative expression level and reasonably free of technical variation, summarily referred to as low-level analysis.The need for a summary function is due to the setup of high-density oligonucleotide arrays, wher
Mapping patterns of complementary and alternative medicine use in cancer: An explorative cross-sectional study of individuals with reported positive "exceptional" experiences
Johanna H?k, Carol Tishelman, Alexander Ploner, Anette Forss, Torkel Falkenberg
BMC Complementary and Alternative Medicine , 2008, DOI: 10.1186/1472-6882-8-48
Abstract: The verbatim transcripts of thirty-eight unstructured interviews were analyzed in two steps. First, manifest content analysis was used to elucidate and map participants' use of CAM, based on the National Center for Complementary Medicine (NCCAM)'s classification system. Second, patterns of CAM use were explored statistically using principal component analysis.The 38 participants reported using a total of 274 specific CAM (median = 4) consisting of 148 different therapeutic modalities. Most reported therapies could be categorized using the NCCAM taxonomy (n = 224). However, a significant number of CAM therapies were not consistent with this categorization (n = 50); consequently, we introduced two additional categories: Spiritual/health literature and Treatment centers. The two factors explaining the largest proportion of variation in CAM usage patterns were a) number of CAM modalities used and b) a category preference for Energy therapies over the categories Alternative Medical Systems and Treatment centers or vice versa.We found considerable heterogeneity in patterns of CAM use. By analyzing users' own descriptions of CAM in relation to the most commonly used predefined professional taxonomy, this study highlights discrepancies between user and professional conceptualizations of CAM not previously addressed. Beyond variations in users' reports of CAM, our findings indicate some patterns in CAM usage related to number of therapies used and preference for different CAM categories.Use of complementary and alternative medicine (CAM) among people with cancer has been found to be common and widespread with estimates ranging between 7–64% [1]. Apart from probable differences in CAM utilization in different settings and countries, this variation is partially related to differences in the instrumentalization of CAM definitions [1]. The wide spectrum of therapies often considered as within the CAM domain is indicated for example in the broad definition by the Cochrane Collabo
Estrogen Receptor Status in Relation to Risk of Contralateral Breast Cancer–A Population-Based Cohort Study
Maria E. C. Sandberg, Per Hall, Mikael Hartman, Anna L. V. Johansson, Sandra Eloranta, Alexander Ploner, Kamila Czene
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046535
Abstract: Background It is unclear whether estrogen receptor (ER)-status of first primary breast cancer is associated with risk of metachronous (non-simultaneous) contralateral breast cancer (CBC), and to what extent endocrine therapy affects this association. Methods We studied the effect of ER-status of the first cancer on the risk of CBC overall, and for different ER-subtypes of CBC, using a large, population-based cohort. The cohort consisted of all women diagnosed with breast cancer in the Stockholm region 1976–2005; 25715 patients, of whom 940 suffered CBC. The relative risk was analyzed mainly using standardized incidence ratios (SIR). Results Women with breast cancer had a doubled risk of CBC compared to the risk of breast cancer in the general female population (SIR: 2.22 [2.08–2.36]), for women with a previous ER-positive cancer: SIR = 2.30 (95% CI:2.11–2.50) and for women with a previous ER-negative cancer: SIR = 2.17 (95% CI:1.82–2.55). The relative risk of ER-positive and ER-negative CBC was very similar for women with ER-positive first cancer (SIR = 2.02 [95%CI: 1.80–2.27] and SIR = 1.89 [95%CI: 1.46–2.41] respectively) while for patients with ER-negative first cancer the relative risk was significantly different (SIR = 1.27 [95% CI:0.94–1.68] for ER-positive CBC and SIR = 4.96 [95%CI:3.67–6.56] for ER-negative CBC). Patients with ER-positive first cancer who received hormone therapy still had a significantly higher risk of CBC than the risk of breast cancer for the general female population (SIR = 1.74 [95% CI:1.47–2.03]). Conclusion The risk of CBC for a breast cancer patient is increased to about two-fold, compared to the risk of breast cancer in the general female population. This excess risk decreases, but does not disappear, with adjuvant endocrine therapy. Patients with ER-positive first cancers have an increased risk for CBC of both ER subtypes, while patients with ER-negative first cancer have a specifically increased risk of ER-negative CBC.
Assessing Perceived Risk and STI Prevention Behavior: A National Population-Based Study with Special Reference to HPV
Amy Leval, Karin Sundstr?m, Alexander Ploner, Lisen Arnheim Dahlstr?m, Catarina Widmark, P?r Sparén
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0020624
Abstract: Introduction To better understand trends in sexually transmitted infection (STI) prevention, specifically low prevalence of condom use with temporary partners, the aim of this study was to examine factors associated with condom use and perceptions of STI risk amongst individuals at risk, with the underlying assumption that STI risk perceptions and STI prevention behaviors are correlated. Methods A national population-based survey on human papillomavirus (HPV) and sexual habits of young adults aged 18–30 was conducted in Sweden in 2007, with 1712 men and 8855 women participating. Regression analyses stratified by gender were performed to measure condom use with temporary partners and STI risk perception. Results Men's condom use was not associated with STI risk perception while women's was. Awareness of and disease severity perceptions were not associated with either condom use or risk perception though education level correlated with condom use. Women's young age at sexual debut was associated with a higher risk of non-condom use later in life (OR 1.95 95% CI: 1.46–2.60). Women with immigrant mothers were less likely to report seldom/never use of condoms with temporary partners compared to women with Swedish-born mothers (OR 0.53 95% CI: 0.37–0.77). Correlates to STI risk perception differ substantially between sexes. Number of reported temporary partners was the only factor associated for both men and women with condom use and STI risk perception. Conclusions Public health interventions advocating condom use with new partners could consider employing tactics besides those which primarily aim to increase knowledge or self-perceived risk if they are to be more effective in STI reduction. Gender-specific prevention strategies could be effective considering the differences found in this study.
Intrinsic molecular signature of breast cancer in a population-based cohort of 412 patients
Stefano Calza, Per Hall, Gert Auer, Judith Bj?hle, Sigrid Klaar, Ulrike Kronenwett, Edison T Liu, Lance Miller, Alexander Ploner, Johanna Smeds, Jonas Bergh, Yudi Pawitan
Breast Cancer Research , 2006, DOI: 10.1186/bcr1517
Abstract: We obtained gene expression and clinical data for 412 breast cancers obtained from population-based cohorts of patients from Stockholm and Uppsala, Sweden. Using the intrinsic set of approximately 500 genes derived in the Norway/Stanford breast cancer data, we validated the existence of five molecular subtypes – basal-like, ERBB2, luminal A/B and normal-like – and characterized these subtypes extensively with the use of conventional clinical variables.We found an overall 77.5% concordance between the centroid prediction of the Swedish cohort by using the Norway/Stanford signature and the k-means clustering performed internally within the Swedish cohort. The highest rate of discordant assignments occurred between the luminal A and luminal B subtypes and between the luminal B and ERBB2 subtypes. The subtypes varied significantly in terms of grade (p < 0.001), p53 mutation (p < 0.001) and genomic instability (p = 0.01), but surprisingly there was little difference in lymph-node metastasis (p = 0.31). Furthermore, current users of hormone-replacement therapy were strikingly over-represented in the normal-like subgroup (p < 0.001). Separate analyses of the patients who received endocrine therapy and those who did not receive any adjuvant therapy supported the previous hypothesis that the basal-like subtype responded to adjuvant treatment, whereas the ERBB2 and luminal B subtypes were poor responders.We found that the intrinsic molecular subtypes of breast cancer are broadly present in a diverse collection of patients from a population-based cohort in Sweden. The intrinsic gene set, originally selected to reveal stable tumor characteristics, was shown to have a strong correlation with progression-related properties such as grade, p53 mutation and genomic instability.A significant reduction of disease burden from breast cancer can be achieved by a better characterization of its potentially fatal forms. Spread of the disease, cell structure, differentiation and growth patte
5-Methoxyleoligin, a Lignan from Edelweiss, Stimulates CYP26B1-Dependent Angiogenesis In Vitro and Induces Arteriogenesis in Infarcted Rat Hearts In Vivo
Barbara Messner, Johann Kern, Dominik Wiedemann, Stefan Schwaiger, Adrian Türkcan, Christian Ploner, Alexander Trockenbacher, Klaus Aumayr, Nikolaos Bonaros, Günther Laufer, Hermann Stuppner, Gerold Untergasser, David Bernhard
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0058342
Abstract: Background Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail. Methods and Results 5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21% 28 days after MI). Conclusion The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI.
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