Consistent Testing for Recurrent Genomic Aberrations

Genomic aberrations, such as somatic copy number alterations, are frequently observed in tumor tissue. Recurrent aberrations, occurring in the same region across multiple subjects, are of interest because they may highlight genes associated with tumor development or progression. A number of tools have been proposed to assess the statistical significance of recurrent DNA copy number aberrations, but their statistical properties have not been carefully studied. Cyclic shift testing, a permutation procedure using independent random shifts of genomic marker observations on the genome, has been proposed to identify recurrent aberrations, and is potentially useful for a wider variety of purposes, including identifying regions with methylation aberrations or overrepresented in disease association studies. For data following a countable-state Markov model, we prove the asymptotic validity of cyclic shift $p$-values under a fixed sample size regime as the number of observed markers tends to infinity. We illustrate cyclic shift testing for a variety of data types, producing biologically relevant findings for three publicly available datasets.Comment: 35 pages, 7 figure

A statistical framework for testing functional categories in microarray data

Ready access to emerging databases of gene annotation and functional pathways has shifted assessments of differential expression in DNA microarray studies from single genes to groups of genes with shared biological function. This paper takes a critical look at existing methods for assessing the differential expression of a group of genes (functional category), and provides some suggestions for improved performance. We begin by presenting a general framework, in which the set of genes in a functional category is compared to the complementary set of genes on the array. The framework includes tests for overrepresentation of a category within a list of significant genes, and methods that consider continuous measures of differential expression. Existing tests are divided into two classes. Class 1 tests assume gene-specific measures of differential expression are independent, despite overwhelming evidence of positive correlation. Analytic and simulated results are presented that demonstrate Class 1 tests are strongly anti-conservative in practice. Class 2 tests account for gene correlation, typically through array permutation that by construction has proper Type I error control for the induced null. However, both Class 1 and Class 2 tests use a null hypothesis that all genes have the same degree of differential expression. We introduce a more sensible and general (Class 3) null under which the profile of differential expression is the same within the category and complement. Under this broader null, Class 2 tests are shown to be conservative. We propose standard bootstrap methods for testing against the Class 3 null and demonstrate they provide valid Type I error control and more power than array permutation in simulated datasets and real microarray experiments.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS146 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Understanding the Novice Decision-Making Process in Forensic Footwear Examinations: Accuracy and Decision Rules

The reproducibility of experienced-based forensic pattern interpretation is founded on the notion that domain-specific knowledge can be successfully distributed and applied among experts within a group. This assumption persists, even when the examination is complicated by variations in case circumstances, such as impression clarity and totality, as well as media, substrate, collection mechanism and enhancement. While it is further theorized that many of these factors (as well as additional confounding factors) are at play during an examination, the manner and extent to which these sources of variability affect the examination of footwear evidence remain unclear. In order to explore this hypothesis, a data mining technique called dominance-based rough set approach (DRSA) was applied to characterize the novice examiners’ decision-making process, due to its ability to capture useful information from a set of hybrid data with latent preference orders and discover knowledge in the form of decision rules. Through this approach, two objectives were addressed: the identification of factors that affect footwear examination and conclusions within the novice group, and the evaluation of decision rule quality as a function of support, strength, certainty and lift factors. The results of the study showed that in general, novice examiners’ case assessments were found to be outside the acceptable conclusion range more than 50\% of the time, with general tendencies to assign ambiguous conclusions, such as ``limited association of class characteristics and ``lacks sufficient detail, rather than more definitive ones such as ``identification or ``exclusion. When assessments were further explored using DRSA, 23 decision rules were induced (13 \textit{certain} and 10 \textit{possible}). Of the 13 \textit{certain} rules, 75\% of the induced rules were dominated by the examiner’s background, rather than case attributes, and 50\% of the \textit{possible} rules indicated that media type was a prevalent factor in the examiners’ determination of similarity/dissimilarity, as they attempted to interpret media-substrate interaction and reconcile this interpretation with SWGTREAD conclusion guidelines. Only when examiner attributes were excluded from the analysis, forcing the induction of rules based on case attributes only, did case-based features become prominent, but only with very low rule-support. In the second phase of work related to this project, the nature and type of rules induced based on expert assessments will be examined and compared to those generated from this novice set in order to compare and interpret the manner in which domain-specific knowledge dominates induced rules

An Empirical Bayes Approach for Multiple Tissue eQTL Analysis

Expression quantitative trait loci (eQTL) analyses, which identify genetic markers associated with the expression of a gene, are an important tool in the understanding of diseases in human and other populations. While most eQTL studies to date consider the connection between genetic variation and expression in a single tissue, complex, multi-tissue data sets are now being generated by the GTEx initiative. These data sets have the potential to improve the findings of single tissue analyses by borrowing strength across tissues, and the potential to elucidate the genotypic basis of differences between tissues. In this paper we introduce and study a multivariate hierarchical Bayesian model (MT-eQTL) for multi-tissue eQTL analysis. MT-eQTL directly models the vector of correlations between expression and genotype across tissues. It explicitly captures patterns of variation in the presence or absence of eQTLs, as well as the heterogeneity of effect sizes across tissues. Moreover, the model is applicable to complex designs in which the set of donors can (i) vary from tissue to tissue, and (ii) exhibit incomplete overlap between tissues. The MT-eQTL model is marginally consistent, in the sense that the model for a subset of tissues can be obtained from the full model via marginalization. Fitting of the MT-eQTL model is carried out via empirical Bayes, using an approximate EM algorithm. Inferences concerning eQTL detection and the configuration of eQTLs across tissues are derived from adaptive thresholding of local false discovery rates, and maximum a-posteriori estimation, respectively. We investigate the MT-eQTL model through a simulation study, and rigorously establish the FDR control of the local FDR testing procedure under mild assumptions appropriate for dependent data.Comment: accepted by Biostatistic

Dampak Krisis Ekonomi Eropa terhadap Perkembangan Ekspor dan Impor Indonesia

This study aims to determine how the impact of the European economic crisis associated with the development of the European Union economy and Indonesia to export and import from Indonesia, whether there is a European economic crisis impacts on the development of Indonesian export commodities and imports and how big the impact of the European economic crisis on the development of trade Indonesia and the European Union.The data used in this study is a secondary data was obtained from the official website of the World Bank, the Central Bureau of Statistics (BPS), the European Statistics (Eurostat) and the Ministry of Commerce and Ministry of Industry of the Republic of Indonesia. Data taken include gross domestic product of Indonesia and the European Union, the rate of inflation in Indonesia and the European Union, Rupiah exchange rate against the Euro and the value of exports and imports of Indonesia and the European Union both oil and non -oil and gas, the period from 1992 to 2011.The method used in this research is a quantitative method to calculate the exchange rate or the terms of trade and the trade is descriptive. The results showed that gross domestic product, inflation rate, exchange rate, and the value of exports and imports showed stunted growth, contagion from the sovereign debt crisis of the European Union have a direct impact on the trade market turmoil in 2009. Followed by a weakening of commodity export and import Indonesia showed that the economic crisis in Europe has a direct impact on export and import trading activities in Indonesia. On the value of the terms of trade of Indonesia and the European Union in 1992-2012, showed an average exchange rate of the European Union and the Indonesian trade by 100 percent, this means that the state of Indonesia and the European Union is still mutually beneficial to undertake export and import trading activities amid economic turmoil global unstable sometimes.Keywords : European Economic Crisis , Export and Import Indonesi

Consistent testing for recurrent genomic aberrations: Table 1.

We consider the detection and identification of recurrent departures from stationary behaviour in genomic or similarly arranged data containing measurements at an ordered set of variables. Our primary focus is on departures that occur only at a single variable, or within a small window of contiguous variables, but involve more than one sample. This encompasses the identification of aberrant markers in genome-wide measurements of DNA copy number and DNA methylation, as well as meta-analyses of genome-wide association studies. We propose and analyse a cyclic shift-based procedure for testing recurrent departures from stationarity. Our analysis establishes the consistency of cyclic shift $$p$$-values for datasets with a fixed set of samples as the number of observed variables tends to infinity, under the assumption that each sample is an independent realization of a stationary Markov chain. Our results apply to any test statistic satisfying a simple invariance condition

Analisa Peranan Retribusi Izin Gangguan (HINDER ORDONANTIE/HO) sebagai Keuangan Pemerintah Kota Pekanbaru

Penelitian dilaksanakan pada Bulan November 2004 sampai Februari 2005 di KotaPekanbaru dengan tujuan untuk mengetahui besarnya peranan retribusi izingangguan sebagai salah satu sumber pendapatan keuangan daerah di KotaPekanbaru dan memotret usaha serta upaya yang dilakukan pemerintah daerahdalam meningkatkan pendapatan keuangan daerah khususnya sektor retribusidaerah.Metode penelitian yang penulis gunakan adalah metode deskriptif dan kuantitatifsedangkan data yang digunakan adalah data primer dan data sekunder. Data primeryaitu hasil wawancara dengan Kepala Bagian Perkotaan Pemko Pekanbaru danKepala Badan Penanggulangan Dampak Lingkungan Hidup (BAPEDALDA) KotaPekanbaru sedangkan data sekunder yaitu Penerimaan Kota Pekanbaru dari DinasPendapatan Daerah Kota Pekanbaru dan Pekanbaru dalam Angka tahun 2003Badan Pusat Statistik Provinsi Riau.Berdasarkan hasil penelitian diketahui bahwa nilai koefisien regresi untuk X sebesar12,871 artinya apabila terjadi peningkatan penerimaan retribusi izin gangguansebesar 1 unit maka akan meningkatkan PAD Kota Pekanbaru sebesar 12,871rupiah. Kemudian dilihat dari angka elastisitas bahwa jumlah retribusi izingangguan di Kota Pekanbaru adalah sebesar 0,45. Artinya apabila terjadi kenaikanJumlah penerimaan retribusi izin gangguan sebesar 1% maka Jumlah PAD KotaPekanbaru akan meningkat sebesar 0,45%