Efficient p-value estimation in massively parallel testing problems

We present a new method to efficiently estimate very large numbers of p-values using empirically constructed null distributions of a test statistic. The need to evaluate a very large number of p-values is increasingly common with modern genomic data, and when interaction effects are of interest, the number of tests can easily run into billions. When the asymptotic distribution is not easily available, permutations are typically used to obtain p-values but these can be computationally infeasible in large problems. Our method constructs a prediction model to obtain a first approximation to the p-values and uses Bayesian methods to choose a fraction of these to be refined by permutations. We apply and evaluate our method on the study of association between 2-way interactions of genetic markers and colorectal cancer using the data from the first phase of a large, genome-wide case–control study. The results show enormous computational savings as compared to evaluating a full set of permutations, with little decrease in accuracy

A factor model to analyze heterogeneity in gene expression

<p>Abstract</p> <p>Background</p> <p>Microarray technology allows the simultaneous analysis of thousands of genes within a single experiment. Significance analyses of transcriptomic data ignore the gene dependence structure. This leads to correlation among test statistics which affects a strong control of the false discovery proportion. A recent method called FAMT allows capturing the gene dependence into factors in order to improve high-dimensional multiple testing procedures. In the subsequent analyses aiming at a functional characterization of the differentially expressed genes, our study shows how these factors can be used both to identify the components of expression heterogeneity and to give more insight into the underlying biological processes.</p> <p>Results</p> <p>The use of factors to characterize simple patterns of heterogeneity is first demonstrated on illustrative gene expression data sets. An expression data set primarily generated to map QTL for fatness in chickens is then analyzed. Contrarily to the analysis based on the raw data, a relevant functional information about a QTL region is revealed by factor-adjustment of the gene expressions. Additionally, the interpretation of the independent factors regarding known information about both experimental design and genes shows that some factors may have different and complex origins.</p> <p>Conclusions</p> <p>As biological information and technological biases are identified in what was before simply considered as statistical noise, analyzing heterogeneity in gene expression yields a new point of view on transcriptomic data.</p

Complex trait subtypes identification using transcriptome profiling reveals an interaction between two QTL affecting adiposity in chicken

<p>Abstract</p> <p>Background</p> <p>Integrative genomics approaches that combine genotyping and transcriptome profiling in segregating populations have been developed to dissect complex traits. The most common approach is to identify genes whose eQTL colocalize with QTL of interest, providing new functional hypothesis about the causative mutation. Another approach includes defining subtypes for a complex trait using transcriptome profiles and then performing QTL mapping using some of these subtypes. This approach can refine some QTL and reveal new ones.</p> <p>In this paper we introduce Factor Analysis for Multiple Testing (FAMT) to define subtypes more accurately and reveal interaction between QTL affecting the same trait. The data used concern hepatic transcriptome profiles for 45 half sib male chicken of a sire known to be heterozygous for a QTL affecting abdominal fatness (AF) on chromosome 5 distal region around 168 cM.</p> <p>Results</p> <p>Using this methodology which accounts for hidden dependence structure among phenotypes, we identified 688 genes that are significantly correlated to the AF trait and we distinguished 5 subtypes for AF trait, which are not observed with gene lists obtained by classical approaches. After exclusion of one of the two lean bird subtypes, linkage analysis revealed a previously undetected QTL on chromosome 5 around 100 cM. Interestingly, the animals of this subtype presented the same q paternal haplotype at the 168 cM QTL. This result strongly suggests that the two QTL are in interaction. In other words, the "q configuration" at the 168 cM QTL could hide the QTL existence in the proximal region at 100 cM. We further show that the proximal QTL interacts with the previous one detected on the chromosome 5 distal region.</p> <p>Conclusion</p> <p>Our results demonstrate that stratifying genetic population by molecular phenotypes followed by QTL analysis on various subtypes can lead to identification of novel and interacting QTL.</p

Spatially clustered resources increase male aggregation and mating duration in Drosophila melanogaster

In environments where females mate multiply, males should adjust their behaviour and physiology in response to the perceived level of sperm competition to maximize their fitness. Evidence of such plasticity has been found in several laboratory and field studies, but little is known about the cues stimulating these responses in natural populations. One way in which males appear to assess sperm competition risk is through encounter rates with conspecific males. Such encounter rates may be driven by the spatial distribution of resources required by males (i.e. food patches or potential mates), which in turn affects local density. However, explicit links between resource distribution, male encounter rates and shifts in behaviour related to sperm competition have not been demonstrated. We found that when group size of Drosophila melanogaster males was held constant, a small decrease in the distance between patches of food resources had striking effects on male behaviour. Compared to those from dispersed resources, males on clustered resources had a significantly reduced intermale distance (and hence encounter rate) and subsequently a longer noncompetitive copulation duration, previously shown to be a reliable indicator of male perception of sperm competition risk. The aggregation of resources, operating via increased encounter rate, can stimulate shifts in behaviour affecting male sperm competition performance. Given that the spatial distribution of resources is typically variable in natural populations (and often unpredictable), selection is likely to favour the evolution of plasticity in sexual behaviour where resource aggregation increases the probability of sperm competition

Ocena opłacalności inwestycji modernizacyjnej dla Zakładu Wzbogacania Rudy Miedzi KGHM SA

This article presents an assessment of the profitability of replacing a fixed asset currently operated or using better consumables for it. These considerations are illustrated with the example of the Ore Concentration Plant of KGHM SA. In order to properly conduct the valuation using the NPV method, cash flows must be correctly determined and the results obtained must be properly interpreted. This article is divided into four parts: an introduction, a presentation of the analysis method, a calculation example and a summary. The chapter dealing with the analysis methodology presents the general assumptions for conducting analyses aimed at determining the profitability of investing in a new fixed asset. It should be noted here that when the appropriate investment profitability analysis is prepared, the proposed method represents only a part of the entire economic analysis. The third part, namely the calculation example, presents the practical approach to the discussed profitability of replacing a fixed asset with a new one or employing new consumables for the one currently used.Niniejszy artykuł został poświęcony ocenie opłacalności wymiany eksploatowanego środka trwałego bądź zastosowania do obecnie używanego lepszych materiałów eksploatacyjnych. Planowane rozważania zostały przedstawione na przykładzie Zakładu Wzbogacania Rudy KGHM SA. Aby można było właściwie przeprowadzić wycenę przy wykorzystaniu metody NPV, należy poprawnie skonstruować przepływy pieniężne oraz dokonać poprawnej interpretacji otrzymanych wyników. Zaprezentowany artykuł składa się z czterech części: wstępu, prezentacji metodologii przeprowadzenia analizy, przykładu obliczeniowego oraz podsumowania. W rozdziale poświęconym metodologii przeprowadzenia analizy przedstawiono ogólne założenia do przeprowadzenia badań związanych z określeniem opłacalności inwestycji w nowy środek trwały. W miejscu tym należy nadmienić, iż przy konstruowaniu właściwej analizy opłacalności inwestycji, zaprezentowana metoda stanowi jedynie część całego opracowania analizy ekonomicznej. W części trzeciej, będącej przykładem obliczeniowym, przedstawiono praktyczne podejście do omawianej opłacalności wymiany środka trwałego na nowy bądź też zastosowanie do obecnie używanego nowych materiałów eksploatacyjnych

Off take agreements as a source of alternative financing in geological mining projects

W artykule zaprezentowano umowy off take (odkupu) jako źródło alternatywnego finansowania w branży górniczej. Wskazano przyczyny szybkiego rozwoju umów odkupu w świetle dekoniunktury na rynkach surowców mineralnych oraz problemów wynikających z pozyskania finansowania na nowe projekty geologiczno-górnicze. Jednocześnie wskazano typy umów off take oraz przedstawiono przykłady ich zastosowania w przypadku realizacji działalności w formule project finance w branży górniczej.This paper presents the ‘off take contracts’ (repurchase agreements) as an alternative form of financing investments in the mining industry. In the paper the reasons for rapid growth of repurchase agreements have been indicated, both in the light of the downturn at the markets of mineral resources, and in the context of problems obtaining financing for new geological-mining projects. The paper indicates the ‚off take contracts’ types and presents the examples of their use in the project finance formula in the mining industry

Zagrożenie porażeniem prądem elektrycznym strażaków podczas działań ratowniczo-gaśniczych

In the article the electrical shock prevention of firemen during fire and rescue operations was described. Experimental data concerning chosen voltage detectors for emergency responders was presented.Artykuł omawia zagrożenie porażenia prądem elektrycznym strażaków. Podejmowany jest problem spełnienia prawnego obowiązku wyposażenia każdej jednostki ratowniczo-gaśniczej w detektor napięcia, wobec braku szczegółowych wymogów. Prezentowane są wyniki badań dwóch dostępnych na rynku urządzeń oraz pożądane cechy detektora, który gwarantowałby pełne bezpieczeństwo porażeniowe strażakom biorącym udział w działaniach ratowniczo-gaśniczych