Towards accurate estimation of the proportion of true null hypotheses in multiple testing

Background

Biomedical researchers are now often faced with situations where it is necessary to test a large number of hypotheses simultaneously, eg, in comparative gene expression studies using high-throughput microarray technology. To properly control false positive errors the FDR (false discovery rate) approach has become widely used in multiple testing. The accurate estimation of FDR requires the proportion of true null hypotheses being accurately estimated. To date many methods for estimating this quantity have been proposed. Typically when a new method is introduced, some simulations are carried out to show the improved accuracy of the new method. However, the simulations are often very limited to covering only a few points in the parameter space.

Results

Here I have carried out extensive in silico experiments to compare some commonly used methods for estimating the proportion of true null hypotheses. The coverage of these simulations is unprecedented thorough over the parameter space compared to typical simulation studies in the literature. Thus this work enables us to draw conclusions globally as to the performance of these different methods. It was found that a very simple method gives the most accurate estimation in a dominantly large area of the parameter space. Given its simplicity and its overall superior accuracy I recommend its use as the first choice for estimating the proportion of true null hypotheses in multiple testing.

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1-4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.

Characterization and parametrization in terms of atomic number of x-ray emission from K-shell filling during ion-surface interactions

When highly charged ions are incident on a surface, part of their potential energy is emitted as characteristic radiation. The energies and yields of these characteristic x rays have been measured for a series of elements at the Tokyo electron-beam ion trap. These data have been used to develop a simple model of the relaxation of the hollow atoms which are formed as the ion approaches the surface, as well as a set of semiempirical scaling laws, which allow for the ready calculation of the K-shell x-ray spectrum which would be produced by an arbitrary slow bare or hydrogenlike ion on a surface. These semiempirical scaling laws can be used to assess the merit of highly charged ion fluorescence x-ray generation in a wide range of applications.

Distribution of the Demmel Condition Number of Wishart Matrices

This paper studies the Demmel condition number of Wishart matrices, a quantity which has numerous applications to wireless communications, such as adaptive switching between beamforming and diversity coding, link adaptation, and spectrum sensing. For complex Wishart matrices, we give an exact analytical expression for the probability density function (p.d.f.) of the Demmel condition number, and also derive simplified expressions for the high tail regime. These results indicate that the condition of complex Wishart matrices is dominantly decided by the difference between the matrix dimension and degree of freedom (DoF), i.e., the probability of drawing a highly ill conditioned matrix decreases considerably when the difference between the matrix dimension and DoF increases. We further investigate real Wishart matrices, and derive new expressions for the p.d.f. of the smallest eigenvalue, when the difference between the matrix dimension and DoF is odd. Based on these results, we succeed to obtain an exact p.d.f. expression for the Demmel condition number, and simplified expressions for the high tail regime.

Possible evidence of asymmetry in SN 2007rt, a type IIn supernova

An optical photometric and spectroscopic analysis of the slowly-evolving type IIn SN 2007rt is presented, covering a duration of 481 days after discovery. Its earliest spectrum, taken approximately 100 days after the explosion epoch, indicates the presence of a dense circumstellar medium, with which the supernova ejecta is interacting. This is supported by the slowly-evolving light curve. A notable feature in the spectrum of SN 2007rt is the presence of a broad He i 5875 line, not usually detected in type IIn supernovae. This may imply that the progenitor star has a high He/H ratio, having shed a significant portion of its hydrogen shell via mass-loss. An intermediate resolution spectrum reveals a narrow Ha P-Cygni profile, the absorption component of which has a width of 128 km s-1. This slow velocity suggests that the progenitor of SN 2007rt recently underwent mass-loss with wind speeds comparable to the lower limits of those detected in luminous blue variables. Asymmetries in the line profiles of H and He at early phases bears some resemblance to double-peaked features observed in a number of Ib/c spectra. These asymmetries may be indicative of an asymmetric or bipolar outflow or alternatively dust formation in the fast expanding ejecta. In addition, the late time spectrum, at over 240 days post-explosion, shows clear evidence for the presence of newly formed dust.

A survey of molecular line emission towards ultracompact HII regions

We have used the JCMT to survey molecular line emission towards 14 ultracompact HII regions (G5.89, G9.62, G10.30, G10.47, G12.21, G13.87, G29.96, G31.41, G34.26, G43.89, G45.12, G45.45, G45.47, and G75.78). For each source, we observed up to ten 1 GHz bands between 200 and 350 GHz, covering lines of more than 30 species including multiple transitions of CO isotopes, CH3OH, CH3CCH, CH3CN and HCOOCH3, and sulphuretted molecules. The number of transitions detected varied by a factor of 20 between sources; which were chosen following observations of high-excitation ammonia (Cesaroni et al. 1994a) and methyl cyanide (Olmi et al. 1993). In half our sample (the line-poor sources), only (CO)-O-17: (CO)-O-18, SO, (CS)-S-34 and CH3OH were detected. In the line-rich sources, we detected over 150 lines, including high excitation lines of CH3CN, HCOOCH3; C2H5CN, CH3OH, and CH3CCH. We have calculated the physical conditions of the molecular gas. To reproduce the emission from the line-rich sources requires both a hot, dense compact core and an ambient cloud consisting of less dense, cooler gas. The hot cores, which are less than 0.1 pc in size; reach densities of at least 10(8) cm(-3) and temperatures of more than 80 K. The line-poor sources can be modelled without a hot core by a 20-30 K, 10(5) cm(-3) cloud. We find no correlation between the size of the HII region and the current physical conditions in the molecular environment. A comparison with chemical models (Millar et al. 1997) confirms that grain surface chemistry is important in hot cores.

Three-dimensional electron number densities in a titanium PLD plasma using interferometry

Interferometry has been used to investigate the spatio-temporal evolution of the electron number density in the initial stages of expansion following 248 nm ablation of a titanium target. Three-dimensional electron number densities are obtained from an interferogram of the plasma plume using the Abel inversion technique.

Surveillance study of a number of synthetic and natural growth promoters in bovine muscle samples using liquid chromatography-tandem mass spectrometry

A simple, new method permitting the simultaneous determination and confirmation of trace residues of 24 different growth promoters and metabolites using liquid chromatography-mass spectrometry was developed and validated. The compounds were extracted from bovine tissue using acetonitrile; sodium sulphate was also added at this stage to aid with purification. The resulting mixture was then evaporated to approximately 1 ml and subsequently centrifuged at high speed and an aliquot injected onto the LC-MS/MS system. The calculated CC values ranged between 0.11 and 0.46 mu g kg-1; calculated CC were in the range 0.19-0.79 mu g kg-1. Accuracy, measurement of uncertainty, repeatability and linearity were also determined for each analyte. The analytical method was applied to a number of bovine tissue samples imported into Ireland from third countries. Levels of progesterone were found in a number of samples at concentrations ranging between 0.28 and 30.30 mu g kg-1. Levels of alpha- and beta-testosterone were also found in a number of samples at concentrations ranging between 0.22 and 8.63 mu g kg-1 and between 0.16 and 2.08 mu g kg-1 respectively.

A technique for mapping three-dimensional number densities of species in laser produced plumes

The potential of a diagnostic technique to provide quantitative three-dimensional (3D) density distributions of species in a low temperature laser-produced plume is shown. An expanded, short pulse, tunable dye laser is used to probe the plume at a set time during the expansion. Simultaneous recording of two-dimensional in-line absorbance maps and orthogonal recording of laser induced fluorescence permits the 3D density mapping by scanning the dye laser frequency. Preliminary data, supported by a simple model, is presented for the case of Ba II ions in a YBCO plume heated by a KrF laser. (C) 1996 American Institute of Physics.

UNUSUAL CHROMOSOME-NUMBER OF GRACILARIA-VERRUCOSA (GRACILARIALES, RHODOPHYTA) IN THE CAPE-GRIS-NEZ AREA, NORTHERN FRANCE

The chromosome number of Gracilaria verrucosa (Hudson) Papenfuss was estimated in numerous individuals from different populations of the Cape Gris-Nez area of Northern France. To optimize estimates and to minimize counting errors, several counts were made on the same nucleus and in different nuclei of the same individual. The haploid chromosome number was estimated in vegetative gametophytic cells and tetrasporocytic cells; the diploid number was estimated from tetrasporophytic vegetative cells. The basic haploid number was n = 17 +/- 1, whereas all other Gracilaria species for which chromosome numbers are available are reported to have n = 24. These include populations of G. verrucosa from Norway and Wales that have previously been shown to be conspecific with the Cape Gris-Nez populations by comparison of plastid DNA data. G. verrucosa is therefore one of the few red algae for which populations with different chromosome numbers are known.

Field-programmable true random number generator

True random number generation is crucial in hardware security applications. Proposed is a voltage-controlled true random number generator that is inherently field-programmable. This facilitates increased entropy as a randomness source because there is more than one configuration state which lends itself to more compact and low-power architectures. It is evaluated through electrical characterisation and statistically through industry-standard randomness tests. To the best of the author's knowledge, it is one of the most efficient designs to date with respect to hardware design metrics.