scholarly journals The Cyclohedron Test for Finding Periodic Genes in Time Course Expression Studies

2007 ◽  
Vol 6 (1) ◽  
Author(s):  
Jason Morton ◽  
Lior Pachter ◽  
Anne Shiu ◽  
Bernd Sturmfels
Keyword(s):  
Measurement Errors ◽  
Multiple Testing ◽  
Time Course ◽  
Algebraic Combinatorics ◽  
Rank Test ◽  
Biological Clocks ◽  
New Approach ◽  
Testing Framework ◽  
Expression Studies ◽  
Molecular Components

The problem of finding periodically expressed genes from time course microarray experiments is at the center of numerous efforts to identify the molecular components of biological clocks. We present a new approach to this problem based on the cyclohedron test, which is a rank test inspired by recent advances in algebraic combinatorics. The test has the advantage of being robust to measurement errors, and can be used to ascertain the significance of top-ranked genes. We apply the test to recently published measurements of gene expression during mouse somitogenesis and find 32 genes that collectively are significant. Among these are previously identified periodic genes involved in the Notch/FGF and Wnt signaling pathways, as well as novel candidate genes that may play a role in regulating the segmentation clock. These results confirm that there are an abundance of exceptionally periodic genes expressed during somitogenesis. The emphasis of this paper is on the statistics and combinatorics that underlie the cyclohedron test and its implementation within a multiple testing framework.

Improved Contrast in Ultra-Low-Field MRI with Time-Dependent Bipolar Prepolarizing Fields: Theory and NMR Demonstrations

2013 ◽  
Vol 20 (3) ◽  
pp. 327-336 ◽  
Author(s):  
Jaakko O. Nieminen ◽  
Jens Voigt ◽  
Stefan Hartwig ◽  
Hans Jürgen Scheer ◽  
Martin Burghoff ◽  
...  
Keyword(s):  
Field Strength ◽  
Time Course ◽  
Signal Strength ◽  
Relaxation Rates ◽  
Resonance Imaging ◽  
New Approach ◽  
Spin Lattice ◽  
Low Field ◽  
Low Field Mri ◽  
Magnetic Resonance Imaging Mri

Abstract The spin-lattice (T1) relaxation rates of materials depend on the strength of the external magnetic field in which the relaxation occurs. This T1 dispersion has been suggested to offer a means to discriminate between healthy and cancerous tissue by performing magnetic resonance imaging (MRI) at low magnetic fields. In prepolarized ultra-low-field (ULF) MRI, spin precession is detected in fields of the order of 10-100 μT. To increase the signal strength, the sample is first magnetized with a relatively strong polarizing field. Typically, the polarizing field is kept constant during the polarization period. However, in ULF MRI, the polarizing-field strength can be easily varied to produce a desired time course. This paper describes how a novel variation of the polarizing-field strength and duration can optimize the contrast between two types of tissue having different T1 relaxation dispersions. In addition, NMR experiments showing that the principle works in practice are presented. The described procedure may become a key component for a promising new approach of MRI at ultra-low fields

scholarly journals 2dFDR: a new approach to confounder adjustment substantially increases detection power in omics association studies

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sangyoon Yi ◽  
Xianyang Zhang ◽  
Lu Yang ◽  
Jinyan Huang ◽  
Yuanhang Liu ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Statistical Power ◽  
Association Studies ◽  
Control Procedure ◽  
Multiple Testing Correction ◽  
New Approach ◽  
False Discovery ◽  
Traditional Procedure ◽  
Extensive Evaluation ◽  
Confounder Adjustment

AbstractOne challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.

scholarly journals Presence and Characterization of Cell-Free Seminal RNA in Healthy Individuals: Implications for Noninvasive Disease Diagnosis and Gene Expression Studies of the Male Reproductive System

2009 ◽  
Vol 55 (11) ◽  
pp. 1967-1976 ◽  
Author(s):  
Shiyun Huang ◽  
Honggang Li ◽  
Xiaofang Ding ◽  
Chengliang Xiong
Keyword(s):  
Reproductive System ◽  
Time Course ◽  
Disease Diagnosis ◽  
Male Reproductive System ◽  
Healthy Individuals ◽  
Microcapillary Electrophoresis ◽  
Expression Studies ◽  
Noninvasive Biomarker ◽  
Gene Expression Studies ◽  
Triton X

Abstract Background: We recently detected cell-free seminal RNA (cfsRNA) and set out to study its concentration, integrity, stability in healthy individuals, and mechanisms for its protection from ribonucleases. Methods: We quantified cfsRNA by reverse-transcription quantitative real-time PCR (RT-qPCR) targeting of the 5′ region of the ACTB (actin, beta) transcript. cfsRNA integrity was analyzed by microcapillary electrophoresis and by amplification of full-length ACTB and DDX4 [DEAD (Asp-Glu-Ala-Asp) box polypeptide 4] transcripts, including measurement of the relative amounts of different regions of ACTB and DDX4 transcripts. Stability of cfsRNA was measured by time-course analysis of different regions of ACTB and DDX4 transcripts. To investigate whether cfsRNA was protected in complexed forms, we processed seminal plasma in 2 ways: filtration through pores of different sizes and Triton X-100 treatment before RNA recovery. Results: cfsRNA concentrations varied from 0.87–3.64 mg/L [mean (SD), 1.75 mg/L (0.92 mg/L)]. Most cfsRNA was present in partially degraded forms, with smaller amounts of middle and 3′ amplicons compared with 5′ amplicons. Although the 3′ region of the DDX4 transcript was degraded completely by 90 min, the 5′ regions of ACTB and DDX4 transcripts were stable up to 24 h. Filtration through 0.22-μm pores reduced ACTB and DDX4 mRNA concentrations by 72% and 61%, respectively. Nearly all seminal ACTB and DDX4 mRNA disappeared after Triton X-100 treatment. Conclusions: Although cfsRNA was partially degraded, it represented diverse transcript species and was abundant, fairly stable, and associated with particles in healthy individuals. cfsRNA may represent a potential noninvasive biomarker of the male reproductive system and of germline epigenetics.

On the Adaptive Control of the False Discovery Rate in Multiple Testing With Independent Statistics

2000 ◽  
Vol 25 (1) ◽  
pp. 60-83 ◽  
Author(s):  
Yoav Benjamini ◽  
Yosef Hochberg
Keyword(s):  
False Discovery Rate ◽  
Multiple Testing ◽  
Meta Analysis ◽  
Test Statistics ◽  
Adaptive Procedure ◽  
New Approach ◽  
False Discovery ◽  
Behavioral Studies ◽  
Simultaneous Testing ◽  
Independent Test

A new approach to problems of multiple significance testing was presented in Benjamini and Hochberg (1995), which calls for controlling the expected ratio of the number of erroneous rejections to the number of rejections–the False Discovery Rate (FDR). The procedure given there was shown to control the FDR for independent test statistics. When some of the hypotheses are in fact false, that procedure is too conservative. We present here an adaptive procedure, where the number of true null hypotheses is estimated first as in Hochberg and Benjamini (1990), and this estimate is used in the procedure of Benjamini and Hochberg (1995). The result is still a simple stepwise procedure, to which we also give a graphical companion. The new procedure is used in several examples drawn from educational and behavioral studies, addressing problems in multi-center studies, subset analysis and meta-analysis. The examples vary in the number of hypotheses tested, and the implication of the new procedure on the conclusions. In a large simulation study of independent test statistics the adaptive procedure is shown to control the FDR and have substantially better power than the previously suggested FDR controlling method, which by itself is more powerful than the traditional family wise error-rate controlling methods. In cases where most of the tested hypotheses are far from being true there is hardly any penalty due to the simultaneous testing of many hypotheses.

scholarly journals Quantification of Fructans in Bioethanol Stillage Based On a Simplified Analytical Method

2021 ◽  
Author(s):  
Andreas Zimmermann ◽  
Martin Kaltschmitt
Keyword(s):  
Analytical Method ◽  
Measurement Errors ◽  
Process Development ◽  
Stationary Phases ◽  
New Approach ◽  
Sample Matrix ◽  
Sample Throughput ◽  
Complex Sample ◽  
Potential Substrate

Abstract Bioethanol stillage, the main by-product of industrial bioethanol production, is a potential substrate for fructans. However, the determination and quantification of fructans in such complex sample matrices is still a challenge for the corresponding analytics to be overcome in order to allow for the identification and utilisation of such unused fructan sources. Especially a possible utilisation or rather the corresponding process development requires appropriate analytics first. Thus, this paper aims to illuminate the basics of fructan quantification in stillage and the corresponding challenges particularly arising with widely used HPLC-RID systems. On this basis, a new approach for fructan quantification is presented based on such HPLC-RID systems allowing for a reliable and especially simple fructan determination in bioethanol stillage for comparably high sample throughput. The developed method performs fructan quantification by determination of fructose and glucose equivalents after a targeted acidic hydrolysis adapted to the respective sample matrix. By means of two different stationary phases, the problem of limited resolution in case of HPLC-RID is overcome and thus measurement errors are reduced. The approach towards the adapted analytical method can be transferred easily to comparable complex sample matrices.

Time course of myogenic and metabolic gene expression in response to acute exercise in human skeletal muscle

2005 ◽  
Vol 98 (5) ◽  
pp. 1745-1752 ◽  
Author(s):  
Yifan Yang ◽  
Andrew Creer ◽  
Bozena Jemiolo ◽  
Scott Trappe
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Acute Exercise ◽  
Vastus Lateralis ◽  
Gene Induction ◽  
Mrna Levels ◽  
Metabolic Gene ◽  
Expression Studies ◽  
Metabolic Gene Expression ◽  
Gene Expression Studies

The aim of this study was to examine the time course activation of select myogenic (MRF4, Myf5, MyoD, myogenin) and metabolic (CD36, CPT1, HKII, and PDK4) genes after an acute bout of resistance (RE) or run (Run) exercise. Six RE subjects [25 ± 4 yr (mean ± SD), 74 ± 14 kg, 1.71 ± 0.11 m] and six Run subjects (25 ± 4 yr, 72 ± 5 kg, 1.81 ± 0.07 m, 63 ± 8 ml·kg−1·min−1) were studied. Eight muscle biopsies were taken from the vastus lateralis (RE) and gastrocnemius (Run) before, immediately after, and 1, 2, 4, 8, 12 and 24 h after exercise. RE increased mRNA of MRF4 (3.7- to 4.5-fold 2–4 h post), MyoD (5.8-fold 8 h post), myogenin (2.6- and 3.5-fold 8–12 h post), HKII (3.6- to 10.5-fold 2–12 h post), and PDK4 (14- to 26-fold 2–8 h post). There were no differences in Myf5, CD36, and CPT1 mRNA levels 0–24 h post-RE. Run increased mRNA of MyoD (5.0- to 8.0-fold), HKII (12- to 16-fold), and PDK4 (32- to 52-fold) at 8–12 h postexercise. There were no differences in MRF4, Myf5, myogenin, CD36 and CPT1 mRNA levels 0–24 h post-Run. These data indicate a myogenic and metabolic gene induction with RE and Run exercise. The timing of the gene induction is variable and generally peaks 4–8 h postexercise with all gene expression not significantly different from the preexercise levels by 24 h postexercise. These data provide basic information for the timing of human muscle biopsy samples for gene-expression studies involving exercise.

A new approach to overcome shortcomings with multiple testing of reproduction data in ecotoxicology

2015 ◽  
Vol 30 (3) ◽  
pp. 871-882 ◽  
Author(s):  
René Lehmann ◽  
Jean Bachmann ◽  
Dirk Maletzki ◽  
Christian Polleichtner ◽  
Hans Toni Ratte ◽  
...  
Keyword(s):  
Multiple Testing ◽  
New Approach

Quantitation of measurement error with Optimal Segments: basis for adaptive time course smoothing

1993 ◽  
Vol 264 (6) ◽  
pp. E902-E911 ◽  
Author(s):  
D. C. Bradley ◽  
G. M. Steil ◽  
R. N. Bergman
Keyword(s):  
Measurement Error ◽  
Measurement Errors ◽  
Time Course ◽  
Smooth Curve ◽  
Random Group ◽  
Smooth Curves ◽  
Original Curve ◽  
Wide Range ◽  
Data Points ◽  
Time Courses

We introduce a novel technique for estimating measurement error in time courses and other continuous curves. This error estimate is used to reconstruct the original (error-free) curve. The measurement error of the data is initially assumed, and the data are smoothed with "Optimal Segments" such that the smooth curve misses the data points by an average amount consistent with the assumed measurement error. Thus the differences between the smooth curve and the data points (the residuals) are tentatively assumed to represent the measurement error. This assumption is checked by testing the residuals for randomness. If the residuals are nonrandom, it is concluded that they do not resemble measurement error, and a new measurement error is assumed. This process continues reiteratively until a satisfactory (i.e., random) group of residuals is obtained. In this case the corresponding smooth curve is taken to represent the original curve. Monte Carlo simulations of selected typical situations demonstrated that this new method ("OOPSEG") estimates measurement error accurately and consistently in 30- and 15-point time courses (r = 0.91 and 0.78, respectively). Moreover, smooth curves calculated by OOPSEG were shown to accurately recreate (predict) original, error-free curves for a wide range of measurement errors (2-20%). We suggest that the ability to calculate measurement error and reconstruct the error-free shape of data curves has wide applicability in data analysis and experimental design.

scholarly journals Cork Taint of Wines: Role of the Filamentous Fungi Isolated from Cork in the Formation of 2,4,6-Trichloroanisole by O Methylation of 2,4,6-Trichlorophenol

2002 ◽  
Vol 68 (12) ◽  
pp. 5860-5869 ◽  
Author(s):  
María Luisa Álvarez-Rodríguez ◽  
Laura López-Ocaña ◽  
José Miguel López-Coronado ◽  
Enrique Rodríguez ◽  
María Jesús Martínez ◽  
...  
Keyword(s):  
Time Course ◽  
Wine Industry ◽  
Ammonium Salts ◽  
Chlorinated Phenols ◽  
High Concentration ◽  
Fungal Strains ◽  
Great Economic Importance ◽  
Expression Studies ◽  
Cork Taint

ABSTRACT Cork taint is a musty or moldy off-odor in wine mainly caused by 2,4,6-trichloroanisole (2,4,6-TCA). We examined the role of 14 fungal strains isolated from cork samples in the production of 2,4,6-TCA by O methylation of 2,4,6-trichlorophenol (2,4,6-TCP). The fungal strains isolated belong to the genera Penicillium (four isolates); Trichoderma (two isolates); and Acremonium, Chrysonilia, Cladosporium, Fusarium, Mortierella, Mucor, Paecilomyces, and Verticillium (one isolate each). Eleven of these strains could produce 2,4,6-TCA when they were grown directly on cork in the presence of 2,4,6-TCP. The highest levels of bioconversion were carried out by the Trichoderma and Fusarium strains. One strain of Trichoderma longibrachiatum could also efficiently produce 2,4,6-TCA in liquid medium. However, no detectable levels of 2,4,6-TCA production by this strain could be detected on cork when putative precursors other than 2,4,6-TCP, including several anisoles, dichlorophenols, trichlorophenols, or other highly chlorinated compounds, were tested. Time course expression studies with liquid cultures showed that the formation of 2,4,6-TCA was not affected by a high concentration of glucose (2% or 111 mM) or by ammonium salts at concentrations up to 60 mM. In T. longibrachiatum the O methylation of 2,4,6-TCP was catalyzed by a mycelium-associated S-adenosyl-l-methionine (SAM)-dependent methyltransferase that was strongly induced by 2,4,6-TCP. The reaction was inhibited by S-adenosyl-l-homocysteine, an inhibitor of SAM-dependent methylation, suggesting that SAM is the natural methyl donor. These findings increase our understanding of the mechanism underlying the origin of 2,4,6-TCA on cork, which is poorly understood despite its great economic importance for the wine industry, and they could also help us improve our knowledge about the biodegradation and detoxification processes associated with chlorinated phenols.

scholarly journals The chronoarchitecture of the cerebral cortex

2005 ◽  
Vol 360 (1456) ◽  
pp. 733-750 ◽  
Author(s):  
Andreas Bartels ◽  
Semir Zeki
Keyword(s):  
Cerebral Cortex ◽  
Time Course ◽  
A Priori ◽  
Spatial Location ◽  
Connectivity Pattern ◽  
Anatomical Connectivity ◽  
Natural Conditions ◽  
Single Experiment ◽  
New Approach ◽  
Spatio Temporal

We review here a new approach to mapping the human cerebral cortex into distinct subdivisions. Unlike cytoarchitecture or traditional functional imaging, it does not rely on specific anatomical markers or functional hypotheses. Instead, we propose that the unique activity time course (ATC) of each cortical subdivision, elicited during natural conditions, acts as a temporal fingerprint that can be used to segregate cortical subdivisions, map their spatial extent, and reveal their functional and potentially anatomical connectivity. We argue that since the modular organisation of the brain and its connectivity evolved and developed in natural conditions, these are optimal for revealing its organisation. We review the concepts, methodology and first results of this approach, relying on data obtained with functional magnetic resonance imaging (fMRI) when volunteers viewed traditional stimuli or a James Bond movie. Independent component analysis (ICA) was used to identify voxels belonging to distinct functional subdivisions, based on their differential spatio-temporal fingerprints. Many more regions could be segregated during natural viewing, demonstrating that the complexity of natural stimuli leads to more differential responses in more functional modules. We demonstrate that, in a single experiment, a multitude of distinct regions can be identified across the whole brain, even within the visual cortex, including areas V1, V4 and V5. This differentiation is based entirely on the differential ATCs of different areas during natural viewing. Distinct areas can therefore be identified without any a priori hypothesis about their function or spatial location. The areas we identified corresponded anatomically across subjects, and their ATCs showed highly area-specific inter-subject correlations. Furthermore, natural conditions led to a significant de-correlation of interregional ATCs compared to rest, indicating an increase in regional specificity during natural conditions. In contrast, the correlation between ATCs of distant regions of known substantial anatomical connections increased and reflected their known anatomical connectivity pattern. We demonstrate this using the example of the language network involving Broca's and Wernicke's area and homologous areas in the two hemispheres. In conclusion, this new approach to brain mapping may not only serve to identify novel functional subdivisions, but to reveal their connectivity as well.

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