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1.

Background  

In many microarray experiments, analysis is severely hindered by a major difficulty: the small number of samples for which expression data has been measured. When one searches for differentially expressed genes, the small number of samples gives rise to an inaccurate estimation of the experimental noise. This, in turn, leads to loss of statistical power.  相似文献   

2.

Background  

Complexity and noise in expression quantitative trait loci (eQTL) studies make it difficult to distinguish potential regulatory relationships among the many interactions. The predominant method of identifying eQTLs finds associations that are significant at a genome-wide level. The vast number of statistical tests carried out on these data make false negatives very likely. Corrections for multiple testing error render genome-wide eQTL techniques unable to detect modest regulatory effects.  相似文献   

3.

Background  

The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T 2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other.  相似文献   

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Background  

cDNA microarrays are a powerful means to screen for biologically relevant gene expression changes, but are often limited by their ability to detect small changes accurately due to "noise" from random and systematic errors. While experimental designs and statistical analysis methods have been proposed to reduce these errors, few studies have tested their accuracy and ability to identify small, but biologically important, changes. Here, we have compared two cDNA microarray experimental design methods with northern blot confirmation to reveal changes in gene expression that could contribute to the early antiproliferative effects of neuregulin on MCF10AT human breast epithelial cells.  相似文献   

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Background

High-density oligonucleotide microarrays provide a powerful tool for assessing differential mRNA expression levels. Characterizing the noise resulting from the enzymatic and hybridization steps, called type I noise, is essential for attributing significance measures to the differential expression scores. We introduce scoring functions for expression ratios, and associated quality measures. Both the PM (Perfect Match) probes and PM-MM differentials (MM is the single MisMatch) are considered as raw intensities. We then characterize the log-ratio noise structure using robust estimates of their intensity dependent variance.

Results

We show the relationships between the obtained ratios and their quality measures. The complementarity of PM and PM-MM methods is emphasized by the probe sets signal to noise measures. Using a large set of replicate experiments, we demonstrate that the noise structure in the log-ratios very closely follows a local log-normal distribution for both the PM and PM-MM cases. Therefore, significance relative to the type I noise can be quantified reliably using the local STD. We discuss the intensity dependence of the STD and show that ratio scores >1.25 are significant in the mid- to high-intensity range.

Conclusions

The ratio noise structure inherent to high-density oligonucleotide arrays can be well described in terms of local log-normal ratio distributions with characteristic intensity dependence. Therefore, robust estimates of the local STD of these distributions provide a simple and powerful way for assessing significance (relative to type I noise) in differential gene expression. This approach will be helpful for improving the reliability of predictions from hybridization experiments in general.  相似文献   

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Background

Information transmission and processing in the nervous system has stochastic nature. Multiple factors contribute to neuronal trial-to-trial variability. Noise and variations are introduced by the processes at the molecular and cellular level (thermal noise, channel current noise, membrane potential variations, biochemical and diffusion noise at synapses etc). The stochastic processes are affected by different physical (temperature, electromagnetic field) and chemical (drugs) factors. The aim of this study was experimental investigation of hypotheses that increase in the noise level in the brain affects processing of visual information. Change in the noise level was introduced by an external factor producing excess noise in the brain.

Methods

An exposure to 450 MHz low-frequency modulated microwave radiation was applied to generate excess noise. Such exposure has been shown to increase diffusion, alter membrane resting potential, gating variables and intracellular Calcium efflux. Nine healthy volunteers passed the experimental protocol at the lower (without microwave) and the higher (with microwave) noise level. Two photos (visual stimuli) of unfamiliar, young male faces were presented to the subjects, one picture after another. The task was to identify later the photos from a group of six photos and to decide in which order they were presented. Each subject had a total of eight sessions at the lower and eight at the higher noise level. Each session consisted of 50 trials; altogether a subject made 800 trials, 400 at the lower and 400 at the higher noise level. Student t-test was applied for statistical evaluation of the results.

Results

Correct recognition of both stimuli in the right order was better at the lower noise level. All the subjects under investigation showed higher numbers of right answers in trials at the lower noise level. Average number of correct answers from n=400 trials with microwave exposure was 50.3, without exposure 54.4, difference 7.5%, p<0.002. No difference between results at the lower and the higher noise level was revealed in the case of only partly correct or incorrect answers.

Conclusions

Our experimental results showed that introduced excess noise reduced significantly ability of the nervous system in correct processing of visual information.
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11.

Background  

Cluster analysis is an important technique for the exploratory analysis of biological data. Such data is often high-dimensional, inherently noisy and contains outliers. This makes clustering challenging. Mixtures are versatile and powerful statistical models which perform robustly for clustering in the presence of noise and have been successfully applied in a wide range of applications.  相似文献   

12.
Ptitsyn A 《PloS one》2008,3(3):e1842

Background

Microarrays are widely used for estimation of expression of thousands of genes in a biological sample. The resolution ability of this method is limited by the background noise. Low expressed genes are detected with insufficient reliability and expression of many genes is never detected at all.

Methodology/Principal Findings

We have applied the principles of stochastic resonance to detect expression of genes from microarray signals below the background noise level. We report the periodic pattern detected in genes called “Absent” by traditional analysis. The pattern is consistent with expression of the conventionally detected genes and specific to the tissue of origin. This effect is corroborated by the analysis of oscillating gene expression in mouse (M.musculus) and yeast (S. cerevisae).

Conclusion/Significance

Most genes usually considered silent are in fact expressed at a very low level. Stochastic resonance can be applied to detect changes in expression pattern of low-expressed genes as well as for the validation of the probe performance in microarrays.  相似文献   

13.

Background

When genomics researchers design a high-throughput study to test for differential expression, some biological systems and research questions provide opportunities to use paired samples from subjects, and researchers can plan for a certain proportion of subjects to have paired samples. We consider the effect of this paired samples proportion on the statistical power of the study, using characteristics of both count (RNA-Seq) and continuous (microarray) expression data from a colorectal cancer study.

Results

We demonstrate that a higher proportion of subjects with paired samples yields higher statistical power, for various total numbers of samples, and for various strengths of subject-level confounding factors. In the design scenarios considered, the statistical power in a fully-paired design is substantially (and in many cases several times) greater than in an unpaired design.

Conclusions

For the many biological systems and research questions where paired samples are feasible and relevant, substantial statistical power gains can be achieved at the study design stage when genomics researchers plan on using paired samples from the largest possible proportion of subjects. Any cost savings in a study design with unpaired samples are likely accompanied by underpowered and possibly biased results.
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Objective

To evaluate noise reduction and image quality improvement in low-radiation dose chest CT images in children using adaptive statistical iterative reconstruction (ASIR) and a full model-based iterative reconstruction (MBIR) algorithm.

Methods

Forty-five children (age ranging from 28 days to 6 years, median of 1.8 years) who received low-dose chest CT scans were included. Age-dependent noise index (NI) was used for acquisition. Images were retrospectively reconstructed using three methods: MBIR, 60% of ASIR and 40% of conventional filtered back-projection (FBP), and FBP. The subjective quality of the images was independently evaluated by two radiologists. Objective noises in the left ventricle (LV), muscle, fat, descending aorta and lung field at the layer with the largest cross-section area of LV were measured, with the region of interest about one fourth to half of the area of descending aorta. Optimized signal-to-noise ratio (SNR) was calculated.

Result

In terms of subjective quality, MBIR images were significantly better than ASIR and FBP in image noise and visibility of tiny structures, but blurred edges were observed. In terms of objective noise, MBIR and ASIR reconstruction decreased the image noise by 55.2% and 31.8%, respectively, for LV compared with FBP. Similarly, MBIR and ASIR reconstruction increased the SNR by 124.0% and 46.2%, respectively, compared with FBP.

Conclusion

Compared with FBP and ASIR, overall image quality and noise reduction were significantly improved by MBIR. MBIR image could reconstruct eligible chest CT images in children with lower radiation dose.  相似文献   

19.

Background

As studies of molecular biology system attempt to achieve a comprehensive understanding of a particular system, Type 1 errors may be a significant problem. However, few investigators are inclined to accept the increase in Type 2 errors (false positives) that may result when less stringent statistical cut-off values are used. To address this dilemma, we developed an analysis strategy that used a stringent statistical analysis to create a list of differentially expressed genes that served as "bait" to "fish out" other genes with similar patterns of expression.

Results

Comparing two strains of mice (NOD and C57Bl/6), we identified 93 genes with statistically significant differences in their patterns of expression. Hierarchical clustering identified an additional 39 genes with similar patterns of expression differences between the two strains. Pathway analysis was then employed: 1) identify the central genes and define biological processes that may be regulated by the genes identified, and 2) identify genes on the lists that could not be connected to each other in pathways (potential false positives). For networks created by both gene lists, the most connected (central) genes were interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). These two cytokines are relevant to the biological differences between the two strains of mice. Furthermore, the network created by the list of 39 genes also suggested other biological differences between the strains.

Conclusion

Taken together, these data demonstrate how stringent statistical analysis, combined with hierarchical clustering and pathway analysis may offer deeper insight into the biological processes reflected from a set of expression array data. This approach allows us to 'recapture" false negative genes that otherwise would have been missed by the statistical analysis.
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20.

Objective

Over 5% of the world's population suffers from disabling hearing loss. Stem cell homing in target tissue is an important aspect of cell‐based therapy, which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can induce the Akt activation, and phosphorylation status of AKT (p‐AKT) upregulates CXC chemokine receptor‐4 (CXCR4) expression. We examined whether DFO can enhance mesenchymal stem cells (MSCs) homing in noise‐induced damaged cochlea by PI3K/AKT dependent mechanism.

Materials and Methods

Mesenchymal stem cells were treated with DFO. AKT, p‐AKT protein and hypoxia inducible factor 1‐ α (HIF‐1α) and CXCR4 gene and protein expression was evaluated by RT‐ PCR and Western blot analysis. For in vivo assay, rats were assigned to control, sham, noise exposure groups without any treatment or receiving normal, DFO‐treated and DFO +LY294002 (The PI3K inhibitor)‐treated MSCs. Following chronic exposure to 115 dB white noise, MSCs were injected into the rat cochlea through the round window. Number of Hoechst‐ labelled cells was determined in the endolymph after 24 hours.

Results

Deferoxamine increased P‐AKT, HIF‐1α and CXCR4 expression in MSCs compared to non‐treated cells. DFO pre‐conditioning significantly increased the homing ability of MSCs into injured ear compared to normal MSCs. These effects of DFO were blocked by LY294002.

Conclusions

Pre‐conditioning of MSCs by DFO before transplantation can improve stem cell homing in the damaged cochlea through PI3K/AKT pathway activation.
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