Dataset Information

Reporting FDR analogous confidence intervals for the log fold change of differentially expressed genes.

ABSTRACT:

Background

Gene expression experiments are common in molecular biology, for example in order to identify genes which play a certain role in a specified biological framework. For that purpose expression levels of several thousand genes are measured simultaneously using DNA microarrays. Comparing two distinct groups of tissue samples to detect those genes which are differentially expressed one statistical test per gene is performed, and resulting p-values are adjusted to control the false discovery rate. In addition, the expression change of each gene is quantified by some effect measure, typically the log fold change. In certain cases, however, a gene with a significant p-value can have a rather small fold change while in other cases a non-significant gene can have a rather large fold change. The biological relevance of the change of gene expression can be more intuitively judged by a fold change then merely by a p-value. Therefore, confidence intervals for the log fold change which accompany the adjusted p-values are desirable.

Results

In a new approach, we employ an existing algorithm for adjusting confidence intervals in the case of high-dimensional data and apply it to a widely used linear model for microarray data. Furthermore, we adopt a concept of different relevance categories for effects in clinical trials to assess biological relevance of genes in microarray experiments. In a brief simulation study the properties of the adjusting algorithm are maintained when being combined with the linear model for microarray data. In two cancer data sets the adjusted confidence intervals can indicate significance of large fold changes and distinguish them from other large but non-significant fold changes. Adjusting of confidence intervals also corrects the assessment of biological relevance.

Conclusions

Our new combination approach and the categorization of fold changes facilitates the selection of genes in microarray experiments and helps to interpret their biological relevance.

SUBMITTER: Jung K

PROVIDER: S-EPMC3154206 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Publications

Reporting FDR analogous confidence intervals for the log fold change of differentially expressed genes.

Jung Klaus K Friede Tim T Beissbarth Tim T

BMC bioinformatics 20110715

<h4>Background</h4>Gene expression experiments are common in molecular biology, for example in order to identify genes which play a certain role in a specified biological framework. For that purpose expression levels of several thousand genes are measured simultaneously using DNA microarrays. Comparing two distinct groups of tissue samples to detect those genes which are differentially expressed one statistical test per gene is performed, and resulting p-values are adjusted to control the false ...[more]

PMID: 21756370

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Project description:In the analysis of networks we frequently require the statistical significance of some network statistic, such as measures of similarity for the properties of interacting nodes. The structure of the network may introduce dependencies among the nodes and it will in general be necessary to account for these dependencies in the statistical analysis. To this end we require some form of Null model of the network: generally rewired replicates of the network are generated which preserve only the degree (number of interactions) of each node. We show that this can fail to capture important features of network structure, and may result in unrealistic significance levels, when potentially confounding additional information is available.We present a new network resampling Null model which takes into account the degree sequence as well as available biological annotations. Using gene ontology information as an illustration we show how this information can be accounted for in the resampling approach, and the impact such information has on the assessment of statistical significance of correlations and motif-abundances in the Saccharomyces cerevisiae protein interaction network. An algorithm, GOcardShuffle, is introduced to allow for the efficient construction of an improved Null model for network data.We use the protein interaction network of S. cerevisiae; correlations between the evolutionary rates and expression levels of interacting proteins and their statistical significance were assessed for Null models which condition on different aspects of the available data. The novel GOcardShuffle approach results in a Null model for annotated network data which appears better to describe the properties of real biological networks.An improved statistical approach for the statistical analysis of biological network data, which conditions on the available biological information, leads to qualitatively different results compared to approaches which ignore such annotations. In particular we demonstrate the effects of the biological organization of the network can be sufficient to explain the observed similarity of interacting proteins.

Project description:BackgroundDespite much discussion in the epidemiologic literature surrounding the use of null hypothesis significance testing (NHST) for inferences, the reporting practices of veterinary researchers have not been examined. We conducted a survey of articles published in Preventive Veterinary Medicine, a leading veterinary epidemiology journal, aimed at (a) estimating the frequency of reporting p values, confidence intervals and statistical significance between 1997 and 2017, (b) determining whether this varies by article section and (c) determining whether this varies over time.MethodsWe used systematic cluster sampling to select 985 original research articles from issues published in March, June, September and December of each year of the study period. Using the survey data analysis menu in Stata, we estimated overall and yearly proportions of article sections (abstracts, results-texts, results-tables and discussions) reporting p values, confidence intervals and statistical significance. Additionally, we estimated the proportion of p values less than 0.05 reported in each section, the proportion of article sections in which p values were reported as inequalities, and the proportion of article sections in which confidence intervals were interpreted as if they were significance tests. Finally, we used Generalised Estimating Equations to estimate prevalence odds ratios and 95% confidence intervals, comparing the occurrence of each of the above-mentioned reporting elements in one article section relative to another.ResultsOver the 20-year period, for every 100 published manuscripts, 31 abstracts (95% CI [28-35]), 65 results-texts (95% CI [61-68]), 23 sets of results-tables (95% CI [20-27]) and 59 discussion sections (95% CI [56-63]) reported statistical significance at least once. Only in the case of results-tables, were the numbers reporting p values (48; 95% CI [44-51]), and confidence intervals (44; 95% CI [41-48]) higher than those reporting statistical significance. We also found that a substantial proportion of p values were reported as inequalities and most were less than 0.05. The odds of a p value being less than 0.05 (OR = 4.5; 95% CI [2.3-9.0]) or being reported as an inequality (OR = 3.2; 95% CI [1.3-7.6]) was higher in the abstracts than in the results-texts. Additionally, when confidence intervals were interpreted, on most occasions they were used as surrogates for significance tests. Overall, no time trends in reporting were observed for any of the three reporting elements over the study period.ConclusionsDespite the availability of superior approaches to statistical inference and abundant criticism of its use in the epidemiologic literature, NHST is substantially the most common means of inference in articles published in Preventive Veterinary Medicine. This pattern has not changed substantially between 1997 and 2017.

Dataset Information

Reporting FDR analogous confidence intervals for the log fold change of differentially expressed genes.

Background

Results

Conclusions

Publications

Reporting FDR analogous confidence intervals for the log fold change of differentially expressed genes.

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