Data filtering based on removing non-informative features, with unchanged signal between compared experimental conditions, can significantly increase sensitivity of methods used to detect differentially expressed genes or other molecular components measured in high-throughput biological experiments. Criteria for data filtering can be stated on the basis of averages or variances of signal levels across samples. The crucial parts of feature filtering are selection of filter type and cut-off threshold, which are specific to the particular dataset. In this paper, we present an algorithm and a stand-alone application, GaMRed, for adaptive filtering insignificant features in high-throughput data, based on Gaussian mixture decomposition. We have tested the performance of our algorithm using datasets from three different high-throughput biological experiments. We estimated the number of differentially expressed features after applying multiple testing correction and performed functional analysis of obtained features using Gene Ontology terms. Also, we checked if the control of false discovery rate and family-wise error rate after applying feature filtering remains at appropriate level. GaMRed is fast, automatic, and does not require expert knowledge in parameter tuning. The algorithm increases sensitivity of methods used to find differentially expressed features and biological validity of the findings. The program can be downloaded from: http://zaed.aei.polsl.pl/index.php/pl/oprogramowanie-zaed.

MOTIVATION: In contemporary biological experiments, bias, which interferes with the measurements, requires attentive processing. Important sources of bias in high-throughput biological experiments are batch effects and diverse methods towards removal of batch effects have been established. These include various normalization techniques, yet many require knowledge on the number of batches and assignment of samples to batches. Only few can deal with the problem of identification of batch effect of unknown structure. For this reason, an original batch identification algorithm through dynamical programming is introduced for omics data that may be sorted on a timescale. RESULTS: BatchI algorithm is based on partitioning a series of high-throughput experiment samples into sub-series corresponding to estimated batches. The dynamic programming method is used for splitting data with maximal dispersion between batches, while maintaining minimal within batch dispersion. The procedure has been tested on a number of available datasets with and without prior information about batch partitioning. Datasets with a priori identified batches have been split accordingly, measured with weighted average Dice Index. Batch effect correction is justified by higher intra-group correlation. In the blank datasets, identified batch divisions lead to improvement of parameters and quality of biological information, shown by literature study and Information Content. The outcome of the algorithm serves as a starting point for correction methods. It has been demonstrated that omitting the essential step of batch effect control may lead to waste of valuable potential discoveries. AVAILABILITY AND IMPLEMENTATION: The implementation is available within the BatchI R package at http://zaed.aei.polsl.pl/index.php/pl/111-software. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: DNA microarrays are used for discovery of genes expressed differentially between various biological conditions. In microarray experiments the number of analyzed samples is often much lower than the number of genes (probe sets) which leads to many false discoveries. Multiple testing correction methods control the number of false discoveries but decrease the sensitivity of discovering differentially expressed genes. Concerning this problem, filtering methods for improving the power of detection of differentially expressed genes were proposed in earlier papers. These techniques are two-step procedures, where in the first step some pool of non-informative genes is removed and in the second step only the pool of the retained genes is used for searching for differentially expressed genes. RESULTS: A very important parameter to choose is the proportion between the sizes of the pools of removed and retained genes. A new method, which we propose, allow to determine close to optimal threshold values for sample means and sample variances for gene filtering. The method is adaptive and based on the decomposition of the histogram of gene expression means or variances into mixture of Gaussian components. CONCLUSIONS: By performing analyses of several publicly available datasets and simulated datasets we demonstrate that our adaptive method increases sensitivity of finding differentially expressed genes compared to previous methods of filtering microarray data based on using fixed threshold values.