The meaning of the term “Big Data” is still subject to debate, in spite of being widely used in biomedical publications. This confusion in definition leads to missed opportunities for peers to exchange knowledge and practices. A better understanding of Big Data may help researchers to identify themselves with the Big Data community. In this study, we investigate the most distinguishing features in “Big Data”-labelled publications by comparing them against publication without this label (nonBig Data), using text mining and machine learning methods. Furthermore, the usage of the term Big Data was analysed over time. Our models could successfully make a distinction between publications labelled with `Big Data' and those without. The most distinguishing features consisted of terms such as `omics', `computing', `storage', and `mining'. We observed that publications that do not use the term Big Data may also address topics that fall under well-accepted definitions of Big Data. Trends suggest that, while the use of the term Big Data increased, it is used less reliably now as compared to earlier years.

UNLABELLED: Currently, the Gene Expression Omnibus (GEO) contains public data of over 1 million samples from more than 40 000 microarray-based functional genomics experiments. This provides a rich source of information for novel biological discoveries. However, unlocking this potential often requires retrieving and storing a large number of expression profiles from a wide range of different studies and platforms. The compendiumdb R package provides an environment for downloading functional genomics data from GEO, parsing the information into a local or remote database and interacting with the database using dedicated R functions, thus enabling seamless integration with other tools available in R/Bioconductor. AVAILABILITY AND IMPLEMENTATION: The compendiumdb package is written in R, MySQL and Perl. Source code and binaries are available from CRAN (http://cran.r-project.org/web/packages/compendiumdb/) for all major platforms (Linux, MS Windows and OS X) under the GPLv3 license. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: Two-dimensional differential gel electrophoresis (2D-DIGE) provides a powerful technique to separate proteins on their isoelectric point and apparent molecular mass and quantify changes in protein expression. Abundantly available proteins in spots can be identified using mass spectrometry-based approaches. However, identification is often not possible for low-abundant proteins. RESULTS: We present a novel computational approach to prioritize candidate proteins for unidentified spots. Our approach exploits noisy information on the isoelectric point and apparent molecular mass of a protein spot in combination with functional similarities of candidate proteins to already identified proteins to select and rank candidates. We evaluated our method on a 2D-DIGE dataset comparing protein expression in uninfected and HIV-1 infected T-cells. Using leave-one-out cross-validation, we show that the true-positive rate for the top-5 ranked proteins is 43.8%. CONCLUSIONS: Our approach shows good performance on a 2D-DIGE dataset comparing protein expression in uninfected and HIV-1 infected T-cells. We expect our method to be highly useful in (re-)mining other 2D-DIGE experiments in which especially the low-abundant protein spots remain to be identified.

For some classification tasks the data can be partitioned into disjoint subsets based on some attribute, for example a disease subtype. It then seems logical to train a classifier with the same classes as the original classification problem for each subtype separately, such that the performance per subtype is optimized. Unfortunately, the influence of the subtype performances on the aggregated overall performance depends strongly on the performance measure used and can be very counterintuitive. We show that for some performance measures (e.g., classification accuracy, precision, recall, Fi) the aggregated performance is a simple linear combination of subtype performances. In these cases, improving the performance of a subtype-specific classifier implies that the overall performance improves. However, for other performance measures (e.g., balanced accuracy rate, area under the ROC curve) and also for performance measures in survival analysis (concordance index), additional cross terms appear in the aggregation of the subtype performances. These cross terms are heavily dependent on both the overall class imbalance and the subtype class imbalances. For these measures, improving subtype performances may actually result in a decrease of the overall performance.

The accurate representation of all aspects of a metabolic network in a structured format, such that it can be used for a wide variety of computational analyses, is a challenge faced by a growing number of researchers. Analysis of five major metabolic pathway databases reveals that each database has made widely different choices to address this challenge, including how to deal with knowledge that is uncertain or missing. In concise overviews, we show how concepts such as compartments, enzymatic complexes and the direction of reactions are represented in each database. Importantly, also concepts which a database does not represent are described. Which aspects of the metabolic network need to be available in a structured format and to what detail differs per application. For example, for in silico phenotype prediction, a detailed representation of gene-protein-reaction relations and the compartmentalization of the network is essential. Our analysis also shows that current databases are still limited in capturing all details of the biology of the metabolic network, further illustrated with a detailed analysis of three metabolic processes. Finally, we conclude that the conceptual differences between the databases, which make knowledge exchange and integration a challenge, have not been resolved, so far, by the exchange formats in which knowledge representation is standardized.

SUMMARY: The discovery of functionally related groups in a set of significantly abundant proteins from a mass spectrometry experiment is an important step in a proteomics analysis pipeline. Here we describe NetWeAvers (Network Weighted Averages) for analyzing groups of regulated proteins in a network context, e.g. as defined by clusters of protein-protein interactions. NetWeAvers is an R package that provides a novel method for analyzing proteomics data integrated with biological networks. The method includes an algorithm for finding dense clusters of proteins and a permutation algorithm to calculate cluster P-values. Optional steps include summarizing quantified peptide values to single protein values and testing for differential expression, such that the data input can simply be a list of identified and quantified peaks. AVAILABILITY AND IMPLEMENTATION: The NetWeAvers package is written in R, is open source and is freely available on CRAN and from netweavers.erasmusmc.nl under the GPL-v2 license. CONTACT: [email protected]

BACKGROUND: Large discrepancies in signature composition and outcome concordance have been observed between different microarray breast cancer expression profiling studies. This is often ascribed to differences in array platform as well as biological variability. We conjecture that other reasons for the observed discrepancies are the measurement error associated with each feature and the choice of preprocessing method. Microarray data are known to be subject to technical variation and the confidence intervals around individual point estimates of expression levels can be wide. Furthermore, the estimated expression values also vary depending on the selected preprocessing scheme. In microarray breast cancer classification studies, however, these two forms of feature variability are almost always ignored and hence their exact role is unclear. RESULTS: We have performed a comprehensive sensitivity analysis of microarray breast cancer classification under the two types of feature variability mentioned above. We used data from six state of the art preprocessing methods, using a compendium consisting of eight different datasets, involving 1131 hybridizations, containing data from both one and two-color array technology. For a wide range of classifiers, we performed a joint study on performance, concordance and stability. In the stability analysis we explicitly tested classifiers for their noise tolerance by using perturbed expression profiles that are based on uncertainty information directly related to the preprocessing methods. Our results indicate that signature composition is strongly influenced by feature variability, even if the array platform and the stratification of patient samples are identical. In addition, we show that there is often a high level of discordance between individual class assignments for signatures constructed on data coming from different preprocessing schemes, even if the actual signature composition is identical. CONCLUSION: Feature variability can have a strong impact on breast cancer signature composition, as well as the classification of individual patient samples. We therefore strongly recommend that feature variability is considered in analyzing data from microarray breast cancer expression profiling experiments.

The backpropagation algorithm is widely used for training multilayer neural networks. In this publication the gain of its activation function(s) is investigated. In specific, it is proven that changing the gain of the activation function is equivalent to changing the learning rate and the weights. This simplifies the backpropagation learning rule by eliminating one of its parameters. The theorem can be extended to hold for some well-known variations on the backpropagation algorithm, such as using a momentum term, flat spot elimination, or adaptive gain. Furthermore, it is successfully applied to compensate for the nonstandard gain of optical sigmoids for optical neural networks.