Analysis of gene set (GS) enrichment is an essential part of functional omics studies. Here, we complement the established evaluation metrics of GS enrichment algorithms with a novel approach to assess the practical reproducibility of scientific results obtained from GS enrichment tests when applied to related data from different studies. We evaluated eight established and one novel algorithm for reproducibility, sensitivity, prioritization, false positive rate and computational time. In addition to eight established algorithms, we also included Coincident Extreme Ranks in Numerical Observations (CERNO), a flexible and fast algorithm based on modified Fisher P-value integration. Using real-world datasets, we demonstrate that CERNO is robust to ranking metrics, as well as sample and GS size. CERNO had the highest reproducibility while remaining sensitive, specific and fast. In the overall ranking Pathway Analysis with Down-weighting of Overlapping Genes, CERNO and over-representation analysis performed best, while CERNO and GeneSetTest scored high in terms of reproducibility. tmod package implementing the CERNO algorithm is available from CRAN (cran.r-project.org/web/packages/tmod/index.html) and an online implementation can be found at http://tmod.online/. The datasets analyzed in this study are widely available in the KEGGdzPathwaysGEO, KEGGandMetacoreDzPathwaysGEO R package and GEO repository. Supplementary data are available at Bioinformatics online.

Lung cancer is responsible for more fatalities than any other cancer worldwide, with 1.76 million associated deaths reported in 2018. The key issue in the fight against this disease is the detection and diagnosis of all pulmonary nodules at an early stage. Artificial intelligence (AI) algorithms play a vital role in the automated detection, segmentation, and computer-aided diagnosis of malignant lesions. Among the existing algorithms, radiomics and deep-learning-based types appear to show the most promise. Radiomics is a growing field related to the extraction of a set of features from an image, which allows for automated classification of medical images into a predefined group. The process comprises a series of consecutive steps including image acquisition and pre-processing, segmentation of the desired region of interest, calculation of defined features, feature engineering, and construction of the classification model. The features calculated in this process are mainly shape features, as well as first- and higher-order texture features. To date, more than 100 features have been defined, although this number varies depending on the application. The greatest challenge in radiomics is building a cross-validated model based on a selected set of calculated features known as the radiomic signature. Numerous radiomic signatures have successfully been developed; however, reproducibility and clinical validity of the results obtained constitutes a considerable challenge of modern radiomics. Deep learning algorithms are another rapidly evolving technique and are recognized as a valuable tool in the field of medical image analysis for the detection, characterization, and assessment of lesions. Such an approach involves the design of artificial neural network architecture while upholding the goal of high classification accuracy. This paper illuminates the evolution and current state of artificial intelligence methods in lung imaging and the detection and diagnosis of pulmonary nodules, with a particular emphasis on radiomics and deep learning methods.

We propose a new method that employs transfer learning techniques to effectively correct sampling selection errors introduced by sparse annotations during supervised learning for automated tumor segmentation. The practicality of current learning-based automated tissue classification approaches is severely impeded by their dependency on manually segmented training databases that need to be recreated for each scenario of application, site, or acquisition setup. The comprehensive annotation of reference datasets can be highly labor-intensive, complex, and error-prone. The proposed method derives high-quality classifiers for the different tissue classes from sparse and unambiguous annotations and employs domain adaptation techniques for effectively correcting sampling selection errors introduced by the sparse sampling. The new approach is validated on labeled, multi-modal MR images of 19 patients with malignant gliomas and by comparative analysis on the BraTS 2013 challenge data sets. Compared to training on fully labeled data, we reduced the time for labeling and training by a factor greater than 70 and 180 respectively without sacrificing accuracy. This dramatically eases the establishment and constant extension of large annotated databases in various scenarios and imaging setups and thus represents an important step towards practical applicability of learning-based approaches in tissue classification.

There exist many methods for describing the complex relation between changes of gene expression in molecular pathways or gene ontologies under different experimental conditions. Among them, Gene Set Enrichment Analysis seems to be one of the most commonly used (over 10,000 citations). An important parameter, which could affect the final result, is the choice of a metric for the ranking of genes. Applying a default ranking metric may lead to poor results. In this work 28 benchmark data sets were used to evaluate the sensitivity and false positive rate of gene set analysis for 16 different ranking metrics including new proposals. Furthermore, the robustness of the chosen methods to sample size was tested. Using k-means clustering algorithm a group of four metrics with the highest performance in terms of overall sensitivity, overall false positive rate and computational load was established i.e. absolute value of Moderated Welch Test statistic, Minimum Significant Difference, absolute value of Signal-To-Noise ratio and Baumgartner-Weiss-Schindler test statistic. In case of false positive rate estimation, all selected ranking metrics were robust with respect to sample size. In case of sensitivity, the absolute value of Moderated Welch Test statistic and absolute value of Signal-To-Noise ratio gave stable results, while Baumgartner-Weiss-Schindler and Minimum Significant Difference showed better results for larger sample size. Finally, the Gene Set Enrichment Analysis method with all tested ranking metrics was parallelised and implemented in MATLAB, and is available at https://github.com/ZAEDPolSl/MrGSEA . Choosing a ranking metric in Gene Set Enrichment Analysis has critical impact on results of pathway enrichment analysis. The absolute value of Moderated Welch Test has the best overall sensitivity and Minimum Significant Difference has the best overall specificity of gene set analysis. When the number of non-normally distributed genes is high, using Baumgartner-Weiss-Schindler test statistic gives better outcomes. Also, it finds more enriched pathways than other tested metrics, which may induce new biological discoveries.

Aims/hypothesis We analysed the temporal changes in the incidence of childhood type 1 diabetes and its demographic determinants in Poland from 1989 to 2004, validating the model with data from 1970 to 1989. We also estimated a predictive model of the trends in childhood diabetes incidence for the near future. Methods Children under 15 years with newly diagnosed type 1 diabetes mellitus and drawn from seven regional registries in Poland were ascertained prospectively using the Epidemiology and Prevention of Diabetes study (EURODIAB) criteria. The type 1 diabetes incidence rates (IRs) were analysed in dependency of age, sex, seasonality, geographical region and population density. Time trends in IR were modelled using several approaches. Results The average incidence, standardised by age and sex, for 1989 to 2004 was 10.2 per 100,000 persons per year and increased from 5.4 to 17.7. No difference was found between boys and girls, or between urban and rural regions. In children above 4 years, IR was significantly higher in the population of northern Poland than in that of the country’s southern part, as well as in the autumn–winter season, this finding being independent of child sex. Based on the trend model obtained, almost 1,600 Polish children aged 0 to 14 years are expected to develop type 1 diabetes in 2010, rising to more than 4,800 in 2025. The estimates suggest at least a fourfold increase of IR between 2005 and 2025, with the highest dynamics of this increment in younger children. Conclusions/interpretation These estimates show that Poland will have to face a twofold higher increase in childhood type 1 diabetes than predicted for the whole European population. The dramatic increase could have real downstream effects on Poland’s healthcare system.