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Combining data from experiments on multispecies studies provides invaluable contributions to the understanding of basic disease mechanisms and pathophysiology of pathogens crossing species boundaries. The task of multispecies gene expression analysis, however, is often challenging given annotation inconsistencies and in cases of small sample sizes due to bias caused by batch effects. In this work we aim to demonstrate that an alternative approach to standard differential expression analysis in single cell RNA-sequencing (scRNA-seq) based on effect size profiles is suitable for the fusion of data from small samples and multiple organisms. The analysis pipeline is based on effect size metric profiles of samples in specific cell clusters. The effect size substitutes standard differentiation analyses based on p-values and profiles identified based on these effect size metrics serve as a tool to link cell type clusters between the studied organisms. The algorithms were tested on published scRNA-seq data sets derived from several species and subsequently validated on own data from human and bovine peripheral blood mononuclear cells stimulated with Mycobacterium tuberculosis. Correlation of the effect size profiles between clusters allowed for the linkage of human and bovine cell types. Moreover, effect size ratios were used to identify differentially regulated genes in control and stimulated samples. The genes identified through effect size profiling were confirmed experimentally using qPCR. We demonstrate that in situations where batch effects dominate cell type variation in single cell small sample size multispecies studies, effect size profiling is a valid alternative to traditional statistical inference techniques. [ABSTRACT FROM AUTHOR]

Ageing is a continuous process that can cause neurodevelopmental changes in the body. Several studies have examined its effects, but few have focused on how time affects biological processes in the early stages of brain development. As studying the changes that occur in the early stages of life is important to prevent age-related neurological and psychiatric disorders, we aim to focus on these changes. The transcriptomic markers of ageing that are common to the analysed brain regions of C57Bl/6J mice were identified after conducting two-way ANOVA tests and effect size analysis on the time courses of gene expression profiles in various mouse brain regions. A total of 16,374 genes (59.9%) significantly changed their expression level, among which 7600 (27.8%) demonstrated tissue-dependent differences only, and 1823 (6.7%) displayed time-dependent and tissue-independent responses. Focusing on genes with at least a large effect size gives the list of potential biomarkers 12,332 (45.1%) and 1670 (6.1%) genes, respectively. There were 305 genes that exhibited similar significant time response trends (independently of the brain region). Samples from an 11-day-old mouse embryo validated the identified early-stage brain ageing markers. The overall functional analysis revealed tRNA and rRNA processing in the mitochondrion and contact activation system (CAS), as well as the kallikrein/kinin system (KKS), together with clotting cascade and defective factor F9 activation being affected by ageing. Most ageing-related pathways were significantly enriched, especially those that are strongly connected to development processes and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Given the steadily rising incidence of type 1 diabetes (T1D), particularly among the youngest preschool children, coupled with well-documented challenges of achieving and maintaining optimal metabolic control in this age group, there is a growing need for advanced technological devices. OBJECTIVE: To evaluate glycaemic control in children below the age of seven with type 1 diabetes (T1D) and assess the safety of the advanced hybrid closed loop (AHCL) system in comparison to the previous treatment method, a sensor-augmented pump with predictive low-glucose suspend (SAP-PLGS). METHOD: Data from 10 children (aged 2.60–6.98 years) with T1D who transitioned to the AHCL system from SAP-PLGS were analysed. SAP-PLGS records from two weeks prior to the initiation of AHCL were compared with records from the initial four weeks post-switch (excluding the training period). These data were examined at two 2-week intervals and compared with records from two weeks post six-month usage of the AHCL. RESULTS: A significant decrease in the average nighttime glucose concentration was observed compared to pre-AHCL values (p = 0.001, concordance W = 0.53). The Glucose Management Indicator (GMI) value significantly decreased from 6.88 ± 0.37% to 6.52 ± 0.32% (p = 0.018, rbc = 0.93) immediately following the device switch and stabilized at 6.50 ± 0.28% (p = 0.001, W = 0.53) and 6.55 ± 0.41% (p = 0.001, W = 0.53) at subsequent stages of the study. An improvement was also observed in mean glucose values for time spent < 54 mg/dl, while the proportion of time within this range was maintained, both during the day (p < 0.001, W = 0.58) and at night (p = 0.002, W = 0.83). CONCLUSION: The AHCL MiniMed 780GTM system improved glycaemic control in the studied group of children under seven years of age with T1D compared to previous SAP-PLGS therapy. It proved to be safe for delivering insulin in this age group. [ABSTRACT FROM AUTHOR]

Background and aims: MiniMed 780G is the first Advanced Hybrid Closed Loop (AHCL) system in Poland, approved in the EU in 2020. To date, observations of glycemic control up to 12 months have been published. This study aimed to analyze glycemic control and anthropometric parameters in children and adolescents with type 1 diabetes (T1D) after two years of using the AHCL system. Materials and Methods: We prospectively collected anthropometric data, pump, and continuous glucose records of fifty T1D children (9.9 ± 2.4 years, 24 (48%) boys, T1D for 3.9 ± 2.56 years) using an AHCL system. We compared the twoweek AHCL records obtained after AHCL enrollment with data 6, 12, and 24 months after starting AHCL. Results: Time in range (70-180 mg/dl) and BMI z-score did not change during the 2 years of observation (p>0.05). The percentage of autocorrection in total daily insulin increased significantly (p<0.005). Conclusion: Glycemic control in the investigated group of children with T1D treated with the AHCL system for 2 years remained stable. Children in this group maintained weight and optimal metabolic control, most likely due to autocorrection boluses. [ABSTRACT FROM AUTHOR]

Cancer and ionizing radiation exposure are associated with inflammation. To identify a set of radiation-specific signatures of inflammation-associated genes in the blood of partially exposed radiotherapy patients, differential expression of 249 inflammatory genes was analyzed in blood samples from cancer patients and healthy individuals. The gene expression analysis on a cohort of 63 cancer patients (endometrial, head and neck, and prostate cancer) before and during radiotherapy (24 h, 48 h, ~1 week, ~4–8 weeks, and 1 month after the last fraction) identified 31 genes and 15 up- and 16 down-regulated genes. Transcription variability under normal conditions was determined using blood drawn on three separate occasions from four healthy donors. No difference in inflammatory expression between healthy donors and cancer patients could be detected prior to radiotherapy. Remarkably, repeated sampling of healthy donors revealed an individual endogenous inflammatory signature. Next, the potential confounding effect of concomitant inflammation was studied in the blood of seven healthy donors taken before and 24 h after a flu vaccine or ex vivo LPS (lipopolysaccharide) treatment; flu vaccination was not detected at the transcriptional level and LPS did not have any effect on the radiation-induced signature identified. Finally, we identified a radiation-specific signature of 31 genes in the blood of radiotherapy patients that were common for all cancers, regardless of the immune status of patients. Confirmation via MQRT-PCR was obtained for BCL6, MYD88, MYC, IL7, CCR4 and CCR7. This study offers the foundation for future research on biomarkers of radiation exposure, radiation sensitivity, and radiation toxicity for personalized radiotherapy treatment. [ABSTRACT FROM AUTHOR]

Radiomics is an emerging approach to support the diagnosis of pulmonary nodules detected via low-dose computed tomography lung cancer screening. Serum metabolome is a promising source of auxiliary biomarkers that could help enhance the precision of lung cancer diagnosis in CT-based screening. Thus, we aimed to verify whether the combination of these two techniques, which provides local/morphological and systemic/molecular features of disease at the same time, increases the performance of lung cancer classification models. The collected cohort consists of 1086 patients with radiomic and 246 patients with serum metabolomic evaluations. Different machine learning techniques, i.e., random forest and logistic regression were applied for each omics. Next, model predictions were combined with various integration methods to create a final model. The best single omics models were characterized by an AUC of 83% in radiomics and 60% in serum metabolomics. The model integration only slightly increased the performance of the combined model (AUC equal to 85%), which was not statistically significant. We concluded that radiomics itself has a good ability to discriminate lung cancer from benign lesions. However, additional research is needed to test whether its combination with other molecular assessments would further improve the diagnosis of screening-detected lung nodules. [ABSTRACT FROM AUTHOR]

The focus of this research is to combine statistical and machine learning tools in application to a high-throughput biological data set on ionizing radiation response. The analyzed data consist of two gene expression sets obtained in studies of radiosensitive and radioresistant breast cancer patients undergoing radiotherapy. The data sets were similar in principle; however, the treatment dose differed. It is shown that introducing mathematical adjustments in data preprocessing, differentiation and trend testing, and classification, coupled with current biological knowledge, allows efficient data analysis and obtaining accurate results. The tools used to customize the analysis workflow were batch effect filtration with empirical Bayes models, identifying gene trends through the Jonckheere–Terpstra test and linear interpolation adjustment according to specific gene profiles for multiple random validation. The application of non-standard techniques enabled successful sample classification at the rate of 93.5% and the identification of potential biomarkers of radiation response in breast cancer, which were confirmed with an independent Monte Carlo feature selection approach and by literature references. This study shows that using customized analysis workflows is a necessary step towards novel discoveries in complex fields such as personalized individual therapy.

Background: The diversity of the antigenic T cell receptor (TCR) repertoire clonally expressed on T lymphocytes is a key element of the adaptive immune system protective functions. A decline in diversity in the older adults is associated with health deterioration. This diversity is generated by the rearrangement of TRB genes coding for TCR chains during lymphocyte differentiation in the thymus, but is essentially maintained by peripheral T lymphocytes proliferation for most of life. Deep sequencing of rearranged TRB genes from blood cells allows the monitoring of peripheral T cell repertoire dynamics. We analysed two aspects of rearranged TRB diversity, related to T lymphocyte proliferation and to the distribution of the T cell clone size, in a collection of repertoires obtained from 1 to 74 years-old donors. Results: Our results show that peripheral T lymphocytes expansion differs according to the recombination status of their TRB loci. Their proliferation rate changes with age, with different patterns in men and women. T cell clone size becomes more heterogeneous with time, and, in adults, is always more even in women. Importantly, a longitudinal analysis of TRB repertoires obtained at ten years intervals from individual men and women confirms the findings of this cross-sectional study. Conclusions: Peripheral T lymphocyte proliferation partially depends on their thymic developmental history. The rate of proliferation of T cells differing in their TRB rearrangement status is different in men and women before the age of 18 years old, but similar thereafter. [ABSTRACT FROM AUTHOR]

Introduction: The search for biomarkers to predict radiosensitivity is important not only to individualize radiotherapy of cancer patients but also to forecast radiation exposure risks. The aim of this study was to devise a machine-learning method to stratify radiosensitivity and to investigate its association with genomewide copy number variations (CNVs) as markers of sensitivity to ionizing radiation. Methods: We used the Affymetrix CytoScan HD microarrays to survey common CNVs in 129 fibroblast cell strains. Radiosensitivity was measured by the surviving fraction at 2 Gy (SF2). We applied a dynamic programming (DP) algorithm to create a piecewise (segmented) multivariate linear regression model predicting SF2 and to identify SF2 segment-related distinctive CNVs. Results: SF2 ranged between 0.1384 and 0.4860 (mean=0.3273 The DP algorithm provided optimal segmentation by defining batches of radiosensitive (RS), normally-sensitive (NS), and radio-resistant (RR) responders. The weighted mean relative errors (MRE) decreased with increasing the segments' number. The borders of the utmost segments have stabilized after partitioning SF2 into 5 subranges. Discussion: The 5-segment model associated C-3SFBP marker with the most-RS and C-7IUVU marker with the most-RR cell strains. Both markers were mapped to gene regions (MCC and SLC1A6, respectively). In addition, C-3SFBP marker is also located in enhancer and multiple binding motifs. Moreover, for most CNVs significantly correlated with SF2, the radiosensitivity increased with the copynumber decrease. In conclusion, the DP-based piecewise multivariate linear regression method helps narrow the set of CNV markers from the whole radiosensitivity range to the smaller intervals of interest. Notably, SF2 partitioning not only improves the SF2 estimation but also provides distinctive markers. Ultimately, segment-related markers can be used, potentially with tissues’ specific factors or other clinical data, to identify radiotherapy patients who are most RS and require reduced doses to avoid complications and the most RR eligible for dose escalation to improve outcomes. [ABSTRACT FROM AUTHOR]

Background/objective: This long-term study aimed to analyze the associations between BMI Z-score, HbA1c, and daily insulin requirement (DIR) and the prevalence and duration of partial remission (PR) in children and adolescents with type 1 diabetes (T1D). Methods: After retrieving retrospective data for 195 patients from their health records at 24, 48, and 72 months after T1D diagnosis, the study group was comprised of 119 (57 girls) children with a complete dataset for all 6 years. PR was defined according to the ISPAD guidelines. Analyses were carried out in the whole group and subgroups according to PR duration: no PR at all (NPR), PR lasting less than 2 years (PR < 2), and PR at least 2 years (PR ≥ 2). Results: PR was observed in 63% of the patients (78.9% of overweight and 100% of obese patients). NPR patients showed the lowest mean initial BMI Z-score [−0.65 ± 1.29 vs. 0.02 ± 1.42, (PR < 2), p = 0.01 and vs. 0.64 ± 1.43 (PR ≥ 2), p = 0.17]. The dissimilarity in BMI across patients declined over time. Within the NPR group, the initial mean BMI Z-score significantly increased within the first 2 years (unadjusted p < 0.001) and remained constant afterward. In the PR <2 group, the highest increase in BMI Z-score occurred after 4 years (p < 0.001) and then decreased (p = 0.04). In the PR ≥2, the BMI Z-score slightly decreased within the first 2 years (p = 0.02), then increased (p = 0.03) and remained unchanged for the last 2 years. Six years after T1D started, the mean DIRs do not differ among the patient groups (ANOVA p = 0.272). Conclusion: During 6 years of follow-up, PR occurred in almost two-thirds of the studied children including almost all overweight and obese children. We observed a gradual normalization of the BMI Z-score at the end of the follow-up. BMI Z-score increased slightly in children with no remission initially but remained later constant until the end of observation. In both remitter groups, the increase in BMI Z-score appeared later when the protective honeymoon period ended. Regardless of BMI Z-score, the β-cell destruction process progresses, and after 6 years, the DIR is similar for all patients. [ABSTRACT FROM AUTHOR]

Cell subtype identification from mass cytometry data presents a persisting challenge, particularly when dealing with millions of cells. Current solutions are consistently under development, however, their accuracy and sensitivity remain limited, particularly in rare cell-type detection due to frequent downsampling. Additionally, they often lack the capability to analyze large data sets. To overcome these limitations, a new method was suggested to define an extended feature space. When combined with the robust clustering algorithm for big data, it results in more efficient cell clustering. Each marker's intensity distribution is presented as a mixture of normal distributions (Gaussian Mixture Model, GMM), and the expanded space is created by spanning over all obtained GMM components. The projection of the initial flow cytometry marker domain into the expanded space employs GMM-based membership functions. An evaluation conducted on three established cellular identification algorithms (FlowSOM, ClusterX, and PARC) utilizing the most substantial publicly available annotated dataset by Samusik et al. demonstrated the superior performance of the suggested approach in comparison to the standard. Although our approach identified 20 cell clusters instead of the expected 24, their intra-cluster homogeneity and inter-cluster differences were superior to the 24-cluster FlowSOM-based solution. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a heterogeneous disease, and several attempts have been made to subtype it. Based on the abundance of 86 proteins, we identified six subpopulations of breast cancer patients: one basal subtype, one HER2-enriched subtype, and four luminal subtypes. We then evaluated them demographically and clinically, and we found significant differences in survival. The new luminal subpopulations vary in prognoses. One, marked as A2, showed similar or even worse survival than HER2-enriched and basal cases. The observed poorer survival cannot be explained by clinical and demographic factors, as there was no substantial association with race, ethnicity, metastasis, tumor size, cancer stage, and age at diagnosis. It suggests that the molecular profiles underlie the cohort heterogeneity rather than the patient background. The subpopulations identified may potentially complement established breast cancer classifications and, with further molecular investigation, may find application in clinical routine. As a highly heterogeneous disease, breast cancer (BRCA) demonstrates a diverse molecular portrait. The well-established molecular classification (PAM50) relies on gene expression profiling. It insufficiently explains the observed clinical and histopathological diversity of BRCAs. This study aims to demographically and clinically characterize the six BRCA subpopulations (basal, HER2-enriched, and four luminal ones) revealed by their proteomic portraits. GMM-based high variate protein selection combined with PCA/UMAP was used for dimensionality reduction, while the k-means algorithm allowed patient clustering. The statistical analysis (log-rank and Gehan–Wilcoxon tests, hazard ratio HR as the effect size ES) showed significant differences across identified subpopulations in Disease-Specific Survival (p = 0.0160) and Progression-Free Interval (p = 0.0264). Luminal subpopulations vary in prognosis (Disease-Free Interval, p = 0.0277). The A2 subpopulation is of the poorest, comparable to the HER2-enriched subpopulation, prognoses (HR = 1.748, referenced to Luminal B, small ES), while A3 is of the best (HR = 0.250, large ES). Similar to PAM50 subtypes, no substantial dependency on demographic and clinical factors was detected across Luminal subpopulations, as measured by χ2 test and Cramér's V for ES, and ANOVA with appropriate post hocs combined with η2 or Cohen's d-type ES, respectively. Progesterone receptors can serve as the potential A2 biomarker within Luminal patients. Further investigation of molecular differences is required to examine the potential prognostic or clinical applications. [ABSTRACT FROM AUTHOR]

Background: Detecting early-stage Alzheimer's disease (AD) is still problematic in clinical practice. This work aimed to find T1-weighted MRI-based markers for AD and mild cognitive impairment (MCI) to improve the screening process. Objective: Our assumption was to build a screening model that would be accessible and easy to use for physicians in their daily clinical routine. Methods: The multinomial logistic regression was used to detect status: AD, MCI, and normal control (NC) combined with the Bayesian information criterion for model selection. Several T1-weighted MRI-based radiomic features were considered explanatory variables in the prediction model. Results: The best radiomic predictor was the relative brain volume. The proposed method confirmed its quality by achieving a balanced accuracy of 95.18%, AUC of 93.25%, NPV of 97.93%, and PPV of 90.48% for classifying AD versus NC for the European DTI Study on Dementia (EDSD). The comparison of the two models: with the MMSE score only as an independent variable and corrected for the relative brain value and age, shows that the addition of the T1-weighted MRI-based biomarker improves the quality of MCI detection (AUC: 67.04% versus 71.08%) while maintaining quality for AD (AUC: 93.35% versus 93.25%). Additionally, among MCI patients predicted as AD inconsistently with the original diagnosis, 60% from ADNI and 76.47% from EDSD were re-diagnosed as AD within a 48-month follow-up. It shows that our model can detect AD patients a few years earlier than a standard medical diagnosis. Conclusion: The created method is non-invasive, inexpensive, clinically accessible, and efficiently supports AD/MCI screening. [ABSTRACT FROM AUTHOR]

Large-scale comprehensive single-cell experiments are often resource- intensive and require the involvement of many laboratories and/or taking measurements at various times. This inevitably leads to batch effects, and systematic variations in the data that might occur due to different technology platforms, reagent lots, or handling personnel. Such technical differences confound biological variations of interest and need to be corrected during the data integration process. Data integration is a challenging task due to the overlapping of biological and technical factors, which makes it difficult to distinguish their individual contribution to the overall observed effect. Moreover, the choice of integration method may impact the downstream analyses, including searching for differentially expressed genes. From the existing data integration methods, we selected only those that return the full expression matrix. We evaluated six methods in terms of their influence on the performance of differential gene expression analysis in two single-cell datasets with the same biological study design that differ only in the way the measurement was done: one dataset manifests strong batch effects due to the measurements of each sample at a different time. Integrated data were visualized using the UMAP method. The evaluation was done both on individual gene level using parametric and non-parametric approaches for finding differentially expressed genes and on gene set level using gene set enrichment analysis. As an evaluation metric, we used two correlation coefficients, Pearson and Spearman, of the obtained test statistics between reference, test, and corrected studies. Visual comparison of UMAP plots highlighted ComBat-seq, limma, and MNN, which reduced batch effects and preserved differences between biological conditions. Most of the tested methods changed the data distribution after integration, which negatively impacts the use of parametric methods for the analysis. Two algorithms, MNN and Scanorama, gave very poor results in terms of differential analysis on gene and gene set levels. Finally, we highlight ComBat-seq as it led to the highest correlation of test statistics between reference and corrected dataset among others. Moreover, it does not distort the original distribution of gene expression data, so it can be used in all types of downstream analyses. [ABSTRACT FROM AUTHOR]

Background: Information on the influence of insulin treatment using advanced hybrid closed loop systems (AHCL) on body weight of young patients with type 1 diabetes (T1D) is scarce. The aim of this studywas to observewhether therewere any changes in body mass index (BMI) of children and adolescents with T1D treated using the Medtronic Minimed 780G AHCL after 1 year of follow up and to analyze potential associations between these changes and the insulin doses. Materials and methods: For 50 children and adolescents (age 5.4-16.8 years, 24 (48%) boys, T1D for 3.9 ± 2.56 years) using an AHCL system anthropometric and AHCL data were collected prospectively. BMI Z-scores and two-week AHCL records obtained after AHCL enrollment were compared with data after 6 months and also 1 year after starting AHCL. Results: The BMI Z-score of the patients at 1 year follow-up did not change from time of AHCL initiation (0.51 ± 2.79 vs 0.57 ± 2.85, p>0.05). There was a slight increase in total daily insulin per kg of body weight (0.67 ± 0.21 U/kg vs 0.80 ± 0.21 U/kg, p <0.001), but the percent of basal insulin was unchanged (34.88 ± 6.91% vs 35.08 ± 6.30%, p>0.05). We observed also no change (AHCL start vs after 1 year) in glycemic control parameters: average sensor glucose (131.36± 11.04 mg/dL vs 132.45 ± 13.42 mg/dL, p>0.05), coefficient of variation (34.99± 5.17% vs 34.06 ± 5.38%, p>0.05), glucose management indicator (6.45 ± 0.26% vs 6.48 ± 0.32%, p>0.05), and time spent in the range of 70--180 mg/dL (79.28 ± 8.12% vs 80.40 ± 8.25%, p>0.05). Conclusion: During the 1 year of follow-up the BMI of children and adolescents with T1D treated with an AHCL system remained stable. Although there was a slight increase in the total daily insulin dose, the percent of basal insulin was unchanged. The patients maintained recommended glycemic control. [ABSTRACT FROM AUTHOR]

Tumor-infiltrating lymphocytes (TILs), identified on HE-stained histopathological images in the cancer area, are indicators of the adaptive immune response against cancers and play a major role in personalized cancer immunotherapy. Recent works indicate that the spatial organization of TILs may be prognostic of disease-specific survival and recurrence. However, there are a limited number of methods that were proposed and tested in analyses of the spatial structure of TILs. In this work, we evaluated 14 different spatial measures, including the one developed for other omics data, on 10,532 TIL maps from 23 cancer types in terms of reproducibility, uniqueness, and impact on patient survival. For each spatial measure, 16 different scenarios for the definition of prognostic factor were tested. We found no difference in survival prediction when TIL maps were stored as binary images or continuous TIL probability scores. When spatial measures were discretized into a low and high category, a higher correlation with survival was observed. Three measures with the highest cancer prognosis capability were spatial autocorrelation, GLCM M1, and closeness centrality. Most of the tested measures could be further tuned to increase prediction performance. [ABSTRACT FROM AUTHOR]

A typical genome-wide association study (GWAS) analyzes millions of single-nucleotide polymorphisms (SNPs), several of which are in a region of the same gene. To conduct gene set analysis (GSA), information from SNPs needs to be unified at the gene level. A widely used practice is to use only the most relevant SNP per gene; however, there are other methods of integration that could be applied here. Also, the problem of nonrandom association of alleles at two or more loci is often neglected. Here, we tested the impact of incorporation of different integrations and linkage disequilibrium (LD) correction on the performance of several GSA methods. Matched normal and breast cancer samples from The Cancer Genome Atlas database were used to evaluate the performance of six GSA algorithms: Coincident Extreme Ranks in Numerical Observations (CERNO), Gene Set Enrichment Analysis (GSEA), GSEA-SNP, improved GSEA for GWAS (i-GSEA4GWAS), Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA), and Over-Representation Analysis (ORA). Association of SNPs to phenotype was calculated using modified McNemar's test. Results for SNPs mapped to the same gene were integrated using Fisher and Stouffer methods and compared with the minimum p -value method. Four common measures were used to quantify the performance of all combinations of methods. Results of GSA analysis on GWAS were compared to the one performed on gene expression data. Comparing all evaluation metrics across different GSA algorithms, integrations, and LD correction, we highlighted CERNO, and MAGENTA with Stouffer as the most efficient. Applying LD correction increased prioritization and specificity of enrichment outcomes for all tested algorithms. When Fisher or Stouffer were used with LD, sensitivity and reproducibility were also better. Using any integration method was beneficial in comparison with a minimum p -value method in specific combinations. The correlation between GSA results from genomic and transcriptomic level was the highest when Stouffer integration was combined with LD correction. We thoroughly evaluated different approaches to GSA in GWAS in terms of performance to guide others to select the most effective combinations. We showed that LD correction and Stouffer integration could increase the performance of enrichment analysis and encourage the usage of these techniques. [ABSTRACT FROM AUTHOR]

New diseases constantly endanger the lives of populations, and, nowadays, they can spread easily and constitute a global threat. The COVID-19 pandemic has shown that the fight against a new disease may be difficult, especially at the initial stage of the epidemic, when medical knowledge is not complete and the symptoms are ambiguous. The use of machine learning tools can help to filter out those sick patients who do not need to be tested for spreading the pathogen, especially in the event of an overwhelming increase in disease transmission. This work presents a screening support system that can precisely identify patients who do not carry the disease. The decision of the system is made on the basis of patient survey data that are easy to collect. A case study on a data set of symptomatic COVID-19 patients shows that the system can be effective in the initial phase of the epidemic. The case study presents an analysis of two classifiers that were tuned to achieve an assumed acceptable threshold of negative predictive values during classification. Additionally, an explanation of the obtained classification models is presented. The explanation enables the users to understand the basis of the decision made by the model. The obtained classification models provide the basis for the DECODE service, which could serve as support in screening patients with COVID-19 disease at the initial stage of the pandemic. Moreover, the data set constituting the basis for the analyses performed is made available to the research community. This data set, consisting of more than 3000 examples, is based on questionnaires collected at a hospital in Poland. [ABSTRACT FROM AUTHOR]