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Zhakparov, D.

Publications and source records attributed to Zhakparov, D..

2 recordsLinked to original sources

GeneSelectR: An R Package Workflow for Enhanced Feature Selection from RNA Sequencing Data

MotivationHigh-dimensional Bulk RNA sequencing (RNAseq) datasets pose a considerable challenge in identifying biologically relevant features for downstream analyses and data mining efforts. The standard approach involves differential gene expression (DGE) analysis, but its effectiveness can be limited depending on the data due to its univariate nature. In complex datasets, an alternative approach involves employing a variety of machine learning (ML) tools, which attempt to understand non-linear relationships between features and focus on generalizability rather than statistical significance. This approach will result in the generation of multiple feature lists, which might exhibit similarities in terms of classification performance metrics. Therefore, there is an urgent need for a cohesive workflow that seamlessly integrates robust feature selection using diverse ML methods while also evaluating the biological relevance of the resulting feature lists. This combined approach would enable the prioritization of the best-performing list, considering both sets of criteria. ResultsWe introduce GeneSelectR, an open-source R package that innovatively combines ML and bioinformatic data mining approaches for enhanced feature selection. With GeneSelectR, features can be selected from a normalized RNAseq dataset with a variety of ML methods and user-defined parameters. This is followed by an assessment of their biological relevance with Gene Ontology (GO) enrichment analysis, along with a semantic similarity analysis of the resulting GO terms. Additionally, similarity coefficients and fractions of the GO terms of interest are calculated. With this, GeneSelectR optimizes ML performance and rigorously assesses the biological relevance of the various lists, offering a means to prioritize feature lists with regard to the biological question. When applied to the TCGA-BRCA dataset, the GeneSelectR workflow generated several feature lists using different ML methods and a DGE analysis. By leveraging the various functions in GeneSelectR, the different lists could be evaluated based on both ML performance and biological relevance. This comprehensive evaluation facilitated the selection of the best-performing list, which exhibited both strong machine learning performance and high relevance to the biological question while maintaining a manageable number of highly specific features. AvailabilityThe package is available on CRAN. To install it, run: install.packages( GeneSelectR) Contactdzhakparov@gmail.com Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

Distribution of ACE2, CD147, cyclophilins, CD26 and other SARS-CoV-2 associated molecules in human tissues and immune cells in health and disease

BackgroundMorbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. MethodsWe performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. ResultsACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA and PPIB), CD26 (DPP4) and related molecules were expressed in both, epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of ACE2- and CD147-related genes in the lesional skin of patients with atopic dermatitis. ConclusionsOur data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related with age, gender, obesity and smoking, as well as with the disease status might contribute to COVID-19 morbidity and severity patterns.

immunology↗