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NOODAI: a webserver for network-oriented multi-omics data analysis and integration pipeline.

SUMMARY: Omics profiling has proven of great use for unbiased and comprehensive identification of key features that define biological phenotypes and underlie medical conditions. While each omics profile assists characterization of specific molecular components relevant for the studied phenotype, their joint evaluation can offer deeper insights into the overall mechanistic functioning of biological systems. Here, we introduce an approach where, starting from representative traits (e.g. differentially expressed elements) obtained for each omics profile, we construct and analyze joint interaction networks. The resulting networks rely on the existing knowledge of confident interactions among biological entities. We use these maps to identify and describe central elements, which connect multiple entities characteristic of the studied phenotypes and we leverage MONET network decomposition tool in order to highlight functionally connected network modules. In order to enable broad usage of this approach, we developed the NOODAI software platform, which enables integrative omics analysis through a user-friendly interface. The analysis outcomes are presented both as raw output tables as well as informative summary plots and written reports. Since the MONET tool enables the use of algorithms with strong performance in identifying disease-relevant modules, NOODAI software platform can be of a high value for analyzing clinical multi-omics datasets. AVAILABILITY AND IMPLEMENTATION: NOODAI is freely accessible at https://omics-oracle.com. Source code is available under GPL3 at: https://github.com/TotuTiberiu/NOODAI with the DOI: 10.5281/zenodo.17203984.

Software

BRIDGE: an interactive application for multi-omics data analysis, visualization and integration.

SUMMARY: BRIDGE is a Shiny-based application that provides an accessible, modular platform for individual and integrative multi-omics analysis. Using an independent SQLite database backend, it offers a local, private, and user-friendly environment that requires no prior computational expertise. The application supports proteomics, phospho-proteomics, and RNA-seq analyses through a comprehensive suite of visualization and analytical modules, together with an integrated multi-omics analysis pipeline. Built-in caching and asynchronous processing improve responsiveness, enabling efficient exploration, analysis, and visualization of multi-omics datasets on moderate hardware. AVAILABILITY AND IMPLEMENTATION: BRIDGE is implemented in R using Shiny and is freely available as a Docker container at https://ghcr.io/paulilab/bridge. A public demonstration server with example datasets is available at https://bridge.imp.ac.at. Code and datasets are also available at https://github.com/paulilab/BRIDGE and under DOI: https://doi.org/10.5281/zenodo.20215824.

Multiomics

Some interrelationships between plasma levels of LH, FSH, oestradiol 17beta, androgens and semen analysis data in male infertility patients.

Serum LH, FSH and immunoreactive testosterone-like substances (TLS) have been measured by radioimmunoassay in 130 male infertility patients and oestradiol 17beta in 26 cases. A weak but significant negative correlation was found between FSH and sperm count (rs = -0.19, p less than 0.05) but not LH and sperm count. However, LH and FSH were strongly correlated in the azoospermic (rs = 0.71, p less than 0.01) and oligozoospermic (rs = 0.53, p less than 0.01) groups and levels of both gonadotrophins were significantly elevated in the azoospermic and oligozoospermic as compared to the normozoospermic group. The elevated LH levels in the oligozoo- and azoospermic groups could not be explained by reduced negative feedback of testosterone or oestradiol 17beta since firstly, TLS and oestradiol 17beta levels were similar in all three groups and, secondly, within-group correlations between LH and TLS were either non-significant or positive (azoospermic group r = 0.37, p = 0.06). It is suggested that spermatogenesis-related feedback factor(s) may inhibit LH as well as FSH secretion. No role for oestradiol 17beta as a selective inhibitor of FSH secretion seemed likely as oestradiol 17beta levels were similar in the three groups and were correlated (r = 0.51, p less than 0.01) to TLS levels i.e. to leydig cell rather than spermatogenic function. Seminal fructose was negatively correlated (r = -0.26, p less than 0.01) with sperm count but not significantly with plasma TLS. It would thus seem unlikely that the tendency for seminal fructose levels to increase as sperm count decreases is due to increased androgen production or that seminal fructose can be used as an index of a patient's androgenic status. Patients with varicoceles had hormone levels similar to other patients of similar sperm count. Both sperm morphology and motility were strongly correlated to log sperm count (r = 0.84 and 0.55 respectively) and semen volume was significantly greater in oligozoospermic than normozoospermic patients (p less than 0.01).

Androgens

Rapid hypotonic method for flow cytofluorometry of monolayer cell cultures. Some pitfalls in staining and data analysis.

The rapid hypotonic staining procedure developed by Krishan for DNA determinations by flow cytofluorometry has been proven accurate for in vivo cell samples and for cell lines growing in suspension culture. We show that the unmodified procedure may produce distorted DNA histograms when used for staining cells growing in monolayer cultures, however. To eliminate these distortions, it was necessary to avoid the use of trypsin by staining the attached cells directly, using a hypotonic fluorochrome solution to which nonionic detergent was added. Two sublines of HeLa S3 cells are shown to exhibit major differences in their staining characteristics. By using our revised staining procedure, the two sublines appear to produce very satisfactory DNA histograms. However, in only one subline does the S phase fraction calculated from the histograms agree with the autoradiographical labeling index. Mitotic cells remain intact under these staining conditions, and the principal observed effect of nonionic detergents in this case is to decrease the coefficient of variation of fluorescence intensity.

Cells, Cultured

Identifying key palmitoylation-associated genes in endometriosis through genomic data analysis.

BACKGROUND: Palmitoylation, a post-translational lipid modification, has garnered increasing attention for its role in inflammatory processes and tumorigenesis. Emerging evidence suggests a potential association between palmitoylation and inflammatory responses in the pathogenesis of endometriosis. However, the precise mechanistic interplay remains elusive, necessitating further investigation. METHODS: This study integrated transcriptomic analysis and Mendelian randomization (MR) to identify a causal gene set implicated in endometriosis. Differentially expressed genes (DEGs) were first identified in the training dataset using the limma package in R. Weighted gene co-expression network analysis (WGCNA) was subsequently performed, leveraging Single Sample Gene Set Enrichment Analysis (ssGSEA)-derived scores of palmitoylation-related genes (PRGs) as phenotypic traits to identify key modular genes. The intersection of these key modular genes with DEGs yielded a refined gene set. Machine learning algorithms were then applied to further optimize gene selection, followed by external validation, immune infiltration analysis, RNA network construction, and exploration of potential targeted drug candidates. RESULTS: Through a rigorous screening process, VRK1, GALNT12, and RMI1 emerged as key genes associated with palmitoylation, exhibiting significant downregulation in endometriosis samples (P <&#x2009;0.05), indicative of a potential protective role. Immune infiltration analysis further revealed strong correlations between these genes and M2 macrophages as well as resting Natural Killer (NK) cells. Additionally, investigations into the targeted RNA network and drug association profiling provided novel insights, laying the groundwork for future high-quality validation studies. CONCLUSIONS: This study employed a comprehensive analytical framework to identify palmitoylation-associated key genes in endometriosis. The integration of immunoinfiltration analysis, RNA network construction, and drug association profiling offers valuable insights for advancing clinical diagnostics, disease monitoring, and therapeutic development in endometriosis.

Humans

Age-related genomic characterization and therapeutic targets in Chinese breast cancer: insights from prospective targeted sequencing and clinical data analysis.

BACKGROUND: In China, breast cancer occurs at a much younger age and has a higher recurrence and mortality rate. However, with changes in lifestyle, there has been a trend towards an older age of breast cancer incidence in Chinese women. There is a paucity of large-scale next-generation sequencing cohorts for the analysis of genomic characterization in these populations and the identification of potential therapeutic targets. METHODS: To address this gap, we performed prospective targeted sequencing of tumor and blood samples from Chinese patients and collected detailed clinical information. We then categorized patients into two groups based on age (<&#x2009;40&#xa0;years, n&#x2009;=&#x2009;637;&#x2009;&#x2265;&#x2009;40&#xa0;years, n&#x2009;=&#x2009;3442) and proceeded to provide comprehensive descriptions of somatic and germline mutations in both groups. RESULTS: The somatic mutation analysis revealed that PIK3CA, FOXA1, and TBX3 mutations were more prevalent in elderly patients. By leveraging the aforementioned mutational characteristics, we employed our institution's FUTURE-SUPER clinical trial, an umbrella study targeting metastatic breast cancer, to confirm the potential benefits of PI3K-AKT-mTOR pathway inhibitors among elderly patients with breast cancer. Furthermore, TP53 and ERBB2 were more likely to be co-mutated in young women. Patients with TP53 and ERBB2 co-mutation tend to have a poorer prognosis, but through investigation of the SPARK cohort, patients carrying the TP53 and ERBB2 co-mutation are more likely to benefit from immune checkpoint inhibitor combination with tyrosine kinase inhibitor therapy. In our study, we observed a higher frequency of mutations in the DNA homology-dependent recombination pathway in young patients with breast cancer, which was associated with an elevated Ki67 index. Additionally, we confirmed a significant prevalence of germline breast cancer susceptibility gene 1 (gBRCA1) mutations in young patients, whereas germline checkpoint kinase 2 (gCHEK2) mutations are more common in elderly patients. CONCLUSIONS: Our study, which makes use of the largest Chinese breast cancer sequencing cohort, sought to characterize the age-related genomic profile of breast cancer patients and identify novel therapeutic opportunities for individuals with breast cancer.

Adult

[Functional state of the human adrenals according to morphological analysis data and some remarks on the method of studying them].

When studying the morphology of the adrenals sufficiently exact criteria for their evaluation are necessary. Some of them may be obtained from complex macro- and microscopical investigations with the use of biometry and mathematical statistics. The work analyzes macroscopical (weight, volume, specific gravity) and microscopical (qualitative -- plethora, content of lipids, foci of cytolysis, mosaity etc. and quantitative -- absolute and relative dimensions of zones, cyto- and karyometry, interrelationship of zones, their relationship with KNP as a whole) data. On their grounds the estimation of the functional state of the adrenal cortex is made depending on the mechanism and causes of death as well as on duration of the disease.

Adolescent