Search Results (90)

Coronavirus Disease 2019 (COVID-19) and other lower respiratory tract diseases (LRTDs), including bacterial pneumonia and acute respiratory distress syndrome, share overlapping clinical features but arise from distinct pathophysiological mechanisms. The molecular signatures that distinguish these diseases remain insufficiently characterized in African populations, where genetic background, endemic infections, and environmental exposures may substantially shape immune responses. We integrated spatially resolved single-cell transcriptomic profiles from lung autopsy specimens of 30 Malawian patients, including 10 with COVID-19, 12 with other LRTDs, and 8 non-LRTD controls. In total, 61,391 cells representing 15 cell types and 36,602 gene expression features were analyzed. Using an integrated machine learning framework that combined nine feature-ranking algorithms with incremental feature selection, we identified potential molecular signatures that could discriminate among disease states within this cohort. The optimal classification models achieved weighted F1 scores greater than 0.94, demonstrating a robust capacity to differentiate COVID-19 from other LRTDs in our dataset. Notably, the macrophage-associated state in COVID-19 was dominated by an IFN-γ response with upregulation of CD163 and HLA-DQA2, contrasting sharply with the type I/III interferon signature reported in European cohorts. In addition, we observed cell-type-specific COVID-19 signatures, including downregulation of CAV1 in AT1 cells, consistent with epithelial damage; dysregulation of SFTPC in AT2 cells, suggesting surfactant dysfunction; and upregulation of NFKBIA in neutrophils, indicating altered inflammatory regulation. Gene Ontology enrichment further revealed universal disruption of protein synthesis machinery, along with cell-type-specific alterations in immune activation, epithelial repair, and inflammatory signaling pathways. Full article

Trichomonas vaginalis is the causative agent of trichomoniasis, the most common non-viral sexually transmitted infection worldwide. In these cases, 5-Nitroimidazoles, particularly metronidazole (MTZ), remain the primary treatment option; however, resistance to MTZ has been increasingly reported. This study aimed to evaluate the in vitro activity of D-form synthetic antimicrobial peptides and investigate transcriptional differences associated with MTZ resistance and peptide treatment in T. vaginalis. D-form synthetic peptides (D-TN1, D-TN3, and D-TN6) developed in the R&D Laboratory of Acibadem University were tested against metronidazole-susceptible (T. vaginalis ATCC 30236) and metronidazole-resistant (T. vaginalis ATCC 50143) strains by minimum lethal concentration (MLC) assays. D-TN1 exhibited an MLC of 16 µg/mL in both strains, whereas D-TN3 and D-TN6 exhibited MLC values of 32 µg/mL and 16–32 µg/mL, respectively. Comparative transcriptomic analysis was conducted to investigate transcriptional differences. Differential gene expression analysis identified 3395 genes between the resistant and susceptible isolates and 3060 genes in the D-TN1-treated resistant isolate (FDR < 0.05, |log₂FC| ≥ 1). D-TN1 treatment in the resistant isolate was associated with downregulation of ribosomal and metabolic pathways. If confirmed with further in vivo studies, this new antimicrobial peptide may become a new therapeutic alternative in the treatment of trichomoniasis in the future. Full article

Chickens are a primary source of protein in the human diet, with demand increasing annually. However, research on genes that promote chicken meat development remains relatively limited. Therefore, in this study, breast muscle samples (pectoralis major, n = 10 per group) from chickens at five developmental stages (D1, D35, D70, D105, and D140) were selected to investigate genetic-level changes and identify additional genes influencing chicken meat development. Differential expression analysis between adjacent stages (|FC| > 1.5, p < 0.05) revealed 42 differentially expressed genes (DEGs) shared across four comparisons, primarily enriched in muscle development pathways such as focal adhesion, the regulation of the actin cytoskeleton, and Wnt signaling. Weighted gene coexpression network analysis (WGCNA) revealed that four modules were significantly correlated with body weight and breast muscle weight phenotypes. By integrating the hub genes of the four modules and the DEGs, we identified key genes, including MEGF10, MYOM2, TM4SF1, HNMT, NR4A3, and Wnt5a. Furthermore, we conducted a comparative analysis of key gene expression trends across commercial broilers (CBs) and Beijing You (BJY) chickens. MYOM2 and Wnt5a exhibited distinct expression patterns during the early developmental stage of Xianju (XJ) chickens, suggesting that these genes may be critical factors distinguishing XJ chicken breast muscle development from that of other breeds. In all three chicken breeds analyzed, the expression levels of HNMT and MEGF10 gradually decreased with increasing age, indicating that their functions are universal in poultry muscle development. In summary, our findings revealed key regulatory genes that influence breast muscle development, offering candidate targets for marker-assisted selection in poultry breeding programs. Full article

Background/Objectives: Alloantigen H is one of thirteen systems in the chicken. Little is known about this system which has two serological alleles. The objectives of this study were (1) to identify the genetic region encoding the chicken alloantigen H, and (2) to develop DNA detection-based methods to aid H system allele identification. Methods: SNP genotypes from Axiom chicken SNP arrays were established for samples with known H system serological types. Sources of DNA included two elite Hy-Line White Leghorn lines segregating for alloantigen H, non-pedigreed samples from the Northern Illinois University (NIU) DNA bank, plus inbred line samples. Sequence information was also available for the commercial and inbred lines. Results: GWAS results from the elite Hy-Line lines and NIU DNA bank samples showed a very strong peak in the same 4.20–4.30 Mbp region on chromosome 24. Predicted cell membrane expression and the presence of non-synonymous SNP were criteria to identify candidate genes. Seven genes in this region have membrane-associated products: MCAM (CD146), THY1, MFRP, CLDN25, KCNJ14L, ABCG4, and PDZD3. However, only MCAM had an SNP variation that matched the serological haplotypes. Lines known to be segregating for the H system had concordance rates between serological results and SNP haplotype of 95% for both the elite HYL lines and 99% for the NIU samples, indicating that the MCAM (CD146) gene encodes the chicken H blood system. Conclusions: The gene product is a cell adhesion molecule affecting multiple activities including angiogenesis, development, cell differentiation, cell migration, signaling transduction, and immune responses. Long, short, and soluble isoforms are found in chickens. The described DNA-based typing methods facilitate future investigations to examine H haplotype frequencies in lines with identified differential responses such as growth or immune responses. Determining H haplotype association with egg production, feed conversion, and other traits with economic importance will aid in determining the significance of this immune-related gene in overall poultry health. Full article

Accurate normalization of RT-qPCR data requires selecting stable internal control genes, particularly in models characterized by dynamic metabolic transitions, such as 3T3-L1 adipocytes. The current study compares the expression stability of nine widely used housekeeping genes (HKGs) (peptidylprolyl isomerase A (Ppia), glyceraldehyde-3-phosphate dehydrogenase (Gapdh), beta-2 microglobulin (B2M), ribosomal protein, large, P0 (36b4), hydroxymethylbilane synthase (Hmbs), hypoxanthine guanine phosphoribosyl transferase (Hprt), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (Ywhaz), 18S ribosomal RNA (18S), and β-actin (Actb)) across key stages of differentiation (days 0, 9, and 18) and under treatments with palmitic acid and docosahexaenoic acid. Stability was assessed using four classical algorithms—geNorm, NormFinder, BestKeeper, and RefFinder—supplemented by the ΔCt method, conventional statistical testing, correlation, and regression analysis relative to two target genes, fatty acid-binding protein 4 (Fabp4) and sterol regulatory element binding transcription factor 1 (Srebf1). The obtained data indicate that no single HKG remains universally stable across these experimental conditions, and the expression of traditionally used reference genes (Gapdh, Actb, Hprt, 18S) is highly influenced by both the stage of adipogenesis and exposure to lipid-modulating factors. In contrast, Ppia, 36b4, and B2M—despite some of them being underestimated in use as references—consistently display the lowest variability across most analytical tools, forming a reliable and functionally diverse normalization panel. It should be noted that our initial stability assessment revealed apparent discrepancies among mathematical evaluation methods, emphasizing the need for a holistic, multiple-level approach strategy. The applied combination of algorithmic and statistical methods provides a more rigorous and objective framework for assessing the stability of reference genes, which is highly recommended in such a complex adipocyte-based model. Full article

Glioblastoma (GBM) shows extensive epigenetic heterogeneity. In IDH-wildtype (IDH-WT) GBM, promoter DNA methylation may regulate lineage programs influencing tumor evolution and prognosis; here, we systematically profiled promoter-level methylation dynamics across longitudinal tumors. Genome-wide DNA methylation data were obtained from the publicly available Gene Expression Omnibus (GEO; GSE279073) dataset, comprising a longitudinal cohort of 226 IDH-wildtype glioblastomas profiled on the Illumina Infinium EPIC 850K array across primary and recurrent stages at the University of California, San Francisco. From 333 Gene Ontology gliogenesis-annotated genes (GO:0042063), a 48-gene promoter panel was derived, with ≥2 probes per gene. Promoter methylation was summarized as the median β-value and tested using one-sample Wilcoxon with FDR correction. Functional enrichment, longitudinal variation, and patient-level methylation burden were assessed. Validation analyses were performed using independent IDH-wildtype GBM datasets from The Cancer Genome Atlas (RNA-seq and 450K methylation; n = 347). Promoter hypomethylation predominated across all stages, with 25 genes consistently hypomethylated and 7 hypermethylated. Functional enrichment highlighted gliogenesis, glial cell differentiation, neurogenesis, and Notch-related signaling. In TCGA, promoter methylation inversely correlated with expression for 11 of 33 genes (FDR < 0.05). An Expression Score contrasting hypomethylated and hypermethylated genes was positively associated with improved overall survival, where higher scores predicted better outcome (HR = 0.87, p = 0.016; Q4 vs. Q1 HR = 0.68, p = 0.025), and a complementary Methylation Score showed that higher promoter hypermethylation predicted poorer outcome (HR = 1.73, p < 0.001). CNTN2 and TSPAN2 were adverse prognostic genes (FDR < 0.05). The Expression Score was highest in Proneural tumors and lowest in Mesenchymal tumors (p < 0.001), reflecting a proneural-like state associated with better prognosis. Promoter methylation within gliogenesis genes defines a stable yet prognostically informative epigenetic signature in IDH-WT GBM. Hypomethylation promotes transcriptional activation and a favorable outcome, whereas hypermethylation represses lineage programs and predicts poorer survival. Full article

Microcystin-LR (MC-LR), produced by Cyanobacteria, is being detected in many types of waters, posing a universal threat to aquatic animals. However, there have been few comprehensive endpoints assessed, including oxidative stress, transcriptome changes, intestinal microbiota, and histopathology, in anurans exposed to MC-LR. In this study, all these effects of MC-LR on Chinese brown frog (Rana chensinensis David, 1875) tadpoles were investigated by exposing the tadpoles to MC-LR at different concentrations (0, 0.1, 1.0, 5.0, and 10.0 μg/L) for 7 days. Our results revealed that treatment of tadpoles with the high MC-LR dosage (10.0 μg/L) induced a significant increase in malondialdehyde (MDA) content and decreases in superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, and total antioxidant capacity (TAC). RNA-seq analysis of the liver showed that the number of differentially expressed genes (DEGs) was 2361 under lower MC-LR stress (1.0 μg/L), while the number of DEGs increased to 3185 under higher MC-LR stress (10.0 μg/L). Gene Ontology analysis showed that several biological processes and molecular functions related to digestion were enriched in both MC-LR treated groups, such as digestion, serine-type endopeptidase activity, and serine-type peptidase activity. KEGG enrichment analysis also indicated that the digestion for pancreatic secretion, protein digestion and absorption, and fat digestion and absorption pathways were significantly enriched in the treatment groups. Additionally, the bacterial richness was elevated by MC-LR exposure. At the phylum level, treatment with MC-LR changed the relative abundances of Desulfobacterota, Fusobacteriota, and Actinobacteriota. At the genus level, MC-LR caused significant alterations in the abundances of 23 genera. Furthermore, examination of sections obtained from the livers and intestines of tadpoles in the treatment groups showed damaged histological structure. The knowledge from this study will have potential value for understanding the mechanisms related to MC-LR toxicity in anurans. Full article

Circular RNAs (circRNAs) are small, non-coding RNAs in which the 5′ and 3′ ends are linked covalently by back-splicing of exons from a single pre-mRNA. More and more scientific evidence is gathered for their wide distribution in the animal world, playing the role of regulators for biological processes, being cell- and tissue-specific. They can influence cellular physiology by various molecular mechanisms, finally modulating gene expression. CircRNAs are believed nowadays to be expressed in both receptive and cancerous endometrium. Due to their abundant expression in the endometrial tissue and their small size and stability, they have been considered potential diagnostic markers and treatment targets for endometrial-related diseases. The regulation of proliferation and differentiation is essential for the formation of receptive endometrium and for endometrial cancer emergence and progression. The receptive endometrium can be regarded as the most highly differentiated state of the endometrium. In contrast, the cancerous endometrium is characterized by a high level of proliferation and the lowest degree of differentiation. These endometria could be conditionally considered opposites. We are investigating the circRNA–miRNA–mRNA regulatory networks that can promote or suppress the proliferation and differentiation of endometrial cells by activating specific signaling pathways in both receptive and cancerous endometria. It could be worth knowing whether there are universal endometrial switches responsible for proliferation and differentiation processes that can alter the balance between them. We are interested in their clinical application as biomarkers and therapeutic targets for both endometrial receptivity issues and EC cases, particularly in diagnosis, progression assessment, and outcome prediction. Full article

Background: Ovarian cancer (OC) is the second most common gynecologic malignancy in the United States and remains the leading cause of death among cancers of the female reproductive system. Alarmingly, mortality rates have risen disproportionately among women of African ancestry compared to those of European or Asian descent. Identifying microRNA (miRNA) signatures that contribute to these disparities may enhance prognostic accuracy and inform personalized therapeutic strategies. Methods: In this study, we identified prognostic markers of overall survival in serous ovarian cancer (SOC) using data from The Cancer Genome Atlas (TCGA) and the Human Protein Atlas. Integrative bioinformatic analyses revealed three key prognostic genes—TIMP3 (Tissue Inhibitor of Metalloproteinases-3), BRAF (v-raf murine sarcoma viral oncogene homolog B), and ITGB1 (Integrin Beta-1)—as critical molecular determinants associated with survival in patients with SOC. Candidate miRNAs regulating these genes were predicted using TargetScanHuman v8.0, identifying a core regulatory set comprising miR-192, miR-30d, miR-16-5p, miR-143-3p, and miR-20a-5p. To validate their clinical relevance, formalin-fixed, paraffin-embedded (FFPE) and fresh SOC tumor samples were obtained from African American and Caucasian patients who underwent surgery at Loma Linda University (LLU) between 2010 and 2023. Results and Discussion: Among all these, ITGB1 (p = 0.00033), TIMP3 (p = 0.0035), and BRAF (p = 0.026) emerged as statistically significant predictors. Following total RNA extraction, cDNA synthesis, and quantitative reverse transcription PCR (qRT-PCR), the expression levels of these miRNAs and their target genes were quantified. In the LLU cohort, ITGB1 and TIMP3 were significantly upregulated in African American patients compared to Caucasian patients (p < 0.01 and p < 0.02, respectively). Among the miRNAs, miR-192-5p was particularly noteworthy, showing marginally differential expression in LLU samples (p = 0.0712) but strong statistical significance in the TCGA cohort (p = 0.00013), where elevated expression correlated with poorer overall survival (p = 0.021). Pathway enrichment and gene ontology analyses (miRTargetLink2.0, Enrichr) revealed interconnected regulatory networks linking miR-192, miR-16-5p, miR-143-3p, and miR-20a-5p to ITGB1; miR-143-3p/miR-145-5p to BRAF; and miR-16-5p and miR-30c/d to TIMP3. Conclusions: Collectively, these findings identify distinct miRNA–mRNA regulatory signatures—particularly the miR-192-5p–ITGB1/TIMP3 axis—as potential clinically relevant biomarkers that may contribute to racial disparities and disease progression in ovarian cancer. Full article

Prognostic uncertainty and missed diagnoses of sepsis remain frequent after cardiopulmonary bypass (CPB) surgery, where systemic inflammatory response (SIRS) arises from surgical trauma, blood activation in the extracorporeal circuit, ischemia/reperfusion injury, and endotoxin release. Among innovative biomarkers, pro-adrenomedullin (pro-ADM), particularly its stable fragment mid-regional pro-adrenomedullin (MR-proADM), has shown promise for detecting endothelial dysfunction and predicting organ failure in sepsis. SeptiCyte^® RAPID (Seattle, WA, USA) also represents a novel diagnostic tool that assesses the host immune response by quantifying PLA2G7 and PLAC8 gene expression in whole blood, offering potential for early differentiation between sepsis and sterile inflammation. We analyzed traditional and innovative biomarkers within 24 h post-CPB in a pilot group of patients admitted to the cardiac Intensive Care Unit of the “Città della Salute e della Scienza” University Hospital (Turin, Italy) between June and November 2023. Data from the following 14 patients were collected: 7 undergoing surgery for infective endocarditis (IE, Group 1) and 7 having standard elective cardiac surgery (Group 2). Procalcitonin (PCT), lactate, and pro-ADM increased in Group 1 but not in Group 2. SeptiCyte^® RAPID showed a moderate, borderline increase in Group 1. The innovative biomarkers had a good performance in patients exhibiting signs of organ dysfunction and in subjects demonstrating at least cardiovascular and/or pulmonary damage and under vasopressor and inotropic support. Although limited by the small sample, our preliminary data suggest no biomarker alterations in patients with standard elective cardiac surgery, unlike in those with IE. Full article

Excessive abdominal fat deposition accompanying rapid growth in broiler chickens seriously affects production efficiency. Using divergently selected broiler lines from Northeast Agricultural University, we integrated transcriptome sequencing, whole-genome resequencing, and three-dimensional genomic data to identify key SNPs affecting abdominal fat deposition. From 3,850,758 initial SNPs, 22,721 high-quality SNPs were selected (|ΔAF| ≥ 0.9) and validated to obtain 7341 reliable SNPs. GWAS identified 16 SNPs significantly associated with abdominal fat weight, while LD analysis revealed 22 highly linked SNPs, finally determining 2302 candidate SNPs. Transcriptome analysis identified 825 differentially expressed genes (p ≤ 0.05, |FC| ≥ 1.5). Functional annotation revealed 201 SNPs located in differentially expressed gene regions, including 8 coding SNPs and 193 non-coding SNPs, with an additional 15 SNPs potentially regulating through long-range chromatin interactions. Mechanistic analysis showed that coding SNPs regulate gene expression by altering codon translation rates or mRNA stability, while non-coding SNPs regulate transcription by affecting transcription factor binding. Phenotypic association analysis demonstrated that all 213 SNPs can cause ≥2-fold differences in abdominal fat weight, with 182 SNPs causing ≥3-fold differences. This study successfully identified 213 functional SNPs affecting abdominal fat deposition in broilers and revealed their molecular basis for regulating fat metabolism through multiple mechanisms, providing important genetic markers for low-fat breeding in broilers. Full article

Language, a uniquely human cognitive faculty, is fundamentally characterized by its capacity for complex thoughts and structured expressions. This review examines two critical measures of linguistic performance: idea density (ID) and grammatical complexity (GC). ID quantifies the richness of information conveyed per unit of language, reflecting semantic efficiency and conceptual processing. GC, conversely, measures the structural sophistication of syntax, indicative of hierarchical organization and rule-based operations. We explore the neurobiological underpinnings of these measures, identifying key brain regions and white matter pathways involved in their generation and comprehension. This includes linking ID to a distributed network of semantic hubs, like the anterior temporal lobe and temporoparietal junction, and GC to a fronto-striatal procedural network encompassing Broca’s area and the basal ganglia. Moreover, a central theme is the integration of Chomsky’s theories of Universal Grammar (UG), which posits an innate human linguistic endowment, with their neurobiological correlates. This integration analysis bridges foundational models that first mapped syntax (Friederici’s work) to distinct neural pathways with contemporary network-based theories that view grammar as an emergent property of dynamic, inter-regional neural oscillations. Furthermore, we examine the genetic factors influencing ID and GC, including genes implicated in neurodevelopmental and neurodegenerative disorders. A comparative anatomical perspective across human and non-human primates illuminates the evolutionary trajectory of the language-ready brain. Also, we emphasize that, clinically, ID and GC serve as sensitive neurocognitive markers whose power lies in their often-dissociable profiles. For instance, the primary decline of ID in Alzheimer’s disease contrasts with the severe grammatical impairment in nonfluent aphasia, aiding in differential diagnosis. Importantly, as non-invasive and scalable metrics, ID and GC also provide a critical complement to gold-standard but costly biomarkers like CSF and PET. Finally, the review considers the emerging role of AI and Natural Language Processing (NLP) in automating these linguistic analyses, concluding with a necessary discussion of the critical challenges in validation, ethics, and implementation that must be addressed for these technologies to be responsibly integrated into clinical practice. Full article

Given the critical role of manganese (Mn) as an essential micronutrient in wheat growth and development and the high efficiency of foliar fertilization in optimizing nutrient uptake and improving crop quality, this study aimed to elucidate the regulatory effects of exogenous manganese sulfate application on wheat grain yield and carotenoid accumulation. Methods: Field experiments were conducted from 2022 to 2024 at the Shuitou Experimental Station of the Cotton Research Institute, Shanxi Agricultural University (35°11′ N, 111°05′ E), using the wheat cultivar ‘Jinmai 110’. Foliar applications of manganese sulfate were administered at concentrations of 0.5 g/kg, 1.0 g/kg, and 1.5 g/kg, with water serving as the control (CTRL). Spraying was conducted on the upper canopy during the flowering and grain-filling stages, applied every 7 days for a total of three times. Samples for transcriptomic analysis were collected within 24 h of the final application. At maturity, yield-related traits and grain carotenoid contents were assessed. Results: Foliar application of 1.0 g/kg MnSO₄ significantly enhanced both grain yield and carotenoid content in wheat. Transcriptome sequencing revealed that treatment with 1.0 g/kg manganese sulfate (M2) resulted in 4761 differentially expressed genes (DEGs), including 2933 upregulated and 1828 downregulated genes, relative to CTRL. Gene Ontology (GO) analysis showed that in the M2 vs. CTRL comparison, 819 GO terms were significantly enriched among upregulated DEGs and 630 among downregulated DEGs. Specifically, upregulated genes were associated with 427 biological process terms and 299 cellular component terms, while downregulated genes were linked to 361 biological processes and 211 cellular components. Enriched functions primarily included cellular processes, metabolic processes, catalytic activity, and binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed 809 annotations for upregulated DEGs and 330 for downregulated DEGs, mainly related to photosynthesis, carotenoid biosynthesis, phenylpropanoid biosynthesis, and plant hormone signal transduction. In total, 43,395 alternative splicing (AS) events were identified from 17,165 genes, including 445 upregulated and 319 downregulated AS events, primarily enriched in photosynthesis and plant hormone-related pathways. Conclusion: Foliar application of manganese sulfate significantly modulates gene expression in wheat grains, thereby improving both yield and carotenoid accumulation. Key biological processes affected include photosynthesis, plant hormone signal transduction, and the carotenoid biosynthetic pathway. The interactions among these regulatory networks constitute a complex molecular mechanism through which exogenous Mn influences agronomic traits. These findings provide mechanistic insights and practical implications for enhancing wheat productivity and nutritional quality through foliar manganese application. Full article

Cortical transcriptional dysregulation is widespread in Huntington’s disease (HD). We re-examined prefrontal Brodmann Area 9 (BA9) RNA-seq (GSE64810; 20 HD, 49 controls) using BH-FDR and GEO2R to obtain differential-expression statistics for downstream in silico integration. A compact, direction-aware 80-gene panel was assembled for visualization/ranking only, while inference relied on validated target sets and full-universe testing. At FDR < 0.05, we detected Up = 2923 and Down = 2448 genes (ratio 1.19), indicating a mild predominance of up-regulation. MIR219A2 was strongly down-regulated, and four experimentally validated targets (FOXC1, NFKBIA, SLC38A2, SLC6A20) overlapped the up-regulated core; as expected for n = 4, no GO/KEGG/Reactome term met FDR < 0.05, and STRING returned no high-confidence edges. Beyond the curated panel, we tested MIR219A2 (hsa-miR-219a-5p; hsa-miR-219a-1-3p; hsa-miR-219a-2-3p) targets against the full FDR-significant BA9 up-regulated universe. Two orthogonal, experimentally supported resources—miRTarBase functional assays and ENCORI/starBase CLIP—showed direction-consistent, FDR-controlled enrichment, with effect sizes and uncertainty reported in the main text, supporting a BA9-specific, MIR219A2-aligned association signal. On the TF axis, MSigDB C3:TFT (gene symbols) revealed significant over-representation of TF target sets among BA9-Up under the same BA9 expressed-gene background after BH-FDR (e.g., NFAT motifs, C/EBP, FOXA/HNF3), while TRRUST v2 applied to the MIR219A2 CLIP–BA9-Up subset provided target-level transparency. MIR219A2 enrichments were robust to composition sensitivity analyses (marker-excluded and neuron/glia-stratified backgrounds). Exploratory GO–Biological Process bubbles are shown for trend summarization only; no term met FDR < 0.05 in the primary analysis. All conclusions are analysis-only; no wet-lab or biofluid/peripheral assays were performed, and findings are BA9-specific—generalization to other regions remains hypothesis-generating. Full article

Background: The amount of data produced from biological experiments has increased geometrically, posing a challenge for the development of new methodologies that could enable their interpretation. We propose a novel approach for the analysis of transcriptomic data derived from acute lymphoblastic leukemia (ALL) and rhabdomyosarcoma (RMS) cell lines, using bioinformatics, systems biology and geometrical approaches. Methods: The expression profile of each cell line was investigated using microarrays, and identified genes were used to create a systems pathway model, which was then simulated using differential equations. The transcriptomic profile used involved genes with similar expression levels. The simulated results were further analyzed using geometrical approaches to identify common expressional dynamics. Results: We simulated and analyzed the system network using time series, regression analysis and helical functions, detecting predictable structures after iterating the modelled biological network, focusing on TIE1, STAT1, MAPK14 and ADAM17. Our results show that such common attributes in gene expression patterns can lead to more effective treatment options and help in the discovery of universal tumor biomarkers. Discussion: Our approach was able to identify complex structures in gene expression patterns, indicating that such approaches could prove useful towards the understanding of the complex tumor dynamics. Full article