Nov 14, 2025 | 2025, Cells, Computational and structural biotechnology journal, Journal publications
Abstract
The use of molecular biomarkers to support disease diagnosis, monitor its progression, and guide drug treatment has gained traction in the last decades. While only a dozen biomarkers have been approved for their exploitation in the clinic by the FDA, many more are evaluated in the context of translational research and clinical trials. Furthermore, the information on which biomarkers are measured, for which purpose, and in relation to which conditions are not readily accessible: biomarkers used in clinical studies available through resources such as ClinicalTrials.gov are described as free text, posing significant challenges in finding, analyzing, and processing them by both humans and machines. We present a text mining strategy to identify proteomic and genomic biomarkers used in clinical trials and classify them according to the methodologies by which they are measured. We find more than 3000 biomarkers used in the context of 2600 diseases. By analyzing this dataset, we uncover patterns of use of biomarkers across therapeutic areas over time, including the biomarker type and their specificity. These data are made available at the Clinical Biomarker App at https://www.disgenet.org/biomarkers/, a new portal that enables the exploration of biomarkers extracted from the clinical studies available at ClinicalTrials.gov and enriched with information from the scientific literature. The App features several metrics that assess the specificity of the biomarkers, facilitating their selection and prioritization. Overall, the Clinical Biomarker App is a valuable and timely resource about clinical biomarkers, to accelerate biomarker discovery, development, and application.
Nov 14, 2025 | 2025, Cells, Journal publications
Abstract
Synchronized oscillatory fluctuations in intracellular calcium concentration across extended neuronal networks represent a functional indicator of connectivity and signal coordination. In this study, a model of human immature neurons (differentiated from LUHMES precursors) has been used to establish a robust protocol for generating reproducible intracellular Ca2+ oscillations in both two-dimensional monolayers and three-dimensional spheroids. Oscillatory activity was induced by defined ionic conditions in combination with potassium channel blockade. It was characterized by stable frequencies of approximately 0.2 Hz and high synchronization indices across millimeter-scale cultures. These properties were consistently reproduced in independent experiments and across laboratories. Single-cell imaging confirmed that oscillations were coordinated throughout large cell populations. Pharmacological interventions demonstrated that neither excitatory nor inhibitory chemical synaptic transmission influenced oscillatory dynamics. Gap junction blockers completely disrupted synchronization, while leaving individual cell activity unaffected. Functional dye-transfer assays provided additional evidence for electrical coupling. This was further supported by connexin-43 expression profiles and immunostaining. Collectively, these findings indicate that synchronized Ca2+ oscillations in LUHMES cultures are mediated by gap junctional communication rather than by conventional synaptic mechanisms. This system offers a practical platform for studying fundamental principles of network coordination and for evaluating pharmacological or toxicological modulators of intercellular coupling. Moreover, it may provide a relevant human-based model to explore aspects of neuronal maturation and to assess compounds with potential neurodevelopmental toxicity.
