In this perspective we discuss how tumor heterogeneity and therapy resistance necessitate a focus on more personalized approaches, prompting a shift toward precision medicine. At the heart of the shift towards personalized medicine, omics-driven systems biology becomes a driving force as it leverages high-throughput technologies and novel bioinformatics tools. These enable the creation of systems-based maps, providing a comprehensive view of individual tumor's functional plasticity. We highlight the innovative PHENOSTAMP program, which leverages high-dimensional data to construct a visually intuitive and user-friendly map. This map was created to encapsulate complex transitional states in cancer cells, such as Epithelial-Mesenchymal Transition (EMT) and Mesenchymal-Epithelial Transition (MET), offering a visually intuitive way to understand disease progression and therapeutic responses at single-cell resolution in relation to EMT-related single-cell phenotypes. Most importantly, PHENOSTAMP functions as a reference map, which allows researchers and clinicians to assess one clinical specimen at a time in relation to their phenotypic heterogeneity, setting the foundation on constructing phenotypic maps for personalized medicine. This perspective argues that such dynamic predictive maps could also catalyze the development of personalized cancer treatment. They hold the potential to transform our understanding of cancer biology, providing a foundation for a future where therapy is tailored to each patient's unique molecular and cellular tumor profile. As our knowledge of cancer expands, these maps can be continually refined, ensuring they remain a valuable tool in precision oncology.
Introduction: The seemingly periodic human gait exhibits stride-to-stride variations as it adapts to the changing task constraints. The optimal movement variability hypothesis (OMVH) states that healthy stride-to-stride variations exhibit "fractality"-a specific temporal structure in consecutive strides that are ordered, stable but also variable, and adaptable. Previous research has primarily focused on a single fractality measure, "monofractality." However, this measure can vary across time; strideto-stride variations can show "multifractality." Greater multifractality in stride-tostride variations would highlight the ability to tune and adjust movements more. Methods: We investigated monofractality and multifractality in a cohort of eight healthy adults during self-paced walking and running trials, both on a treadmill and overground. Footfall data were collected through force-sensitive sensors positioned on their heels and feet. We examined the effects of self-paced walking vs. running and treadmill vs. overground locomotion on the measure of monofractality, α-DFA, in addition to the multifractal spectrum width, W, and the asymmetry in the multifractal spectrum, WAsym, of stride interval time series. Results: While the α-DFA was larger than 0.50 for almost all conditions, α-DFA was higher in running and locomoting overground than walking and locomoting on a treadmill. Similarly, W was greater while locomoting overground than on a treadmill, but an opposite trend indicated that W was greater in walking than running. Larger WAsym values in the negative direction suggest that walking exhibits more variation in the persistence of shorter stride intervals than running. However, the ability to tune and adjust movements does not differ between treadmill and overground, although both exhibit more variation in the persistence of shorter stride intervals. Discussion: Hence, greater heterogeneity in shorter than longer stride intervals contributed to greater multifractality in walking compared to running, indicated by larger negative WAsym values. Our results highlight the need to incorporate multifractal methods to test the predictions of the OMVH.
This study aims to identify the most significant features in physiological signals representing a biphasic pattern in the menstrual cycle using circular statistics which is an appropriate analytic method for the interpretation of data with a periodic nature. The results can be used empirically to determine menstrual phases. A non-uniform pattern was observed in ovulating subjects, with a significant periodicity (p0.05) in mean temperature, heart rate (HR), Inter-beat Interval (IBI), mean tonic component of Electrodermal Activity (EDA), and signal magnitude area (SMA) of the EDA phasic component in the frequency domain. In contrast, non-ovulating cycles displayed a more uniform distribution (p0.05). There was a significant difference between ovulating and non-ovulating cycles (p0.05) in temperature, IBI, and EDA but not in mean HR. Selected features were used in training an Autoregressive Integrated Moving Average (ARIMA) model, using data from at least one cycle of a subject, to predict the behavior of the signal in the last cycle. By iteratively retraining the algorithm on a per-day basis, the mean temperature, HR, IBI and EDA tonic values of the next day were predicted with root mean square error (RMSE) of 0.13 ± 0.07 (C°), 1.31 ± 0.34 (bpm), 0.016 ± 0.005 (s) and 0.17 ± 0.17 (μS), respectively.
β-cells within the endocrine pancreas are fundamental for glucose, lipid and protein homeostasis. Gap junctions between cells constitute the primary coupling mechanism through which cells synchronize their electrical and metabolic activities. This evidence is still only partially investigated through models and numerical simulations. In this contribution, we explore the effect of combined electrical and metabolic coupling in β-cell clusters using a detailed biophysical model. We add heterogeneity and stochasticity to realistically reproduce β-cell dynamics and study networks mimicking arrangements of β-cells within human pancreatic islets. Model simulations are performed over different couplings and heterogeneities, analyzing emerging synchronization at the membrane potential, calcium, and metabolites levels. To describe network synchronization, we use the formalism of multiplex networks and investigate functional network properties and multiplex synchronization motifs over the structural, electrical, and metabolic layers. Our results show that metabolic coupling can support slow wave propagation in human islets, that combined electrical and metabolic synchronization is realized in small aggregates, and that metabolic long-range correlation is more pronounced with respect to the electrical one.