Biology subjects

Perez-Yarza, G.

Publications and source records attributed to Perez-Yarza, G..

8 recordsLinked to original sources

bioRxiv2026

Systemic and kinematic properties of Amoeba proteus migration correlate strongly across environments

Recent work has shown that cell migration is a systemic property of the whole cell, yet how the different properties of a migratory trajectory relate to one another remains largely uncharacterized. Here we quantified the migration of 150 Amoeba proteus cells under three experimental scenarios (absence of stimuli, a direct-current electric field, and a chemotactic peptide gradient) with eleven metrics that describe either the systemic dynamics of the trajectory (long-range correlations, long-term persistence, super-diffusive exploration, regularity of the move steps and memory of the velocity) or its kinematic output (net displacement, straightness and speed). Screening all 55 metric pairs for statistical dependence with distance covariance identified six couplings that held in all three experimental scenarios, besides the pairs linked by definition. Long-term persistence and super-diffusive exploration were coupled with each other, in agreement with the scaling relation expected for self-similar trajectories, and each of them was coupled with the net displacement and the straightness of the trajectory: more persistent and more super-diffusive cells moved farther and along straighter paths. In addition, the long-range correlations of the move steps were coupled with the memory of speed between consecutive steps. All six couplings were positive and monotonic, with no trend reversal over the observed range. The stimuli shifted six of the eleven metrics, the electric field mainly increasing the straightness and the net displacement of the trajectories and the chemical gradient mainly increasing the speed memory, but they left the six couplings intact and reorganized part of the dependence structure around speed. These results show that several systemic and kinematic properties of Amoeba proteus migration are not independent observables but vary together as parts of an integrated system whose couplings are preserved across environments.

cell biology↗

bioRxiv2026

Quantifying the Information Capacity of DNA Methylation as an Epigenetic Memory System

The information content of the genome has been extensively analyzed. However, a comparable quantitative framework for DNA methylation is still lacking. Without such quantification, the magnitude of this regulatory and dynamic epigenetic structure remains conceptually imprecise, even though methylation dysregulation is strongly linked to disease-related phenotypes and altered cellular identity. Here we address this gap by applying Shannon information theory to DNA methylation. We first consider methylation marks as binary or probabilistic regulatory states and estimate the theoretical upper-bound information capacity of the human methylome under simplifying assumptions. We then progressively refine this estimate by incorporating biologically relevant constraints, including methylation bias, bimodal methylation distributions, local CpG correlation, genomic regulatory class, and cell-type-discriminative methylation patterns. This approach allows us to distinguish between theoretical methylation capacity, statistical methylation entropy, and biologically interpretable regulatory information. Finally, we consider methylation information from a discriminative perspective, analyzing its contribution to distinguishing cell types and regulatory cellular states. Within this framework, mutual information between methylation patterns and cell identity provides a biologically constrained estimate of methylations role as an epigenetic identity code. Our layered analysis reconciles megabit-scale methylome capacity with compact, biologically interpretable identity signatures. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/735086v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@44dc66org.highwire.dtl.DTLVardef@e1ba03org.highwire.dtl.DTLVardef@17b2acborg.highwire.dtl.DTLVardef@136b1ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2026

Multi-timescale PTM architecture in human RNA polymerase II

Human RNA Polymerase II (Pol II) is characterized by a dense layer of over 775 post-translational modifications (PTMs) that form a dynamic, rewritable regulatory architecture integrating large numbers of cellular signals to coordinate transcription initiation, elongation, termination, and co-transcriptional RNA processing. While genomic information has been extensively catalogued, the potential information capacity associated with Pol II PTM patterns has remained largely unquantified. Here, we analyze the PTM sites across the human Pol II complex (Rpb1-Rpb12) and estimate the state-space information capacity using Shannon entropy theory. We first provide a theoretical upper bound of ~707.98 bits per Pol II molecule (~88.50 bytes) corresponding to ~5.68 x 107 bits per nucleus (~7.10 MB), assuming ~80,200 Pol II molecules per cell. We distinguish this maximal capacity from a conservative, kinetically addressable estimate of ~114.88 bits per molecule (~1.15 MB per nucleus), reflecting physiological kinetic constraints and site coupling that restrict the simultaneously addressable PTM state space in vivo. Finally, we show that major PTM classes (phosphorylation, proline isomerization, O-GlcNAcylation and ubiquitination) operate over distinct lifetimes, from seconds to minutes and hours-scale processes, supporting a multi-timescale biochemical architecture of this enzyme. Together, these results provide a quantitative information framework that distinguishes maximal PTM state-space capacity from kinetically addressable physiological regulatory capacity, supporting a view of Pol II PTM patterning as a high-dimensional, dynamically reconfigurable, multi-timescale regulatory information layer. HighlightsA systems-level framework quantifies regulatory information in Pol II PTMs Known PTM modification sites provide 707.98 bits per Pol II as a regulatory upper bound Physiological kinetic constraints reduce accessible regulatory capacity to 114.88 bits Distinct PTM modification classes define fast, intermediate, and slow regulatory layers Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/734958v1_ufig1.gif" ALT="Figure 1"> View larger version (84K): org.highwire.dtl.DTLVardef@1101c1borg.highwire.dtl.DTLVardef@a551fcorg.highwire.dtl.DTLVardef@1a97bd3org.highwire.dtl.DTLVardef@68db_HPS_FORMAT_FIGEXP M_FIG C_FIG

Systems Biology↗

bioRxiv2024

Systemic migrations in enucleated cells

Directional locomotion is a fundamental characteristic of many cells with great relevance in essential physiological and human pathological processes. For decades, research efforts have focused on studying specific individual processes and their corresponding biomolecular components involved in cellular locomotion movements. However, the notion that migratory displacements are functionally integrated and regulated at the systemic level has never been recognized. Recently, we have shown that locomotion movements correspond to an emergent systemic behavior which depends on a complex integrated self-organized system carefully regulated at a global cellular level. Here, to study the forces driving the locomotion movement of the cell, and to corroborate the thesis on the systemic character of the cellular migratory responses we have carried out an extensive study of locomotion movements with enucleated cells (cytoplasts) belonging to Amoeba proteus. The migratory behavior of both enucleated and non-enucleated cells has been individually studied in four different scenarios: in absence of stimuli, under a galvanotactic field, in chemotactic gradient, and under very complex conditions such as simultaneous galvanotactic and chemotactic stimuli. All these experimental displacement trajectories, obtained on flat two-dimensional surfaces, have been analyzed using advanced non-linear quantitative approaches. Our results show that both non-enucleated amoebas and cytoplasts display the same complex kind of dynamic structure in their migratory trajectories. The locomotion displacements of enucleated cells are regulated by complex self-organized integrative dynamics, modulated at a global-systemic level which seems to depend on the cooperative interaction of most, if not all, molecular components of cells.

systems biology↗

bioRxiv2024

Forces directing the systemic correlations of cell migration

Directional motility is an essential property of cells. Despite its enormous relevance in many fundamental physiological and pathological processes, how cells control their locomotion movements remains an unresolved question. Here we have addressed the systemic processes driving the directed locomotion of cells. Specifically, we have performed an exhaustive study analyzing the trajectories of 700 individual cells belonging to three different species (Amoeba proteus, Metamoeba leningradensis and Amoeba borokensis) in four different scenarios: in absence of stimuli, under an electric field (galvanotaxis), in a chemotactic gradient (chemotaxis), and under simultaneous galvanotactic and chemotactic stimuli. All movements were analyzed using advanced quantitative tools. The results show that the trajectories are mainly characterized by coherent integrative responses that operate at the global cellular scale. These systemic migratory movements depend on the cooperative non-linear interaction of most, if not all, molecular components of cells. SignificanceCellular migration is a cornerstone issue in many human physiological and pathological processes. For years, the scientific attention has been focused on the individualized study of the diverse molecular parts involved in directional motility; however, locomotion movements have never been regarded as a systemic process that operates at a global cellular scale. In our quantitative experimental analysis essential systemic properties underlying locomotion movements were detected. Such emergent systemic properties are not found specifically in any of the molecular parts, partial mechanisms, or individual processes of the cell. Cellular displacements seem to be regulated by integrative processes operating at systemic level.

systems biology↗

bioRxiv2019

A new clinical tool to predict outcome in early-stage melanoma patients

Around 25% of early-stage melanoma patients eventually develop metastasis. Thus, we set out to define serological biomarkers that could be used along with clinical and histopathological features of the disease to predict these events. We previously demonstrated that in stage II melanoma patients, serum levels of dermcidin (DCD) were associated with metastatic progression. Based on the relevance of the immune response on the cancer progression and the recent association of DCD with local and systemic immune response against cancer cells, serum DCD was analyzed in a new cohort of patients along with IL-4, IL-6, IL-10, IL-17A, IFN{gamma} TGF{beta} and GM-CSF. We included 448 melanoma patients, 323 of whom were diagnosed as stages I-II according to AJCC. Levels of selected cytokines were determined by ELISA and Luminex and obtained data were analyzed employing Machine Learning and Kaplan-Meier techniques to define an algorithm capable of accurately classifying early-stage melanoma patients with a high and low risk of developing metastasis. The results show that in early-stage melanoma patients, serum levels of the cytokines IL-4, GM-CSF and DCD together with the Breslow thickness are those that best predict melanoma metastasis. Moreover, resulting algorithm represents a new tool to discriminate subjects with good prognosis from those with high risk for a future metastasis. Novelty and ImpactWe have developed a prognostic equation that considers the serum IL-4, GM-CSF and DCD levels, along with the Breslow thickness to accurately classify melanoma outcome in patients. In this sense, a rigorous follow-up is recommended for early-stage melanoma patients with a high Breslow thickness, high serum IL-4 levels and low GM-CSF and DCD levels at the time of diagnosis, given the elevated risk for these patients to develop metastasis during follow-up.

pathology↗

bioRxiv2018

Evidences of conditioned behavior in Amoeba proteus

Associative memory is the main type of learning wherein complex organisms endowed with evolved nervous systems respond efficiently to determined environmental stimuli. This fundamental cognitive property has been evidenced in different multicellular species, from cephalopods to Humans, but never in individual cells. Here, following Pavlovs experiments with dogs that founded the principles of classical conditioning, we have observed the development of an associative memory in Amoeba proteus, which corresponds to the emergence of a new systemic motility pattern. In our cellular version of this conditioning behavior, we have used a controlled direct current electric field as the conditioned stimulus and a specific chemotactic peptide as the non-conditioned stimulus. Our study allowed us to demonstrate that Amoeba proteus are capable of linking two independent past events, and the induced associative memory can be recorded for up to at least four hours. For the first time, it has been observed that a systemic response to a specific stimulus can be modified by learning in unicellular organisms. This finding opens up a new framework in the understanding of the mechanisms underlying the complex systemic behavior involved in the cellular migration and the adaptive capacity of cells to the external medium.

systems biology↗

bioRxiv2017

Long-Term Memory In The Migration Movements Of Enucleated Amoeba proteus

How motile, free unicellular organisms maximize the rate at which they encounter resources and develop optimal search strategies remains largely unknown. In fact, cell foraging is a very complex activity in which unicellular organisms integrate a diversity of external cues and develop efficient systemic movements to localize nourishment. These foraging strategies are critical when cells face conditions of scarce resources or they dont possess information on where food is located. Here, in order to determine whether nuclear activity is directly involved in cell migration, we placed single, well-isolated, enucleated and non-enucleated starved Amoeba proteus on nutrient-free petri dishes, and we then analyzed their trajectories of movement using non-linear dynamic tools. We found that despite being enucleated, the systemic responses of the protoplasm exhibited typical biological behaviors, moving with apparent normality, creeping along the substrate, developing pseudopodia and gobbling up prey. Our quantitative studies show that both the non-enucleated and enucleated amoebas display a similar migration structure, characterized by super-diffusivity, non-trivial long-term correlations and move-step fluctuations with scale invariant properties. In conclusion, the nuclear activity does not seem to directly control the systemic cellular movements involved in locating sparse resources.

systems biology↗