Publications by authors named "Luis M Rocha"

Cellular automata (CA) are discrete dynamical systems with a prominent place in the history and study of artificial life. Here, we focus on the density classification task (DCT) in which a 1-dimensional lattice of Boolean (on/off) automata must perform a form of rudimentary quorum sensing. Typically, the ring lattice consists of 149 cells (though we consider other sizes as well) that update their state according to their own state and its six nearest neighbors in the previous time step.

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Article Synopsis
  • Male germ cells across animal species share a common origin, indicating they likely follow a conserved genetic program crucial for their identity.
  • The research employs network analysis of the spermatocyte transcriptome from various species to explore the evolutionary origin of male germ cells at the molecular level, revealing a core set of genes and functional associations that have been preserved through evolution.
  • By disrupting male germ cell identity, the study identifies 161 new spermatogenesis-related genes and highlights their implications for human infertility, while promoting a cross-species approach that can be applied to other cell types and diseases.
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Minimum spanning trees and forests are powerful sparsification techniques that remove cycles from weighted graphs to minimize total edge weight while preserving node reachability, with applications in computer science, network science, and graph theory. Despite their utility and ubiquity, they have several limitations, including that they are only defined for undirected networks, they significantly alter dynamics on networks, and they do not generally preserve important network features such as shortest distances, shortest path distribution, and community structure. In contrast, distance backbones, which are subgraphs formed by all edges that obey a generalized triangle inequality, are well defined in directed and undirected graphs and preserve those and other important network features.

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Background: The co-administration of drugs known to interact greatly impacts morbidity, mortality, and health economics. This study aims to examine the drug-drug interaction (DDI) phenomenon with a large-scale longitudinal analysis of age and gender differences found in drug administration data from three distinct healthcare systems.

Methods: This study analyzes drug administrations from population-wide electronic health records in Blumenau (Brazil; 133 K individuals), Catalonia (Spain; 5.

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Complex living systems are thought to exist at the "edge of chaos" separating the ordered dynamics of robust function from the disordered dynamics of rapid environmental adaptation. Here, a deeper inspection of 72 experimentally supported discrete dynamical models of cell processes reveals previously unobserved order on long time scales, suggesting greater rigidity in these systems than was previously conjectured. We find that propagation of internal perturbations is transient in most cases, and that even when large perturbation cascades persist, their phenotypic effects are often minimal.

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In weighted graphs the shortest path between two nodes is often reached through an indirect path, out of all possible connections, leading to structural redundancies which play key roles in the dynamics and evolution of complex networks. We have previously developed a parameter-free, algebraically-principled methodology to uncover such redundancy and reveal the distance backbone of weighted graphs, which has been shown to be important in transmission dynamics, inference of important paths, and quantifying the robustness of networks. However, the method was developed for undirected graphs.

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Epilepsy is a common chronic neurological disease. People with epilepsy (PWE) and their caregivers face several challenges related to their epilepsy management, including quality of care, care coordination, side effects, and stigma management. The sociotechnical issues of the information management contexts and challenges for epilepsy care may be mitigated through effective information management.

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Given the large size and complexity of most biochemical regulation and signaling networks, there is a non-trivial relationship between the micro-level logic of component interactions and the observed macro-dynamics. Here we address this issue by formalizing the concept of pathway modules developed by [1], which are sequences of state updates that are guaranteed to occur (barring outside interference) in the causal dynamics of automata networks after the perturbation of a subset of driver nodes. We present a novel algorithm to automatically extract pathway modules from networks and characterize the interactions that may take place between the modules.

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Biomolecular network dynamics are thought to operate near the critical boundary between ordered and disordered regimes, where large perturbations to a small set of elements neither die out nor spread on average. A biomolecular automaton (e.g.

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The structure of social networks strongly affects how different phenomena spread in human society, from the transmission of information to the propagation of contagious diseases. It is well-known that heterogeneous connectivity strongly favors spread, but a precise characterization of the redundancy present in social networks and its effect on the robustness of transmission is still lacking. This gap is addressed by the metric backbone, a weight- and connectivity-preserving subgraph that is sufficient to compute all shortest paths of weighted graphs.

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The co-administration of drugs known to interact has a high impact on morbidity, mortality, and health economics. We study the drug-drug interaction (DDI) phenomenon by analyzing drug administrations from population-wide Electronic Health Records (EHR) in Blumenau (Brazil), Catalonia (Spain), and Indianapolis (USA). Despite very different health care systems and drug availability, we find a common large risk of DDI administration that affected 13 to 20% of patients in these populations.

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The optimization problem aiming at the identification of minimal sets of nodes able to drive the dynamics of Boolean networks toward desired long-term behaviors is central for some applications, as for example the detection of key therapeutic targets to control pathways in models of biological signaling and regulatory networks. Here, we develop a method to solve such an optimization problem taking inspiration from the well-studied problem of influence maximization for spreading processes in social networks. We validate the method on small gene regulatory networks whose dynamical landscapes are known by means of brute-force analysis.

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The discovery of drug-drug interactions (DDIs) that have a translational impact among in vitro pharmacokinetics (PK), in vivo PK and clinical outcomes depends largely on the quality of the annotated corpus available for text mining. We have developed a new DDI corpus based on an annotation scheme that builds upon and extends previous ones, where an abstract is fragmented and each fragment is then annotated along eight dimensions, namely, focus, polarity, certainty, evidence, directionality, study type, interaction type and mechanism. The guideline for defining these dimensions has undergone refinement during the annotation process.

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Sudden Unexpected Death in Epilepsy (SUDEP) remains a leading cause of death in people with epilepsy. Despite the constant risk for patients and bereavement to family members, to date the physiological mechanisms of SUDEP remain unknown. Here we explore the potential to identify putative predictive signals of SUDEP from online digital behavioral data using text and sentiment analysis tools.

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Living systems comprise interacting biochemical components in very large networks. Given their high connectivity, biochemical dynamics are surprisingly not chaotic but quite robust to perturbations-a feature C.H.

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Redundancy needs more precise characterization as it is a major factor in the evolution and robustness of networks of multivariate interactions. We investigate the complexity of such interactions by inferring a connection transitivity that includes all possible measures of path length for weighted graphs. The result, without breaking the graph into smaller components, is a distance backbone subgraph sufficient to compute all shortest paths.

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There are over three million people living with epilepsy in the U.S. People with epilepsy experience multiple daily challenges such as seizures, social isolation, social stigma, experience of physical and emotional symptoms, medication side effects, cognitive and memory deficits, care coordination difficulties, and risks of sudden unexpected death.

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The ability to map causal interactions underlying genetic control and cellular signaling has led to increasingly accurate models of the complex biochemical networks that regulate cellular function. These network models provide deep insights into the organization, dynamics, and function of biochemical systems: for example, by revealing genetic control pathways involved in disease. However, the traditional representation of biochemical networks as binary interaction graphs fails to accurately represent an important dynamical feature of these multivariate systems: some pathways propagate control signals much more effectively than do others.

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Social media data have been increasingly used to study biomedical and health-related phenomena. From cohort-level discussions of a condition to population-level analyses of sentiment, social media have provided scientists with unprecedented amounts of data to study human behavior associated with a variety of health conditions and medical treatments. Here we review recent work in mining social media for biomedical, epidemiological, and social phenomena information relevant to the multilevel complexity of human health.

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Article Synopsis
  • Clinical translation of drug-drug interaction (DDI) studies is challenging due to knowledge gaps that hinder the connection between DDI evidence and clinical outcomes.
  • To address this, researchers created information retrieval models to analyze 25 million PubMed abstracts, categorizing DDI evidence into in vitro pharmacokinetic (PK), clinical PK, and clinical pharmacodynamic (PD) studies for both FDA approved and withdrawn drugs.
  • The study identified numerous unique DDI and drug-gene interaction (DGI) pairs, uncovering new pharmacogenetic hypotheses that enhance our understanding of drug interactions and their mechanisms.
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The occurrence of drug-drug-interactions (DDI) from multiple drug dispensations is a serious problem, both for individuals and health-care systems, since patients with complications due to DDI are likely to reenter the system at a costlier level. We present a large-scale longitudinal study (18 months) of the DDI phenomenon at the primary- and secondary-care level using electronic health records (EHR) from the city of Blumenau in Southern Brazil (pop. ≈340,000).

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Logical models offer a simple but powerful means to understand the complex dynamics of biochemical regulation, without the need to estimate kinetic parameters. However, even simple automata components can lead to collective dynamics that are computationally intractable when aggregated into networks. In previous work we demonstrated that automata network models of biochemical regulation are highly canalizing, whereby many variable states and their groupings are redundant (Marques-Pita and Rocha, 2013).

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A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

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Human reproduction does not happen uniformly throughout the year and what drives human sexual cycles is a long-standing question. The literature is mixed with respect to whether biological or cultural factors best explain these cycles. The biological hypothesis proposes that human reproductive cycles are an adaptation to the seasonal (hemisphere-dependent) cycles, while the cultural hypothesis proposes that conception dates vary mostly due to cultural factors, such as holidays.

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