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Hernán E. Grecco

Publications and source records attributed to Hernán E. Grecco.

2 recordsLinked to original sources

EFECT: A Method to Quantify the Reproducibility of Stochastic Simulations

Reproducibility is a fundamental requirement for validating scientific claims in computational research. Stochastic computational models are widely used in fields such as systems biology, financial modeling and environmental sciences. However, achieving reproducibility in stochastic simulations remains challenging, as each run can produce different outcomes. Existing infrastructure and software tools do not address independent reproduction of simulation results. Without independent reproducibility, results and conclusions lack credibility, as it remains unclear whether observed findings reflect model behavior or are artifacts of stochastic variation or an underpowered study. To bridge this gap, we introduce the Empirical Characteristic Function Equality Convergence Test (EFECT), a data-driven method to quantify the reproducibility of stochastic simulation results. EFECT employs empirical characteristic functions to compare reported results with those independently generated by assessing distributional inequality, termed EFECT error. Additionally, we establish the EFECT convergence point, a quantitative metric for determining the required number of simulation runs to achieve an EFECT error value of a priori significance. EFECT is applicable to all bounded, real-valued outputs, regardless of the model type or simulation method that produced them. We tested EFECT with over 40 use cases to demonstrate its broad applicability and effectiveness. EFECT standardizes stochastic simulation reproducibility, establishing a workflow that guarantees reliable results, supporting a wide range of stakeholders, and thereby enhancing validation of stochastic simulation studies, across a model's lifecycle. To promote standardization, we are developing the open-source software library libSSR in multiple programming languages for easy integration of EFECT.

stat.ME↗

Effective description of bistability and irreversibility in apoptosis

Apoptosis is a mechanism of programmed cell death in which cells engage in a controlled demolition and prepare to be digested without damaging their environment. In normal conditions apoptosis is repressed, until it is irreversibly induced by an appropriate signal. In adult organisms apoptosis is a natural way to dispose of damaged cells, and its disruption or excess is associated with cancer and autoimmune diseases. Apoptosis is regulated by a complex signaling network controlled by caspases, specialized enzymes that digest essential cellular components and promote the degradation of genomic DNA. In this work we propose an effective description of the signaling network focused on caspase-3 as a readout of cell fate. We integrate intermediate network interactions into a nonlinear feedback function acting on caspase-3 and introduce the effect of pro-apoptotic stimuli and regulatory elements as a saturating activation function. We find that the theory has a robust bistable regime where two possible states coexist, representing survival and cell death fates. For a broad range of parameters, strong stimuli can induce an irreversible switch to the death fate. We use the theory to explore dynamical stimulation conditions and determine how cell fate depends on different stimuli patterns. This analysis reveals a critical relation between transient stimuli intensity and duration to trigger irreversible apoptosis.

q-bio.MN↗