Computational Intelligence methods, which include Evolutionary Computation and Swarm Intelligence, can e ciently and e↵ectively identify optimal solutions to complex optimization problems by exploiting the cooperative and competitive interplay among their individuals. The exploration and exploitation capabilities of these meta-heuristics are typically assessed by considering well-known suites of benchmark functions, specifically designed for numerical global optimization purposes. However, their performances could drastically change in the case of real-world optimization problems. In this paper, we investigate this issue by considering the Parameter Estimation (PE) of biochemical systems, a common computational problem in the field of Systems Biology. In order to evaluate the e↵ectiveness of various meta-heuristics in solving the PE problem, we compare their performance by considering a set of benchmark functions and a set of synthetic biochemical models characterized by a search space with an increasing number of dimensions. Our results show that some state-of-the-art optimization ⇤

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Motivation The elucidation of dysfunctional cellular processes that can induce the onset of a disease is a challenging issue from both the experimental and computational perspectives. Here we introduce a novel computational method based on the coupling between fuzzy logic modeling and a global optimization algorithm, whose aims are to (1) predict the emergent dynamical behaviors of highly heterogeneous systems in unperturbed and perturbed conditions, regardless of the availability of quantitative parameters, and (2) determine a minimal set of system components whose perturbation can lead to a desired system response, therefore facilitating the design of a more appropriate experimental strategy. Results We applied this method to investigate what drives K-ras-induced cancer cells, displaying the typical Warburg effect, to death or survival upon progressive glucose depletion. The optimization analysis allowed to identify new combinations of stimuli that maximize pro-apoptotic processes. Namely, our results provide different evidences of an important protective role for protein kinase A in cancer cells under several cellular stress conditions mimicking tumor behavior. The predictive power of this method could facilitate the assessment of the response of other complex heterogeneous systems to drugs or mutations in fields as medicine and pharmacology, therefore paving the way for the development of novel therapeutic treatments. Availability and implementation The source code of FUMOSO is available under the GPL 2.0 license on GitHub at the following URL: https://github.com/aresio/FUMOSO Supplementary information Supplementary data are available at Bioinformatics online.

The process of inferring a full haplotype of a cell is known as haplotyping, which consists in assigning all heterozygous Single Nucleotide Polymorphisms (SNPs) to exactly one of the two chromosomes. In this work, we propose a novel computational method for haplotype assembly based on Genetic Algorithms (GAs), named GenHap. Our approach could efficiently solve large instances of the weighted Minimum Error Correction (wMEC) problem, yielding optimal solutions by means of a global search process. wMEC consists in computing the two haplotypes that partition the sequencing reads into two unambiguous sets with the least number of corrections to the SNP values. Since wMEC was proven to be an NP-hard problem, we tackle this problem exploiting GAs, a population-based optimization strategy that mimics Darwinian processes. In GAs, a population composed of randomly generated individuals undergoes a selection mechanism and is modified by genetic operators. Based on a quality measure (i.e., the fitness value), inspired by Darwin’s “survival of the fittest” laws, each individual is involved in a selection process. Our preliminary experimental results show that GenHap is able to achieve correct solutions in short running times. Moreover, this approach can be used to compute haplotypes in organisms with different ploidity. The proposed evolutionary technique has the advantage that it could be formulated and extended using a multi-objective fitness function taking into account additional insights, such as the methylation patterns of the different chromosomes or the gene proximity in maps achieved through Chromosome Conformation Capture (3C) experiments.

Many researchers have used fuzzy set theory and fuzzy logic in a variety of applications related to computer science and engineering, given the capability of fuzzy inference systems to deal with uncertainty, represent vague concepts, and connect human language to numerical data. In this work we propose Simpful, a general-purpose and user-friendly Python library designed to facilitate the definition, analysis, and interpretation of fuzzy inference systems. Simpful provides a lightweight Application Programming Interface that allows to intuitively define fuzzy sets and fuzzy rules, and to perform fuzzy inference. Worthy of note, in Simpful the fuzzy rules are specified by means of strings of text written in natural language. We provide here some practical examples to show that Simpful represents a valuable addition to the open-source software that supports fuzzy reasoning.

Motivation Acute myeloid leukemia (AML) is one of the most common hematological malignancies, characterized by high relapse and mortality rates. The inherent intra-tumor heterogeneity in AML is thought to play an important role in disease recurrence and resistance to chemotherapy. Although experimental protocols for cell proliferation studies are well established and widespread, they are not easily applicable to in vivo contexts, and the analysis of related time-series data is often complex to achieve. To overcome these limitations, model-driven approaches can be exploited to investigate different aspects of cell population dynamics. Results In this work, we present ProCell, a novel modeling and simulation framework to investigate cell proliferation dynamics that, differently from other approaches, takes into account the inherent stochasticity of cell division events. We apply ProCell to compare different models of cell proliferation in AML, notably leveraging experimental data derived from human xenografts in mice. ProCell is coupled with Fuzzy Self-Tuning Particle Swarm Optimization, a swarm-intelligence settings-free algorithm used to automatically infer the models parameterizations. Our results provide new insights on the intricate organization of AML cells with highly heterogeneous proliferative potential, highlighting the important role played by quiescent cells and proliferating cells characterized by different rates of division in the progression and evolution of the disease, thus hinting at the necessity to further characterize tumor cell subpopulations. Availability and implementation The source code of ProCell and the experimental data used in this work are available under the GPL 2.0 license on GITHUB at the following URL: https://github.com/aresio/ProCell. Supplementary information Supplementary data are available at Bioinformatics online.

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