Centre of Statistics and its Applications

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Publications

Generalized r-Lambert function in the analysis of fixed points and bifurcations of homographic 2-Ricker maps

Publication . Rocha, J. Leonel; TAHA, Abdel-Kaddous

This paper aims to study the nonlinear dynamics and bifurcation structures of a new mathematical model of the γ-Ricker population model with a Holling type II per-capita birth function, where the Allee effect parameter is γ = 2. A generalized r-Lambert function is defined on the 3D parameters space to determine the existence and variation of the number of nonzero fixed points of the homographic 2-Ricker maps considered. The singularity points of the generalized r-Lambert function are identified with the cusp points on a fold bifurcation of the homographic 2-Ricker maps. In this approach, the application of the transcendental generalized r-Lambert function is demonstrated based on the analysis of local and global bifurcation structures of this three-parameter family of homographic maps. Some numerical studies are included to illustrate the theoretical results.

2021-08-19Journal article

Restricted access

COVID-19: nothing is normal in this pandemic

Publication . Gonçalves, Luzia; Turkman; Brás-Geraldes, Carlos; Marques, Tiago A.; SOUSA, LISETE

This manuscript brings attention to inaccurate epidemiological concepts that emerged during the COVID-19 pandemic. In social media and scientific journals, some wrong references were given to a "normal epidemic curve" and also to a "log-normal curve/distribution". For many years, textbooks and courses of reputable institutions and scientific journals have disseminated misleading concepts. For example, calling histogram to plots of epidemic curves or using epidemic data to introduce the concept of a Gaussian distribution, ignoring its temporal indexing. Although an epidemic curve may look like a Gaussian curve and be eventually modelled by a Gauss function, it is not a normal distribution or a log-normal, as some authors claim. A pandemic produces highly-complex data and to tackle it effectively statistical and mathematical modelling need to go beyond the "onesize-fits-all solution". Classical textbooks need to be updated since pandemics happen and epidemiology needs to provide reliable information to policy recommendations and actions.

2021-06Journal article

Open access

Fast identification of off-target liabilities in early antibiotic discovery with Fourier-transform infrared spectroscopy

Publication . Ribeiro Da Cunha, Bernardo; Aleixo, Sandra M.; Fonseca, Luís P. P.; Calado, Cecília

Structural modifications of known antibiotic scaffolds have kept the upper hand on resistance, but we are on the verge of not having antibiotics for many common infections. Mechanism-based discovery assays reveal novelty, exclude off-target liabilities, and guide lead optimization. For that, we developed a fast and automatable protocol using high-throughput Fourier-transform infrared spectroscopy (FTIRS). Metabolic fingerprints of Staphylococcus aureus and Escherichia coli exposed to 35 compounds, dissolved in dimethyl sulfoxide (DMSO) or water, were acquired. Our data analysis pipeline identified biomarkers of off-target effects, optimized spectral preprocessing, and identified the top-performing machine learning algorithms for off-target liabilities and mechanism of action (MOA) identification. Spectral bands with known biochemical associations more often yielded more significant biomarkers of off-target liabilities when bacteria were exposed to compounds dissolved in water than DMSO. Highly discriminative models distinguished compounds with predominant off-target effects from antibiotics with well-defined MOA (AUROC > 0.87, AUPR > 0.79, F1 > 0.81), and from the latter predicted their MOA (AUROC > 0.88, AUPR > 0.70, F1 > 0.70). The compound solvent did not affect predictive models. FTIRS is fast, simple, inexpensive, automatable, and highly effective at predicting MOA and off-target liabilities. As such, FTIRS mechanism-based screening assays can be applied for hit discovery and to guide lead optimization during the early stages of antibiotic discovery.

2021-08Journal article

Open access

Herpesviruses serology distinguishes different subgroups of patients from the United Kingdom myalgic encephalomyelitis/chronic fatigue syndrome biobank

Publication . Domingues, Tiago Dias; Grabowska, Anna D.; Lee, Ji-Sook; Ameijeiras-Alonso, Jose; Westermeier, Francisco; Scheibenbogen, Carmen; Cliff, Jacqueline M.; Nacul, Luis; Lacerda, Eliana M.; Mouriño, Helena; Sepulveda, Nuno

The evidence of an association between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and chronic herpesviruses infections remains inconclusive. Two reasons for the lack of consistent evidence are the large heterogeneity of the patients’ population with different disease triggers and the use of arbitrary cutoffs for defining seropositivity. In this work we re-analyzed previously published serological data related to 7 herpesvirus antigens. Patients with ME/CFS were subdivided into four subgroups related to the disease triggers: S0-42 patients who did not know their disease trigger; S1-43 patients who reported a non-infection trigger; S2-93 patients who reported an infection trigger, but that infection was not confirmed by a lab test; and S3-48 patients who reported an infection trigger and that infection was confirmed by a lab test. In accordance with a sensitivity analysis, the data were compared to those from 99 healthy controls allowing the seropositivity cutoffs to vary within a wide range of possible values. We found a negative association between S1 and seropositivity to Epstein-Barr virus (VCA and EBNA1 antigens) and Varicella-Zoster virus using specific seropositivity cutoff. However, this association was not significant when controlling for multiple testing. We also found that S3 had a lower seroprevalence to the human cytomegalovirus when compared to healthy controls for all cutoffs used for seropositivity and after adjusting for multiple testing using the Benjamini-Hochberg procedure. However, this association did not reach statistical significance when using Benjamini-Yekutieli procedure. In summary, herpesviruses serology could distinguish subgroups of ME/CFS patients according to their disease trigger, but this finding could be eventually affected by the problem of multiple testing.

2021Journal article

Open access