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Abstract Background In recent years, human microbiome studies have received increasing attention as this field is considered a potential source for clinical applications. With the advancements in omics technologies and AI, research focused on the discovery for potential biomarkers in the human microbiome using machine learning tools has produced positive outcomes. Despite the promising results, several issues can still be found in these studies such as datasets with small number of samples, inconsistent results, lack of uniform processing and methodologies, and other additional factors lead to lack of reproducibility in biomedical research. In this work, we propose a methodology that combines the DADA2 pipeline for 16s rRNA sequences processing and the Recursive Ensemble Feature Selection (REFS) in multiple datasets to increase reproducibility and obtain robust and reliable results in biomedical research. Results Three experiments were performed analyzing microbiome data from patients/cases in Inflammatory Bowel Disease (IBD), Autism Spectrum Disorder (ASD), and Type 2 Diabetes (T2D). In each experiment, we found a biomarker signature in one dataset and applied to 2 other as further validation. The effectiveness of the proposed methodology was compared with other feature selection methods such as K-Best with F-score and random selection as a base line. The Area Under the Curve (AUC) was employed as a measure of diagnostic accuracy and used as a metric for comparing the results of the proposed methodology with other feature selection methods. Additionally, we use the Matthews Correlation Coefficient (MCC) as a metric to evaluate the performance of the methodology as well as for comparison with other feature selection methods. Conclusions We developed a methodology for reproducible biomarker discovery for 16s rRNA microbiome sequence analysis, addressing the issues related with data dimensionality, inconsistent results and validation across independent datasets. The findings from the three experiments, across 9 different datasets, show that the proposed methodology achieved higher accuracy compared to other feature selection methods. This methodology is a first approach to increase reproducibility, to provide robust and reliable results.

Odor is central to food quality. Still, a major challenge is to understand how the odorants present in a given food contribute to its specific odor profile, and how to predict this olfactory outcome from the chemical composition. In this proof-of-concept study, we seek to develop an integrative model that combines expert knowledge, fuzzy logic, and machine learning to predict the quantitative odor description of complex mixtures of odorants. The model output is the intensity of relevant odor sensory attributes calculated on the basis of the content in odor-active comounds. The core of the model is the mathematically formalized knowledge of four senior flavorists, which provided a set of optimized rules describing the sensory-relevant combinations of odor qualities the experts have in mind to elaborate the target odor sensory attributes. The model first queries analytical and sensory databases in order to standardize, homogenize, and quantitatively code the odor descriptors of the odorants. Then the standardized odor descriptors are translated into a limited number of odor qualities used by the experts thanks to an ontology. A third step consists of aggregating all the information in terms of odor qualities across all the odorants found in a given product. The final step is a set of knowledge-based fuzzy membership functions representing the flavorist expertise and ensuring the prediction of the intensity of the target odor sensory descriptors on the basis of the products' aggregated odor qualities; several methods of optimization of the fuzzy membership functions have been tested. Finally, the model was applied to predict the odor profile of 16 red wines from two grape varieties for which the content in odorants was available. The results showed that the model can predict the perceptual outcome of food odor with a certain level of accuracy, and may also provide insights into combinations of odorants not mentioned by the experts.

Abstract As the COVID-19 pandemic winds down, it leaves behind the serious concern that future, even more disruptive pandemics may eventually surface. One of the crucial steps in handling the SARS-CoV-2 pandemic was being able to detect the presence of the virus in an accurate and timely manner, to then develop policies counteracting the spread. Nevertheless, as the pandemic evolved, new variants with potentially dangerous mutations appeared. Faced by these developments, it becomes clear that there is a need for fast and reliable techniques to create highly specific molecular tests, able to uniquely identify VOCs. Using an automated pipeline built around evolutionary algorithms, we designed primer sets for SARS-CoV-2 (main lineage) and for VOC, B.1.1.7 (Alpha) and B.1.1.529 (Omicron). Starting from sequences openly available in the GISAID repository, our pipeline was able to deliver the primer sets for the main lineage and each variant in a matter of hours. Preliminary in-silico validation showed that the sequences in the primer sets featured high accuracy. A pilot test in a laboratory setting confirmed the results: the developed primers were favorably compared against existing commercial versions for the main lineage, and the specific versions for the VOCs B.1.1.7 and B.1.1.529 were clinically tested successfully.

Abstract Background Not being well controlled by therapy with inhaled corticosteroids and long‐acting β2 agonist bronchodilators is a major concern for severe‐asthma patients. The current treatment option for these patients is the use of biologicals such as anti‐IgE treatment, omalizumab, as an add‐on therapy. Despite the accepted use of omalizumab, patients do not always benefit from it. Therefore, there is a need to identify reliable biomarkers as predictors of omalizumab response. Methods Two novel computational algorithms, machine‐learning based Recursive Ensemble Feature Selection (REFS) and rule‐based algorithm Logic Explainable Networks (LEN), were used on open accessible mRNA expression data from moderate‐to‐severe asthma patients to identify genes as predictors of omalizumab response. Results With REFS, the number of features was reduced from 28,402 genes to 5 genes while obtaining a cross‐validated accuracy of 0.975. The 5 responsiveness predictive genes encode the following proteins: Coiled‐coil domain‐ containing protein 113 (CCDC113), Solute Carrier Family 26 Member 8 (SLC26A), Protein Phosphatase 1 Regulatory Subunit 3D (PPP1R3D), C‐Type lectin Domain Family 4 member C (CLEC4C) and LOC100131780 (not annotated). The LEN algorithm found 4 identical genes with REFS: CCDC113, SLC26A8 PPP1R3D and LOC100131780. Literature research showed that the 4 identified responsiveness predicting genes are associated with mucosal immunity, cell metabolism, and airway remodeling. Conclusion and clinical relevance Both computational methods show 4 identical genes as predictors of omalizumab response in moderate‐to‐severe asthma patients. The obtained high accuracy indicates that our approach has potential in clinical settings. Future studies in relevant cohort data should validate our computational approach.

Microbiome data predictive analysis within a machine learning (ML) workflow presents numerous domain-specific challenges involving preprocessing, feature selection, predictive modeling, performance estimation, model interpretation, and the extraction of biological information from the results. To assist decision-making, we offer a set of recommendations on algorithm selection, pipeline creation and evaluation, stemming from the COST Action ML4Microbiome. We compared the suggested approaches on a multi-cohort shotgun metagenomics dataset of colorectal cancer patients, focusing on their performance in disease diagnosis and biomarker discovery. It is demonstrated that the use of compositional transformations and filtering methods as part of data preprocessing does not always improve the predictive performance of a model. In contrast, the multivariate feature selection, such as the Statistically Equivalent Signatures algorithm, was effective in reducing the classification error. When validated on a separate test dataset, this algorithm in combination with random forest modeling, provided the most accurate performance estimates. Lastly, we showed how linear modeling by logistic regression coupled with visualization techniques such as Individual Conditional Expectation (ICE) plots can yield interpretable results and offer biological insights. These findings are significant for clinicians and non-experts alike in translational applications.

Food safety is a common concern at the household level, with important variations across different countries and cultures. Nevertheless, identifying the factors that best explain similarities and differences in consumer awareness pertaining to this topic is not straightforward. Starting from a questionnaire administered in seven countries from four continents (Argentina, Brazil, Colombia, Ghana, India, Peru, and the United Kingdom), we present an analysis of the answers related to food safety concerns, aimed at identifying possible explanatory factors. As classical statistical approaches can be limited when dealing with complex datasets, we propose an analysis with machine learning techniques, that can take into account both categorical and numerical values. With the questionnaire as a base, we task a machine learning algorithm, Random Forest, with predicting consumers’ answers to the target questions using information from all other answers. Once the algorithm is trained, it becomes possible to obtain a ranking of the questions considered the most important for the prediction, with the top-ranked questions likely representing explanatory factors. Top-ranked questions are then analyzed using a Random Forest regression algorithm, to test possible correlations. The results show that the most significant explanatory variables of safety concerns seem to be estimates of carbon footprints and calories associated with food products, and primarily with beef and chicken meat. These results tend to indicate that people who are most concerned about food safety are also those who are highly aware of environmental and nutritional impacts of food, hinting at differences in food education as a possible underlying explanation for the data.