A comprehensive evaluation framework for benchmarking multi-objective feature selection in omics-based biomarker discovery.

Machine learning algorithms have been extensively used for accurate classification of cancer subtypes driven by gene expression-based biomarkers. However, biomarker models combining multiple gene expression signatures are often not reproducible in external validation datasets and their feature set size is often not optimized, jeopardizing their translatability into cost-effective clinical tools. We investigated how to solve the multi-objective problem of finding the best trade-offs between classification performance and set size applying seven algorithms for machine learning-driven feature subset selection and analyse how they perform in a benchmark with eight large-scale transcriptome datasets of cancer, covering both training and external validation sets.

Identifying gene expression-based biomarkers in online learning environments.

Motivation: Gene expression-based classifiers are often developed using historical data by training a model on a small set of patients and a large set of features. Models trained in such a way can be afterwards applied for predicting the output for new unseen patient data. However, very often the accuracy of these models starts to decrease as soon as new data is fed into the trained model.

Improved NSGA-II algorithms for multi-objective biomarker discovery.

Motivation: In modern translational research, the development of biomarkers heavily relies on use of omics technologies, but implementations with basic data mining algorithms frequently lead to false positives. Non-dominated Sorting Genetic Algorithm II (NSGA2) is an extremely effective algorithm for biomarker discovery but has been rarely evaluated against large-scale datasets. The exploration of the feature search space is the key to NSGA2 success but in specific cases NSGA2 expresses a shallow exploration of the space of possible feature combinations, possibly leading to models with low predictive performances.

Risk Prediction Models for Depression in Community-Dwelling Older Adults.

Objective: To develop streamlined Risk Prediction Models (Manto RPMs) for late-life depression.

Design: Prospective study.

Setting: The Survey of Health, Ageing and Retirement in Europe (SHARE) study.

Nextcast: A software suite to analyse and model toxicogenomics data.

The recent advancements in toxicogenomics have led to the availability of large omics data sets, representing the starting point for studying the exposure mechanism of action and identifying candidate biomarkers for toxicity prediction. The current lack of standard methods in data generation and analysis hampers the full exploitation of toxicogenomics-based evidence in regulatory risk assessment. Moreover, the pipelines for the preprocessing and downstream analyses of toxicogenomic data sets can be quite challenging to implement.

Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation.

The pharmacological arsenal against the COVID-19 pandemic is largely based on generic anti-inflammatory strategies or poorly scalable solutions. Moreover, as the ongoing vaccination campaign is rolling slower than wished, affordable and effective therapeutics are needed. To this end, there is increasing attention toward computational methods for drug repositioning and de novo drug design.

Network Analysis of Microarray Data.

DNA microarrays are widely used to investigate gene expression. Even though the classical analysis of microarray data is based on the study of differentially expressed genes, it is well known that genes do not act individually. Network analysis can be applied to study association patterns of the genes in a biological system.

Unsupervised Algorithms for Microarray Sample Stratification.

The amount of data made available by microarrays gives researchers the opportunity to delve into the complexity of biological systems. However, the noisy and extremely high-dimensional nature of this kind of data poses significant challenges. Microarrays allow for the parallel measurement of thousands of molecular objects spanning different layers of interactions.

Supervised Methods for Biomarker Detection from Microarray Experiments.

Biomarkers are valuable indicators of the state of a biological system. Microarray technology has been extensively used to identify biomarkers and build computational predictive models for disease prognosis, drug sensitivity and toxicity evaluations. Activation biomarkers can be used to understand the underlying signaling cascades, mechanisms of action and biological cross talk.

Transcriptomics in Toxicogenomics, Part II: Preprocessing and Differential Expression Analysis for High Quality Data.

Preprocessing of transcriptomics data plays a pivotal role in the development of toxicogenomics-driven tools for chemical toxicity assessment. The generation and exploitation of large volumes of molecular profiles, following an appropriate experimental design, allows the employment of toxicogenomics (TGx) approaches for a thorough characterisation of the mechanism of action (MOA) of different compounds. To date, a plethora of data preprocessing methodologies have been suggested.

Transcriptomics in Toxicogenomics, Part I: Experimental Design, Technologies, Publicly Available Data, and Regulatory Aspects.

The starting point of successful hazard assessment is the generation of unbiased and trustworthy data. Conventional toxicity testing deals with extensive observations of phenotypic endpoints in vivo and complementing in vitro models. The increasing development of novel materials and chemical compounds dictates the need for a better understanding of the molecular changes occurring in exposed biological systems.

Transcriptomics in Toxicogenomics, Part III: Data Modelling for Risk Assessment.

Transcriptomics data are relevant to address a number of challenges in Toxicogenomics (TGx). After careful planning of exposure conditions and data preprocessing, the TGx data can be used in predictive toxicology, where more advanced modelling techniques are applied. The large volume of molecular profiles produced by omics-based technologies allows the development and application of artificial intelligence (AI) methods in TGx.

Development of a clinical prediction model for the onset of functional decline in people aged 65-75 years: pooled analysis of four European cohort studies.

Background: Identifying those people at increased risk of early functional decline in activities of daily living (ADL) is essential for initiating preventive interventions. The aim of this study is to develop and validate a clinical prediction model for onset of functional decline in ADL in three years of follow-up in older people of 65-75 years old.

Methods: Four population-based cohort studies were pooled for the analysis: ActiFE-ULM (Germany), ELSA (United Kingdom), InCHIANTI (Italy), LASA (Netherlands).

Risk Prediction Model for Late Life Depression: Development and Validation on Three Large European Datasets.

Assessing the risk to develop a specific disease is the first step towards prevention, both at individual and population levels. The development and validation of risk prediction models (RPMs) is the norm within different fields of medicine but still underused in psychiatry, despite the global impact of mental disorders. In particular, there is a lack of RPMs to assess the risk of developing depression, the first worldwide cause of disability and harbinger of functional decline in old age.

Predicting Trajectories of Functional Decline in 60- to 70-Year-Old People.

Background: Early identification of people at risk of functional decline is essential for delivering targeted preventive interventions.

Objective: The aim of this study is to identify and predict trajectories of functional decline over 9 years in males and females aged 60-70 years.

Methods: We included 403 community-dwelling participants from the InCHIANTI study and 395 from the LASA study aged 60-70 years at baseline, of whom the majority reported no functional decline at baseline (median 0, interquartile range 0-1).

Predictive Performance of a Fall Risk Assessment Tool for Community-Dwelling Older People (FRAT-up) in 4 European Cohorts.

Background And Objective: The fall risk assessment tool (FRAT-up) is a tool for predicting falls in community-dwelling older people based on a meta-analysis of fall risk factors. Based on the fall risk factor profile, this tool calculates the individual risk of falling over the next year. The objective of this study is to evaluate the performance of FRAT-up in predicting future falls in multiple cohorts.

FRAT-up, a Web-based fall-risk assessment tool for elderly people living in the community.

Background: About 30% of people over 65 are subject to at least one unintentional fall a year. Fall prevention protocols and interventions can decrease the number of falls. To be effective, a prevention strategy requires a prior step to evaluate the fall risk of the subjects.