Improving Machine Learning-based Prediction of Frailty in Elderly People with Digital Wearables : Data from the Berlin Aging Study II (BASE-II)

Poster (2022, October 26)

Frailty is a geriatric medical condition that is highly associated with age and age-related diseases. The multidimensional consequences of frailty are heavily impacting the quality of life, and will ... [more ▼]

Frailty is a geriatric medical condition that is highly associated with age and age-related diseases. The multidimensional consequences of frailty are heavily impacting the quality of life, and will inevitably increase the burden on healthcare systems in the future. Most importantly, the lack of a universal standard to describe, diagnose, or let alone treat frailty, is further complicating the situation in the long-term. Nowadays, more and more frailty assessment tools are being developed on a regional and institutional basis, which is continuing to drive the heterogeneity in the characterization of frailty further apart. Gaining better insights into the underlying causes and pathophysiology of frailty, and how it is developing in patients is, therefore, required to establish strong and accurately tailored response schemes for frail patients, where currently only symptoms are treated. Thus, in this study, we deployed machine learning-based classification and optimization techniques to predict frailty in elderly people aged 65 or above from the Berlin Aging Study II (BASE-II, n=1512, frail=484) and revealed some of the most informative biomedical information to characterize frailty, including new potential biomarkers. Frailty in BASE-II was measured by the Fried et al. 5-item frailty index, composed of the clinical variables grip strength, weight loss, exhaustion, physical activity, and gait. The level of frailty in BASE-II was adapted for binary classification purposes by merging the pre-frail and frail levels as frail. A configurable in-house pipeline was developed for pre-processing the clinical data and predicting the target disease by deploying Support Vector Machines Classification. The most informative and essential subgroup of clinical measurements with regards to frailty was investigated by re-optimizing an initially full data-driven model by sequentially leaving out one subgroup. The best prediction power was yielded with resampling and dimensionality reduction techniques using the F-beta-2 score, and was further improved by adding one item of the Fried et al. frailty index. Furthermore, differences between the gender in the data set led to the investigation of gender-specific model configurations, followed by re-optimizations. As a result, we were able to specifically increase the predictive power in gender-specific groups, and will simultaneously emphasize on the differences between the most informative clinical biomarkers as well as the most essential subgroups for mixed and gender-specific BASE-II. The results herein suggest that a combination of the detected easy-to-obtain biomedical information on frailty risk factors together with one Fried et al. phenotype information provided by i.e., smart wearable devices (gait, grip strength, …) could significantly improve the frailty prediction power in mixed and gender-specific clinical cohort data. [less ▲]

Bruceine D Identified as a Drug Candidate against Breast Cancer by a Novel Drug Selection Pipeline and Cell Viability Assay.

in Pharmaceuticals (Basel, Switzerland) (2022), 15(2),

The multi-target effects of natural products allow us to fight complex diseases like cancer on multiple fronts. Unlike docking techniques, network-based approaches such as genome-scale metabolic modelling ... [more ▼]

The multi-target effects of natural products allow us to fight complex diseases like cancer on multiple fronts. Unlike docking techniques, network-based approaches such as genome-scale metabolic modelling can capture multi-target effects. However, the incompleteness of natural product target information reduces the prediction accuracy of in silico gene knockout strategies. Here, we present a drug selection workflow based on context-specific genome-scale metabolic models, built from the expression data of cancer cells treated with natural products, to predict cell viability. The workflow comprises four steps: first, in silico single-drug and drug combination predictions; second, the assessment of the effects of natural products on cancer metabolism via the computation of a dissimilarity score between the treated and control models; third, the identification of natural products with similar effects to the approved drugs; and fourth, the identification of drugs with the predicted effects in pathways of interest, such as the androgen and estrogen pathway. Out of the initial 101 natural products, nine candidates were tested in a 2D cell viability assay. Bruceine D, emodin, and scutellarein showed a dose-dependent inhibition of MCF-7 and Hs 578T cell proliferation with IC(50) values between 0.7 to 65 μM, depending on the drug and cell line. Bruceine D, extracted from Brucea javanica seeds, showed the highest potency. [less ▲]

Drug Target Prediction Using Context-Specific Metabolic Models Reconstructed from rFASTCORMICS.

in Methods in Molecular Biology (2022)

Metabolic modeling is a powerful computational tool to analyze metabolism. It has not only been used to identify metabolic rewiring strategies in cancer but also to predict drug targets and candidate ... [more ▼]

Metabolic modeling is a powerful computational tool to analyze metabolism. It has not only been used to identify metabolic rewiring strategies in cancer but also to predict drug targets and candidate drugs for repurposing. Here, we will elaborate on the reconstruction of context-specific metabolic models of cancer using rFASTCORMICS and the subsequent prediction of drugs for repurposing using our drug prediction workflow. [less ▲]

DCcov: Repositioning of drugs and drug combinations for SARS-CoV-2 infected lung through constraint-based modeling.

in iScience (2021), 24(11), 103331

The 2019 coronavirus disease (COVID-19) became a worldwide pandemic with currently no approved effective antiviral drug. Flux balance analysis (FBA) is an efficient method to analyze metabolic networks ... [more ▼]

The 2019 coronavirus disease (COVID-19) became a worldwide pandemic with currently no approved effective antiviral drug. Flux balance analysis (FBA) is an efficient method to analyze metabolic networks. Here, FBA was applied on human lung cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to reposition metabolic drugs and drug combinations against the virus replication within the host tissue. Making use of expression datasets of infected lung tissue, genome-scale COVID-19-specific metabolic models were reconstructed. Then, host-specific essential genes and gene pairs were determined through in silico knockouts that permit reducing the viral biomass production without affecting the host biomass. Key pathways that are associated with COVID-19 severity in lung tissue are related to oxidative stress, ferroptosis, and pyrimidine metabolism. By in silico screening of Food and Drug Administration (FDA)-approved drugs on the putative disease-specific essential genes and gene pairs, 85 drugs and 52 drug combinations were predicted as promising candidates for COVID-19 (https://github.com/sysbiolux/DCcov). [less ▲]