UMD Data Collection
Permanent URI for this collectionhttp://hdl.handle.net/1903/27670
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Item Supplementary material for Applying Wearable Sensors and Machine Learning to the Diagnostic Challenge of Distinguishing Parkinson's Disease from Other Forms of Parkinsonism(2025) Khalil, Rana M.; Shulman, Lisa M.; Gruber-Baldini, Ann L.; Reich, Stephen G.; Savitt, Joseph M.; Hausdorff, Jeffrey M.; von Coelln, Rainer; Cummings, Michael P.Parkinson's Disease (PD) and other forms of parkinsonism share motor symptoms, including tremor, bradykinesia, and rigidity. This overlap in the clinical presentation creates a diagnostic challenge, underscoring the need for objective differentiation. However, applying machine learning (ML) to clinical datasets faces challenges such as imbalanced class distributions, small sample sizes for non-PD parkinsonism, and heterogeneity within the non-PD group. This study analyzed wearable sensor data from 260 PD participants and 18 individuals with etiologically diverse forms of non-PD parkinsonism during clinical mobility tasks, using a single sensor placed on the lower-back. We evaluated the performance of ML models in distinguishing these two groups and identified the most informative mobility tasks for classification. Additionally, we examined clinical characteristics of misclassified participants and presented case studies of common challenges in clinical practice, including diagnostic uncertainty at the initial visit and changes in diagnosis over time. We also suggested potential steps to address dataset challenges which limited the models' performance. We demonstrate that ML-based analysis is a promising approach for distinguishing idiopathic PD from non-PD parkinsonism, though its accuracy remains below that of expert clinicians. Using the Timed Up and Go test as a single mobility task outperformed the use of all tasks combined, achieving a balanced accuracy of 78.2%. We also identified differences in some clinical scores between participants correctly and falsely classified by our models. These findings demonstrate the feasibility of using ML and wearable sensors for differentiating PD from other parkinsonian disorders, addressing key challenges in diagnosis, and streamlining diagnostic workflows.Item Supplementary material for machine learning and statistical analyses of sensor data reveal variability between repeated trials in Parkinson’s disease mobility assessments(2024) Khalil, Rana M.; Shulman, Lisa M.; Gruber-Baldini, Ann L.; Shakya, Sunita; Hausdorff, Jeffrey M.; von Coelln, Rainer; Cummings, Michael P.Mobility tasks like the Timed Up and Go test (TUG), cognitive TUG (cogTUG), and walking with turns provide insight into motor control, balance, and cognitive functions affected by Parkinson’s disease (PD). We assess the test-retest reliability of these tasks in 262 PD participants and 50 controls by evaluating machine learning models based on wearable sensor-derived measures and statistical metrics. This evaluation examines total duration, subtask duration, and other quantitative measures across two trials. We show that the diagnostic accuracy for distinguishing PD from controls decreases by a mean of 1.8% between the first and the second trial, suggesting that task repetition may not be necessary for accurate diagnosis. Although the total duration remains relatively consistent between trials (intraclass correlation coefficient (ICC) = 0.62 to 0.95), greater variability is seen in subtask duration and sensor-derived measures, reflected in machine learning performance and statistical differences. Our findings also show that this variability differs not only between controls and PD participants but also among groups with varying levels of PD severity, indicating the need to consider population characteristics. Relying solely on total task duration and conventional statistical metrics to gauge the reliability of mobility tasks may fail to reveal nuanced variations in movement.Item Supplementary material for Machine learning analysis of wearable sensor data from mobility testing distinguishes Parkinson's disease from other forms of parkinsonism(2024-03-13) Khalil, Rana M.; Shulman, Lisa M.; Gruber-Baldini, Ann L.; Hausdorff, Jeffrey M.; von Coelln, Rainer; Cummings, Michael P.; Cummings, Michael P.Parkinson's Disease (PD) and other forms of parkinsonism share characteristic motor symptoms, including tremor, bradykinesia, and rigidity. This overlap in the clinical presentation creates a diagnostic challenge, underscoring the need for objective differentiation tools. In this study, we analyzed wearable sensor data collected during mobility testing from 260 PD participants and 18 participants with etiologically diverse forms of parkinsonism. Our findings illustrate that machine learning-based analysis of data from a single wearable sensor can effectively distinguish idiopathic PD from non-PD parkinsonism with a balanced accuracy of 83.5%, comparable to expert diagnosis. Moreover, we found that diagnostic performance can be improved through severity-based partitioning of participants, achieving a balanced accuracy of 95.9%, 91.2% and 100% for mild, moderate and severe cases, respectively. Beyond its diagnostic implications, our results suggest the possibility of streamlining the testing protocol by using the Timed Up and Go test as a single mobility task. Furthermore, we present a detailed analysis of several case studies of challenging scenarios commonly encountered in clinical practice, including diagnostic uncertainty at the initial visit, and changes in clinical diagnosis at a subsequent visit. Together, these findings demonstrate the potential of applying machine learning on sensor-based measures of mobility to distinguish between PD and other forms of parkinsonism.Item Supplementary materials for statistical and machine learning analyses demonstrate test-retest reliability assessment is misled by focusing on total duration of mobility tasks in Parkinson's disease(2023) Khalil, Rana M.; Shulman, Lisa M.; Gruber-Baldini, Ann L.; Shakya, Sunita; Hausdorff, Jeffrey M.; von Coelln, Rainer; Cummings, Michael P.; Cummings, Michael P.Mobility tasks like the Timed Up and Go test (TUG), cognitive TUG (cogTUG), and walking with turns provide insight into dynamic motor control, balance, and cognitive functions affected by Parkinson’s disease (PD). We evaluate the test-retest reliability of these tasks by assessing the performance of machine learning models based on quantitative sensor-derived measures, and statistical measures to examine total duration, subtask duration, and other quantitative measures across both trials. We show that the diagnostic accuracy of differentiating between PD and control participants decreases from the first to the second trial of our mobility tasks, suggesting that mobility testing can be simplified by not repeating tasks without losing relevant information. Although the total duration remains relatively consistent between trials, there is more variability in subtask duration and sensor-derived measures, evident in the differences in machine learning model performance and statistical metrics. Relying solely on total task duration and conventional statistical metrics to gauge the reliability of mobility tasks overlooks the nuanced variations in movement captured by other quantitative measures.Item Supplementary material for machine learning analysis of data from a simplified mobility testing procedure with a single sensor and single task accurately differentiates Parkinson's disease from controls(2023) Khalil, Rana M.; Shulman, Lisa M.; Gruber-Baldini, Ann L.; Shakya, Sunita; von Coelln, Rainer; Cummings, Michael P.; Fenderson, Rebecca; van Hoven, Maxwell; Hausdorff, Jeffrey M.; Cummings, Michael P.Quantitative mobility analysis using wearable sensors, while promising as a diagnostic tool for Parkinson's disease (PD), is not commonly applied in clinical settings. Major obstacles include uncertainty regarding the best protocol for instrumented mobility testing and subsequent data processing, as well as the added workload and complexity of this multi-step process. To simplify sensor-based mobility testing in diagnosing PD, we analyzed data from 262 PD participants and 50 controls performing several motor tasks wearing a sensor on the lower back containing a triaxial accelerometer and a triaxial gyroscope. Using ensembles of heterogeneous machine learning models incorporating a range of classifiers trained on a large set of sensor features, we show that our models effectively differentiate between participants with PD and controls, both for mixed-stage PD (92.6% accuracy) and a group selected for mild PD only (89.4% accuracy). Omitting algorithmic segmentation of complex mobility tasks decreased the diagnostic accuracy of our models, as did the inclusion of kinesiological features. Feature importance analysis revealed Timed Up & Go (TUG) tasks to contribute highest-yield predictive features, with only minor decrease in accuracy for models based on cognitive TUG as a single mobility task. Our machine learning approach facilitates major simplification of instrumented mobility testing without compromising predictive performance.Item Supplementary materials for Plasmodium vivax antigen candidate prediction improves with the addition of Plasmodium falciparum data(2023) Chou, Renee Ti; Ouattara, Amed; Takala-Harrison, Shannon; Cummings, Michael P.Intensive malaria control and elimination efforts have led to substantial reductions in malaria incidence over the past two decades. However, the reduction in Plasmodium falciparum malaria cases has led to a species shift in some geographic areas, with P. vivax predominating in many areas outside of Africa. Despite its wide geographic distribution, P. vivax vaccine development has lagged far behind that for P. falciparum, in part due to the inability to cultivate P. vivax in vitro, hindering traditional approaches for antigen identification. In a prior study, we have used a positive-unlabeled random forest (PURF) machine learning approach to identify P. falciparum antigens for consideration in vaccine development efforts. Here we integrate systems data from P. falciparum (the better-studied species) to improve PURF models to predict potential P. vivax vaccine antigen candidates. We further show that inclusion of known antigens from the other species is critical for model performance, but the inclusion of unlabeled proteins the other species can result in misdirection of the model toward predictors of species classification, rather than antigen identification. Beyond malaria, incorporating antigens from a closely related species may aid in vaccine development for emerging pathogens having few or no known antigens.Item Supplementary materials for positive-unlabeled learning identifies vaccine candidate antigens in the malaria parasite Plasmodium falciparum(2023) Chou, Renee Ti; Ouattara, Amed; Adams, Matthew; Berry, Andrea A.; Takala-Harrison, Shannon; Cummings, Michael P.Malaria vaccine development is hampered by extensive antigenic variation and complex life stages of Plasmodium species. Vaccine development has focused on a small number of antigens identified prior to availability of the P. falciparum genome. In this study, we implement a machine learning-based reverse vaccinology approach to predict potential new malaria vaccine candidate antigens. We assemble and analyze P. falciparum proteomic, structural, functional, immunological, genomic, and transcriptomic data, and use positive-unlabeled learning to predict potential antigens based on the properties of known antigens and remaining proteins. We prioritize candidate antigens based on model performance on reference antigens with different genetic diversity and quantify the protein properties that contribute the most to identifying top candidates. Candidate antigens are characterized by gene essentiality, gene ontology, and gene expression in different life stages to inform future vaccine development. This approach provides a framework for identifying and prioritizing candidate vaccine antigens for a broad range of pathogens.Item Supplementary materials for machine learning-driven multifunctional peptide engineering for sustained ocular drug delivery(2023) Chou, Renee Ti; Hsueh, Henry T.; Rai, Usha; Liyanage, Wathsala; Kim, Yoo Chun; Appell, Matthew B.; Pejavar, Jahnavi; Leo, Kirby T.; Davison, Charlotte; Kolodziejski, Patricia; Mozzer, Ann; Kwon, HyeYoung; Sista, Maanasa; Anders, Nicole M.; Hemingway, Avelina; Rompicharla, Sri Vishnu Kiran; Edwards, Malia; Pitha, Ian; Hanes, Justin; Cummings, Michael P.; Ensign, Laura M.; Cummings, Michael P.; Ensign, Laura M.Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We developed a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) was conjugated to brimonidine, an intraocular pressure (IOP)-lowering drug that is prescribed for three times per day topical dosing, IOP reduction was observed for up to 18 days after a single intracameral HR97-brimonidine injection in rabbits. Further, the cumulative IOP-lowering effect was increased ~17-fold compared to free brimonidine injection. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond.