References of "Glaab, Enrico 50001863"
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See detailMachine learning applied to higher order functional representations of omics data reveals biological pathways associated with Parkinson‘s Disease
Gómez de Lope, Elisa UL; Glaab, Enrico UL

Poster (2022, September 18)

Background: Despite the increasing prevalence of Parkinson’s Disease (PD) and research efforts to understand its underlying molecular pathogenesis, early diagnosis of PD remains a challenge. Machine ... [more ▼]

Background: Despite the increasing prevalence of Parkinson’s Disease (PD) and research efforts to understand its underlying molecular pathogenesis, early diagnosis of PD remains a challenge. Machine learning analysis of blood-based omics data is a promising non-invasive approach to finding molecular fingerprints associated with PD that may enable an early and accurate diagnosis. Description: We applied several machine learning classification methods to public omics data from PD case/control studies. We used aggregation statistics and Pathifier’s pathway deregulation scores to generate higher order functional representations of the data such as pathway-level features. The models’ performance and most relevant predictive features were compared with individual feature level predictors. The resulting diagnostic models from individual features and Pathifier’s pathway deregulation scores achieve significant Area Under the Curve (AUC, a receiver operating characteristic curve) scores for both cross-validation and external testing. Furthermore, we identify plausible biological pathways associated with PD diagnosis. Conclusions: We have successfully built machine learning models at pathway-level and single-feature level to study blood-based omics data for PD diagnosis. Plausible biological pathway associations were identified. Furthermore, we show that pathway deregulation scores can serve as robust and biologically interpretable predictors for PD. [less ▲]

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See detailBody-First Subtype of Parkinson's Disease with Probable REM-Sleep Behavior Disorder Is Associated with Non-Motor Dominant Phenotype
Pavelka, Lukas; Rauschenberger, Armin UL; Landoulsi, Zied UL et al

in Journal of Parkinson's Disease (2022)

Background: The hypothesis of body-first vs. brain-first subtype of PD has been proposed with REM-Sleep behavior disorder (RBD) defining the former. The body-first PD presumes an involvement of the ... [more ▼]

Background: The hypothesis of body-first vs. brain-first subtype of PD has been proposed with REM-Sleep behavior disorder (RBD) defining the former. The body-first PD presumes an involvement of the brainstem in the pathogenic process with higher burden of autonomic dysfunction. Objective: To identify distinctive clinical subtypes of idiopathic Parkinson’s disease (iPD) in line with the formerly proposed concept of body-first vs. brain-first subtypes in PD, we analyzed the presence of probable RBD (pRBD), sex, and the APOE ɛ4 carrier status as potential sub-group stratifiers. Methods: A total of 400 iPD patients were included in the cross-sectional analysis from the baseline dataset with a completed RBD Screening Questionnaire (RBDSQ) for classifying as pRBD by using the cut-off RBDSQ≥6. Multiple regression models were applied to explore (i) the effect of pRBD on clinical outcomes adjusted for disease duration and age, (ii) the effect of sex on pRBD, and (iii) the association of APOE ɛ4 and pRBD. Results: iPD-pRBD was significantly associated with autonomic dysfunction (SCOPA-AUT), level of depressive symptoms (BDI-I), MDS-UPDRS I, hallucinations, and constipation, whereas significantly negatively associated with quality of life (PDQ-39) and sleep (PDSS). No significant association between sex and pRBD or APOE ɛ4 and pRBD in iPD was found nor did we determine a significant effect of APOE ɛ4 on the PD phenotype. Conclusion: We identified an RBD-specific PD endophenotype, characterized by predominant autonomic dysfunction, hallucinations, and depression, corroborating the concept of a distinctive body-first subtype of PD. We did not observe a significant association between APOE ɛ4 and pRBD suggesting both factors having an independent effect on cognitive decline in iPD. [less ▲]

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