Interpretable multimodal machine learning (IMML) framework reveals pathological signatures of distal sensorimotor polyneuropathy

Nguyeb, Phong B. H.; Garger, Daniel; Lu, Diyuan; Maalmi, Haifa ; Prokisch, Holger ; Thorand, Barbara ; Adamski, Jerzy ; Kastenmüller, Gabi ; Waldenberger, Melanie ; Gieger, Christian ; Peters, Annette ; Suhre, Karsten ; Bönhof, Gidon J. ; Rathmann, Wolfgang ; Roden, Michael ; Grallert, Harald ; Ziegler, Dan ; Herder, Christian und Menden, Michael P. (16. Dezember 2024): Interpretable multimodal machine learning (IMML) framework reveals pathological signatures of distal sensorimotor polyneuropathy. In: Communications Medicine, Bd. 4, 265

Abstract

Background: Distal sensorimotor polyneuropathy (DSPN) is a common neurological disorder in elderly adults and people with obesity, prediabetes and diabetes and is associated with high morbidity and premature mortality. DSPN is a multifactorial disease and not fully understood yet.

Methods: Here, we developed the Interpretable Multimodal Machine Learning (IMML) framework for predicting DSPN prevalence and incidence based on sparse multimodal data. Exploiting IMMLs interpretability further empowered biomarker identification. We leveraged the population-based KORA F4/FF4 cohort including 1091 participants and their deep multimodal characterisation, i.e. clinical data, genomics, methylomics, transcriptomics, proteomics, inflammatory proteins and metabolomics.

Results: Clinical data alone is sufficient to stratify individuals with and without DSPN (AUROC = 0.752), whilst predicting DSPN incidence 6.5 ± 0.2 years later strongly benefits from clinical data complemented with two or more molecular modalities (improved ΔAUROC > 0.1, achieved AUROC of 0.714). Important and interpretable features of incident DSPN prediction include up-regulation of proinflammatory cytokines, down-regulation of SUMOylation pathway and essential fatty acids, thus yielding novel insights in the disease pathophysiology.

Conclusions: These may become biomarkers for incident DSPN, guide prevention strategies and serve as proof of concept for the utility of IMML in studying complex diseases.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2730-664X
• Sprache: Englisch