Proteomic profiling of low muscle and high fat mass: a machine learning approach in the KORA S4/FF4 study
Abstract Background The coexistence of low muscle mass and high fat mass, two interrelated conditions strongly associated with declining health status, has been characterized by only a few protein biomarkers. High‐throughput proteomics enable concurrent measurement of numerous proteins, facilitating...
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Wiley
2021-08-01
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Series: | Journal of Cachexia, Sarcopenia and Muscle |
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Online Access: | https://doi.org/10.1002/jcsm.12733 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marie‐Theres Huemer Alina Bauer Agnese Petrera Markus Scholz Stefanie M. Hauck Michael Drey Annette Peters Barbara Thorand |
spellingShingle |
Marie‐Theres Huemer Alina Bauer Agnese Petrera Markus Scholz Stefanie M. Hauck Michael Drey Annette Peters Barbara Thorand Proteomic profiling of low muscle and high fat mass: a machine learning approach in the KORA S4/FF4 study Journal of Cachexia, Sarcopenia and Muscle Appendicular skeletal muscle mass Body fat mass index Fat mass Muscle mass Machine learning Proteomics |
author_facet |
Marie‐Theres Huemer Alina Bauer Agnese Petrera Markus Scholz Stefanie M. Hauck Michael Drey Annette Peters Barbara Thorand |
author_sort |
Marie‐Theres Huemer |
title |
Proteomic profiling of low muscle and high fat mass: a machine learning approach in the KORA S4/FF4 study |
title_short |
Proteomic profiling of low muscle and high fat mass: a machine learning approach in the KORA S4/FF4 study |
title_full |
Proteomic profiling of low muscle and high fat mass: a machine learning approach in the KORA S4/FF4 study |
title_fullStr |
Proteomic profiling of low muscle and high fat mass: a machine learning approach in the KORA S4/FF4 study |
title_full_unstemmed |
Proteomic profiling of low muscle and high fat mass: a machine learning approach in the KORA S4/FF4 study |
title_sort |
proteomic profiling of low muscle and high fat mass: a machine learning approach in the kora s4/ff4 study |
publisher |
Wiley |
series |
Journal of Cachexia, Sarcopenia and Muscle |
issn |
2190-5991 2190-6009 |
publishDate |
2021-08-01 |
description |
Abstract Background The coexistence of low muscle mass and high fat mass, two interrelated conditions strongly associated with declining health status, has been characterized by only a few protein biomarkers. High‐throughput proteomics enable concurrent measurement of numerous proteins, facilitating the discovery of potentially new biomarkers. Methods Data derived from the prospective population‐based Cooperative Health Research in the Region of Augsburg S4/FF4 cohort study (median follow‐up time: 13.5 years) included 1478 participants (756 men and 722 women) aged 55–74 years in the cross‐sectional and 608 participants (315 men and 293 women) in the longitudinal analysis. Appendicular skeletal muscle mass (ASMM) and body fat mass index (BFMI) were determined through bioelectrical impedance analysis at baseline and follow‐up. At baseline, 233 plasma proteins were measured using proximity extension assay. We implemented boosting with stability selection to enable false positives‐controlled variable selection to identify new protein biomarkers of low muscle mass, high fat mass, and their combination. We evaluated prediction models developed based on group least absolute shrinkage and selection operator (lasso) with 100× bootstrapping by cross‐validated area under the curve (AUC) to investigate if proteins increase the prediction accuracy on top of classical risk factors. Results In the cross‐sectional analysis, we identified kallikrein‐6, C‐C motif chemokine 28 (CCL28), and tissue factor pathway inhibitor as previously unknown biomarkers for muscle mass [association with low ASMM: odds ratio (OR) per 1‐SD increase in log2 normalized protein expression values (95% confidence interval (CI)): 1.63 (1.37–1.95), 1.31 (1.14–1.51), 1.24 (1.06–1.45), respectively] and serine protease 27 for fat mass [association with high BFMI: OR (95% CI): 0.73 (0.61–0.86)]. CCL28 and metalloproteinase inhibitor 4 (TIMP4) constituted new biomarkers for the combination of low muscle and high fat mass [association with low ASMM combined with high BFMI: OR (95% CI): 1.32 (1.08–1.61), 1.28 (1.03–1.59), respectively]. Including protein biomarkers selected in ≥90% of group lasso bootstrap iterations on top of classical risk factors improved the performance of models predicting low ASMM, high BFMI, and their combination [delta AUC (95% CI): 0.16 (0.13–0.20), 0.22 (0.18–0.25), 0.12 (0.08–0.17), respectively]. In the longitudinal analysis, N‐terminal prohormone brain natriuretic peptide (NT‐proBNP) was the only protein selected for loss in ASMM and loss in ASMM combined with gain in BFMI over 14 years [OR (95% CI): 1.40 (1.10–1.77), 1.60 (1.15–2.24), respectively]. Conclusions Proteomic profiling revealed CCL28 and TIMP4 as new biomarkers of low muscle mass combined with high fat mass and NT‐proBNP as a key biomarker of loss in muscle mass combined with gain in fat mass. Proteomics enable us to accelerate biomarker discoveries in muscle research. |
topic |
Appendicular skeletal muscle mass Body fat mass index Fat mass Muscle mass Machine learning Proteomics |
url |
https://doi.org/10.1002/jcsm.12733 |
work_keys_str_mv |
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doaj-7e80f4c1e8ca481da048d132309b4a762021-08-09T05:46:55ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092021-08-011241011102310.1002/jcsm.12733Proteomic profiling of low muscle and high fat mass: a machine learning approach in the KORA S4/FF4 studyMarie‐Theres Huemer0Alina Bauer1Agnese Petrera2Markus Scholz3Stefanie M. Hauck4Michael Drey5Annette Peters6Barbara Thorand7Institute of Epidemiology Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) Neuherberg GermanyInstitute of Epidemiology Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) Neuherberg GermanyResearch Unit Protein Science Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) Neuherberg GermanyInstitute for Medical Informatics, Statistics and Epidemiology (IMISE) Universität Leipzig Leipzig GermanyResearch Unit Protein Science Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) Neuherberg GermanyMedizinische Klinik und Poliklinik IV, Schwerpunkt Akutgeriatrie Klinikum der Universität München (LMU) Munich GermanyInstitute of Epidemiology Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) Neuherberg GermanyInstitute of Epidemiology Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH) Neuherberg GermanyAbstract Background The coexistence of low muscle mass and high fat mass, two interrelated conditions strongly associated with declining health status, has been characterized by only a few protein biomarkers. High‐throughput proteomics enable concurrent measurement of numerous proteins, facilitating the discovery of potentially new biomarkers. Methods Data derived from the prospective population‐based Cooperative Health Research in the Region of Augsburg S4/FF4 cohort study (median follow‐up time: 13.5 years) included 1478 participants (756 men and 722 women) aged 55–74 years in the cross‐sectional and 608 participants (315 men and 293 women) in the longitudinal analysis. Appendicular skeletal muscle mass (ASMM) and body fat mass index (BFMI) were determined through bioelectrical impedance analysis at baseline and follow‐up. At baseline, 233 plasma proteins were measured using proximity extension assay. We implemented boosting with stability selection to enable false positives‐controlled variable selection to identify new protein biomarkers of low muscle mass, high fat mass, and their combination. We evaluated prediction models developed based on group least absolute shrinkage and selection operator (lasso) with 100× bootstrapping by cross‐validated area under the curve (AUC) to investigate if proteins increase the prediction accuracy on top of classical risk factors. Results In the cross‐sectional analysis, we identified kallikrein‐6, C‐C motif chemokine 28 (CCL28), and tissue factor pathway inhibitor as previously unknown biomarkers for muscle mass [association with low ASMM: odds ratio (OR) per 1‐SD increase in log2 normalized protein expression values (95% confidence interval (CI)): 1.63 (1.37–1.95), 1.31 (1.14–1.51), 1.24 (1.06–1.45), respectively] and serine protease 27 for fat mass [association with high BFMI: OR (95% CI): 0.73 (0.61–0.86)]. CCL28 and metalloproteinase inhibitor 4 (TIMP4) constituted new biomarkers for the combination of low muscle and high fat mass [association with low ASMM combined with high BFMI: OR (95% CI): 1.32 (1.08–1.61), 1.28 (1.03–1.59), respectively]. Including protein biomarkers selected in ≥90% of group lasso bootstrap iterations on top of classical risk factors improved the performance of models predicting low ASMM, high BFMI, and their combination [delta AUC (95% CI): 0.16 (0.13–0.20), 0.22 (0.18–0.25), 0.12 (0.08–0.17), respectively]. In the longitudinal analysis, N‐terminal prohormone brain natriuretic peptide (NT‐proBNP) was the only protein selected for loss in ASMM and loss in ASMM combined with gain in BFMI over 14 years [OR (95% CI): 1.40 (1.10–1.77), 1.60 (1.15–2.24), respectively]. Conclusions Proteomic profiling revealed CCL28 and TIMP4 as new biomarkers of low muscle mass combined with high fat mass and NT‐proBNP as a key biomarker of loss in muscle mass combined with gain in fat mass. Proteomics enable us to accelerate biomarker discoveries in muscle research.https://doi.org/10.1002/jcsm.12733Appendicular skeletal muscle massBody fat mass indexFat massMuscle massMachine learningProteomics |