TY - JOUR
T1 - The reproducibility of urinary ions in manganese exposed workers
AU - Baker, Marissa G.
AU - Lin, Yvonne S.
AU - Simpson, Christopher D.
AU - Shireman, Laura M.
AU - Searles Nielsen, Susan
AU - Racette, Brad A.
AU - Seixas, Noah
N1 - Funding Information:
Research reported in this publication was supported by the National Institute of Environmental Health Sciences ( R01 ES021488 , R01 ES021488-02S1 , K24 NS060825 ), and the Interdisciplinary Center for Exposures, Diseases, Genomics, and Environment ( P30ES007033 ). MGB was further supported by a National Institute of Environmental Health Sciences Biostatistics, Epidemiologic, and Bioinformatics Training in Environmental Health , Award Number T32ES015459 and Ruth L. Kirschstein National Research Service Award F31ES027304. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Thanks to Tauri Senn, University of Washington Department of Medicinal Chemistry for help with sample analysis and interpretation.
Publisher Copyright:
© 2018
PY - 2019/1
Y1 - 2019/1
N2 - Purpose: Manganese (Mn) is found in environmental and occupational settings, and can cause cognitive and motor impairment. Existing Mn exposure studies have not reached consensus on a valid and reproducible biomarker for Mn exposure. Methods: Previously, global metabolomics data was generated from urine collected in October 2014 using mass spectrometry (MS). Nine ions were found to be different between persons exposed and unexposed to Mn occupationally, though their identity was not able to be determined. Here, we investigated these nine ions in a follow-up set of urine samples taken from the same cohort in January 2015, and in urine samples from a separate Mn-exposed cohort from Wisconsin. We fit an elastic net model fit using the nine ions found in the October 2014 data. Results: The elastic net correctly predicted exposure status in 72% of the follow-up samples collected in January 2015, and the area under the curve of the receiver operating characteristic (ROC) curve was 0.8. In the Wisconsin samples, the elastic net performed no better than chance in predicting exposure, possibly due to differences in Mn exposure levels, or unmeasured occupational or environmental co-exposures. Conclusions: This work underscores the importance of taking repeat samples for replication studies when investigating the human urine metabolome, as both within- and between-person variances were observed. Validating and identifying promising results remains a challenge in harnessing global metabolomics for biomarker discovery in occupational cohorts.
AB - Purpose: Manganese (Mn) is found in environmental and occupational settings, and can cause cognitive and motor impairment. Existing Mn exposure studies have not reached consensus on a valid and reproducible biomarker for Mn exposure. Methods: Previously, global metabolomics data was generated from urine collected in October 2014 using mass spectrometry (MS). Nine ions were found to be different between persons exposed and unexposed to Mn occupationally, though their identity was not able to be determined. Here, we investigated these nine ions in a follow-up set of urine samples taken from the same cohort in January 2015, and in urine samples from a separate Mn-exposed cohort from Wisconsin. We fit an elastic net model fit using the nine ions found in the October 2014 data. Results: The elastic net correctly predicted exposure status in 72% of the follow-up samples collected in January 2015, and the area under the curve of the receiver operating characteristic (ROC) curve was 0.8. In the Wisconsin samples, the elastic net performed no better than chance in predicting exposure, possibly due to differences in Mn exposure levels, or unmeasured occupational or environmental co-exposures. Conclusions: This work underscores the importance of taking repeat samples for replication studies when investigating the human urine metabolome, as both within- and between-person variances were observed. Validating and identifying promising results remains a challenge in harnessing global metabolomics for biomarker discovery in occupational cohorts.
KW - Biomarkers
KW - Exposure assessment
KW - Manganese
KW - Metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85056198133&partnerID=8YFLogxK
U2 - 10.1016/j.jtemb.2018.11.001
DO - 10.1016/j.jtemb.2018.11.001
M3 - Article
C2 - 30466932
AN - SCOPUS:85056198133
SN - 0946-672X
VL - 51
SP - 204
EP - 211
JO - Journal of Trace Elements in Medicine and Biology
JF - Journal of Trace Elements in Medicine and Biology
ER -