TY - JOUR
T1 - Assessing the pre-analytical stability of small- molecule metabolites in cerebrospinal fluid using direct-infusion metabolomics
AU - Haijes, Hanneke A.
AU - Willemse, Eline A. J.
AU - Gerrits, Johan
AU - van der Flier, Wiesje M.
AU - Teunissen, Charlotte E.
AU - Verhoeven-Duif, Nanda M.
AU - Jans, Judith J. M.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Metabolomics studies aiming to find biomarkers frequently make use of historical or multicenter cohorts. These samples often have different pre-analytical conditions that potentially affect metabolite concentrations. We studied the effect of different storage conditions on the stability of small-molecule metabolites in cerebrospinal fluid to aid a reliable interpretation of metabolomics data. Three cerebrospinal fluid pools were prepared from surplus samples from the Amsterdam Dementia Cohort biobank. Aliquoted pools were exposed to different storage conditions to assess the temperature and freeze/thaw stability before final storage at -80 °C: storage up to four months at -20 °C and up to one week at either 5-8 °C or 18-22 °C and exposure to up to seven freeze/thaw cycles. Direct-infusion high-resolution mass spectrometry was performed, resulting in the identification of 1852 m/z peaks. To test the storage stability, principal component analyses, repeated measures analysis of variance, Kruskal-Wallis tests, and fold change analyses were performed, all demonstrating that small-molecule metabolites in the cerebrospinal fluid (CSF) are relatively unaffected by 1-3 freeze/thaw cycles, by storage at -20 °C up to two months, by storage at 5-8 °C for up to 72 h, or by storage at 18-22 °C for up to 8 h. This suggests that these differences do not affect the interpretation of potential small-molecule biomarkers in multicenter or historical cohorts and implies that these cohorts are suitable for biomarker studies.
AB - Metabolomics studies aiming to find biomarkers frequently make use of historical or multicenter cohorts. These samples often have different pre-analytical conditions that potentially affect metabolite concentrations. We studied the effect of different storage conditions on the stability of small-molecule metabolites in cerebrospinal fluid to aid a reliable interpretation of metabolomics data. Three cerebrospinal fluid pools were prepared from surplus samples from the Amsterdam Dementia Cohort biobank. Aliquoted pools were exposed to different storage conditions to assess the temperature and freeze/thaw stability before final storage at -80 °C: storage up to four months at -20 °C and up to one week at either 5-8 °C or 18-22 °C and exposure to up to seven freeze/thaw cycles. Direct-infusion high-resolution mass spectrometry was performed, resulting in the identification of 1852 m/z peaks. To test the storage stability, principal component analyses, repeated measures analysis of variance, Kruskal-Wallis tests, and fold change analyses were performed, all demonstrating that small-molecule metabolites in the cerebrospinal fluid (CSF) are relatively unaffected by 1-3 freeze/thaw cycles, by storage at -20 °C up to two months, by storage at 5-8 °C for up to 72 h, or by storage at 18-22 °C for up to 8 h. This suggests that these differences do not affect the interpretation of potential small-molecule biomarkers in multicenter or historical cohorts and implies that these cohorts are suitable for biomarker studies.
KW - Biomarker stability
KW - Cerebrospinal fluid
KW - DIMS
KW - Direct-infusion mass spectrometry
KW - Metabolomics
KW - Neurometabolic diagnostics
KW - Pre-analytical storage conditions
KW - Small-molecule metabolites
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85075028062&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31635433
UR - http://www.scopus.com/inward/record.url?scp=85075028062&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/metabo9100236
DO - https://doi.org/10.3390/metabo9100236
M3 - Article
C2 - 31635433
SN - 2218-1989
VL - 9
JO - Metabolites
JF - Metabolites
IS - 10
M1 - 236
ER -