Detailed Information on Publication Record
2021
Systematic Feature Filtering in Exploratory Metabolomics: Application toward Biomarker Discovery
GADARA, Darshak Chandulal, Kateřina COUFALÍKOVÁ, Juraj BOSÁK, David ŠMAJS, Zdeněk SPÁČIL et. al.Basic information
Original name
Systematic Feature Filtering in Exploratory Metabolomics: Application toward Biomarker Discovery
Authors
GADARA, Darshak Chandulal (356 India, belonging to the institution), Kateřina COUFALÍKOVÁ (203 Czech Republic, belonging to the institution), Juraj BOSÁK (703 Slovakia, belonging to the institution), David ŠMAJS (203 Czech Republic, belonging to the institution) and Zdeněk SPÁČIL (203 Czech Republic, guarantor, belonging to the institution)
Edition
Analytical chemistry, WASHINGTON, AMER CHEMICAL SOC, 2021, 0003-2700
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
10406 Analytical chemistry
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 8.008
RIV identification code
RIV/00216224:14310/21:00119354
Organization unit
Faculty of Science
UT WoS
000672115800013
Keywords in English
SPECTROMETRY-BASED METABOLOMICS; LC-MS METABOLOMICS; ANNOTATION; TOOLS; CHALLENGES; SOFTWARE; XCMS
Tags
International impact, Reviewed
Změněno: 28/2/2022 11:05, Mgr. Marie Šípková, DiS.
Abstract
V originále
Exploratory mass spectrometry-based metabolomics generates a plethora of features in a single analysis. However, >85% of detected features are typically false positives due to inefficient elimination of chimeric signals and chemical noise not relevant for biological and clinical data interpretation. The data processing is considered a bottleneck to unravel the translational potential in metabolomics. Here, we describe a systematic workflow to refine exploratory metabolomics data and reduce reported false positives. We applied the feature filtering workflow in a case/control study exploring common variable immunodeficiency (CVID). In the first stage, features were detected from raw liquid chromatography-mass spectrometry data by XCMS Online processing, blank subtraction, and reproducibility assessment. Detected features were annotated in metabolomics databases to produce a list of tentative identifications. We scrutinized tentative identifications' physicochemical properties, comparing predicted and experimental reversed-phase liquid chromatography (LC) retention time. A prediction model used a linear regression of 42 retention indices with the cLogP ranging from -6 to 11. The LC retention time probes the physicochemical properties and effectively reduces the number of tentatively identified metabolites, which are further submitted to statistical analysis. We applied the retention time-based analytical feature filtering workflow to datasets from the Metabolomics Workbench (www. metaboloinicsworkbench.org ), demonstrating the broad applicability. A subset of tentatively identified metabolites significantly different in CVID patients was validated by MS/MS acquisition to confirm potential CVID biomarkers' structures and virtually eliminate false positives. Our exploratory metabolomics data processing workflow effectively removes false positives caused by the chemical background and chimeric signals inherent to the analytical technique. It reduced the number of tentatively identified metabolites by 88%, from initially detected 6940 features in XCMS to 839 tentative identifications and streamlined consequent statistical analysis and data interpretation.
Links
| EF15_003/0000469, research and development project |
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| EF17_043/0009632, research and development project |
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| GJ17-24592Y, research and development project |
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| LM2018121, research and development project |
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| MUNI/G/1131/2017, interní kód MU |
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| NV19-08-00472, research and development project |
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