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Mapping Chemical Space Coverage in Non-Targeted Analysis
Citation:
Black, G., C. Lowe, T. Anumol, J. Blade, K. Favela, C. Fisher, Y. Feng, A. Hood, A. Knolhoff, A. McEachran, J. Nunez, K. Peter, N. Quinete, J. Sobus, E. Sussman, W. Watson, A. Williams, AND S. Wickramesekara. Mapping Chemical Space Coverage in Non-Targeted Analysis. SETAC Non-Targeted Analysis Meeting, Durham, NC, May 22 - 25, 2022. https://doi.org/10.23645/epacomptox.20126375
Impact/Purpose:
The methods and software tools implemented in non-targeted analysis (NTA) are numerous, allowing for highly customizable workflows with varying chemical space coverage. Predicting or defining this applicability domain for each workflow remains a challenge. An additional need therefore exists for approaches that can define the region of chemical space detectable by a selected (or planned) NTA method. Such approaches could theoretically enhance performance of NTA methods by minimizing false positives (i.e., instances when an undetectable compound is reported as being present) and increasing confidence in putative positive identifications that fall within the defined method applicability domain. The development of explicit chemical space mapping tools could also give researchers the ability to reduce the vast known chemical universe into lists of plausibly detectable and identifiable compounds. These Amenable Compound Lists (ACLs) could then be used as identification libraries and in annotation efforts as part of data processing workflows. Ultimately, understanding method boundaries will allow researchers to communicate and compare methods and results more easily, and better assess method needs on a project-by-project basis.
Description:
Non-targeted analysis (NTA) using high-resolution mass spectrometry allows scientists to detect and identify a broad range of compounds for further analysis, future monitoring, and potential prioritization for toxicological and exposure assessment in diverse matrices without a priori knowledge of the chemical constituents of the sample. Relative to targeted methods, these NTA methods present the opportunity to describe the constituents of a sample across a multidimensional swath of chemical properties, referred to as¿chemical¿space. However, understanding and communicating which “corner” of chemical space is detectable by an NTA workflow remains challenging and non-standardized. For example, sample collection, preparation, and NTA data acquisition, processing, and filtering steps will all influence the types of chemicals that are detected and identified. Accordingly, it is challenging to assess whether¿analyte non-detection in an NTA study indicates true absence¿in a sample¿(above a detection limit) or is a false negative result driven by limitations of the workflow. Such information gaps can reduce the utility and reliability of chemical screening data, particularly in the context of exposure and risk assessment. Here, we describe the need for accessible approaches that enable chemical space mapping in¿NTA studies. We identify a suite of existing predictive and analytical tools that can be used in combination to generate scores that relate the likelihood that each identified compound was plausibly detected according to the predicted chemical space of the NTA workflow.¿High-scoring compounds, therefore, correlate to a high likelihood that the compound could be¿detected and identified¿in the given workflow, whereas low scoring compounds have a low probability of being¿detected¿(even if truly present in the samples of interest)¿and could¿be used in decoy libraries to help researchers determine appropriate minimum scoring thresholds throughout the analytical workflow. This work also highlights the chemometric tools needed to make such a tool robust and usable across a wide range of NTA disciplines. Ultimately, development of a chemical space mapping tool strives to enable further standardization of¿NTA by improving method transparency and communication around false detection rates, thus allowing for more direct method comparisons between studies and improved reproducibility. This, in turn, is expected to promote further widespread application of NTA beyond research-oriented settings.
URLs/Downloads:
DOI: Mapping Chemical Space Coverage in Non-Targeted Analysis
220405_SETAC_NTA_POSTER.PDF (PDF, NA pp, 2337.661 KB, about PDF)