The effects of indoor conditions (ozone concentration, temperature, relative humidity (RH), and the presence of NO(x)) on heterogeneous squalene oxidation were studied with Attenuated Total Reflectance-Fourier Transform Infrared spectroscopy. The heterogeneous kinetics of squalene-ozone reaction revealed a pseudo-first-order reaction rate constant of 1.22 x 10(-5)/s at [O(3)] = 40 ppb. Oxidation kinetics were insensitive to temperature over the range of 24-58 +/- 2 degrees C as well as to RH and presence of NO(x). Products, however, were affected by the environmental parameters. As temperature was increased, fewer surface products and more low molecular weight gaseous products were observed. Lower air exchange rates also enhanced gas phase reactions, allowing for formation of secondary gas phase products. As RH increased, there was a shift in product distribution from ketones to aldehydes, and the presence of NO(x) during squalene ozonolysis resulted in the formation of nitrated oxidation products. Identified surface products included 6-methyl-5-hepten-2-one, geranyl acetone, and long chain ketones and aldehydes, while gas phase products included formaldehyde, acetone, 4-oxopentanal (4-OPA), glyoxal, and pyruvic acid. Practical Implications Heterogeneous oxidation of squalene resulted in surface products including long chain aldehydes and ketones, and gas phase products including formaldehyde, a known human carcinogen (IARC 2006), and bicarbonyl compounds like: 4-oxopentanal (4-OPA), glyoxal, and pyruvic acid that are characterized as asthma triggers and sensitizers (Anderson et al., 2007; Jarvis et al., 2005). In addition, ozonolysis experiments in the presence of NO(x) showed the formation of nitrated surface oxidation products. Such nitrated products may have higher mutagenicity, carcinogenicity, or allergenic potential than their nitrate free counterparts (Franze et al., 2005; Pitts, 1983). Kinetic studies determined that at moderate ozone levels of 40 ppb (Uhde and Salthammer, 2007), and an estimated skin surface density of 4 x 10(15) molecules/cm(2), surface reaction would lead to a minimum product formation flux of 4 x 10(10) molecules cm(2)/s. As squalene is naturally occurring and continually produced by the human body, its concentration in the indoor environment cannot be controlled. However, this study highlights the importance of regulating air exchange rate, temperature, and ozone level in the indoor environment on the formation of potentially harmful or irritating squalene oxidation products.

Background Untargeted metabolomics datasets contain large proportions of uninformative features that can impede subsequent statistical analysis such as biomarker discovery and metabolic pathway analysis. Thus, there is a need for versatile and data-adaptive methods for filtering data prior to investigating the underlying biological phenomena. Here, we propose a data-adaptive pipeline for filtering metabolomics data that are generated by liquid chromatography-mass spectrometry (LC-MS) platforms. Our data-adaptive pipeline includes novel methods for filtering features based on blank samples, proportions of missing values, and estimated intra-class correlation coefficients. Results Using metabolomics datasets that were generated in our laboratory from samples of human blood, as well as two public LC-MS datasets, we compared our data-adaptive filtering method with traditional methods that rely on non-method specific thresholds. The data-adaptive approach outperformed traditional approaches in terms of removing noisy features and retaining high quality, biologically informative ones. The R code for running the data-adaptive filtering method is provided at https://github.com/courtneyschiffman/Metabolomics-Filtering . Conclusions Our proposed data-adaptive filtering pipeline is intuitive and effectively removes uninformative features from untargeted metabolomics datasets. It is particularly relevant for interrogation of biological phenomena in data derived from complex matrices associated with biospecimens. Electronic supplementary material The online version of this article (10.1186/s12859-019-2871-9) contains supplementary material, which is available to authorized users.

Nicotine dynamics in an indoor environment can be greatly affected by building parameters (e.g. relative humidity (RH), air exchange rate (AER), and presence of ozone), as well as surface parameters (e.g. surface area (SA) and polarity). To better understand the indoor fate of nicotine, these parameter effects on its sorption, desorption, and oxidation rates were investigated on model indoor surfaces that included fabrics, wallboard paper, and wood materials. Nicotine sorption under dry conditions was enhanced by higher SA and higher polarity of the substrate. Interestingly, nicotine sorption to cotton and nylon was facilitated by increased RH, while sorption to polyester was hindered by it. Desorption was affected by RH, AER, and surface type. Heterogeneous nicotine-ozone reaction was investigated by Fourier transform infrared spectrometry with attenuated total reflection (FTIR-ATR), and revealed a pseudo first-order surface reaction rate of 0.035 +/- 0.015 min(-1) (at [O(3)] = 6 +/- 0.3 x 10(15) molecules cm(-3)) that was partially inhibited at high RH. Extrapolation to a lower ozone level ([O(3)] = 42 ppb) showed oxidation on the order of 10(-5) min(-1) corresponding to a half-life of 1 week. In addition, similar surface products were identified in dry and high RH using gas chromatography-mass spectrometry (GC-MS). However, FTIR analysis revealed different product spectra for these conditions, suggesting additional unidentified products and association with surface water. Knowing the indoor fate of condensed and gas phase nicotine and its oxidation products will provide a better understanding of nicotine's impact on personal exposures as well as overall indoor air quality.

Introduction For pediatric diseases like childhood leukemia, a short latency period points to in-utero exposures as potentially important risk factors. Untargeted metabolomics of small molecules in archived newborn dried blood spots (DBS) offers an avenue for discovering early-life exposures that contribute to disease risks. Objectives The purpose of this study was to develop a quantitative method for untargeted analysis of archived newborn DBS for use in an epidemiological study (California Childhood Leukemia Study, CCLS). Methods Using experimental DBS from the blood of an adult volunteer, we optimized extraction of small molecules and integrated measurement of potassium as a proxy for blood hematocrit. We then applied this extraction method to 4.7-mm punches from 106 control DBS samples from the CCLS. Sample extracts were analyzed with liquid chromatography high resolution mass spectrometry (LC-HRMS) and an untargeted workflow was used to screen for metabolites that discriminate population characteristics such as sex, ethnicity, and birth weight. Results Thousands of small molecules were measured in extracts of archived DBS. Normalizing for potassium levels removed variability related to varying hematocrit across DBS punches. Of the roughly 1,000 prevalent small molecules that were tested, multivariate linear regression detected significant associations with ethnicity (3 metabolites) and birth weight (15 metabolites) after adjusting for multiple testing. Conclusions This untargeted workflow can be used for analysis of small molecules in archived DBS to discover novel biomarkers, to provide insights into the initiation and progression of diseases, and to provide guidance for disease prevention.

Tobacco smoking is well-known as a significant source of primary indoor air pollutants. However, only recently has thirdhand smoke (THS) been recognized as a contributor to indoor pollution due to the role of indoor surfaces. Here, the effects of relative humidity (<10% RH and ∼ 45% RH) and substrate (cellulose, cotton, and paper) on secondary organic aerosol (SOA) formation from nicotine-ozone-NO(x) reactions are discussed. SOA formation from the sorbed nicotine-ozone reaction ([O(3)] = 55 ppb) varied in size distribution and number, depending on RH and substrate type, indicating the role of substrate and water interactions in SOA formation. This led to SOA yields from cellulose sorbed nicotine-ozone reaction of ∼ 1 and 2% for wet and dry conditions, respectively. SOA formation from nicotine-NO(x) reactions was not distinguishable from background levels. Simultaneously, cellulose sorbed nicotine-ozone reaction kinetics ([O(3)] = 55 ppb) were obtained and revealed pseudofirst-order surface rate constants of k(1) = (1 ± 0. 5) × 10(-3) and k(1) < 10(-4) min(-1) under <10% and ∼ 45% RH, respectively. Given the toxicity of some of the identified products and that small particles may contribute to adverse health effects, the present study indicates that exposure to THS ozonation products may pose additional health risks.

Exposure to tobacco pollutants that linger indoors after smoking has taken place (thirdhand smoke, THS) can occur over extended periods and is modulated by chemical processes involving atmospheric reactive species. This study investigates the role of ozone and indoor surfaces in chemical transformations of tobacco smoke residues. Gas and particle constituents of secondhand smoke (SHS) as well as sorbed SHS on chamber internal walls and model materials (cotton, paper, and gypsum wallboard) were characterized during aging. After smoldering 10 cigarettes in a 24-m 3 room size chamber, gas-phase nicotine was rapidly removed by sorption to chamber surfaces, and subsequently re-emitted during ventilation with clean air to a level of ~10% that during the smoking phase. During chamber ventilation in the presence of ozone (180 ppb), ozone decayed at a rate of 5.6 h -1 and coincided with a factor of 5 less nicotine sorbed to wallboard. In the presence of ozone, no gas phase nicotine was detected as a result of reemission, and higher concentrations of nicotine oxidation products were observed than when ventilation was performed with ozone-free air. Analysis of the model surfaces showed that heterogeneous nicotine-ozone reaction was faster on paper than cotton, and both were faster than on wallboard. However, wallboard played a dominant role in ozone-initiated reaction in the chamber due to its large total geometric surface area and sink potential compared to the other substrates. This study is the first to show in a roomsized environmental chamber that the heterogeneous ozone chemistry of sorbed nicotine generates THS constituents of concern, as observed previously in bench-top studies. In addition to the main oxidation products (cotinine, myosmine and N-methyl formamide), nicotine-1-oxide was detected for the first time.Petrick et al.

Untargeted metabolomics analysis captures chemical reactions among small molecules. Common mass spectrometry-based metabolomics workflows first identify the small molecules significantly associated with the outcome of interest, then begin exploring their biochemical relationships to understand biological fate or impact. We suggest an alternative by which general chemical relationships including abiotic reactions can be directly retrieved through untargeted high-resolution paired mass distance (PMD) analysis without a priori knowledge of the identities of participating compounds. PMDs calculated from the mass spectrometry data are linked to chemical reactions obtained via data mining of small molecule and reaction databases, i.e. ‘PMD-based reactomics’. We demonstrate applications of PMD-based reactomics including PMD network analysis, source appointment of unknown compounds, and biomarker reaction discovery as complements to compound discovery analyses used in traditional untargeted workflows. An R implementation of reactomics analysis and the reaction/PMD databases is available as the pmd package.

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