Biometric Identification Method for Heart Sound Based on Multimodal Multiscale Dispersion Entropy.

In this paper, a new method of biometric characterization of heart sounds based on multimodal multiscale dispersion entropy is proposed. Firstly, the heart sound is periodically segmented, and then each single-cycle heart sound is decomposed into a group of intrinsic mode functions (IMFs) by improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN). These IMFs are then segmented to a series of frames, which is used to calculate the refine composite multiscale dispersion entropy (RCMDE) as the characteristic representation of heart sound. In the simulation experiments I, carried out on the open heart sounds database Michigan, Washington and Littman, the feature representation method was combined with the heart sound segmentation method based on logistic regression (LR) and hidden semi-Markov models (HSMM), and feature selection was performed through the Fisher ratio (FR). Finally, the Euclidean distance (ED) and the close principle are used for matching and identification, and the recognition accuracy rate was 96.08%. To improve the practical application value of this method, the proposed method was applied to 80 heart sounds database constructed by 40 volunteer heart sounds to discuss the effect of single-cycle heart sounds with different starting positions on performance in experiment II. The experimental results show that the single-cycle heart sound with the starting position of the start of the first heart sound (S1) has the highest recognition rate of 97.5%. In summary, the proposed method is effective for heart sound biometric recognition.

Robust Sampling of Defective Pathways in Multiple Myeloma.

We present the analysis of defective pathways in multiple myeloma (MM) using two recently developed sampling algorithms of the biological pathways: The Fisher's ratio sampler, and the holdout sampler. We performed the retrospective analyses of different gene expression datasets concerning different aspects of the disease, such as the existing difference between bone marrow stromal cells in MM and healthy controls (HC), the gene expression profiling of CD34+ cells in MM and HC, the difference between hyperdiploid and non-hyperdiploid myelomas, and the prediction of the chromosome 13 deletion, to provide a deeper insight into the molecular mechanisms involved in the disease. Our analysis has shown the importance of different altered pathways related to glycosylation, infectious disease, immune system response, different aspects of metabolism, DNA repair, protein recycling and regulation of the transcription of genes involved in the differentiation of myeloid cells. The main difference in genetic pathways between hyperdiploid and non-hyperdiploid myelomas are related to infectious disease, immune system response and protein recycling. Our work provides new insights on the genetic pathways involved in this complex disease and proposes novel targets for future therapies.

Estimation of start and stop numbers for cluster resolution feature selection algorithm: an empirical approach using null distribution analysis of Fisher ratios.

Cluster resolution feature selection (CR-FS) is a hybrid feature selection algorithm which involves the evaluation of ranked variables via sequential backward elimination (SBE) and sequential forward selection (SFS). The implementation of CR-FS requires two main inputs, namely, start and stop number. The start number is the number of the highly ranked variables for the SBE while the stop number is the point at which the search for additional features during the SFS stage is halted. The setting of these critical parameters has always relied on trial and error which introduced subjectivity in the results obtained. The start and stop numbers are known to vary with each dataset. Drawing inspiration from overlapping coefficients, a method for comparing two probability density functions, empirical equations toward the estimation of start and stop number for a dataset were developed. All of the parameters in the empirical equations are obtained from the comparisons of the two probability density functions except the constant termed d. The equations were optimized using three real-world datasets. The optimum range of d was determined to be 0.48 to 0.57. An implementation of CR-FS using two new datasets demonstrated the validity of this approach. Partial least squares discriminant analysis (PLS-DA) model prediction accuracies increased from 90 and 96 to 100% for both datasets using start and stop numbers calculated with this approach. Additionally, there was a twofold increase in the explained variance captured in the first two principal components. Graphical abstract Here, we describe how to determine the start and stop numbers for an automated feature selection routine, ensuring that you get the best model you can for your data with minimal effort.

Comprehensive two-dimensional gas chromatographic profiling and chemometric interpretation of the volatile profiles of sweat in knit fabrics.

Human axillary sweat is a poorly explored biofluid within the context of metabolomics when compared to other fluids such as blood and urine. In this paper, we explore the volatile organic compounds emitted from two different types of fabric samples (cotton and polyester) which had been worn repeatedly during exercise by participants. Headspace solid-phase microextraction (SPME) and comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS) were employed to profile the (semi)volatile compounds on the fabric. Principal component analysis models were applied to the data to aid in visualizing differences between types of fabrics, wash treatment, and the gender of the subject who had worn the fabric. Statistical tools included with commercial chromatography software (ChromaTOF) and a simple Fisher ratio threshold-based feature selection for model optimization are compared with a custom-written algorithm that uses cluster resolution as an objective function to maximize in a hybrid backward-elimination forward-selection approach for optimizing the chemometric models in an effort to identify some compounds that correlate to differences between fabric types. The custom algorithm is shown to generate better models than the simple Fisher ratio approach. Graphical Abstract A route from samples and questions to data and then answers.

Simultaneous discovery of compounds dominated by either molding kinetics or geographical region of origin for moisture damaged cacao beans using orthogonally applied tile-based fisher ratio analysis of GC×GC-TOFMS data.

Herein, two "orthogonal" characteristics of moisture damaged cacao beans (temporally dependent molding kinetics versus the time-independent geographical region of origin) are simultaneously analyzed in a comprehensive two-dimensional (2D) gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS) dataset using tile-based Fisher ratio (F-ratio) analysis. Cacao beans from six geographical regions were analyzed once a day for six days following the initiation of moisture damage to trigger the molding process. Thus, there are two "extremes" to the experimental sample class design: six time points for the molding kinetics versus the six geographical regions of origin, resulting in a 6 × 6 element signal array referred to as a composite chemical fingerprint (CCF) for each analyte. Usually, this study would involve initial generation of two separate hit lists using F-ratio analysis, one hit list from inputting the data with the six time point classes, then another hit list from inputting the dataset from the perspective of geographic region of origin. However, analysis of two separate hit lists with the intent to distill them down to one hit list is extremely time-consuming and fraught with shortcomings due to the challenges associated with attempting to match analytes across two hit lists. To address this challenge, tile-based F-ratio analysis is "orthogonally applied" to each analyte CCF to simultaneously determine two F-ratios at the chromatographic 2D location (F-ratiokinetic and F-ratioregion) for each hit, by ranking a single hit list using the higher of the two F-ratios resulting in the discovery of 591 analytes. Further, using a pseudo-null distribution approach, at the 99.9% threshold over 400 analytes were deemed suitable for PCA classification. Using a more stringent 99.999% threshold, over 100 analytes were explored more deeply using PARAFAC to provide a purified mass spectrum.

Automatic identifying OSAHS patients and simple snorers based on Gaussian mixture models.

Objective.Snoring is a typical symptom of Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS). In this study, an effective OSAHS patient detection system based on snoring sounds is presented.Approach.The Gaussian mixture model (GMM) is proposed to explore the acoustic characteristics of snoring sounds throughout the whole night to classify simple snores and OSAHS patients respectively. A series of acoustic features of snoring sounds of are selected based on the Fisher ratio and learned by GMM. Leave-one-subject-out cross validation experiment based on 30 subjects is conducted to validation the proposed model. There are 6 simple snorers (4 male and 2 female) and 24 OSAHS patients (15 male and 9 female) investigated in this work. Results indicates that snoring sounds of simple snorers and OSAHS patients have different distribution characteristics.Main results.The proposed model achieves average accuracy and precision with values of 90.0% and 95.7% using selected features with a dimension of 100 respectively. The average prediction time of the proposed model is 0.134 ± 0.005 s.Significance.The promising results demonstrate the effectiveness and low computational cost of diagnosing OSAHS patients using snoring sounds at home.

Study of the in vitro properties of oligopeptides from whey protein isolate with high Fisher's ratio and their ability to prevent allergic response to ß-lactoglobulin in vivo.

High Fisher ratio oligopeptides (HFOPs) with molecular weight range from 100 to 800 Da derived from whey protein isolate (WPI) were used to prevent the allergic response induced by ß-lactoglobulin (ßLg) in vivo due to their anti-inflammatory activities to lipopolysaccharide (LPS) treated RAW 264.7 cells and anti-allergicproperties to anti-DNP mouse IgE sensitized RBL-2H3 cells in vitro. The results showed theoverexpressed immunoglobulin E (IgE), unbalanced Th1-/Th2-type immune cytokines and inflammatory factors in ßLg-allergic mice were significantly attenuated by oral administration of HFOPs, resulting in the prevention of inflammatory lesions in spleen and colonic histopathology. Moreover, HFOPs increased ratio of Bacteroidetes/Firmicutes at phylum level in sensitive mice, and improved the abundance of Lactobacillaceae at family level to maintain oral tolerance against ßLg and prevented allergic response. The use of HFOPs may provide a potential alternative for preventing the milk allergy induced by WPI.

Enabling cuboid-based fisher ratio analysis using total-transfer comprehensive three-dimensional gas chromatography with time-of-flight mass spectrometry.

Comprehensive three-dimensional (3D) gas chromatography with time-of-flight mass spectrometry (GC3-TOFMS) is a promising instrumental platform for the separation of volatiles and semi-volatiles due to its increased peak capacity and selectivity relative to comprehensive two-dimensional gas chromatography with TOFMS (GC×GC-TOFMS). Given the recent advances in GC3-TOFMS instrumentation, new data analysis methods are now required to analyze its complex data structure efficiently and effectively. This report highlights the development of a cuboid-based Fisher ratio (F-ratio) analysis for supervised, non-targeted studies. This approach builds upon the previously reported tile-based F-ratio software for GC×GC-TOFMS data. Cuboid-based F-ratio analysis is enabled by constructing 3D cuboids within the GC3-TOFMS chromatogram and calculating F-ratios for every cuboid on a per-mass channel basis. This methodology is evaluated using a GC3-TOFMS data set of jet fuel spiked with both non-native and native components. The neat and spiked jet fuels were collected on a total-transfer (100 % duty cycle) GC3-TOFMS instrument, employing thermal modulation between the first (1D) and second dimension (2D) columns and dynamic pressure gradient modulation between the 2D and third dimension (3D) columns. In total, cuboid-based F-ratio analysis discovered 32 spiked analytes in the top 50 hits at concentration ratios as low as 1.1. In contrast, tile-based F-ratio analysis of the corresponding GC×GC-TOFMS data only discovered 28 of the spiked analytes total, with only 25 of them in the top 50 hits. Along with discovering more analytes, cuboid-based F-ratio analysis of GC3-TOFMS data resulted in fewer false positives. The increased discoverability is due to the added peak capacity and selectivity provided by the 3D column with GC3-TOFMS resulting in improved chromatographic resolution.

Aroma Compounds in Essential Oils: Analyzing Chemical Composition Using Two-Dimensional Gas Chromatography-High Resolution Time-of-Flight Mass Spectrometry Combined with Chemometrics.

Analyzing essential oils is a challenging task for chemists because their composition can vary depending on various factors. The separation potential of volatile compounds using enantioselective two-dimensional gas chromatography coupled with high-resolution time-of-flight mass spectrometry (GC×GC-HRTOF-MS) with three different stationary phases in the first dimension was evaluated to classify different types of rose essential oils. The results showed that selecting only ten specific compounds was enough for efficient sample classification instead of the initial 100 compounds. The study also investigated the separation efficiencies of three stationary phases in the first dimension: Chirasil-Dex, MEGA-DEX DET-ß, and Rt-ßDEXsp. Chirasil-Dex had the largest separation factor and separation space, ranging from 47.35% to 56.38%, while Rt-ßDEXsp had the smallest, ranging from 23.36% to 26.21%. MEGA-DEX DET-ß and Chirasil-Dex allowed group-type separation based on factors such as polarity, H-bonding ability, and polarizability, whereas group-type separation with Rt-ßDEXsp was almost imperceptible. The modulation period was 6 s with Chirasil-Dex and 8 s with the other two set-ups. Overall, the study showed that analyzing essential oils using GC×GC-HRTOF-MS with a specific selection of compounds and stationary phase can be effective in classifying different oil types.

Untargeted region of interest selection for gas chromatography - mass spectrometry data using a pseudo F-ratio moving window.

There are many challenges associated with analysing gas chromatography - mass spectrometry (GC-MS) data. Many of these challenges stem from the fact that electron ionization (EI) can make it difficult to recover molecular information due to the high degree of fragmentation with concomitant loss of molecular ion signal. With GC-MS data there are often many common fragment ions shared among closely-eluting peaks, necessitating sophisticated methods for analysis. Some of these methods are fully automated, but make some assumptions about the data which can introduce artifacts during the analysis. Chemometric methods such as Multivariate Curve Resolution (MCR), or Parallel Factor Analysis (PARAFAC/PARAFAC2) are particularly attractive, since they are flexible and make relatively few assumptions about the data - ideally resulting in fewer artifacts. These methods do require expert user intervention to determine the most relevant regions of interest and an appropriate number of components, k, for each region. Automated region of interest selection is needed to permit automated batch processing of chromatographic data with advanced signal deconvolution. Here, we propose a new method for automated, untargeted region of interest selection that accounts for the multivariate information present in GC-MS data to select regions of interest based on the ratio of the squared first, and second singular values from the Singular Value Decomposition (SVD) of a window that moves across the chromatogram. Assuming that the first singular value accounts largely for signal, and that the second singular value accounts largely for noise, it is possible to interpret the relationship between these two values as a probabilistic distribution of Fisher Ratios. The sensitivity of the algorithm was tested by investigating the concentration at which the algorithm can no longer pick out chromatographic regions known to contain signal. The algorithm achieved detection of features in a GC-MS chromatogram at concentrations below 10 pg on-column. The resultant probabilities can be interpreted as regions that contain features of interest.

Untargeted profiling and differentiation of geographical variants of wine samples using headspace solid-phase microextraction flow-modulated comprehensive two-dimensional gas chromatography with the support of tile-based Fisher ratio analysis.

The volatile fraction of food, also called the food volatilome, is increasingly used to develop new fingerprinting approaches. The characterization of the food volatilome is important to achieve desired flavor profiles in food production processes, or to differentiate different products, with winemaking being one popular area of interest. In the present research, headspace solid-phase microextraction (HS SPME) coupled to flow-modulated comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (FM GC×GC-TOFMS) was used to characterize geographical-based differences in the volatilome of five white "Grillo" wines (of Sicilian origin), comprising the five sample classes. All wines were produced with the same vinification method in 2019. To minimize the influence of minor bottle-to-bottle differences, three bottles of the same wine were randomly selected, and three samples were collected per bottle, resulting in nine sample replicates per wine. Particular emphasis was devoted to the operational conditions of a novel low duty cycle flow modulator. A fast FM GC×GC-TOFMS method with a modulation period of 700 ms and a re-injection period of 80 ms was developed. Following, the instrumental software was exploited to identify class-distinguishing analytes in the dataset via tile-based Fisher ratio analysis (i.e., ChromaTOF Tile). A tile size of 10 modulations (7 s) on the first dimension and 45 spectra (300 ms) on the second dimension was used to encompass average peak widths and to account for minor retention time shifting. Off-line software was used to apply an ANOVA test. A p-value of 0.01 was applied in order to select the most important class-distinguishing analytes, which were input to principal component analysis (PCA). The PCA scores plot showed distinct clustering of the wines according to geographical origin, although the loadings revealed that only a few analytes were necessary to differentiate the wines. However, a comprehensive flavor profile assessment underscored the importance of all the information output by the ChromaTOF Tile software.

Simulating comprehensive two-dimensional gas chromatography mass spectrometry data with realistic run-to-run shifting to evaluate the robustness of tile-based Fisher ratio analysis.

Untargeted analysis of comprehensive two-dimensional (2D) gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS) data has the potential to be hindered by run-to-run retention time shifting. To address this challenge, tile-based Fisher ratio (F-ratio) analysis (FRA) has been developed, which utilizes a supervised, untargeted approach involving a chromatographic segmentation routine termed "tiling" combined with the ANOVA F-ratio statistic to discover class-distinguishing analytes while minimizing false positives arising from shifting. The tiling algorithm is designed to account for retention shifting in both separation dimensions. Although applications of FRA have been reported, there remains a need to thoroughly evaluate the robustness of FRA for different levels of run-to-run retention shifting in order to broaden the scope of its application. To this end, a novel method of simulating GC×GC-TOFMS chromatograms with realistic run-to-run shifting is presented by random generation of low-frequency "shift functions". The dimensionless retention-time precision, <δr>, which is four times the standard deviation in retention time normalized to the peak width-at-base is used as a key modeling variable along with the 2D chromatographic saturation, αe,2D, and within-class relative standard deviation in peak area, RSDwc. We demonstrate that all three of these variables operate together to impact true positive discovery. To quantify the "success" of true positive discovery, GC×GC-TOFMS datasets for various combinations of <δr>, αe,2D, and RSDwc were simulated and then analyzed by FRA using a wide range of relative tile areas (RTA), which is a dimensionless measure of tile size. Since each hit in the FRA hit list was known a priori as either a true or false positive based on the simulation inputs, receiver operating characteristic (ROC) curves were readily constructed. Then, the area under the ROC curve (AUROC) was used as a metric for discovery "success" for various combinations of the modeling variables. Based on the results of this study, recommendations for tile size selection and experimental design are provided, and further supported by comparison to previous tile-based FRA applications. For instance, values for <δr>, αe,2D, and RSDwc obtained from a GC×GC-TOFMS dataset of yeast metabolites suggested an optimum RTA of 6.25, corresponding closely to the RTA of 4.00 employed in the study, implying the simulation results obtained here can be generalized to real datasets.

Computational method for untargeted determination of cycling yeast metabolites using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry.

A computational method for the untargeted determination of cycling yeast metabolites using a comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS) dataset is presented. The yeast metabolomic cycle for the diploid yeast strain CEN.PK with a 5 h cycle period relative to the O2 concentration level is comprehensively examined to determine the metabolites that exhibit cycling. Samples were collected over only two cycles (10 h with a total of 24 time-point sampling intervals at 25 min each) as an experimental constraint. Due to the limited number of cycles expressed in the dataset, a computational method was devised to determine with statistical significance whether or not a given metabolite exhibited a temporal signal pattern that constituted cycling in the context of the 5 h cycle period. The computational method we report compares the experimentally obtained 24 time-point metabolite signal sequences to randomly generated signal sequences coupled with statistically based confidence level LOF metrics to determine whether or not a given metabolite expresses cycling, and if so, what is the phase of the cycling. Initially the GC×GC-TOFMS dataset was analyzed using tile-based Fisher ratio (F-ratio) analysis. Since there were 24 time-point intervals, this constituted 24 sample classes in the F-ratio calculation which produced 672 metabolite hits. Next, application of the computational method determined that there were 210 of the 672 metabolites exhibiting cycling: 55 identified metabolites and 155 unknown metabolites. Furthermore, the 210 cycling metabolites were categorized into four groups, and where applicable, a phase determined: 1 cycle/5 h period (106 metabolites), 2 cycles/5 h period (13 metabolites), spiky pattern (12 metabolites), or multimodal pattern (79 metabolites).

Class comparison enabled mass spectrum purification for comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry.

Tile-based Fisher ratio (F-ratio) analysis is emerging as a versatile data analysis tool for supervised discovery-based experimentation using comprehensive two-dimensional (2D) gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS). None the less, analyte identification can often be marred by poor 2D resolution and low analyte abundance relative to overlapping compounds. Linear algebra-based chemometric methods, in particular multivariate curve resolution alternating least squares (MCR-ALS), parallel factor analysis (PARAFAC) and PARAFAC2, are often applied in an effort to address this situation. However, these chemometric methods can fail to produce an accurate spectrum when the analyte is at low 2D resolution and/or in low relative abundance. To address this challenge, we introduce class comparison enabled mass spectrum purification (CCE-MSP), a method that utilizes the underlying requirement for signal consistency of the background interference compounds between the two classes in the F-ratio analysis to purify the mass spectrum of the analyte hits. CCE-MSP is validated using a dataset obtained for a neat JP-8 jet fuel spiked with 14 sulfur containing compounds at two levels (15 ppm and 30 ppm), using the p-value and lack-of-fit (LOF) for each analyte hit as consistency metrics. A purified mass spectrum was produced for each spiked analyte hit and their mass spectrum match value (MV) was compared to the MV obtained by MCR-ALS, PARAFAC, and PARAFAC2. The resulting MV for CCE-MSP were found to be as good or better than these chemometric methods, eg., for 2-butyl-5-ethylthiophene with an analyte-to-interference relative signal abundance of 1:87 and a 2D resolution of 0.2, CCE-MSP produced a MV of 831, compared to 476 for MCR-ALS, 403 for PARAFAC, and 336 for PARAFAC2. CCE-MSP is also extended to obtain the purified spectrum for more than one analyte, eg., two analyte hits in overlapping hit locations. The spectra produced by CCE-MSP can also be utilized as estimates to facilitate quantitative signal decomposition using MCR-ALS.

Investigation of the limit of discovery using tile-based Fisher ratio analysis with comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry.

Comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS) is followed by tile-based Fisher ratio (F-ratio) analysis to investigate the "limit of discovery" for low concentration levels of sulfur-containing compounds in JP8 jet fuel. A mixture of 14 sulfur-containing compounds was spiked at 30 ppm, 15 ppm, 3 ppm and 1.5 ppm into the neat fuel prior to GC×GC-TOFMS analysis with a "reversed" column format (aka polar first dimension (1D) and non-polar second dimension (2D) column). Prior standard implementation of tile-based F-ratio analysis utilized an average F-ratio requiring a minimum of 3 mass channels (m/z) with the highest F-ratios. Herein, we explore the notion that use of the top F-ratio m/z for hitlist ranking is superior to the standard implementation for analytes near their limit-of-quantitation (LOQ), defined as an analyte concentration that produces a signal equal to ten times the standard deviation of the baseline noise (10σn). Hitlist ranking comparisons revealed that using only the top F-ratio m/z resulted in impressive improvements in discoverability for the low concentration comparisons. Specifically, for the 3 ppm versus neat hitlist, 1,4-oxathiane (LOQ = 2.5 ppm) improved from hit 114 via standard F-ratio analysis, to hit 25. For the 1.5 ppm versus neat hitlist, 2-propylthiophene (LOQ = 0.64 ppm) improved from hit 59 to 17, benzo[b]thiophene (LOQ = 1.1 ppm) from hit 98 to 28, and 2,5-dimethylthiophene (LOQ = 1.3 ppm) from hit 262 to 39. Additional hitlist ranking comparisons revealed the importance of proper tile size selection, as analyte discoverability deteriorated upon using either an inappropriately too small or too large of a tile.

Analytical Determination of the Severity of Potato Taste Defect in Roasted East African Arabica Coffee.

The quality of East African coffee beans has been significantly reduced by a flavor defect known as potato taste defect (PTD) due to the presence of 2-isopropyl-3-methoxypyrazine (IPMP) and 2-isobutyl-3-methoxypyrazine (IBMP). Therefore, the aims of this study were to determine the correlation between these methoxypyrazines and the severity of odor attributed to PTD and discover additional analytes that may be correlated with PTD using Fisher ratio analysis, a supervised discovery-based data analysis method. Specialty ground roasted coffees from East Africa were classified as clean (i.e., no off-odor), mild, medium, or strong PTD. For the samples examined, IPMP was found to discriminate between non-defective and defective samples, while IBMP did not do so. Samples affected by PTD exhibited a wide range of IPMP concentration (1.6-529.9 ng/g). Except for one sample, the IPMP concentration in defective samples was greater than the average IPMP concentration in the non-defective samples (2.0 ng/g). Also, an analysis of variance found that IPMP concentrations were significantly different based on the severity of odor attributed to PTD (p < 0.05). Fisher ratio analysis discovered 21 additional analytes whose concentrations were statistically different based on the severity of PTD odor (p < 0.05). Generally, analytes that were positively correlated with odor severity generally had unpleasant sensory descriptions, while analytes typically associated with desirable aromas were found to be negatively correlated with odor severity. These findings not only show that IPMP concentration can differentiate the severity of PTD but also that changes in the volatile analyte profile of coffee beans induced by PTD can contribute to odor severity.

Statistical inference of mass channel purity from Fisher ratio analysis using comprehensive two-dimensional gas chromatography with time of flight mass spectrometry data.

Tile-based Fisher ratio (F-ratio) analysis has recently been developed and validated for discovery-based studies of highly complex data collected using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS). In previous studies, interpretation and utilization of F-ratio hit lists has relied upon manual decomposition and quantification performed by chemometric methods such as parallel factor analysis (PARAFAC), or via manual translation of the F-ratio hit list information to peak table quantitative information provided by the instrument software (ChromaTOF). Both of these quantification approaches are bottlenecks in the overall workflow. In order to address this issue, a more automatable approach to provide accurate relative quantification for F-ratio analyses was investigated, based upon the mass spectral selectivity provided via the F-ratio spectral output. Diesel fuel spiked with 15 analytes at four concentration levels (80, 40, 20, and 10 ppm) produced three sets of two class comparisons that were submitted to tile-based F-ratio analysis to obtain three hit lists, with an F-ratio spectrum for each hit. A novel algorithm which calculates the signal ratio (S-ratio) between two classes (eg., 80 ppm versus 40 ppm) was applied to all mass channels (m/z) in the F-ratio spectrum for each hit. A lack of fit (LOF) metric was utilized as a measure of peak purity and combined with F-ratio and p-values to study the relationship of each of these metrics with m/z purity. Application of a LOF threshold coupled with a p-value threshold yielded a subset of the most pure m/z for each of the 15 spiked analytes, evident by the low deviations (< 5%) in S-ratio relative to the true concentration ratio. A key outcome of this study was to demonstrate the isolation of pure m/z without the need for higher level signal decomposition algorithms.

Non-targeted discovery-based analysis for gas chromatography with mass spectrometry: A comparison of peak table, tile, and pixel-based Fisher ratio analysis.

The ability to discover minute differences between samples or sample classes for gas chromatography coupled to mass spectrometry (GC-MS) can be a challenging endeavor, especially when those differences are not a priori. Fisher ratio (F-ratio) analysis is an apt technique to probe the differences between GC-MS chromatograms. F-ratio analysis is a supervised, non-targeted, discovery-based method that compares two different samples (or sample classes) to reduce the GC-MS dataset into a hit list composed of class distinguishing compounds. Three different F-ratio techniques, peak table, tile, and pixel-based were used to "discover" nine non-native analytes that were spiked into gasoline at four different nominal concentrations of 250, 85, 25, 5 parts-per-million (ppm). For the tile and pixel-based F-ratio calculations, a novel methodology is introduced to improve the sensitivity of the F-ratio calculations while reducing false positives. Furthermore, we use a combinatorial technique using null class comparisons, termed null distribution analysis, to determine a statistical F-ratio cutoff for analysis of the hit lists. The pixel-based algorithm was the most sensitive method and was able to "discover" all nine spiked analytes at a nominal concentration of 250 ppm albeit with one false positive interspersed towards the bottom of the hit list. The pixel-based software was also able to "discover" more of the spiked analytes at the lower concentrations with seven of the spiked analytes "discovered" at 85 ppm, four of the spiked analytes "discovered" at 25 ppm, and one analyte "discovered" at 5 ppm.

Discovery-based analysis and quantification for comprehensive three-dimensional gas chromatography flame ionization detection data.

Basic principles are introduced for implementing discovery-based analysis with automated quantification of data obtained using comprehensive three-dimensional gas chromatography with flame ionization detection (GC3-FID). The GC3-FID instrument employs dynamic pressure gradient modulation, providing full modulation (100% duty cycle) with a fast modulation period (PM) of 100 ms. Specifically, tile-based Fisher-ratio analysis, previously developed for comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GC×GC-TOFMS), is adapted and applied for GC3-FID where the third chromatographic dimension (3D) is treated as the "spectral" dimension. To evaluate the instrumental platform and software implementation, ten "non-native" compounds were spiked into a ninety-component base mixture to create two classes with a concentration ratio of two for the spiked analyte compounds. The Fisher ratio software identified 95 locations of potential interest (i.e., hits), with all ten spiked analytes discovered within the top fourteen hits. All 95 hits were quantified by a novel signal ratio (S-ratio) algorithm portion of the F-ratio software, which determines the time-dependent S-ratio of the 3D chromatograms from one class to another, thus providing relative quantification. The average S-ratio for spiked analytes was 1.94 ± 0.14 mean absolute error (close to the nominal concentration ratio of two), and 1.06 ± 0.16 mean absolute error for unspiked (i.e., matrix) components. The appearance of the S-ratio as a function of 3D retention time in the GC3 dataset, referred to as an S-ratiogram, provides indication of peak purity for each hit. The unique shape of the S-ratiogram for hit 1, α-pinene, suggested likely 3D overlap. Parallel factor analysis (PARAFAC) decomposition of the hit location confirmed that overlap was occurring and successfully decomposed α-pinene from a highly overlapped (3Rs = 0.1) matrix interferent.

High-Dimensional Analysis of Single-Cell Flow Cytometry Data Predicts Relapse in Childhood Acute Lymphoblastic Leukaemia.

Artificial intelligence methods may help in unveiling information that is hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data, but they have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell Acute Lymphoblastic Leukaemia. In this paper, we analysed flow cytometry data that were obtained at diagnosis from 56 paediatric B-cell Acute Lymphoblastic Leukaemia patients from two local institutions. Our aim was to assess the prognostic potential of immunophenotypical marker expression intensity. We constructed classifiers that are based on the Fisher's Ratio to quantify differences between patients with relapsing and non-relapsing disease. We also correlated this with genetic information. The main result that arises from the data was the association between subexpression of marker CD38 and the probability of relapse.