Delineation of disease phenotypes associated with esophageal adenocarcinoma by MALDI-IMS-MS analysis of serum N-linked glycans.

N-Linked glycans, extracted from patient sera and healthy control individuals, are analyzed by Matrix-assisted laser desorption ionization (MALDI) in combination with ion mobility spectrometry (IMS), mass spectrometry (MS) and pattern recognition methods. MALDI-IMS-MS data were collected in duplicate for 58 serum samples obtained from individuals diagnosed with Barrett's esophagus (BE, 14 patients), high-grade dysplasia (HGD, 7 patients), esophageal adenocarcinoma (EAC, 20 patients) and disease-free control (NC, 17 individuals). A combined mobility distribution of 9 N-linked glycans is established for 90 MALDI-IMS-MS spectra (training set) and analyzed using a genetic algorithm for feature selection and classification. Two models for phenotype delineation are subsequently developed and as a result, the four phenotypes (BE, HGD, EAC and NC) are unequivocally differentiated. Next, the two models are tested against 26 blind measurements. Interestingly, these models allowed for the correct phenotype prediction of as many as 20 blinds. Although applied to a limited number of blind samples, this methodology appears promising as a means of discovering molecules from serum that may have capabilities as markers of disease.

Ion mobility-mass spectrometry analysis of serum N-linked glycans from esophageal adenocarcinoma phenotypes.

Three disease phenotypes, Barrett's esophagus (BE), high-grade dysplasia (HGD), esophageal adenocarcinoma (EAC), and a set of normal control (NC) serum samples are examined using a combination of ion mobility spectrometry (IMS), mass spectrometry (MS), and principal component analysis (PCA) techniques. Samples from a total of 136 individuals were examined, including 7 characterized as BE, 12 as HGD, 56 as EAC, and 61 as NC. In typical data sets, it was possible to assign ∼20 to 30 glycan ions based on MS measurements. Ion mobility distributions for these ions show multiple features. In some cases, such as the [S1H5N4+3Na]3+ and [S1F1H5N4+3Na]3+ glycan ions, the ratio of intensities of high-mobility features to low-mobility features vary significantly for different groups. The degree to which such variations in mobility profiles can be used to distinguish phenotypes is evaluated for 11 N-linked glycan ions. An outlier analysis on each sample class followed by an unsupervised PCA using a genetic algorithm for pattern recognition reveals that EAC samples are separated from NC samples based on 46 features originating from the 11-glycan composite IMS distribution.

Changes in the cuticular hydrocarbon profile of the slave-maker ant queen, Polyergus breviceps emery, after killing a Formica host queen (Hymenoptera: Formicidae).

Queens of the slave-maker ant, Polyergus breviceps, take over nests of their Formica host species by fatally attacking the resident queen. As workers only begin grooming the P. breviceps queen once she has ceased her attack, we investigated whether a change in parasite queen chemistry may account for the change in worker behavior. Cuticular hydrocarbon profiles of newly mated P. breviceps queens and of queens of their two Formica host species were found to be species-specific. Profiles of newly mated P. breviceps queens that had attacked a Formica queen, however, were virtually identical to the queen profile of the species killed. Mass spectral analysis revealed that the hydrocarbons on the cuticles of newly mated P. breviceps changed from primarily normal alkanes to methyl and di-methyl branched alkanes after attacks. The results suggest that cuticular compounds from the host queen were transferred to the parasite queen during their aggressive interaction.

Fuel spill identification using solid-phase extraction and solid-phase microextraction. 1. Aviation turbine fuels.

The water-soluble fraction of aviation jet fuels is examined using solid-phase extraction and solid-phase microextraction. Gas chromatographic profiles of solid-phase extracts and solid-phase microextracts of the water-soluble fraction of kerosene- and nonkerosene-based jet fuels reveal that each jet fuel possesses a unique profile. Pattern recognition analysis reveals fingerprint patterns within the data characteristic of fuel type. By using a novel genetic algorithm (GA) that emulates human pattern recognition through machine learning, it is possible to identify features characteristic of the chromatographic profile of each fuel class. The pattern recognition GA identifies a set of features that optimize the separation of the fuel classes in a plot of the two largest principal components of the data. Because principal components maximize variance, the bulk of the information encoded by the selected features is primarily about the differences between the fuel classes.

Source identification of underground fuel spills by solid-phase microextraction/high-resolution gas chromatography/genetic algorithms.

Solid-phase microextraction (SPME), capillary column gas chromatography, and pattern recognition methods were used to develop a potential method for typing jet fuels so a spill sample in the environment can be traced to its source. The test data consisted of gas chromatograms from 180 neat jet fuel samples representing common aviation turbine fuels found in the United States (JP-4, Jet-A, JP-7, JPTS, JP-5, JP-8). SPME sampling of the fuel's headspace afforded well-resolved reproducible profiles, which were standardized using special peak-matching software. The peak-matching procedure yielded 84 standardized retention time windows, though not all peaks were present in all gas chromatograms. A genetic algorithm (GA) was employed to identify features (in the standardized chromatograms of the neat jet fuels) suitable for pattern recognition analysis. The GA selected peaks, whose two largest principal components showed clustering of the chromatograms on the basis of fuel type. The principal component analysis routine in the fitness function of the GA acted as an information filter, significantly reducing the size of the search space, since it restricted the search to feature subsets whose variance is primarily about differences between the various fuel types in the training set. In addition, the GA focused on those classes and/or samples that were difficult to classify as it trained using a form of boosting. Samples that consistently classify correctly were not as heavily weighted as samples that were difficult to classify. Over time, the GA learned its optimal parameters in a manner similar to a perceptron. The pattern recognition GA integrated aspects of strong and weak learning to yield a "smart" one-pass procedure for feature selection.

Survey of the Anopheles maculatus complex (Diptera: Culicidae) in peninsular Malaysia by analysis of cuticular lipids.

Anopheles maculatus Theobald sensu lato is a species complex now consisting of eight sibling species; An. maculatus is still represented by two cytologically distinct forms; i.e., the widely distributed sensu strictu or B, and E from southern Thailand and adjacent areas in northern Malaysia. Cuticular lipid profiles in conjunction with principal component analysis was used to separate An. maculatus form E from sensu stricto form B in a preliminary survey of the An. maculatus complex at five locations spanning peninsular Malaysia. The relative rank orders, from the areas of the five gas chromatographic peaks used to determine lipid differences for specimens from peninsular Malaysia, matched well with those from cytogenetically identified colony specimens of An. maculatus forms B and E. The two-dimensional principal component pattern of specimens identified as form E was highly clumped, which indicated that very similar cuticular lipids were present within this putative malaria vector. Both forms coexisted in peninsular Malaysia, but form E may be dominant except in the south.

Comparing methods of reporting breast self-examination compliance.

Women volunteers (N = 32) learning breast self-examination (BSE) in one of several small group workshops were asked to practice BSE on a monthly basis and reported BSE practice for the following 6 months. Each workshop was randomly assigned to one of three methods of reporting subsequent instances of BSE: (a) retrospective reporting in which they were called by the experimenter and asked how many times they performed BSE; (b) monthly written reports, in which they mailed in a card after each month's practice of BSE; and (c) an oil-and-tissue method in which, in addition to the card, they mailed in a tissue that they had used to blot oil used as a lubricant in BSE. Rates of self-reported BSE for the three methods were compared, showing no differences between the oil-and-tissue method and the monthly written report method, with rates for both methods significantly lower than for the retrospective report method. It was concluded that the monthly report method provides the same information as the oil-and-tissue method, without its awkwardness and expense, and thus seems the preferred method of self-report in BSE studies.

Cuticular lipid differences between the malaria vector and non-vector forms of the Anopheles maculatus complex.

Two chromosomal forms (E and F) of the Anopheles maculatus Theobald complex were distinguished by gas-liquid chromatographic (GC) analysis of cuticular lipids in association with a multivariate principal component analysis. The GC chromatogram obtained from n-hexane extracts of individual specimens showed no consistent qualitative differences in normalized peak areas between forms. Of the seventeen consistent peaks, five were found to be quantitatively different between forms at a high (99.5-99.95%) level of statistical confidence. Relative ratios of these five quantitatively different GC peaks were used as criteria to distinguish single specimens as either form E or form F. Chemical structures of the five GC peaks were assigned by both electron impact and chemical ionization gas chromatography/mass spectrometry analysis. The first three peaks, which were always doublets, were partially resolved saturated and mono-unsaturated free fatty acids; the other two peaks were n-alkanes. Principal component analysis substantiated that the vector form E has very similar cuticular lipid profiles and is well separated from the non-vector form F.

Temporal changes in colony cuticular hydrocarbon patterns ofSolenopsis invicta : Implications for nestmate recognition.

Heritable cuticular hydrocarbon patterns ofSolenopsis invicta workers are consistent within colonies for a given sampling time but vary sufficiently from colony to colony to distinguish the colonies from each other. In addition, cuticular hydrocarbon patterns change within colonies over time. Nestmate recognition cues found on the individual's cuticle, can be from heritable or environmental sources, and are a subset of colony odor. The cuticular hydrocarbons can be used as a model for heritable nestmate recognition cues. We propose that because potential nestmate recognition cues, both environmental and genetic, are dynamic in nature rather than static, during its lifetime a worker must continually update its perception (template) of colony odor and nestmate recognition cues.

The mastectomy experience: patients' perspectives.

This paper reports information gained from in-depth structured interviews of 27 women who had undergone mastectomy regarding their experiences from time of detection of the breast lump until complete recovery was achieved. Special emphasis was placed on the emotional/psychological aspects of the mastectomy experience. Although the experience was different for all of the women interviewed, some common elements emerged. Nearly all of the women discovered the breast lump themselves. Most of them recalled the reactions of significant others in their environment, including their physician, as supportive, although nearly half of them did not feel that they had been adequately prepared by health care professionals for what to expect from the mastectomy. They overwhelmingly supported the idea of a coordinated program for post-mastectomy patients to ensure that the needs of future patients are met.

Electronic factors and acridine frameshift mutagenicity--a pattern recognition study.

Using the ADAPT and CHEMLAB-II systems for structure-activity analysis, computer-calculated electronic properties of molecules were used to derive structure-activity relationships for predicting the mutagenicity of a set of substituted acridines in strain TA1537 of the Ames Salmonella assay. A collection of 40 acridines, with a variety of substituents, was examined. A set of 4 electronic descriptors was found which could be used to correctly classify all but two of the compounds as mutagenic or nonmutagenic. A negative correlation was found between the sum of the Hammett aromatic substituent parameters and the level of mutagenicity of the structures, expressed as log(number of revertants/plate + 1) at a 20-micrograms dose. This correlation, however, was not high enough to allow precise estimation of the mutagenicity values.

Analysis of chemical signals in a primate species (Saguinus fuscicollis): Use of behavioral, chemical, and pattern recognition methods.

Scent marking with specialized skin glands is a common behavior in the tamarin,Saguinus fuscicollis. The scent marks identify species, subspecies, gender, and individual, and they also contain information on the social position and hormonal condition of an animal. The marks are chemically complex, containing a large number of compounds. Analysis by means of gas chromatography-mass spectrometry has identified 16 major components (squalene and 15 esters of butyric acid). These compounds are present in the marks of males and females of two subspecies,Saguinus f. fuscicollis andSaguinus f. illigeri. Application of computerized pattern recognition techniques has shown that concentration patterns of some of the butyrates are diagnostic of the two subspecies while concentration patterns of other butyrates are diagnostic of males and females regardless of subspecies. Behavioral studies have shown that the concentration patterns of butyrates and squalene alone do not encode information on subspecies and gender. It is, however, likely that this information is partially encoded by these specific butyrate-squalene concentration patterns but that yet unidentified compounds in the scent marks serve as necessary synergists.

Computerized pattern recognition: a new technique for the analysis of chemical communication.

Computerized pattern recognition techniques can be applied to the study of complex chemical communication systems. Analysis of high resolution gas chromatographic concentration patterns of the major volatile components of the scent marks of a South American primate, Saguinus fuscicollis, demonstrates that the concentration patterns can be used to predict the gender and subspecies of unknown donors.

Pattern Recognition Studies of Complex Chromatographic Data Sets.

Chromatographic fingerprinting of complex biological samples is an active research area with a large and growing literature. Multivariate statistical and pattern recognition techniques can be effective methods for the analyisis of such complex data. However, the classification of complex samples on the basis of their chromatographic profiles is complicated by two factors: 1) confounding of the desired group information by experimental variables or other systematic variations, and 2) random or chance classification effects with linear discriminants. We will treat several current projects involving these effects and methods for dealing with the effects. Complex chromatographic data sets often contain information dependent on experimental variables as well as information which differentiates between classes. The existence of these types of complicating relationships is an innate part of fingerprint-type data. ADAPT, an interactive computer software system, has the clustering, mapping, and statistical tools necessary to identify and study these effects in realistically large data sets. In one study, pattern recognition analysis of 144 pyrochromatograms (PyGCs) from cultured skin fibroblasts was used to differentiate cystic fibrosis carriers from presumed normal donors. Several experimental variables (donor gender, chromatographic column number, etc.) were involved in relationships that had to be separated from the sought relationships. Notwithstanding these effects, discriminants were developed from the chromatographic peaks that assigned a given PyGC to its respective class (CF carrier vs normal) largely on the basis of the desired pathological difference. In another study, gas chromatographic profiles of cuticular hydrocarbon extracts obtained from 179 fire ants were analyzed using pattern recognition methods to seek relations with social caste and colony. Confounding relationships were studied by logistic regression. The data analysis techniques used in these two example studies will be presented. Previously, Monte Carlo simulation studies were carried out to assess the probability of chance classification for nonparametric and parametric linear discriminants. The level of expected chance classification as a function of the number of observations, the dimensionality, and the class membership distributions were examined. These simulation studies established limits on the approaches that can be taken with real data sets so that chance classifications are improbable.