scholarly journals Novel Approaches to Visualization and Data Mining Reveals Diagnostic Information in the Low Amplitude Region of Serum Mass Spectra from Ovarian Cancer Patients

2004 ◽  
Vol 19 (4-5) ◽  
pp. 197-207 ◽  
Author(s):  
Donald J. Johann ◽  
Michael D. McGuigan ◽  
Stanimire Tomov ◽  
Vincent A. Fusaro ◽  
Sally Ross ◽  
...  
Keyword(s):  
Data Mining ◽  
Ovarian Cancer ◽  
High Resolution ◽  
Cancer Patients ◽  
Data Reduction ◽  
Mass Spectra ◽  
Diagnostic Information ◽  
Mass Spectral Data ◽  
Mining Operations ◽  
Mass Spectral

The ability to identify patterns of diagnostic signatures in proteomic data generated by high throughput mass spectrometry (MS) based serum analysis has recently generated much excitement and interest from the scientific community. These data sets can be very large, with high-resolution MS instrumentation producing 1–2 million data points per sample. Approaches to analyze mass spectral data using unsupervised and supervised data mining operations would greatly benefit from tools that effectively allow for data reduction without losing important diagnostic information. In the past, investigators have proposed approaches where data reduction is performed bya priori“peak picking” and alignment/warping/smoothing components using rule-based signal-to-noise measurements. Unfortunately, while this type of system has been employed for gene microarray analysis, it is unclear whether it will be effective in the analysis of mass spectral data, which unlike microarray data, is comprised of continuous measurement operations. Moreover, it is unclear where true signal begins and noise ends. Therefore, we have developed an approach to MS data analysis using new types of data visualization and mining operations in which data reduction is accomplished by culling via the intensity of the peaks themselves instead of by location. Applying this new analysis method on a large study set of high resolution mass spectra from healthy and ovarian cancer patients, shows that all of the diagnostic information is contained within the very lowest amplitude regions of the mass spectra. This region can then be selected and studied to identify the exact location and amplitude of the diagnostic biomarkers.

scholarly journals High-resolution serum proteomic features for ovarian cancer detection.

2004 ◽  
Vol 11 (2) ◽  
pp. 163-178 ◽  
Author(s):  
T P Conrads ◽  
V A Fusaro ◽  
S Ross ◽  
D Johann ◽  
V Rajapakse ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Resolution ◽  
Sensitivity And Specificity ◽  
Mass Spectra ◽  
Spectral Feature ◽  
Low Resolution ◽  
Mass Spectral ◽  
High Resolution Mass ◽  
Process Error ◽  
Resolution Mass

Serum proteomic pattern diagnostics is an emerging paradigm employing low-resolution mass spectrometry (MS) to generate a set of biomarker classifiers. In the present study, we utilized a well-controlled ovarian cancer serum study set to compare the sensitivity and specificity of serum proteomic diagnostic patterns acquired using a high-resolution versus a low-resolution MS platform. In blinded testing sets, the high-resolution mass spectral data contained multiple diagnostic signatures that were superior to the low-resolution spectra in terms of sensitivity and specificity (P<0.00001) throughout the range of modeling conditions. Four mass spectral feature set patterns acquired from data obtained exclusively with the high-resolution mass spectrometer were 100% specific and sensitive in their diagnosis of serum samples as being acquired from either unaffected patients or those suffering from ovarian cancer. Important to the future of proteomic pattern diagnostics is the ability to recognize inferior spectra statistically, so that those resulting from a specific process error are recognized prior to their potentially incorrect (and damaging) diagnosis. To meet this need, we have developed a series of quality-assurance and in-process control procedures to (a) globally evaluate sources of sample variability, (b) identify outlying mass spectra, and (c) develop quality-control release specifications. From these quality-assurance and control (QA/QC) specifications, we identified 32 mass spectra out of the total 248 that showed statistically significant differences from the norm. Hence, 216 of the initial 248 high-resolution mass spectra were determined to be of high quality and were remodeled by pattern-recognition analysis. Again, we obtained four mass spectral feature set patterns that also exhibited 100% sensitivity and specificity in blinded validation tests (68/68 cancer: including 18/18 stage I, and 43/43 healthy). We conclude that (a) the use of high-resolution MS yields superior classification patterns as compared with those obtained with lower resolution instrumentation; (b) although the process error that we discovered did not have a deleterious impact on the present results obtained from proteomic pattern analysis, the major source of spectral variability emanated from mass spectral acquisition, and not bias at the clinical collection site; (c) this variability can be reduced and monitored through the use of QA/QC statistical procedures; (d) multiple and distinct proteomic patterns, comprising low molecular weight biomarkers, detected by high-resolution MS achieve accuracies surpassing individual biomarkers, warranting validation in a large clinical study.

scholarly journals The structure of novel C35 pentacyclic terpenes from Acetobacter xylinum

1973 ◽  
Vol 135 (1) ◽  
pp. 133-143 ◽  
Author(s):  
Hans J. Förster ◽  
Klaus Biemann ◽  
W. Geoffrey Haigh ◽  
Neil H. Tattrie ◽  
J. Ross Colvin
Keyword(s):  
High Resolution ◽  
High Resolution Mass Spectrometry ◽  
Carbon Chain ◽  
Acetobacter Xylinum ◽  
Mass Spectrometric ◽  
Hydroxyl Groups ◽  
Mass Spectral Data ◽  
Mass Spectral ◽  
High Resolution Mass ◽  
Resolution Mass

A novel C35 terpene and its monounsaturated analogue were isolated from cultures of Acetobacter xylinum, together with traces of their C36 homologues. These substances were found to be hopane derivatives substituted by a five-carbon chain bearing four vicinal hydroxyl groups. For the parent hydrocarbon the term bacteriohopane is proposed. The elucidation of the structures utilized high-resolution mass spectrometry of the terpenes, degradation to C32 hydrocarbons and detailed mass-spectrometric comparison of these with C32 hydrocarbons synthesized from known pentacyclic triterpenes. High-resolution mass-spectral data of the terpenes are presented. N.m.r. data are in agreement with the proposed structures, which are further supported by the isolation from the same organism of 22-hydroxyhopane and derivative hopene(s).

scholarly journals Novel archaeal macrocyclic diether core membrane lipids in a methane-derived carbonate crust from a mud volcano in the Sorokin Trough, NE Black Sea

Archaea ◽  
2003 ◽  
Vol 1 (3) ◽  
pp. 165-173 ◽  
Author(s):  
Alina Stadnitskaia ◽  
Marianne Baas ◽  
Michael K. Ivanov ◽  
Tjeerd C. E. Van Weering ◽  
Jaap S. Sinninghe Damsté
Keyword(s):  
Black Sea ◽  
Mass Spectra ◽  
Membrane Lipids ◽  
Mud Volcano ◽  
The Novel ◽  
Mass Spectral Data ◽  
Mass Spectral ◽  
Carbonate Formation ◽  
Carbonate Crust ◽  
Archaeal Lipids

A methane-derived carbonate crust was collected from the recently discovered NIOZ mud volcano in the Sorokin Trough, NE Black Sea during the 11th Training-through-Research cruise of the R/V Professor Logachev. Among several specific bacterial and archaeal membrane lipids present in this crust, two novel macrocyclic diphytanyl glycerol diethers, containing one or two cyclopentane rings, were detected. Their structures were tentatively identified based on the interpretation of mass spectra, comparison with previously reported mass spectral data, and a hydrogenation experiment. This macrocyclic type of archaeal core membrane diether lipid has so far been identified only in the deep-sea hydrothermal vent methanogenMethanococcus jannaschii. Here, we provide the first evidence that these macrocyclic diethers can also contain internal cyclopentane rings. The molecular structure of the novel diethers resembles that of dibiphytanyl tetraethers in which biphytane chains, containing one and two pentacyclic rings, also occur. Such tetraethers were abundant in the crust. Compound-specific isotope measurements revealed δ13C values of –104 to –111‰ for these new archaeal lipids, indicating that they are derived from methanotrophic archaea acting within anaerobic methane-oxidizing consortia, which subsequently induce authigenic carbonate formation.

Glandular Trichomes and the Yolatiles Obtained by Steam Distillation of Quercus robur Leaves

1993 ◽  
Vol 48 (9-10) ◽  
pp. 736-744 ◽  
Author(s):  
Ralf Engel ◽  
Paul-Gerhard Gülz ◽  
Thorsten Herrmann ◽  
Adolf Nahrstedt
Keyword(s):  
Electron Microscopy ◽  
Quercus Robur ◽  
Mass Spectra ◽  
Steam Distillation ◽  
Glandular Trichomes ◽  
Retention Indices ◽  
Mass Spectral Data ◽  
Mass Spectral ◽  
Kováts Indices ◽  
Scanning Electron

Glandular trichomes in form of long stretched tubes are present on the lower leaf side of Quercus robur as shown by scanning electron microscopy. The glands contain an essential oil, which was isolated by steam distillation together with volatile waxy components of the leaves in an amount of 0.025% of fresh leaves. The product of steam distillation was analyzed by GC-MS. Identification of com pounds is based on comparison of their mass spectral data with those of authentic samples in combination with retention indices and MS data using the SeKoMS (Search Kovats Indices and Mass Spectra) Library. Altogether 184 components of the product of steam distillation were separated, 155 of which could be identified, another 7 were tentatively assigned. Three groups of substances according to their chemical composition are found: hexenyl derivatives and some acetals (32%); terpenes including monoterpenes (4% ), sesquiterpenes and diterpenes (21%); and alkane derivatives (35%). The residual 8% consist of benzyl alcohol, com pounds which stem from the degradation of carotenes, and miscellaneous constituents

scholarly journals Chemical Constituents of Phoebe poilanei and Their Cytotoxic Activity

2019 ◽  
Vol 14 (5) ◽  
pp. 1934578X1985096
Author(s):  
Nguyen Thi Viet Thanh ◽  
Tran Thi Minh ◽  
Dinh Thi Thu Hien ◽  
Ho Duc Cuong ◽  
Yohan Seo ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
High Resolution ◽  
Cytotoxic Activity ◽  
Spectral Data ◽  
Chemical Constituents ◽  
Flavonol Glycosides ◽  
Ionization Mass ◽  
Mass Spectral Data ◽  
Mass Spectral ◽  
Chemical Structures

Two new flavonol glycosides, rhamnocitrin 3- O-α-L-rhamnopyranosyl-(1→6)-[α-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranoside (1) and quercetin 3- O-6- Z- p-coumaroyl-β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranoside (2), along with 3 flavonol glycosides, isoquercitrin (3), rutin (4), and quercetin 3- O-α-L-rhamnopyranosyl-(1→6)-β-D-galactopyranoside (5), and two known sesquiterpenes, alismol (6) and spathulenol (7), were isolated from the leaves of Phoebe poilanei Kosterm. Their chemical structures were elucidated by analyses of their high-resolution electrospray ionization mass spectral data and nuclear magnetic resonance spectral data and comparison with those reported in the literature. Two sesquiterpenes 6 and 7 were found to exhibit moderate cytotoxic activity with IC50 values ranging from 21.6 to 29.8 µM.

Mass Spectra of Some Carbamates and Related Ureas. II

1968 ◽  
Vol 51 (2) ◽  
pp. 347-365 ◽  
Author(s):  
W R Benson ◽  
J N Damico
Keyword(s):  
Spectral Data ◽  
Relative Abundance ◽  
Mass Spectra ◽  
The Other ◽  
Methyl Isocyanate ◽  
Mass Spectral Data ◽  
Mass Spectral ◽  
Fragmentation Patterns ◽  
Sulfur Containing

Abstract Mass spectral data for fourteen carbamates, live dithiocarbamates, one thiocarbamate, and eight phenylureas are given with some interpretations. Among the compounds examined were some sulfur-containing aliphatic oxime carbamates; these lost the sulfur moieties more easily than the methyl isocyanate moiety. In the aryl IV-methylcarbamate series, the CH3NCO moiety appears to be lost most easily, as it is in pyrolysis. When l-(2-chlorophenyI)-3- methylurea is fragmented, unexpectedly the [HNC0]+ ion is found in high relative abundance. However, the remaining ureas undergo fragmentation in a manner similar to their related carbamates. Although the two ethylene bisdithiocarbamates give essentially identical fragmentation patterns, the spectra of the other four thio- and dithiocarbamates show sufficient differences so that they may be distinguished from one another.

A ROBUST BIOMARKER DISCOVERY PIPELINE FOR HIGH-PERFORMANCE MASS SPECTROMETRY DATA

2007 ◽  
Vol 05 (05) ◽  
pp. 1023-1045 ◽  
Author(s):  
WAYNE G. FISHER ◽  
KEVIN P. ROSENBLATT ◽  
DAVID A. FISHMAN ◽  
GORDON R. WHITELEY ◽  
ALVYDAS MIKULSKIS ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Spectral Data ◽  
High Performance ◽  
Biomarker Discovery ◽  
Mass Spectrometry Data ◽  
Mass Spectral Data ◽  
Data Set ◽  
Mass Spectral ◽  
Peak Finding ◽  
Non Gaussian

A high-throughput software pipeline for analyzing high-performance mass spectral data sets has been developed to facilitate rapid and accurate biomarker determination. The software exploits the mass precision and resolution of high-performance instrumentation, bypasses peak-finding steps, and instead uses discrete m/z data points to identify putative biomarkers. The technique is insensitive to peak shape, and works on overlapping and non-Gaussian peaks which can confound peak-finding algorithms. Methods are presented to assess data set quality and the suitability of groups of m/z values that map to peaks as potential biomarkers. The algorithm is demonstrated with serum mass spectra from patients with and without ovarian cancer. Biomarker candidates are identified and ranked by their ability to discriminate between cancer and noncancer conditions. Their discriminating power is tested by classifying unknowns using a simple distance calculation, and a sensitivity of 95.6% and a specificity of 97.1% are obtained. In contrast, the sensitivity of the ovarian cancer blood marker CA125 is ~50% for stage I/II and ~80% for stage III/IV cancers. While the generalizability of these markers is currently unknown, we have demonstrated the ability of our analytical package to extract biomarker candidates from high-performance mass spectral data.

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