Chemometric and Statistical Analyses of ToF-SIMS Spectra of Increasingly Complex Biological Samples

Journal Article · Wed Oct 24 04:00:00 EDT 2007 · Surface and Interface Analysis

OSTI ID:990410

Berman, E S; Wu, L; Fortson, S L; Nelson, D O; Kulp, K S; Wu, K J

Characterizing and classifying molecular variation within biological samples is critical for determining fundamental mechanisms of biological processes that will lead to new insights including improved disease understanding. Towards these ends, time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to examine increasingly complex samples of biological relevance, including monosaccharide isomers, pure proteins, complex protein mixtures, and mouse embryo tissues. The complex mass spectral data sets produced were analyzed using five common statistical and chemometric multivariate analysis techniques: principal component analysis (PCA), linear discriminant analysis (LDA), partial least squares discriminant analysis (PLSDA), soft independent modeling of class analogy (SIMCA), and decision tree analysis by recursive partitioning. PCA was found to be a valuable first step in multivariate analysis, providing insight both into the relative groupings of samples and into the molecular basis for those groupings. For the monosaccharides, pure proteins and protein mixture samples, all of LDA, PLSDA, and SIMCA were found to produce excellent classification given a sufficient number of compound variables calculated. For the mouse embryo tissues, however, SIMCA did not produce as accurate a classification. The decision tree analysis was found to be the least successful for all the data sets, providing neither as accurate a classification nor chemical insight for any of the tested samples. Based on these results we conclude that as the complexity of the sample increases, so must the sophistication of the multivariate technique used to classify the samples. PCA is a preferred first step for understanding ToF-SIMS data that can be followed by either LDA or PLSDA for effective classification analysis. This study demonstrates the strength of ToF-SIMS combined with multivariate statistical and chemometric techniques to classify increasingly complex biological samples. Applying these techniques to information-rich mass spectral data sets opens the possibilities for new applications including classification of subtly different biological samples that may provide insights into cellular processes, disease progress, and disease diagnosis.

• Research Organization: Lawrence Livermore National Laboratory (LLNL), Livermore, CA
• Sponsoring Organization: USDOE
• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 990410
• Report Number(s): UCRL-JRNL-235865
• Journal Information: Surface and Interface Analysis, Journal Name: Surface and Interface Analysis Journal Issue: 2 Vol. 41; ISSN SIANDQ; ISSN 0142-2421
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CLASSIFICATION
DECISION TREE ANALYSIS
DIAGNOSIS
DISEASES
EMBRYOS
ISOMERS
MASS SPECTROSCOPY
MIXTURES
MONOSACCHARIDES
MULTIVARIATE ANALYSIS
PROTEINS
SIMULATION
SPECTRA