Limits...
On the Fine Isotopic Distribution and Limits to Resolution in Mass Spectrometry.

Dittwald P, Valkenborg D, Claesen J, Rockwood AL, Gambin A - J. Am. Soc. Mass Spectrom. (2015)

Bottom Line: Therefore, the analysis of the fine isotopic distribution becomes an interesting research topic with important practical applications.Our approach uses a broad spectrum of methods ranging from generating functions--that allow us to estimate the variance and the information theory entropy of the distribution--to the theory of thermal energy fluctuations.The presented approach highlights the potential of theoretical analysis of the fine isotopic distribution, which allows modeling the data more accurately, aiming to support the successful experimental measurements.

View Article: PubMed Central - PubMed

Affiliation: Institute of Informatics, University of Warsaw, Warsaw, Poland.

ABSTRACT
Mass spectrometry enables the study of increasingly larger biomolecules with increasingly higher resolution, which is able to distinguish between fine isotopic variants having the same additional nucleon count, but slightly different masses. Therefore, the analysis of the fine isotopic distribution becomes an interesting research topic with important practical applications. In this paper, we propose the comprehensive methodology for studying the basic characteristics of the fine isotopic distribution. Our approach uses a broad spectrum of methods ranging from generating functions--that allow us to estimate the variance and the information theory entropy of the distribution--to the theory of thermal energy fluctuations. Having characterized the variance, spread, shape, and size of the fine isotopic distribution, we are able to indicate limitations to high resolution mass spectrometry. Moreover, the analysis of "thermorelativistic" effects (i.e., mass uncertainty attributable to relativistic effects coupled with the statistical mechanical uncertainty of the energy of an isolated ion), in turn, gives us an estimate of impassable limits of isotopic resolution (understood as the ability to distinguish fine structure peaks), which can be moved further only by cooling the ions. The presented approach highlights the potential of theoretical analysis of the fine isotopic distribution, which allows modeling the data more accurately, aiming to support the successful experimental measurements.

No MeSH data available.


Related in: MedlinePlus

The relationship between variance (a) and spread (b) of the most abundant peak versus Δm (the mass difference between this variant and the monoisotopic one) for the proteins from Uniprot database. In addition, the regression lines were plotted. On (b) we use a conservative estimate that looks at mass difference of additional neutron between nitrogen and hydrogen (for proteins with most abundant peak with 10 additional neutrons we can assume we have at least 10 hydrogens and 10 nitrogens). Note that the spread covers also very tiny peaks of the fine structure, as plotted in Figure 1. Therefore the variance-based estimate (e.g., 6σ) is a much more realistic approach to capture the actual fine structure width
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Fig3: The relationship between variance (a) and spread (b) of the most abundant peak versus Δm (the mass difference between this variant and the monoisotopic one) for the proteins from Uniprot database. In addition, the regression lines were plotted. On (b) we use a conservative estimate that looks at mass difference of additional neutron between nitrogen and hydrogen (for proteins with most abundant peak with 10 additional neutrons we can assume we have at least 10 hydrogens and 10 nitrogens). Note that the spread covers also very tiny peaks of the fine structure, as plotted in Figure 1. Therefore the variance-based estimate (e.g., 6σ) is a much more realistic approach to capture the actual fine structure width

Mentions: Note that Figure 3a illustrates the variance as a function of ∆m (i.e., difference between the mass of the most abundant peak and the mass of the monoisotopic peak). However, given the fact that the most abundant peak is a nearly linear function of the molecular weight (especially at high molecular weight) a qualitatively similar linear relationship is obtained for the dependence of variance on the molecular weight of the protein. Having this linear relationship observed, we built a simple linear regression model linking the variance of the most abundant aggregated isotope peak, denoted by Var(ma), to its center-mass (ma):Figure 3


On the Fine Isotopic Distribution and Limits to Resolution in Mass Spectrometry.

Dittwald P, Valkenborg D, Claesen J, Rockwood AL, Gambin A - J. Am. Soc. Mass Spectrom. (2015)

The relationship between variance (a) and spread (b) of the most abundant peak versus Δm (the mass difference between this variant and the monoisotopic one) for the proteins from Uniprot database. In addition, the regression lines were plotted. On (b) we use a conservative estimate that looks at mass difference of additional neutron between nitrogen and hydrogen (for proteins with most abundant peak with 10 additional neutrons we can assume we have at least 10 hydrogens and 10 nitrogens). Note that the spread covers also very tiny peaks of the fine structure, as plotted in Figure 1. Therefore the variance-based estimate (e.g., 6σ) is a much more realistic approach to capture the actual fine structure width
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4565875&req=5

Fig3: The relationship between variance (a) and spread (b) of the most abundant peak versus Δm (the mass difference between this variant and the monoisotopic one) for the proteins from Uniprot database. In addition, the regression lines were plotted. On (b) we use a conservative estimate that looks at mass difference of additional neutron between nitrogen and hydrogen (for proteins with most abundant peak with 10 additional neutrons we can assume we have at least 10 hydrogens and 10 nitrogens). Note that the spread covers also very tiny peaks of the fine structure, as plotted in Figure 1. Therefore the variance-based estimate (e.g., 6σ) is a much more realistic approach to capture the actual fine structure width
Mentions: Note that Figure 3a illustrates the variance as a function of ∆m (i.e., difference between the mass of the most abundant peak and the mass of the monoisotopic peak). However, given the fact that the most abundant peak is a nearly linear function of the molecular weight (especially at high molecular weight) a qualitatively similar linear relationship is obtained for the dependence of variance on the molecular weight of the protein. Having this linear relationship observed, we built a simple linear regression model linking the variance of the most abundant aggregated isotope peak, denoted by Var(ma), to its center-mass (ma):Figure 3

Bottom Line: Therefore, the analysis of the fine isotopic distribution becomes an interesting research topic with important practical applications.Our approach uses a broad spectrum of methods ranging from generating functions--that allow us to estimate the variance and the information theory entropy of the distribution--to the theory of thermal energy fluctuations.The presented approach highlights the potential of theoretical analysis of the fine isotopic distribution, which allows modeling the data more accurately, aiming to support the successful experimental measurements.

View Article: PubMed Central - PubMed

Affiliation: Institute of Informatics, University of Warsaw, Warsaw, Poland.

ABSTRACT
Mass spectrometry enables the study of increasingly larger biomolecules with increasingly higher resolution, which is able to distinguish between fine isotopic variants having the same additional nucleon count, but slightly different masses. Therefore, the analysis of the fine isotopic distribution becomes an interesting research topic with important practical applications. In this paper, we propose the comprehensive methodology for studying the basic characteristics of the fine isotopic distribution. Our approach uses a broad spectrum of methods ranging from generating functions--that allow us to estimate the variance and the information theory entropy of the distribution--to the theory of thermal energy fluctuations. Having characterized the variance, spread, shape, and size of the fine isotopic distribution, we are able to indicate limitations to high resolution mass spectrometry. Moreover, the analysis of "thermorelativistic" effects (i.e., mass uncertainty attributable to relativistic effects coupled with the statistical mechanical uncertainty of the energy of an isolated ion), in turn, gives us an estimate of impassable limits of isotopic resolution (understood as the ability to distinguish fine structure peaks), which can be moved further only by cooling the ions. The presented approach highlights the potential of theoretical analysis of the fine isotopic distribution, which allows modeling the data more accurately, aiming to support the successful experimental measurements.

No MeSH data available.


Related in: MedlinePlus