Evaluation of complex mass spectrometry data from biological samples

Patent metadata

Field	Value
Publication number	US-2020328069-A1
Application number	US-202016826966-A
Country	US
Kind code	A1
Filing date	Mar 23, 2020
Priority date	Apr 12, 2019
Publication date	Oct 15, 2020
Grant date	—

Abstract

The disclosure relates to a method which is suitable for the quality control and signal correction of mass spectrometry data of biological tissue samples and is based on the analysis of the chemical background signal observed in a spectrum. It exploits the fact that the chemical background signal contains components from a plurality of polymer molecules, whose chemical structure has strong regularities. These regularities mean that the observed masses are subject to certain statistical distributions, which are each characteristic of the class of molecule. By analyzing these statistical properties, it is possible to detect and correct any mass shifts which may be present.

First claim

1 . A method for the evaluation of mass spectrometric measurement data for the analysis of tissue samples, comprising the steps of:
(a) providing a tissue sample which contains polymers having varying linkages of characteristic molecules; (b) processing the tissue sample in order to prepare at least two types of polymers and molecules derived therefrom and render them accessible for a subsequent mass-spectrometric measurement; (c) acquiring mass spectra of the processed tissue sample; (d) determining the mass shift of the polymer mass signals imaged in the mass spectra, where a mass shift represents the deviation of a measured mass signal from the adjacent molecular mass signal to be expected on a mass scale, and the totality of the molecular mass signals to be expected is calculated using a theoretical model of at least one type of polymer; (e) evaluating the mass shifts determined; and (f) assessing a quality of the mass spectra according to the evaluation.

2 . The method according to claim 1 , wherein, in order to create a theoretical model of at least one type of polymer, the mass is assumed to be approximately proportional to the nominal mass, and all natural numbers in a suitably selected range are taken into consideration as possible nominal masses for this type of polymer.

3 . The method according to claim 1 , wherein the polymers comprise biopolymers of the type of proteins, peptides, N-glycans and/or lipids.

4 . The method according to claim 1 , wherein the determination of the mass shifts comprises the calculation of the quantity

Δ
λ



(
m
)

=

ϕ


(

m
λ

+

1
2

)

-

1
2

,

where φ(x)=x−floor(x) (Kendrick shift) for measured mass values m, and a scaling factor λ is selected such that it corresponds to the average ratio between exact mass and nominal mass of the polymers.

5 . The method according to claim 4 , wherein the scaling factor for N-glycans is λ G =1+3.5×10 −4 , and for proteins and peptides λ P =1+4.95×10 −4 .

6 . The method according to claim 4 , wherein the Kendrick profile for a mass spectrum is estimated by: (i) determining the positions of the local maxima of the mass spectrum, plotting them as a point cloud in the Kendrick diagram, and estimating a distribution function by means of standard methods of density estimation; or (ii) forming a two-dimensional histogram from the spectral intensities of a mass spectrum in the plane of the Kendrick diagram so that the intensities occurring in each histogram tile are summed up and, after normalization in the vertical direction, each column corresponds to a numerical approximation of the Kendrick profile for the relevant mass interval.

7 . The method according to claim 4 , wherein the evaluation comprises: (i) the calculation of circular moments greater than the first circular moment in order to detect more than one cluster point of Kendrick shifts; and/or (ii) a Hough-type transform for recognizing the structure.

8 . The method according to claim 7 , wherein the steps to calculate the Kendrick shifts and to calculate circular moments are combined and the nth circular moment is expressed as per the equation

μ

k
,
n

=

1

∫

I
k



S
~



(
t
)


d

t



∫
k



S
~



(
t
)



e

i



n



ω



t


dt

,

with



ω

=

2

π

λ

,

as a Fourier integral of the continuously interpolated spectrum {tilde over (S)} over subintervals I k of the mass scale.

9 . The method according to claim 8 , wherein the deviation in the range of the subinterval I k of the mass scale is calculated from at least two circular moments for different n as per the equation

Δ
k

=

1

2

π

Assignees

• Bruker Daltonik Gmbh

Inventors

• Boskamp Tobias

Classifications

• G01N2496/25

  containing added polymers to stabilise biological material against degradation or maintain viscosity or density, e.g. gelatin, polyacrylamides or polyvinyl alcohol · CPC title

• G01N33/53

  Immunoassay; Biospecific binding assay; Materials therefor · CPC title

• G01N33/5008

  for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics · CPC title

• G01N24/087

  Structure determination of a chemical compound, e.g. of a biomolecule such as a protein · CPC title

• G01N2223/423

  multispectral imaging-multiple energy imaging · CPC title