Fourier transform mass spectrometry of complex biological samples
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Abstract
The present invention relates to methods for high information content (HIC) analysis or screening of complex biological systems using Fourier transform mass spectrometry (FTMS). The present methods are useful for analyzing complex biological mixtures containing both high molecular weight molecules (e.g., polynucleotides, proteins, polysaccharides) and low molecular weight molecules (e.g., oligonucleotides, peptides, lipids, oligosaccharides, steroid hormones, catabolic and metabolic intermediates) permit the elucidation of molecular differences between complex biological samples, and permit the identification of biologically active molecules (e.g. therapeutically active drugs, etc.).
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Citations
58 Claims
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1-22. -22. (canceled)
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23. A method for identifying at least one endogenous molecule that differs in abundance between a first cell population and a second cell population, comprising:
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(a) comparing a first Fourier Transform Mass Spectrometry (FTMS) peak profile obtained from the first cell population with a second FTMS peak profile obtained from the second cell population, wherein the first peak profile and the second peak are obtained independently;
(b) identifying at least one peak that differs in intensity in the first FTMS peak profile relative to the second FTMS peak profile, which said at least one peak corresponds to least one molecule that differs in abundance between a first cell population and a second cell population; and
(c) identifying said at least one molecule that differs in abundance between the first cell population and the second cell population either directly from mass-to-charge (m/z) ratio of said at least one peak or through additional fragmentation of said at least one molecule;
thereby identifying at least one molecules that differ in abundance between a first cell population and a second cell population. - View Dependent Claims (28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57)
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24. A method for identifying at least one endogenous molecule that differs in abundance between a first cell population and a second cell population, comprising:
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(a) comparing a first FTMS peak profile obtained from the first cell population with a second FTMS peak profile obtained from the second cell population, wherein the first peak profile and the second peak profile are not obtained concurrently and wherein the first and second cell populations do not contain a label;
(b) identifying at least one peak that differs in intensity in the first FTMS peak profile relative to the second FTMS peak profile, which said at least one peak corresponds to least one molecule that differs in abundance between a first cell population and a second cell population; and
(c) identifying said at least one molecule that differs in abundance between the first cell population and the second cell population either directly from mass-to-charge (m/z) ratio of said at least one peak or through additional fragmentation of said at least one molecule;
thereby identifying at least one molecules that differ in abundance between a first cell population and a second cell population.
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25. A method for identifying at least one endogenous molecule that differs in abundance between a first cell population and a second cell population, comprising:
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(a) comparing a first FTMS peak profile obtained from the first cell population with a second FTMS peak profile obtained from the second cell population, wherein the first peak profile and the second peak profile are obtained from whole cell extracts;
(b) identifying at least one peak that differs in intensity in the first FTMS peak profile relative to the second FTMS peak profile, which said at least one peak corresponds to least one molecule that differs in abundance between a first cell population and a second cell population; and
(c) identifying said at least one molecule that differs in abundance between the first cell population and the second cell population either directly from mass-to-charge (m/z) ratio of said at least one peak or through additional fragmentation of said at least one molecule;
thereby identifying at least one molecules that differ in abundance between a first cell population and a second cell population. - View Dependent Claims (26, 27)
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58. The method of claim 5747, wherein in the primary cells are primary brain, skin, lung, endothelial, epithelial, adipose, muscle, bone, stomach, colon, spleen, pancreas, kidney, bladder, heart, lymphatic system, blood, or liver cells.
Specification