Reagents, devices and methods for proteomic analysis with applications including diagnostics, vaccines, quality control and research
OwnerGeoffrey Hoffmanninventor
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OwnerGeoffrey Hoffmanninventor
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The invention describes methods for proteomic analysis, with multiple applications that involve the mapping of samples in an N-dimensional shape space. The applications include the classification of samples on the basis of the three-dimensional shapes of substances they contain, which leads to novel diagnostic methods that are linked to new kinds of preventive and therapeutic vaccines. A panel of N reagents, for example proteins, called X(j), with j=1 to N, is used. With N>>1, these reagents are used to define an N-dimensional shape space with approximately orthogonal axes. The binding strength of each of the X(j) reagents to each other, as measured, for example, by an ELISA assay, is a N×N matrix K. The matrix K is used to define another set of N reagents called Y(j), with j=1 to N, each of which is a linear combination of the X(j) reagents and each of which is tailored to be complementary to the corresponding X(j) reagent. Each X(j) reagent together with the corresponding Y(j) reagent is used to define a shape space axis that is approximately orthogonal to each of the N−1 shape space axes defined by the other N−1 reagent pairs X(k) and Y(k), where k≠j. Samples can be mapped with respect to each of the N axes of the shape space by measuring the binding of molecules in the samples to each of the X(j) and Y(j) reagents. This mapping enables the definition and measurement of similarity between samples and sets of samples, including, but not limited to, biological samples. The mapping enables classification of samples with respect to categories. The samples may be simple or diverse at the level of molecular shapes, for example proteins or mixtures of proteins, or antibodies contained in serum samples. Applications include quality control for a broad range of substances. The invention also includes the optional use of P reagents, with P>N, to enhance the orthogonality of the N-dimensional shape space.
A method for mapping a sample i, in an N-dimensional shape space with approximately orthogonal axes, where N is an integer, comprising:
A method for predicting the development of a disease in a vertebrate comprising:
The method of claim 19 or 20, wherein the infectious agent is a virus, a bacterium, or a parasite.
The method of claim 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23, wherein the vaccine additionally contains an adjuvant.
The method of claim 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24, wherein the vertebrate is homo sapiens.
The vaccine of claim 26 or 28, wherein said vaccine is customized for a specific vertebrate i by having ADavX(j) and ADavY(j) in the expressions for Dav(j) replaced by corresponding values for said specific vertebrate, namely AD(i)X(j) and AD(i)Y(j).
The vaccine of claim 26, 28 or 30, that is further customized for a specific vertebrate i by replacing AHavX(j) and AHavY(j) by AHist(i)X(j) and AHist(i)Y(j), where AHist(i)X(j) and AHist(i)Y(j) are obtained using historical samples from when the vertebrate i was healthy.
The vaccine of claim 26, 28, 30 or 31, wherein the disease is an autoimmune disease, a cancer, an allergy, or is immunity to a graft.
The vaccine of claim 27 or 29, wherein the infectious agent is a virus, a bacterium, or a parasite.
The vaccine of claim 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 or 38, wherein the vaccine additionally contains an adjuvant.
A plate for measurement of Proteomic Analyser points, said plate comprising 2N wells, wherein a first group of N wells are each coated with one of N reagents X(j) and a second group of N wells are each coated with one of N reagents Y(j),
A plate for measurement of Proteomic Analyser points, said plate comprising 2N wells, wherein a first group of N wells are each coated with one of N reagents X(j) and a second group of N wells are each coated with one of N reagents Y(j),
A set of reagents for use in classification of samples, medical diagnosis, therapeutic treatment of disease, vaccination, or immunization, said set of reagents comprising 2N reagents, wherein said set of reagents is made up of NX(j) reagents and NY(j) reagents, wherein said Y(j) reagents are linear combinations of said X(j) reagents such that concentrations of kth components of Y(j) (j=1 to N, k=1 to N) are proportional to binding signals of X(j) to X(k), wherein together said X(j) and said Y(j) reagents define an approximately orthogonal set of axes in shape space.
A set of reagents for use in classification of samples, medical diagnosis, therapeutic treatment of disease, vaccination, or immunization, said set of reagents comprising 2N reagents, wherein said set of reagents is made up of NX(j) reagents and NY(j) reagents, wherein said Y(j) reagents are linear combinations of said X(j) reagents such that concentrations of kth components of Y(j) (j=1 to N, k=1 to P, where P>N) are proportional to binding signals of X(j) to X(k), wherein together said X(j) and said Y(j) reagents define an approximately orthogonal set of axes in shape space.
A set of reagents according to claim 47 or 48, wherein said binding signals are measured by an ELISA or RIA assay.
Dependencies are inferred from the claim text.