Specimen-linked G protein coupled receptor database

• US 20030027223A1
• Filed: 06/28/2002
• Published: 02/06/2003
• Est. Priority Date: 06/29/2001
• Status: Abandoned Application

• Current Assignee: Protea Biosciences, Inc. (Protea Biosciences Group, Inc.)
• Original Assignee: Protea Biosciences, Inc. (Protea Biosciences Group, Inc.)
• Inventors: Muraca, Patrick J.
• Application Number:
  US10/184,694
• Publication Number:
  US 20030027223A1
• Time in Patent Office: Days
• US Class Current: 435/7.21
• CPC Class Codes: C40B 30/04 by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: G01N 2333/726 G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
• CPC Class Codes: G01N 33/567 utilising isolate of tissue or organ as binding agent
• CPC Class Codes: G01N 33/6845 Methods of identifying protein-protein interactions in protein mixtures
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/30 Microarray design
• CPC Class Codes: G16B 40/00 ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
• CPC Class Codes: G16B 40/20 Supervised data analysis
• CPC Class Codes: G16B 40/30 Unsupervised data analysis
• CPC Class Codes: G16B 50/00 ICT programming tools or database systems specially adapted for bioinformatics
• CPC Class Codes: G16B 50/20 Heterogeneous data integration

Abstract

The invention relates to a method and system for identifying and evaluating the physiological responses of an organism to a condition, such as a disease or other pathological condition, a drug or agent, an environmental condition, and the like, by evaluating the expression of one or more GPCR pathway biomolecules in tissue microarrays from a plurality of patients. In one aspect, a tissue information system is provided comprising a specimen-linked database and an information management system for accessing, organizing, and displaying tissue information obtained from tissue microarrays. Preferably, the system is used to model and validate GPCR pathways affected during one or more physiological responses to a condition.

Claims

1. An information system comprising:

a tissue microarray having a plurality of samples;

a specimen-linked database containing a plurality of clinical information of each sample and a plurality of information relating to G-protein coupled receptor pathway molecules of each sample; and

an information management system for searching the specimen-linked database and determining relationships between the plurality of clinical information and the plurality of information relating to G-protein coupled receptors pathway biomolecules.

2. The information system of claim 1 further comprising a plurality of tissue microarrays.

3. The information system of claim 2 wherein an at least one tissue microarray is a control tissue microarray.

4. The information system of claim 1 wherein the tissue microarray comprises a plurality of sublocations.

5. The information system of claim 4 wherein each of the plurality of sublocations comprises a set of coordinates.

6. The information system of claim 4 wherein each of the plurality of sublocations comprises a tissue sample wherein the tissue sample has an at least one known biological characteristic.

7. The information system of claim 1 wherein the tissue microarray comprises a substrate for handling of the tissue microarray through at least one molecular procedure.

8. The information system of claim 7 wherein the substrate comprises a location for placing an identifier.

9. The information system of claim 1 wherein the plurality of samples are a plurality of tissues.

10. The information system of claim 1 wherein the plurality of samples are a plurality of cells.

11. The information system of claim 1 wherein each of the plurality of samples are derived from a single organism.

12. The information system of claim 1 wherein each of the plurality of samples has a similar trait.

13. The information system of claim 1 wherein each of the plurality of samples comprise a particular patient demographic group.

14. The information system of claim 1 wherein each of the plurality of samples are taken from a plurality of individuals with a particular disease.

15. The information system of claim 14 wherein the disease is a neurodegenerative disease.

16. The information system of claim 14 wherein the disease is a neuropsychiatric disease.

17. The information system of claim 1 wherein the plurality of samples represents a plurality of different stages of a cell proliferative disorder.

18. The information system of claim 1 wherein each of the plurality of samples are taken from a plurality of individuals who have been exposed to a drug.

19. The information system of claim 1 wherein each of the plurality of samples is taken from a plurality of individuals who have been exposed to an environmental condition.

20. An information system comprising:

a tissue microarray having a plurality of samples;

a specimen-linked database containing a plurality of clinical information of each sample and a plurality of information relating to G-protein coupled receptor pathway molecules of each sample;

an information management system for searching the specimen-linked database and determining relationships between the plurality of clinical information and the plurality of information relating to G-protein coupled receptors pathway biomolecules; and

a user device connected to a network.

21. The information system of claim 20 further comprising a plurity of user devices located at a plurality of physical locations.

22. The information system of claim 20 wherein the user device comprises an interface.

23. The information system of claim 22 wherein the interface provides a link to an identifier associated with the tissue microarray.

24. The information system of claim 23 wherein the interface further provides a link to a set of coordinates wherein the set of coordinates represents a single sample of the plurality of samples.

25. The information system of claim 22 wherein the interface comprises a link to the specimen-linked database.

26. The information system of claim 20 wherein the user device comprises a processor.

27. The information system of claim 20 wherein the user device comprises an operating system.

28. The information system of claim 27 wherein the user device further comprises a web browser.

29. The information system of claim 20 wherein the user device comprises a text input element.

30. The information system of claim 20 wherein the user device is coupled to a navigating device.

31. The information system of claim 20 further comprising an at least one server.

32. The information system of claim 31 wherein the at least one server provides access to an at least one data storage media.

33. The information system of claim 20 wherein the information management system further comprises an application program wherein the application program is capable of searching the specimen-linked database.

34. The information system of claim 20 further comprising an information output module wherein the information output module is capable of outputting and reporting information from the specimen-linked database.

35. The information system of claim 20 further comprising an information input module.

36. The information system of claim 20 wherein the user device is coupled to a molecular profiling system.

37. An information system comprising:

at least one tissue microarray wherein the at least one tissue micro array includes a plurality of sublocations wherein each sublocation comprises a sample;

a specimen-linked database containing a plurality of clinical information of each sample and a plurality of information relating to G-protein coupled receptor pathway molecules of each sample; and

an information management system for searching the specimen-linked database and determining relationships between the plurality of clinical information and the plurality of information relating to G-protein coupled receptors pathway biomolecules.

38. The information system of claim 37 wherein the specimen-linked database includes a data model wherein the data model organizes a plurality of information.

39. The information system of claim 38 wherein the data model is selected from the group consisting of a flat file model, an indexed file model, a network data model, a hierarchial data model, and a relational data model.

40. The information system of claim 37 wherein the specimen-linked database comprises a database dictionary having a set of parameters specified by a system operator.

41. The information system of claim 40 wherein the database dictionary further comprises a plurality of word equivalents for searching the specimen-linked database.

42. The information system of claim 41 wherein the database dictionary further comprises a plurality of codes for searching the specimen-linked database.

43. The information system of claim 42 wherein the plurality of codes are selected from the group consisting of a plurality of SNOWMED codes, a plurality of DSM-IV-TR codes, and a plurality of UNIGENE codes.

44. The information system of claim 37 further comprising a temporary database wherein a plurality of information entered into the temporary database is subject to validation by a system operator prior to the plurality of information being included into the specimen-linked database.

45. The information system of claim 37 wherein the specimen-linked database comprises a plurality of information representing a whole body tissue microarray.

46. The information system of claim 37 wherein the specimen-linked database comprises information from a plurality of tissue microarrays.

47. The information system of claim 37 wherein the specimen-linked database comprises information relating to a plurality of samples from a plurality of different recombinant inbred strains of a single individual.

48. The information system of claim 37 wherein the specimen-linked database comprises a plurality of information obtained from an at least one sample assayed independently of the tissue miocroarray.

49. The information system of claim 37 wherein the specimen-linked database comprises a plurality of subdatabases wherein each subdatabase comprises information relating to a particular category of sample information.

50. The information system of claim 37 wherein the specimen-linked database comprises a series of uncompressed raw data files.

51. The information system of claim 37 wherein the specimen-linked database further comprises a genomic medicine database wherein the genomic medicine database comprises a plurality of subdatabases comprising a set of information about a plurality of GPCR pathway biomolecules.

52. The information system of claim 37 wherein the specimen-linked database further comprises a physiological response database comprising information relating to a plurality of physiological responses of patients to a plurality of conditions.

53. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating to kinetic parameters which govern a plurality of physiological responses.

54. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating to a plurality of biomolecules which are expressed or inhibited upon activation of a particular GPCR pathway biomolecule.

55. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of at least one DNA repair gene.

56. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in cholesterol metabolism.

57. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in apoptosis.

58. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in blood clotting.

59. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in the flt-3 pathway.

60. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in the JAK/STATS signaling pathway.

61. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in a MAP kinase signaling pathway.

62. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in a PI 3 kinase pathway.

63. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in a ras activation pathway.

64. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in a SIP signaling pathway.

65. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in a TGF-β

signaling pathway.

66. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in a T cell receptor based signaling pathway.

67. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating the expression of an at least one biomolecule involved in a MHC-1 mediated antigen presentation.

68. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating to the expression of a plurality of pathway molecules in addition to GPCR pathway molecules expressed within whole body tissue microarrays obtained from a plurality of patients.

69. The information system of claim 68 wherein the physiological response database further comprise a plurality of subdatabases including information relating to a plurality of specific pathways.

70. The information system of claim 68 further comprising a plurality of information relating to the biological impact of the expression of the plurality of GPCR pathway biomolecules.

71. The information system of claim 52 wherein the physiological response database comprises a plurality of information relating to the expression of an at least one tyrosine kinase pathway molecule.

72. The system of claim 37 wherein the specimen-linked database comprises a plurality of information relating to a plurality of treatment options.

73. An information system comprising:

an at least one tissue microarray wherein the at least one tissue microarray comprises a plurality of sublocations wherein each sublocation comprises a sample;

a specimen-linked database containing a plurality of clinical information of each sample and a plurality of information relating to G-protein coupled receptor pathway molecules of each sample;

an information management system for searching the specimen-linked database and for determining relationships between the plurality of clinical information and the plurality of information relating to G-protein coupled receptors pathway biomolecules; and

a user device connected to a network.

74. The information system of claim 73 wherein the information management system displays a plurality of information on an interface of the user device.

75. The information system of claim 73 wherein the information management system is stored within an at least one server and the information management system is accessible remotely through the network.

76. The information system of claim 73 wherein the information management system is accessible through a readable medium.

77. The information system of claim 73 wherein the information management system is capable of understanding a set of natural language query terms.

78. The information system of claim 73 wherein the information management system is capable of understanding Boolean operators and truncation symbols.

79. The information system of claim 73 wherein the information management system generates a plurality of search data from a plurality of terms inputted into an interface of the user device and transfers the plurality of search data to an at least one search engine to initiate a search.

80. The information system of claim 73 wherein the information management system generates a plurality of search data through a selection of options which are displayed on an interface.

81. The information system of claim 73 wherein the information management system is capable of mapping a plurality of data points obtained from the specimen-linked database.

82. The information system of claim 73 wherein the information management system is cabable of classifying a plurality of tissue information by type or attribute.

83. The information system of claim 73 wherein the information management system is capable of assigning a relationship identification number to each of a plurality of attributes and storing the relationship identification numbers in the specimen-linked database where the attributes are indexed by the relationship identification number and provided with a descriptor.

84. The information system of claim 73 wherein the information management system comprises a statistical program to identify a plurality of attributes as representing a particular relationship.

85. The information system of claim 84 wherein the information management system is capable of analyzing a particular relationship between a plurality of data in the specimen-linked database using any of the methods in the group consisting of regression, decision trees, neural networks, and fuzzy logic.

86. The information system of claim 73 wherein the information management system further comprises an expert system.

87. The information system of claim 86 wherein the expert system is capable of identifying biomolecules which are likely to belong to a GPCR pathway.

88. The information system of claim 87 wherein the expert system further comprises a transaction manager wherein the transaction manager directs and outputs requests between an at least one server of the information system and an at least one interface of an at least one user devices of the system.

89. The information system of claim 88 further comprising an expression profile interface on which is displayed a representation of an at least one level of expression of an at least one selected GPCR pathway biomolecule in a plurality of samples.

90. The information system of claim 89 further comprising an at least one information category link identifying a plurality of physiological response categories.

91. A method of relating a plurality of information comprising:

creating a tissue microarray wherein the tissue microarray includes a plurality of sublocations and a plurality of samples wherein each sublocation includes a sample;

identifying the tissue microarray with an identifier and identifying each sublocation with a set of coordinates;

treating each of the plurality of samples with a molecular probe;

entering a plurality of clinical information relating to each sample into a specimen-linked database and entering a plurality of information relating to at least one G-protein coupled receptor pathway biomolecule of each sample into the specimen-linked database; and

correlating the identifier of the tissue microarray and the coordinates of a sublocation with the plurality of clinical information and the plurality of information relating to at least one G-protein coupled receptor pathway biomolecule of the sublocation using an information management system.

92. The method of claim 91 further comprising a plurality of tissue microarrays.

93. The method of claim 92 wherein an at least one tissue microarray is a control tissue micro array.

94. The method of claim 91 wherein each of the plurality of sublocations comprises a tissue sample wherein the tissue sample has an at least one known biological characteristic.

95. The method of claim 91 wherein the plurality of samples are a plurality of tissues.

96. The method of claim 91 wherein each of the plurality of samples are derived from a single organism.

97. The method of claim 91 wherein each of the plurality of samples has a similar trait.

98. The method of claim 91 wherein each of the plurality of samples comprise a particular patient demographic group.

99. The method of claim 91 wherein each of the plurality of samples are taken from a plurality of individuals with a particular disease.

100. The method of claim 91 wherein the plurality of samples represents a plurality of different stages of a cell proliferative disorder.

101. The method of claim 91 wherein at least one of the plurality of samples is taken from an individual that has been exposed to a drug.

102. The method of claim 91 wherein at least one of the plurality of samples is taken from an individual that has been exposed to an environmental condition.

103. The method of claim 91 further comprising displaying a link to the identifier associated with the tissue microarray wherein the link is displayed on an interface of a user device.

104. The method of claim 91 further comprising displaying a link to the set of coordinates wherein the set of coordinates represents a single sample of the plurality of samples.

105. The method of claim 91 further comprising displaying a link to the specimen-linked database.

106. The method of claim 91 wherein the interface allows a user to enter search terms.

107. The method of claim 91 further comprising searching the specimen-linked database with an information management system.

108. A method of relating a plurality of information comprising:

creating a tissue microarray wherein the tissue microarray includes a plurality of sublocations and a plurality of samples wherein each sublocation includes a sample;

entering a plurality of clinical information relating to each sample into a specimen-linked database and entering a plurality of information relating to at least one G-protein coupled receptor pathway biomolecule of each sample into the specimen-linked database;

correlating the identifier of the tissue microarray and the coordinates of a sublocation with the plurality of clinical information and the plurality of information relating to at least one G-protein coupled receptor pathway biomolecule of the sublocation using an information management system; and

searching the specimen-linked database with the information management system and displaying a plurality of search results on an interface of a user device.

109. The method of claim 108 further comprising comparing a first plurality of information, wherein the first plurality of information has been incorporated into the specimen-linked database, with a second plurality of information, wherein the second plurality of information has not been incorporated into the specimen-linked database.

110. The method of claim 109 wherein the information management system is capable of determining a plurality of relationships between the first plurality of information and the second plurality of information.

111. The method of claim 110 further comprising displaying the plurality of relationships on the interface of the user device.

112. The method of claim 108 wherein the user device is coupled to a molecular profiling system.

113. The method of claim 108 wherein the specimen-linked database includes a data model wherein the data model organizes a plurality of information.

114. The method of claim 108 wherein the information management system is stored within an at least one server and the information management system is accessible remotely through a network.

115. The method of claim 108 wherein the information management system is capable of understanding a set of natural language query terms.

116. The method of claim 108 wherein the information management system is capable of understanding Boolean operators and truncation symbols.

117. The method of claim 108 wherein the information management system generates a plurality of search data through a selection of options which are displayed on the interface.

118. The method of claim 108 wherein the information management system is capable of mapping a plurality of data points obtained from the specimen-linked database.

119. The method of claim 108 wherein the information management system is capable of classifying a plurality of tissue information by a type or an attribute.

120. The method of claim 108 wherein the information management system is capable of assigning a relationship identification number to each of a plurality of attributes and storing the relationship identification numbers in the specimen-linked database where the plurality of attributes are indexed by the relationship identification number and provided with a descriptor.

121. The method of claim 108 wherein the information management system comprises a statistical program to identify a plurality of attributes as representing a particular relationship.

122. The method of claim 121 wherein the information management system is capable of analyzing a particular relationship between a plurality of data in the specimen-linked database using any of the methods in the group consisting of regression, decision trees, neural networks, and fuzzy logic.

123. The method of claim 108 wherein the information management system is coupled to an expert system.

124. The method of claim 123 wherein the expert system is capable of identifying biomolecules which are likely to belong to a GPCR pathway.

125. The method of claim 124 wherein the expert system further comprises a transaction manager wherein the transaction manager directs and outputs requests between an at least one server and an at least one interface of an at least one user device of the system.

126. The method of claim 125 further comprising displaying a representation of an at least one level of expression of an at least one selected GPCR pathway biomolecule in a plurality of samples.