Ultra-sensitive detection systems using alterable peptide tags
First Claim
1. A set of reporter signals comprising a plurality of reporter signal peptides,wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered forms of each reporter signal peptide can be distinguished from every other altered form of reporter signal peptide.
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Accused Products
Abstract
Disclosed are compositions and methods for sensitive detection of one or multiple analytes. In general, the methods involve the use of special label components, referred to as reporter signals, that can be associated with, incorporated into, or otherwise linked to the analytes. In some embodiments, the reporter signals can be altered such that the altered forms of different reporter signals can be distinguished from each other. In some embodiments, sets of reporter signals can be used where two or more of the reporter signals in a set have one or more common properties that allow the reporter signals having the common property to be distinguished and/or separated from other molecules lacking the common property. In other embodiments, sets of reporter signal/analyte conjugates can be used where two or more of the reporter signal/analyte conjugates in a set have one or more common properties that allow the reporter signal/analyte conjugates having the common property to be distinguished and/or separated form other molecules lacking the common property. Reporter signals can also be in conjunction with analytes (such as in mixtures of reporter signals and analytes), where no significant physical association between the reporter signals and analytes occurs; or alone, where no analyte is present.
122 Citations
513 Claims
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1. A set of reporter signals comprising a plurality of reporter signal peptides,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered forms of each reporter signal peptide can be distinguished from every other altered form of reporter signal peptide.
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21. A method comprising:
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(a) separating a set of reporter signal peptides, where each reporter signal peptide has a common property, from molecules lacking the common property, (b) altering the reporter signal peptides, (c) detecting and distinguishing the altered forms the reporter signal peptides from each other. - View Dependent Claims (22, 23, 24, 25, 26, 27, 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, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77)
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78. A kit comprising:
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(a) a set of reporter molecules, wherein each reporter molecule comprises a reporter signal peptide and a decoding tag, wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered forms of each reporter signal peptide can be distinguished from every other altered form of reporter signal peptide, wherein each different reporter molecule comprises a different decoding tag and a different reporter signal peptide, (b) a set of coding molecules, wherein each coding molecule comprises a specific binding molecule and a coding tag, wherein each specific binding molecule can interact specifically with a different analyte, wherein each coding tag can interact specifically with a different decoding tag.
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79. A method comprising:
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(a) separating one or more reporter signal peptides, where each reporter signal peptide has a common property, from molecules lacking the common property in each of a plurality of samples, (b) altering the reporter signal peptides, (c) detecting and distinguishing the altered forms the reporter signal peptides from each other.
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80. A set of labeled proteins wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, wherein the reporter signal peptides have a common property, wherein the common property allows the labeled proteins comprising the same protein or peptide to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered forms of each reporter signal peptide can be distinguished from every other altered form of reporter signal peptide, wherein alteration of the reporter signal peptides alters the labeled proteins, wherein altered forms of each labeled protein can be distinguished from every other altered form of labeled protein.
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81. A kit comprising a set of reporter molecules, wherein each reporter molecule comprises a reporter signal peptide and a coupling tag, wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered forms of each reporter signal peptide can be distinguished from every other altered form of reporter signal peptide, wherein each different reporter molecule comprises a different coupling tag and a different reporter signal peptide.
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82. A set of labeled proteins wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, wherein the labeled proteins have a common property, wherein the common property allows the labeled proteins comprising the same protein or peptide to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered forms of each reporter signal peptide can be distinguished from every other altered form of reporter signal peptide, wherein alteration of the reporter signal peptides alters the labeled proteins, wherein altered forms of each labeled protein can be distinguished from every other altered form of labeled protein.
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83. A set of labeled proteins wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, wherein the reporter signal peptides are capable of being altered, wherein the altered forms of each reporter signal peptide can be distinguished from every other altered form of reporter signal peptide, wherein alteration of the reporter signal peptides alters the labeled proteins, wherein altered forms of each labeled protein can be distinguished from every other altered form of labeled protein.
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84. A method comprising
(a) separating a set of labeled proteins, wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, wherein each reporter signal peptide has a common property, wherein the common property allows the labeled proteins comprising the same protein or peptide to be distinguished or separated from molecules lacking the common property, (b) altering the reporter signal peptides, thereby altering the labeled proteins, (c) detecting and distinguishing the altered forms of the labeled proteins from each other.
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90. A set of labeled proteins wherein each labeled protein comprises a protein or a peptide and a reporter signal attached to the protein or peptide, wherein the reporter signals comprise peptides, wherein the reporter signal peptides have the same mass-to-charge ratio.
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91. A method comprising:
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(a) separating one or more labeled proteins, wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, wherein each reporter signal peptide has a common property, wherein the common property allows the labeled proteins comprising the same protein or peptide to be distinguished or separated from molecules lacking the common property in each of one or more samples, (b) altering the reporter signal peptides, thereby altering the labeled proteins, (c) detecting and distinguishing the altered forms the labeled proteins from each other. - View Dependent Claims (92, 93)
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94. A method comprising:
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(a) separating a set of labeled proteins, wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, wherein each labeled protein has a common property, wherein the common property allows the labeled proteins comprising the same protein or peptide to be distinguished or separated from molecules lacking the common property, (b) altering the reporter signal peptides, thereby altering the labeled proteins, (c) detecting and distinguishing the altered forms of the labeled proteins from each other.
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95. A method comprising:
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(a) altering labeled proteins, wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, wherein the labeled proteins are altered by altering the reporter signal peptides, (b) detecting and distinguishing the altered forms of the labeled proteins from each other.
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96. A method comprising
(a) separating one or more labeled proteins from other molecules, wherein the labeled proteins are derived from one or more samples, wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, (b) altering the reporter signal peptides, thereby altering the labeled proteins, (c) detecting and distinguishing the altered forms the labeled proteins from each other.
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106. A catalog of proteins and peptides comprising, proteins and peptides in a sample detected by:
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(a) separating one or more labeled proteins from other molecules, wherein the labeled proteins are derived from the sample, wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, (b) altering the reporter signal peptides, thereby altering the labeled proteins, (c) detecting and distinguishing the altered forms the labeled proteins from each other.
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107. A catalog of proteins and peptides comprising, proteins and peptides in one or more samples detected by:
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(a) separating one or more labeled proteins from other molecules, wherein the labeled proteins are derived from the one or more samples, wherein each labeled protein comprises a protein or peptide and a reporter signal peptide attached to the protein or peptide, (b) altering the reporter signal peptides, thereby altering the labeled proteins, (c) detecting and distinguishing the altered forms the labeled proteins from each other.
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108. A method of producing a protein signature, the method comprising:
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(a) treating a protein sample to produce protein fragments, wherein the protein fragments comprise a set of target protein fragments, wherein the target protein fragments can be altered, wherein the altered forms of the target protein fragments can be distinguished from the other altered forms of the target protein fragments, (b) mixing the target protein fragments with a set of reporter signal calibrators, wherein the reporter signal calibrators comprise peptides, wherein each target protein fragment shares a common property with at least one of the reporter signal calibrators, wherein the common property allows the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property, (c) separating the target protein fragments and reporter signal calibrators from other molecules based on the common properties of the target protein fragments and reporter signal calibrators, (d) altering the target protein fragments and reporter signal calibrators, (e) detecting the altered forms of the target protein fragments and reporter signal calibrators, wherein the presence, absence, amount, or presence and amount of the altered forms of the target protein fragments indicates the presence, absence, amount, or presence and amount in the protein sample of the target protein fragments from which the altered forms of the target protein fragments are derived, wherein the presence, absence, amount, or presence and amount of the target protein fragments in the protein sample constitutes a protein signature of the protein sample. - View Dependent Claims (109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151)
performing steps (a) through (e) on a control protein sample, identifying differences between the protein signatures produced from the protein sample and the control protein sample. -
124. The method of claim 108 further comprising performing steps (a) through (e) on a plurality of protein samples.
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125. The method of claim 124 further comprising identifying differences between the protein signatures produced from the protein samples.
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126. The method of claim 124 further comprising performing steps (a) through (e) on a control protein sample, identifying differences between the protein signatures produced from the protein samples and the control protein sample.
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127. The method of claim 126 wherein the differences are differences in the presence, amount, presence and amount, or absence of target protein fragments in the protein samples and the control protein sample.
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128. The method of claim 124 wherein the steps (a) through (e) are performed on a control protein sample and a tester protein sample,
wherein the tester protein sample, or the source of the tester protein sample, is treated, prior to step (a), so as to destroy, disrupt or eliminate one or more protein molecules in the tester protein sample, wherein the target protein fragments corresponding to the destroyed, disrupted, or eliminated protein molecules will be produced from the control protein sample but not the tester protein sample. -
129. The method of claim 128 wherein the tester protein sample is treated so as to destroy, disrupt or eliminate one or more protein molecules in the tester protein sample.
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130. The method of claim 129 wherein one or more protein molecules in the tester sample are eliminated by separating the one or more protein molecules from the tester protein sample.
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131. The method of claim 130 wherein the one or more protein molecules are separated by affinity separation.
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132. The method of claim 128 wherein the source of the tester protein sample is treated so as to destroy, disrupt or eliminate one or more protein molecules in the tester protein sample.
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133. The method of claim 132 wherein the treatment of the source is accomplished by exposing cells from which the tester sample will be derived with a compound, composition, or condition that will reduce or eliminate expression of one or more genes.
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134. The method of claim 128 further comprising identifying differences in the target protein fragments in the control protein sample and tester protein sample.
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135. The method of claim 124 further comprising identifying differences between the target protein fragments in the protein samples.
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136. The method of claim 124 wherein the plurality of protein samples are produced by a separation procedure, wherein the separation procedure comprises liquid chromatography, gel electrophoresis, two-dimensional chromatography, two-dimensional gel electrophoresis, isoelectric focusing, thin layer chromatography, centrifugation, filtration, ion chromatography, immunoaffinity chromatography, membrane separation, or a combination of these.
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137. The method of claim 136 wherein the protein samples are different fractions or samples produced by the same separation procedure.
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138. The method of claim 108 further comprising performing steps (a) through (e) on a second protein sample.
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139. The method of claim 108 further comprising producing a second protein signature from a second protein sample and comparing the first protein signature and second protein signature, wherein differences in the first and second protein signatures indicate differences in source or condition of the source of the first and second protein samples.
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140. The method of claim 108 further comprising producing a second protein signature from a second protein sample and comparing the first protein signature and second protein signature, wherein differences in the first and second protein signatures indicate differences in protein modification of the first and second protein samples.
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141. The method of claim 140 wherein the second protein sample is a sample from the same type of cells as the first protein sample except that the cells from which the first protein sample is derived are modification-deficient relative to the cells from which the second protein sample is derived.
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142. The method of claim 140 wherein the second protein sample is a sample from a different type of cells than the first protein sample, and wherein the cells from which the first protein sample is derived are modification-deficient relative to the cells from which the second protein sample is derived.
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143. The method of claim 108 wherein the protein sample is derived from one or more cells.
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144. The method of claim 143 wherein the protein signature indicates the physiological state of the cells.
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145. The method of claim 143 wherein the protein signature indicates the effect of a treatment of the cells.
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146. The method of claim 145 wherein the cells are derived from an organism, wherein the cells are treated by treating the organism.
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147. The method of claim 146 wherein the organism is treated by administering a compound to the organism.
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148. The method of claim 146 wherein the organism is human.
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149. The method of claim 108 wherein the protein sample is produced by a separation procedure, wherein the separation procedure comprises liquid chromatography, gel electrophoresis, two-dimensional chromatography, two-dimensional gel electrophoresis, isoelectric focusing, thin layer chromatography, centrifugation, filtration, ion chromatography, immunoaffinity chromatography, membrane separation, or a combination of these.
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150. The method of claim 108 wherein the set of reporter signal calibrators consists of a single reporter signal calibrator.
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151. The method of claim 150 wherein the protein signature of the protein sample represents the presence, absence, amount, or presence and amount of the target protein fragment in the protein sample that corresponds to the reporter signal calibrator.
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152. A method of producing a protein signature, the method comprising detecting altered forms of target protein fragments and reporter signal calibrators, wherein the reporter signal calibrators comprise peptides, wherein the altered forms of the target protein fragments can be distinguished from the other altered forms of the target protein fragments,
wherein each target protein fragment shares a common property with at least one of the reporter signal calibrators, wherein the common property allows the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property, wherein the presence, absence, amount, or presence and amount of the altered forms of the target protein fragments indicates the presence, absence, amount, or presence and amount in a protein sample of the target protein fragments from which the altered forms of the target protein fragments are derived, wherein the presence, absence, amount, or presence and amount of the target protein fragments in the protein sample constitutes a protein signature of the protein sample.
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156. A method of producing a protein signature, the method comprising
(a) treating a protein sample to produce protein fragments, wherein the protein fragments comprise a set of target protein fragments, wherein the target protein fragments can be altered, wherein the altered forms of the target protein fragments can be distinguished from the other altered forms of the target protein fragments, (b) separating the target protein fragments from other protein fragments in the protein sample, (c) altering the target protein fragments, (d) detecting the altered forms of the target protein fragments, wherein the presence, absence, amount, or presence and amount of the altered forms of the target protein fragments indicates the presence, absence, amount, or presence and amount in the protein sample of the target protein fragments from which the altered forms of the target protein fragments are derived, wherein the presence, absence, amount, or presence and amount of the target protein fragments in the protein sample constitutes a protein signature of the protein sample.
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158. A method of producing a protein signature, the method comprising
(a) separating a plurality of target protein fragments from other protein fragments in a protein sample, (b) altering the target protein fragments, (c) detecting the altered forms of the target protein fragments, wherein the presence, absence, amount, or presence and amount of the altered forms of the target protein fragments indicates the presence, absence, amount, or presence and amount in the protein sample of the target protein fragments from which the altered forms of the target protein fragments are derived, wherein the presence, absence, amount, or presence and amount of the target protein fragments in the protein sample constitutes a protein signature of the protein sample.
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159. A method of analyzing a protein sample, the method comprising
(a) mixing a protein sample with a predetermined amount of a reporter signal calibrator, wherein the reporter signal calibrator comprises a peptide, wherein the protein sample has a known amount of protein, wherein the protein sample comprises a target protein fragment, wherein the target protein fragment can be altered, wherein the reporter signal calibrator are capable of being altered, wherein the altered form of the reporter signal calibrator can be distinguished from the altered form of the target protein fragment, (b) altering the target protein fragment and reporter signal calibrator, (c) detecting the altered forms of the target protein fragment and reporter signal calibrator.
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161. A method of analyzing a protein sample, the method comprising
(a) treating a protein sample to produce protein fragments, wherein the protein sample has a known amount of protein, wherein the protein sample comprises a target protein, wherein the protein fragments comprise a target protein fragment derived from the target protein, (b) mixing the protein sample with a predetermined amount of a reporter signal calibrator, wherein the reporter signal calibrator comprises peptides, wherein the target protein fragment can be altered, wherein the reporter signal calibrator are capable of being altered, wherein the altered form of the reporter signal calibrator can be distinguished from the altered form of the target protein fragment, (c) altering the target protein fragment and reporter signal calibrator, (d) detecting the altered forms of the target protein fragment and reporter signal calibrator.
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163. A set of reporter signal calibrators,
wherein each reporter signal calibrator comprises a peptide, wherein each reporter signal calibrator shares a common property with a target protein fragment in a set of target protein fragments, wherein the common property allows the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein the target protein fragments can be altered, wherein the altered forms of the target protein fragments can be distinguished from the other altered forms of the target protein fragments, wherein the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property.
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168. A kit for producing a protein signature, the kit comprising
(a) a set of reporter signal calibrators, wherein each reporter signal calibrator comprises a peptide, wherein each reporter signal calibrator shares a common property with a target protein fragment in a set of target protein fragments, wherein the common property allows the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein the target protein fragments can be altered, wherein the altered forms of the target protein fragments can be distinguished from the other altered forms of the target protein fragments, wherein the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property, (b) one or more reagents for treating a protein sample to produce protein fragments.
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169. A mixture comprising a set of reporter signal calibrators and a set of target protein fragments,
wherein each reporter signal calibrator comprises a peptide, wherein each reporter signal calibrator shares a common property with a target protein fragment in the set of target protein fragments, wherein the common property allows the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein the target protein fragments can be altered, wherein the altered forms of the target protein fragments can be distinguished from the other altered forms of the target protein fragments, wherein the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property.
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170. A set of target protein fragments,
wherein each target protein fragment shares a common property with a reporter signal calibrator in a set of reporter signal calibrators, wherein each reporter signal calibrator comprises a peptide, wherein the common property allows the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein the target protein can be altered, wherein the altered forms of the target protein fragments can be distinguished from the other altered forms of the target protein fragments, wherein the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property.
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171. A method of producing a protein signature, the method comprising
(a) treating a protein sample to produce protein fragments, wherein the protein fragments comprise a set of target protein fragments, wherein each of the target protein fragments can be altered, wherein the altered forms of each target protein fragment can be distinguished from every other altered form of target protein fragment, (b) mixing the target protein fragments with a set of reporter signal calibrators, wherein each reporter signal calibrator comprises a peptide, wherein each target protein fragment shares a common property with at least one of the reporter signal calibrators, wherein the common property allows each of the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein each of the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property, (c) separating the target protein fragments and reporter signal calibrators from other molecules based on the common properties of the target protein fragments and reporter signal calibrators, (d) altering the target protein fragments and reporter signal calibrators, (e) detecting the altered forms of the target protein fragments and reporter signal calibrators, wherein the presence, absence, amount, or presence and amount of the altered forms of the target protein fragments indicates the presence, absence, amount, or presence and amount in the protein sample of the target protein fragments from which the altered forms of the target protein fragments are derived, wherein the presence, absence, amount, or presence and amount of the target protein fragments in the protein sample constitutes a protein signature of the protein sample.
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172. A method of producing a protein signature, the method comprising detecting altered forms of target protein fragments and reporter signal calibrators, wherein each reporter signal calibrator comprises a peptide,
wherein the altered forms of each target protein fragment can be distinguished from every other altered form of target protein fragment, wherein each target protein fragment shares a common property with at least one of the reporter signal calibrators, wherein the common property allows each of the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property, wherein the presence, absence, amount, or presence and amount of the altered forms of the target protein fragments indicates the presence, absence, amount, or presence and amount in a protein sample of the target protein fragments from which the altered forms of the target protein fragments are derived, wherein the presence, absence, amount, or presence and amount of the target protein fragments in the protein sample constitutes a protein signature of the protein sample.
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173. A method of producing a protein signature, the method comprising
(a) treating a protein sample to produce protein fragments, wherein the protein fragments comprise a set of target protein fragments, wherein each of the target protein fragments can be altered, wherein the altered forms of each target protein fragment can be distinguished from every other altered form of target protein fragment, (b) separating the target protein fragments from other protein fragments in the protein sample, (c) altering the target protein fragments, (d) detecting the altered forms of the target protein fragments, wherein the presence, absence, amount, or presence and amount of the altered forms of the target protein fragments indicates the presence, absence, amount, or presence and amount in the protein sample of the target protein fragments from which the altered forms of the target protein fragments are derived, wherein the presence, absence, amount, or presence and amount of the target protein fragments in the protein sample constitutes a protein signature of the protein sample.
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175. A set of reporter signal calibrators, wherein each reporter signal calibrator comprises a peptide,
wherein each reporter signal calibrator shares a common property with a target protein fragment in a set of target protein fragments, wherein the common property allows each of the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein each of the target protein fragments can be altered, wherein the altered forms of each target protein fragment can be distinguished from every other altered form of target protein fragment, wherein each of the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property.
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176. A kit for producing a protein signature, the kit comprising
(a) a set of reporter signal calibrators, wherein each reporter signal calibrator comprises a peptide, wherein each reporter signal calibrator shares a common property with a target protein fragment in a set of target protein fragments, wherein the common property allows each of the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein each of the target protein fragments can be altered, wherein the altered forms of each target protein fragment can be distinguished from every other altered form of target protein fragment, wherein each of the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property, (b) one or more reagents for treating a protein sample to produce protein fragments.
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177. A mixture comprising a set of reporter signal calibrators and a set of target protein fragments, wherein each reporter signal calibrator comprises a peptide,
wherein each reporter signal calibrator shares a common property with a target protein fragment in the set of target protein fragments, wherein the common property allows each of the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein each of the target protein fragments can be altered, wherein the altered forms of each target protein fragment can be distinguished from every other altered form of target protein fragment, wherein each of the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property.
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178. A set of target protein fragments,
wherein each target protein fragment shares a common property with a reporter signal calibrator in a set of reporter signal calibrators, wherein each reporter signal calibrator comprises a peptide, wherein the common property allows each of the target protein fragments and reporter signal calibrators having the common property to be distinguished or separated from molecules lacking the common property, wherein the target protein fragment and reporter signal calibrator that share a common property correspond to each other, wherein each of the target protein fragments can be altered, wherein the altered forms of each target protein fragment can be distinguished from every other altered form of target protein fragment, wherein each of the reporter signal calibrators are capable of being altered, wherein the altered form of each reporter signal calibrator can be distinguished from the altered form of the target protein fragment with which the reporter signal calibrator shares a common property.
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179. A set of nucleic acid molecules wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides.
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270. A set of nucleic acid molecules wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein alteration of the reporter signal peptides alters the amino acid segments, wherein the altered form of each amino acid segment can be distinguished from the altered forms of the other amino acid segments.
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271. A set of nucleic acid molecules wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the amino acid segments have a common property, wherein the common property allows the amino acid segments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides.
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272. A set of nucleic acid molecules wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the amino acid segments have a common property, wherein the common property allows the amino acid segments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein alteration of the reporter signal peptides alters the amino acid segments, wherein the altered form of each amino acid segment can be distinguished from the altered forms of the other amino acid segments.
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273. A set of nucleic acid molecules wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the amino acid segments each comprise an amino acid subsegment, wherein each amino acid subsegment comprises a portion of the protein or peptide of interest and all or a portion of the reporter signal peptide,
wherein the amino acid subsegments have a common property, wherein the common property allows the amino acid subsegments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides.
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274. A set of nucleic acid molecules wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the amino acid segments each comprise an amino acid subsegment, wherein each amino acid subsegment comprises a portion of the protein or peptide of interest and all or a portion of the reporter signal peptide,
wherein the amino acid subsegments have a common property, wherein the common property allows the amino acid subsegments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein alteration of the reporter signal peptides alters the amino acid subsegments, wherein the altered form of each amino acid subsegment can be distinguished from the altered forms of the other amino acid subsegments.
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275. A set of amino acid segments wherein each amino acid segment comprises a reporter signal peptide and a protein or peptide of interest,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides.
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278. A cell comprising a set of nucleic acid molecules wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides.
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279. A set of cells wherein each cell comprises a nucleic acid molecule wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides.
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283. An organism comprising a set of nucleic acid molecules wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides.
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284. A set of organisms each organism comprises a nucleic acid molecule wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides.
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288. A method of detecting expression, the method comprising detecting a target altered reporter signal peptide derived from one or more expression samples, wherein the one or more expression samples collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides, wherein the target altered reporter signal peptide is one of the altered reporter signal peptides, wherein detection of the target altered reporter signal peptide indicates expression of the amino acid segment that comprises the reporter signal peptide from which the target altered reporter signal peptide is derived.
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468. A method of detecting expression, the method comprising detecting a target altered reporter signal peptide derived from one or more expression samples, wherein the one or more expression samples collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides, wherein the target altered reporter signal peptide is one of the altered reporter signal peptides, wherein detection of the target altered reporter signal peptide indicates expression of the nucleotide segment encoding the amino acid segment that comprises the reporter signal peptide from which the target altered reporter signal peptide is derived.
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474. A method of detecting expression, the method comprising detecting a target altered amino acid segment derived from one or more expression samples, wherein the one or more expression samples collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest,
wherein the amino acid segments have a common property, wherein the common property allows the amino acid segments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein alteration of the reporter signal peptides alters the amino acid segments, wherein the altered form of each amino acid segment can be distinguished from the altered forms of the other amino acid segments, wherein the target altered amino acid segment is one of the altered amino acid segments, wherein detection of the target altered amino acid segment indicates expression of the amino acid segment from which the target altered amino acid segment is derived.
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475. A method of detecting expression, the method comprising detecting an altered amino acid subsegment derived from one or more expression samples,
wherein the one or more expression samples collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the amino acid segments each comprise an amino acid subsegment, wherein each amino acid subsegment comprises a portion of the protein or peptide of interest and all or a portion of the reporter signal peptide, wherein the amino acid subsegments have a common property, wherein the common property allows the amino acid subsegments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein alteration of the reporter signal peptides alters the amino acid subsegments, wherein the altered form of each amino acid subsegment can be distinguished from the altered forms of the other amino acid subsegments, wherein the target altered amino acid subsegment is one of the altered amino acid subsegments, wherein detection of the target altered amino acid subsegment indicates expression of the amino acid segment from which the target altered amino acid subsegment is derived.
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476. A method of detecting cells, the method comprising
detecting a target altered reporter signal peptide derived from one or more cells, wherein the one or more cells collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides, wherein the target altered reporter signal peptide is one of the altered reporter signal peptides, wherein detection of the target altered reporter signal peptide indicates the presence of the cell from which the target altered reporter signal peptide is derived.
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485. A method of detecting cell samples, the method comprising detecting a target altered reporter signal peptide derived from one or more cell samples,
wherein the one or more cell samples collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides, wherein the target altered reporter signal peptide is one of the altered reporter signal peptides, wherein detection of the target altered reporter signal peptide indicates the presence of the cell sample from which the target altered reporter signal peptide is derived.
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489. A method of detecting cells, the method comprising detecting a target altered reporter signal peptide derived from one or more cells,
wherein the one or more cells collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides, wherein the target altered reporter signal peptide is one of the altered reporter signal peptides, wherein detection of the target altered reporter signal peptide indicates the presence of the cell from which the target altered reporter signal peptide is derived.
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490. A method of detecting cells, the method comprising detecting a target altered amino acid segment derived from one or more cells,
wherein the one or more cells collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the amino acid segments have a common property, wherein the common property allows the amino acid segments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein alteration of the reporter signal peptides alters the amino acid segments, wherein the altered form of each amino acid segment can be distinguished from the altered forms of the other amino acid segments, wherein the target altered amino acid segment is one of the altered amino acid segments, wherein detection of the target altered amino acid segment indicates the presence of the cell from which the target altered amino acid segment is derived.
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491. A method of detecting cells, the method comprising detecting an altered amino acid subsegment derived from one or more cells,
wherein the one or more cells collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the amino acid segments each comprise an amino acid subsegment, wherein each amino acid subsegment comprises a portion of the protein or peptide of interest and all or a portion of the reporter signal peptide, wherein the amino acid subsegments have a common property, wherein the common property allows the amino acid subsegments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein alteration of the reporter signal peptides alters the amino acid subsegments, wherein the altered form of each amino acid subsegment can be distinguished from the altered forms of the other amino acid subsegments, wherein the target altered amino acid subsegment is one of the altered amino acid subsegments, wherein detection of the target altered amino acid subsegment indicates the presence of the cell which the target altered amino acid subsegment is derived.
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492. A method of detecting organisms, the method comprising detecting a target altered reporter signal peptide derived from one or more organisms,
wherein the one or more organisms collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides, wherein the target altered reporter signal peptide is one of the altered reporter signal peptides, wherein detection of the target altered reporter signal peptide indicates the presence of the organism from which the target altered reporter signal peptide is derived.
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501. A method of detecting organisms, the method comprising detecting a target altered reporter signal peptide derived from one or more organisms,
wherein the one or more organisms collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the reporter signal peptides have a common property, wherein the common property allows the reporter signal peptides to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein the altered form of each reporter signal peptide can be distinguished from the altered forms of the other reporter signal peptides, wherein the target altered reporter signal peptide is one of the altered reporter signal peptides, wherein detection of the target altered reporter signal peptide indicates the presence of the organism from which the target altered reporter signal peptide is derived.
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502. A method of detecting organisms, the method comprising detecting a target altered amino acid segment derived from one or more organisms,
wherein the one or more organisms collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the amino acid segments have a common property, wherein the common property allows the amino acid segments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein alteration of the reporter signal peptides alters the amino acid segments, wherein the altered form of each amino acid segment can be distinguished from the altered forms of the other amino acid segments, wherein the target altered amino acid segment is one of the altered amino acid segments, wherein detection of the target altered amino acid segment indicates the presence of the organism from which the target altered amino acid segment is derived.
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503. A method of detecting organisms, the method comprising detecting an altered amino acid subsegment derived from one or more organisms,
wherein the one or more organisms collectively comprise a set of nucleic acid molecules, wherein each nucleic acid molecule comprises a nucleotide segment encoding an amino acid segment comprising a reporter signal peptide and a protein or peptide of interest, wherein the amino acid segments each comprise an amino acid subsegment, wherein each amino acid subsegment comprises a portion of the protein or peptide of interest and all or a portion of the reporter signal peptide, wherein the amino acid subsegments have a common property, wherein the common property allows the amino acid subsegments to be distinguished or separated from molecules lacking the common property, wherein the reporter signal peptides are capable of being altered, wherein alteration of the reporter signal peptides alters the amino acid subsegments, wherein the altered form of each amino acid subsegment can be distinguished from the altered forms of the other amino acid subsegments, wherein the target altered amino acid subsegment is one of the altered amino acid subsegments, wherein detection of the target altered amino acid subsegment indicates the presence of the organism from which the target altered amino acid subsegment is derived.
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504. A method comprising:
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(a) associating one of a plurality of reporter signal peptides with one or more analytes in each of a plurality of samples, wherein each reporter signal has a common property, wherein the common property allows each reporter signal to be separated from molecules lacking the common property, (b) separating the analytes contained in each sample, (c) altering the reporter signals, and (d) detecting the altered forms the reporter signals. - View Dependent Claims (505, 506, 507)
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508. A method comprising:
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(a) associating one of a plurality of coding tags with one or more analytes in at least one sample, (b) separating the analytes contained in each sample;
(c) associating the coding tags with one or more reporter molecules, wherein each reporter molecule comprises a reporter signal peptide and a decoding tag, wherein each reporter signal peptide has a common property, wherein the common property allows each reporter signal peptide to be separated from molecules lacking the common property, wherein each decoding tag is specific for one or more of the coding tags, (d) altering the reporter signal peptides, and (e) detecting the altered forms the reporter signal peptides. - View Dependent Claims (509)
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510. A method comprising:
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(a) associating one of a plurality of coding tags with one or more analytes in at least one sample, (b) separating the analytes contained in each sample;
(c) associating the coding tags with one or more reporter signal peptides, wherein each reporter signal peptide has a common property, wherein the common property allows each reporter signal peptide to be separated from molecules lacking the common property, wherein each reporter signal peptide is specific for one or more of the coding tags, (d) altering the reporter signal peptides, and (e) detecting the altered forms the reporter signal peptides. - View Dependent Claims (511)
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512. A method comprising:
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(a) associating one of a plurality of reporter signal peptides with one or more analytes in each of a plurality of samples to form reporter signal/analyte conjugates, wherein each reporter signal/analyte conjugate has a common property, wherein the common property allows each reporter signal/analyte conjugate to be separated from molecules lacking the common property, (b) separating the analytes contained in each sample, wherein separation is not based on the common property of the reporter signal/analyte conjugates, (c) altering the reporter signal peptides thereby altering the reporter signal/analyte conjugates, and (d) detecting the altered forms the reporter signal/analyte conjugates.
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513. A method comprising:
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(a) associating one of a plurality of coding tags with one or more analytes in at least one sample, (b) separating the analytes contained in each sample;
(c) associating the coding tags with one or more reporter molecules, wherein each reporter molecule comprises a reporter signal peptide and a decoding tag, wherein each reporter molecule has a common property, wherein the common property allows each reporter molecule to be separated from molecules lacking the common property, wherein each decoding tag is specific for one or more of the coding tags, (d) altering the reporter signal peptides thereby altering the reporter molecules, and (e) detecting the altered forms the reporter molecules.
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Specification