METHODS OF SELECTING BINDING REAGENTS
Methods and systems are provided herein for selecting an affinity reagent which binds a desired peptide epitope in a plurality of sequence contexts. The method relies on obtaining a peptide library, each peptide having the sequence αXβ, wherein X is the desired peptide epitope, wherein each of α and β comprise an amino acid, using the peptide library to select an affinity reagent.
1 .- 112 . (canceled)
113 . A method of forming a model for an affinity reagent for an epitope X, comprising:
(a) providing the affinity reagent for the epitope X;
(b) obtaining binding measurements between the affinity reagent and a plurality of known protein sequences, wherein the plurality of known protein sequences contains protein sequences containing the epitope X and protein sequences that do not contain the epitope X;
(c) based upon the binding measurements of the affinity reagent to the plurality of known protein sequences, determining the model for the affinity reagent, wherein the model infers a binding probability of the affinity reagent to any protein given a sequence of the protein; and
(d) storing the model for the affinity reagent on a non-transitory storage medium.
114 . The method of claim 113 , wherein the plurality of known protein sequences comprises at least 50 known protein sequences.
115 . The method of claim 114 , wherein the plurality of known protein sequences comprises at least 100 known protein sequences.
116 . The method of claim 113 , wherein the plurality of known protein sequences contains known protein sequences derived from a proteome.
117 . The method of claim 116 , wherein the known protein sequences are derived from the human proteome.
118 . The method of claim 113 , wherein obtaining the binding measurements between the affinity reagent and the plurality of known protein sequences comprises: (i) providing an array comprising a plurality of sites, wherein each site of the plurality of sites contains a known protein sequence of the plurality of known protein sequences, (ii) contacting the affinity reagent to the array, wherein the affinity reagent is fluorescently labeled; and (iii) detecting a fluorescent signal from the affinity reagent at a site of the plurality of sites of the array.
119 . The method of claim 113 , further comprising obtaining binding measurements between the affinity reagent and a plurality of peptides containing the epitope X.
120 . The method of claim 119 , wherein the plurality of peptides containing the epitope X comprises a first set of peptides containing secondary structures and a second set of peptides that do not contain secondary structures.
121 . The method of claim 119 , further comprising updating the model for the affinity reagent based upon the binding measurements between the affinity reagent and the plurality of peptides containing the epitope X.
122 . The method of claim 113 , wherein the model comprises a statistical model.
123 . The method of claim 113 , wherein the model is determined by a machine learning algorithm.
124 . The method of claim 113 , wherein the affinity reagent comprises an antibody or an antibody fragment.
125 . The method of claim 113 , wherein the affinity reagent comprises an aptamer or a peptamer.
126 . The method of claim 113 , wherein the epitope comprises between 2 and 7 amino acids.
127 . The method of claim 126 , wherein the epitope X further comprises a post-translational modification.
128 . The method of claim 113 , wherein the non-transitory storage medium further comprises a model for a second affinity reagent, wherein the binding specificity of the second affinity reagent differs from the affinity reagent for the epitope X.
129 . The method of claim 113 , wherein the plurality of known protein sequences comprises a protein sequence having no known natural origin.
130 . The method of claim 113 , wherein the plurality of known protein sequences comprises a protein sequence having a modified or non-natural amino acid.
131 . A method of forming a model for an affinity reagent for an epitope X, comprising:
(a) providing the affinity reagent for the epitope X, wherein the epitope X contains between 2 and 7 amino acids;
(b) obtaining binding measurements between the affinity reagent and a plurality of known protein sequences, wherein the plurality of known protein sequences contains at least 50 known proteins sequences;
(c) based upon the binding measurements of the affinity reagent to the plurality of known protein sequences, determining the model for the affinity reagent, wherein the model infers a binding probability of the affinity reagent to any protein given a sequence of the protein; and
(d) storing the binding model for the affinity reagent on a non-transitory storage medium.
132 . A non-transitory storage medium comprising a model for an affinity reagent for an epitope X, wherein the epitope X contains between 2 and 7 amino acids, wherein the binding model provides an inferred binding probability for any protein given a sequence of the protein, and wherein the model is based upon binding measurements between the affinity reagent for the epitope X and a plurality of known protein sequences, wherein the plurality of known protein sequences contains protein sequences containing the epitope X and protein sequences that do not contain the epitope X.