Methods for identifying polypeptides

A method for identifying at least one polypeptide present in a sample comprising a plurality of polypeptides, the method comprising:

• (a) performing an encoding assay using the plurality of polypeptides and a set of binders, wherein each binder of the set of binders is attached to a nucleic acid coding tag that comprises an encoder barcode that comprises identifying information regarding the binder, the encoding assay comprising:
• (i) attaching the plurality of polypeptides or fragments thereof to a solid support, wherein each polypeptide or a fragment thereof is associated with a nucleic acid recording tag, thereby generating a plurality of immobilized polypeptides;
• (ii) contacting the plurality of immobilized polypeptides with binders of the set of binders;
• (iii) following binding of a binder of the set of binders to an immobilized polypeptide of the plurality of immobilized polypeptides, transferring an encoder barcode from a nucleic acid coding tag attached to the binder to a nucleic acid recording tag associated with the immobilized polypeptide;
• and
• (iv) repeating steps (ii)-(iii) at least one time, thereby generating a plurality of extended nucleic acid recording tags associated with the plurality of immobilized polypeptides;
• (b) determining a nucleic acid sequence of each extended nucleic acid recording tag of the plurality of extended nucleic acid recording tags or complements thereof, thereby generating, at one or more processors, a plurality of nucleic acid sequences, wherein each of the plurality of nucleic acid sequences comprises a series of encoder barcode sequences;
• (c) generating, using the one or more processors, a binder identifier string for each nucleic acid sequence of the plurality of nucleic acid sequences based on a corresponding series of encoder barcode sequences, thereby generating a plurality of binder identifier strings corresponding to the plurality of nucleic acid sequences;
• (d) inferring, using one or more processors, an amino acid sequence of a polypeptide of the plurality of polypeptides from binder identifiers of a binder identifier string of the plurality of binder identifier strings based on (i) binding profiles of the binders from the set of binders that correspond to the binder identifiers of the binder identifier string, and (ii) calculated probability scores of an association between one or more binder identifiers of the binder identifier string and one or more amino acid sequences of polypeptides of the plurality of polypeptides;
• and
• (e) determining, using the one or more processors, at least one of:
• (i) at least a partial identity of at least one polypeptide present in the sample, or
• (ii) a quantity of at least one the at least one polypeptide present in the sample, based on the calculated probability scores and the inferred amino acid sequences.