Abstract: In aspects, a method includes: dividing a sample including a mixture of polypeptides into at least two factions that include a starting fraction and at least one other fraction; contacting polypeptides in each of the other fraction(s) with at least one agent for cleavage of the polypeptides, to provide at least one fragmented fraction; analyzing polypeptides in the starting fraction and polypeptides in the fragmented fraction(s) to provide starting sequences for the starting fraction and fragment sequences for the fragmented fraction(s); grouping the starting sequences and the fragment sequences into at least one cluster, where each of the cluster(s) include at least one starting sequence and at least one fragment sequence; and for each cluster, generating a computed sequence, based on values in the at least one starting sequence and values in the at least one fragment sequence of the respective cluster, for a polypeptide in the sample.