A method of identifying immunologically protective neo-epitopes in a cancer patient, comprising (i) identifying a putative neo-epitope set by a method comprising: sequencing at least a portion of the cancer patient's RNA or DNA in both a healthy tissue and a cancer tissue, to produce a healthy tissue RNA or DNA sequence and a cancer tissue RNA or DNA sequence, comparing the healthy tissue RNA or DNA sequence and the cancer tissue RNA or DNA sequence and identifying differences between the healthy tissue RNA or DNA sequence and the cancer tissue RNA or DNA sequence to produce a difference DNA marker set, analyzing the difference DNA marker set to produce a tumor-specific epitope set, wherein the tumor-specific epitope set comprises one or more tumor-specific epitopes, providing a numerical value called the Differential Agretopic Index for each epitope in the tumor-specific epitope set, wherein the Differential Agretopic Index is calculated by subtracting a score for a normal epitope from a score for the tumor-specific epitope, wherein the score for a normal epitope and the score for the tumor-specific epitope are produced using a predictive algorithm that determines the binding of epitope peptides to MHC molecules, and ranking the tumor-specific epitope set according to the Differential Agretopic Index and selecting a putative neo-epitope set from the tumor-specific epitope set based on the ranking; (ii) determining the conformational stability of at least a portion of each putative neo-epitope in the putative neo-epitope set and its corresponding wild type epitope, bound to an MHC I or MHC II protein; and (iii) selecting from the putative neo-epitope set immunologically protective neo-epitopes, wherein the immunologically protective neo-epitopes have higher conformational stability compared to a corresponding wild type epitope when bound to the MHC I or MHC II protein. (i) identifying a putative neo-epitope set by a method comprising: sequencing at least a portion of the cancer patient's RNA or DNA in both a healthy tissue and a cancer tissue, to produce a healthy tissue RNA or DNA sequence and a cancer tissue RNA or DNA sequence, comparing the healthy tissue RNA or DNA sequence and the cancer tissue RNA or DNA sequence and identifying differences between the healthy tissue RNA or DNA sequence and the cancer tissue RNA or DNA sequence to produce a difference DNA marker set, analyzing the difference DNA marker set to produce a tumor-specific epitope set, wherein the tumor-specific epitope set comprises one or more tumor-specific epitopes, providing a numerical value called the Differential Agretopic Index for each epitope in the tumor-specific epitope set, wherein the Differential Agretopic Index is calculated by subtracting a score for a normal epitope from a score for the tumor-specific epitope, wherein the score for a normal epitope and the score for the tumor-specific epitope are produced using a predictive algorithm that determines the binding of epitope peptides to MHC molecules, and ranking the tumor-specific epitope set according to the Differential Agretopic Index and selecting a putative neo-epitope set from the tumor-specific epitope set based on the ranking; sequencing at least a portion of the cancer patient's RNA or DNA in both a healthy tissue and a cancer tissue, to produce a healthy tissue RNA or DNA sequence and a cancer tissue RNA or DNA sequence, comparing the healthy tissue RNA or DNA sequence and the cancer tissue RNA or DNA sequence and identifying differences between the healthy tissue RNA or DNA sequence and the cancer tissue RNA or DNA sequence to produce a difference DNA marker set, analyzing the difference DNA marker set to produce a tumor-specific epitope set, wherein the tumor-specific epitope set comprises one or more tumor-specific epitopes, providing a numerical value called the Differential Agretopic Index for each epitope in the tumor-specific epitope set, wherein the Differential Agretopic Index is calculated by subtracting a score for a normal epitope from a score for the tumor-specific epitope, wherein the score for a normal epitope and the score for the tumor-specific epitope are produced using a predictive algorithm that determines the binding of epitope peptides to MHC molecules, and ranking the tumor-specific epitope set according to the Differential Agretopic Index and selecting a putative neo-epitope set from the tumor-specific epitope set based on the ranking; (ii) determining the conformational stability of at least a portion of each putative neo-epitope in the putative neo-epitope set and its corresponding wild type epitope, bound to an MHC I or MHC II protein; and (iii) selecting from the putative neo-epitope set immunologically protective neo-epitopes, wherein the immunologically protective neo-epitopes have higher conformational stability compared to a corresponding wild type epitope when bound to the MHC I or MHC II protein.