TAPINTO: A Novel Algorithm for Tumor-Associated Antigen Prediction Based on Information about Target Overexpression.

Identifying the tumor-associated antigens (TAAs) overexpressed in a subgroup of tumor patients is a substantial challenge for cancer treatment. Although there are several methods based on the concept of differential expression, there is a lack of proper algorithms based on the heterogeneous transcriptome expression for exploring effective TAAs. Here, we propose an algorithm, TAPINTO, to objectively predict overexpressed TAAs whose expression is heterogeneous in cancer patients. This algorithm exploits the dispersion of expression in a subgroup of patients to create 3 quantitative parameters (the specific average expression, frequency, and fold change) for evaluating potential TAAs and has a good performance compared with other approaches. Based on these parameters, TAPINTO successfully identified HER2, a famous therapeutic target, and other potential TAAs (CXCL9, KCNJ3, SQLE, MMP11, and SLC7A2) in breast cancer; moreover, these parameters were dramatically consistent with the trend of clinical outcomes (objective response rate, progression-free survival, and serious adverse effects) of therapeutic antibodies. The ability of TAPINTO to capture heterogeneous expression patterns among patients was further validated in cancer hallmarks, subtypes, and prognosis. This study suggests that this novel method will enable potential TAAs to facilitate the subgroup of patients for diagnosis, prognostication, and therapy to overcome the tumor heterogeneity.