Compared with other labor-intensive epitope identification methods that rely on identifying critical residues in escape mutants and crystal structures, the method used here gives a direct and panoramic mapping of the antigenic regions of viral proteins recognized by antisera in a facile and high-throughput way. Our approach likely contains an inherent bias for shorter peptides, but nonetheless complements the more classical approaches that favor longer antigenic peptides or full antigenic domains. The scanning of antigenic peptides based on phage, bacterial or yeast surface display methods has been increasingly used in recent years. Our approach presents two advantages. First, technically we adopt an easy-to-implement scheme for generating a controllable size of peptides and our screening typically involves only one round of FACS-based sorting, in contrast to multiple rounds of panning or sorting used in the literature [15, 16, 18] . Although the latter results in many repeat sequences, we argue that much information is lost in the enrichment process. Second and more importantly, since simple alignment of antigenic peptides with the corresponding viral protein yields only limited information [15, 17, 39] , we employ a novel statistical means of summarizing the frequency for each residue appearing in the antigenic peptides at both the primary sequence and structural level, which enables a direct mapping of the antigenic structure of a viral protein. Along this line, it is interesting to note that, using our statistical approach, we reevaluate the highly repeated antigenic peptides identified for the H5N1 HA protein in a recent report [15] . Several major peaks are clearly revealed (Fig. S7) , which should be useful for further characterization of the antigenic peptides for H5N1 HA. (H1N1) influenza vaccine, and a mixture of 9 samples with the highest activity among 110 samples as judged by ELISA. These samples were provided by Dr. Boping Zhou of Shenzhen East Lake Hospital (Shenzhen, China), and written informed consent was obtained from all study participants. All samples were de-identified prior to analysis, and the protocols were approved by the Institutional Review Board (IRB) of Shenzhen East Lake Hospital. All viral strains are closely related.