ABSTRACT
By developing a high-density murine immunophenotyping platform compatible with high-throughput genetic screening, we have established profound contributions of genetics and structure to immune variation (http://www.immunophenotype.org). Specifically, high-throughput phenotyping of 530 unique mouse gene knockouts identified 140 monogenic 'hits', of which most had no previous immunologic association. Furthermore, hits were collectively enriched in genes for which humans show poor tolerance to loss of function. The immunophenotyping platform also exposed dense correlation networks linking immune parameters with each other and with specific physiologic traits. Such linkages limit freedom of movement for individual immune parameters, thereby imposing genetically regulated 'immunologic structures', the integrity of which was associated with immunocompetence. Hence, we provide an expanded genetic resource and structural perspective for understanding and monitoring immune variation in health and disease.
Subject(s)
Enterobacteriaceae Infections/immunology , Genetic Variation/genetics , High-Throughput Screening Assays/methods , Immunophenotyping/methods , Salmonella Infections/immunology , Animals , Citrobacter/immunology , Enterobacteriaceae Infections/microbiology , Female , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Animal , Salmonella/immunology , Salmonella Infections/microbiologyABSTRACT
Groupwise image registration algorithms seek to establish dense correspondences between sets of images. Typically, they involve iteratively improving the registration between each image and an evolving mean. A variety of methods have been proposed, which differ in their choice of objective function, representation of deformation field, and optimization methods. Given the complexity of the task, the final accuracy is significantly affected by the choices made for each component. Here, we present a groupwise registration algorithm which can take advantage of the statistics of both the image intensities and the range of shapes across the group to achieve accurate matching. By testing on large sets of images (in both 2D and 3D), we explore the effects of using different image representations and different statistical shape constraints. We demonstrate that careful choice of such representations can lead to significant improvements in overall performance.