RESUMEN
SUMMARY: Visium HD by 10X Genomics is the first commercially available platform capable of capturing full scale transcriptomic data paired with a reference morphology image from archived FFPE blocks at sub-cellular resolution. However, aggregation of capture regions to single cells poses challenges. Bin2cell reconstructs cells from the highest resolution data (2 µm bins) by leveraging morphology image segmentation and gene expression information. It is compatible with established Python single cell and spatial transcriptomics software, and operates efficiently in a matter of minutes without requiring a GPU. We demonstrate improvements in downstream analysis when using the reconstructed cells over default 8 µm bins on mouse brain and human colorectal cancer data. AVAILABILITY AND IMPLEMENTATION: Bin2cell is available at https://github.com/Teichlab/bin2cell, along with documentation and usage examples, and can be installed from pip. Probe design functionality is available at https://github.com/Teichlab/gene2probe.
Asunto(s)
Programas Informáticos , Ratones , Animales , Humanos , Encéfalo/metabolismo , Encéfalo/citología , Análisis de la Célula Individual/métodos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Transcriptoma , Perfilación de la Expresión Génica/métodos , Genómica/métodos , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Forty years ago, the first General Purpose Raster Graphics Processor made the transition from research project to commercial product. This is the story of the creation of a new graphics system and the startup company that produced it in the early days of raster computer graphics.
RESUMEN
If immunized with an antigen of interest, transgenic mice with large portions of unrearranged human immunoglobulin loci can produce fully human antigen-specific antibodies; several such antibodies are in clinical use. However, technical limitations inherent to conventional transgenic technology and sequence divergence between the human and mouse immunoglobulin constant regions limit the utility of these mice. Here, using repetitive cycles of genome engineering in embryonic stem cells, we have inserted the entire human immunoglobulin variable-gene repertoire (2.7 Mb) into the mouse genome, leaving the mouse constant regions intact. These transgenic mice are viable and fertile, with an immune system resembling that of wild-type mice. Antigen immunization results in production of high-affinity antibodies with long human-like complementarity-determining region 3 (CDR3H), broad epitope coverage and strong signatures of somatic hypermutation. These mice provide a robust system for the discovery of therapeutic human monoclonal antibodies; as a surrogate readout of the human antibody response, they may also aid vaccine design efforts.