regulatory pathway analysis by high-throughput in situ hybridization高通量原位杂交的监管途径分析.pdfVIP

Regulatory Pathway Analysis by High-Throughput In Situ Hybridization 1,2 3 1 1 1 1 4 Axel Visel , James Carson , Judit Oldekamp , Marei Warnecke , Vladimira Jakubcakova , Xunlei Zhou , Chad A. Shaw , 1 1* Gonzalo Alvarez-Bolado , Gregor Eichele 1 Department of Genes and Behavior, Max Planck Institute of Biophysical Chemistry, Goettingen, Germany, 2 Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America, 3 Biological Monitoring and Modeling Department, Pacific Northwest National Laboratory, Richland, Washington, United States of America, 4 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America Automated in situ hybridization enables the construction of comprehensive atlases of gene expression patterns in mammals. Such atlases can become Web-searchable digital expression maps of individual genes and thus offer an entryway to elucidate genetic interactions and signaling pathways. Towards this end, an atlas housing ;1,000 spatial gene expression patterns of the midgestation mouse embryo was generated. Patterns were textually annotated using a controlled vocabulary comprising .90 anatomical features. Hierarchical clustering of annotations was carried out using distance scores calculated from the similarity between pairs of patterns across all anatomical structures. This process ordered hundreds of complex expression patterns into a matrix that reflects the embryonic architecture and the relatedness of patterns of expression. Clustering yielded 12 distinct groups of expression patterns. Because of the similarity of expression patterns within a group, members of each group may be components of regulator