Epithelial and stromal tissues are components of the tumor microenvironment and play a major role in tumor initiation and progression.Distinguishing stroma from epithelial tissues is critically important for spatial c...Epithelial and stromal tissues are components of the tumor microenvironment and play a major role in tumor initiation and progression.Distinguishing stroma from epithelial tissues is critically important for spatial characterization of the tumor microenvironment.Here,we propose BrcaSeg,an image analysis pipeline based on a convolutional neural network(CNN)model to classify epithelial and stromal regions in whole-slide hematoxylin and eosin(H&E)stained histopathological images.The CNN model is trained using well-annotated breast cancer tissue microarrays and validated with images from The Cancer Genome Atlas(TCGA)Program.BrcaSeg achieves a classification accuracy of 91.02%,which outperforms other state-of-the-art methods.Using this model,we generate pixel-level epithelial/stromal tissue maps for 1000 TCGA breast cancer slide images that are paired with gene expression data.We subsequently estimate the epithelial and stromal ratios and perform correlation analysis to model the relationship between gene expression and tissue ratios.Gene Ontology(GO)enrichment analyses of genes that are highly correlated with tissue ratios suggest that the same tissue is associated with similar biological processes in different breast cancer subtypes,whereas each subtype also has its own idiosyncratic biological processes governing the development of these tissues.Taken all together,our approach can lead to new insights in exploring relationships between image-based phenotypes and their underlying genomic events and biological processes for all types of solid tumors.BrcaSeg can be accessed at https://github.com/Serian1992/ImgBio.展开更多
The strategy of using Fe_(3)O_(4) amphiphilic Janus nanoparticles(Fe_(3)O_(4)@AJNPs)bearing b-cyclodextrin(b-CD)and aminopyridine(APD)functionalized polymethyl methacrylate(PGMA)to construct pH-stimuli responsive co-a...The strategy of using Fe_(3)O_(4) amphiphilic Janus nanoparticles(Fe_(3)O_(4)@AJNPs)bearing b-cyclodextrin(b-CD)and aminopyridine(APD)functionalized polymethyl methacrylate(PGMA)to construct pH-stimuli responsive co-assemblies through host-guest interactions between b-CD and APD was proposed.The spherical co-assemblies with an average diameter about 210nm were excellent magnetic responsive and quite stable even up to 2 months in deionized water.The pH-liable capability of these co-assemblies was revealed by disassembly of the formed superstructures with destruction of the built inclusion complexes.The disassembly process was monitored by SEM,TEM,DLS and fluorescent molecules probe.After disassembly of the co-assemblies caused by protonation of nitrogens in APD,hydrophobic PGMA-APD lacking of interactions with the Fe_(3)O_(4)@AJNPs chains was precipitated,and the remained Fe_(3)O_(4)@AJNPs turned to re-assemble to selfassemblies.Besides,the recyclable Fe_(3)O_(4)@APJNs could reassembly with additional PGMA-APD to build co-assemblies with a uniform morphology for several times.These pH-sensitive co-assemblies with high stability,good magnetic responsiveness and cytocompatibility could be used as pH-responsive vehicles within which to encapsulate drugs for subsequent controlled release.展开更多
基金supported by Indiana University Precision Health Initiative to KH and JZthe NSFC-Guangdong Joint Fund of China (Grant No. U1501256) to QFShenzhen Peacock Plan (Grant No. KQTD2016053112051497) to XZ and ND.
文摘Epithelial and stromal tissues are components of the tumor microenvironment and play a major role in tumor initiation and progression.Distinguishing stroma from epithelial tissues is critically important for spatial characterization of the tumor microenvironment.Here,we propose BrcaSeg,an image analysis pipeline based on a convolutional neural network(CNN)model to classify epithelial and stromal regions in whole-slide hematoxylin and eosin(H&E)stained histopathological images.The CNN model is trained using well-annotated breast cancer tissue microarrays and validated with images from The Cancer Genome Atlas(TCGA)Program.BrcaSeg achieves a classification accuracy of 91.02%,which outperforms other state-of-the-art methods.Using this model,we generate pixel-level epithelial/stromal tissue maps for 1000 TCGA breast cancer slide images that are paired with gene expression data.We subsequently estimate the epithelial and stromal ratios and perform correlation analysis to model the relationship between gene expression and tissue ratios.Gene Ontology(GO)enrichment analyses of genes that are highly correlated with tissue ratios suggest that the same tissue is associated with similar biological processes in different breast cancer subtypes,whereas each subtype also has its own idiosyncratic biological processes governing the development of these tissues.Taken all together,our approach can lead to new insights in exploring relationships between image-based phenotypes and their underlying genomic events and biological processes for all types of solid tumors.BrcaSeg can be accessed at https://github.com/Serian1992/ImgBio.
基金supported by the National Natural Science Foundation of China(NSFC,21571134,31771037)the National Key Research and Development Program of China(2016YFC1102701)+1 种基金the Project in the Science and Technology Support Program of Sichuan Province(18ZDYF0823)the Project of Huimin Technology Research and Development of Chengdu(2015-HM01-00379-SF).
文摘The strategy of using Fe_(3)O_(4) amphiphilic Janus nanoparticles(Fe_(3)O_(4)@AJNPs)bearing b-cyclodextrin(b-CD)and aminopyridine(APD)functionalized polymethyl methacrylate(PGMA)to construct pH-stimuli responsive co-assemblies through host-guest interactions between b-CD and APD was proposed.The spherical co-assemblies with an average diameter about 210nm were excellent magnetic responsive and quite stable even up to 2 months in deionized water.The pH-liable capability of these co-assemblies was revealed by disassembly of the formed superstructures with destruction of the built inclusion complexes.The disassembly process was monitored by SEM,TEM,DLS and fluorescent molecules probe.After disassembly of the co-assemblies caused by protonation of nitrogens in APD,hydrophobic PGMA-APD lacking of interactions with the Fe_(3)O_(4)@AJNPs chains was precipitated,and the remained Fe_(3)O_(4)@AJNPs turned to re-assemble to selfassemblies.Besides,the recyclable Fe_(3)O_(4)@APJNs could reassembly with additional PGMA-APD to build co-assemblies with a uniform morphology for several times.These pH-sensitive co-assemblies with high stability,good magnetic responsiveness and cytocompatibility could be used as pH-responsive vehicles within which to encapsulate drugs for subsequent controlled release.