RESUMEN

Cell-cell communication (CCC) is essential to how life forms and functions. However, accurate, high-throughput mapping of how expression of all genes in one cell affects expression of all genes in another cell is made possible only recently through the introduction of spatially resolved transcriptomics (SRT) technologies, especially those that achieve single-cell resolution. Nevertheless, substantial challenges remain to analyze such highly complex data properly. Here, we introduce a multiple-instance learning framework, Spacia, to detect CCCs from data generated by SRTs, by uniquely exploiting their spatial modality. We highlight Spacia's power to overcome fundamental limitations of popular analytical tools for inference of CCCs, including losing single-cell resolution, limited to ligand-receptor relationships and prior interaction databases, high false positive rates and, most importantly, the lack of consideration of the multiple-sender-to-one-receiver paradigm. We evaluated the fitness of Spacia for three commercialized single-cell resolution SRT technologies: MERSCOPE/Vizgen, CosMx/NanoString and Xenium/10x. Overall, Spacia represents a notable step in advancing quantitative theories of cellular communications.

RESUMEN

Cell-cell communication (CCC) is essential to how life forms and functions. However, accurate, high-throughput mapping of how expression of all genes in one cell affects expression of all genes in another cell is made possible only recently, through the introduction of spatially resolved transcriptomics technologies (SRTs), especially those that achieve single cell resolution. However, significant challenges remain to analyze such highly complex data properly. Here, we introduce a Bayesian multi-instance learning framework, spacia, to detect CCCs from data generated by SRTs, by uniquely exploiting their spatial modality. We highlight spacia's power to overcome fundamental limitations of popular analytical tools for inference of CCCs, including losing single-cell resolution, limited to ligand-receptor relationships and prior interaction databases, high false positive rates, and most importantly the lack of consideration of the multiple-sender-to-one-receiver paradigm. We evaluated the fitness of spacia for all three commercialized single cell resolution ST technologies: MERSCOPE/Vizgen, CosMx/Nanostring, and Xenium/10X. Spacia unveiled how endothelial cells, fibroblasts and B cells in the tumor microenvironment contribute to Epithelial-Mesenchymal Transition and lineage plasticity in prostate cancer cells. We deployed spacia in a set of pan-cancer datasets and showed that B cells also participate in PDL1/PD1 signaling in tumors. We demonstrated that a CD8+ T cell/PDL1 effectiveness signature derived from spacia analyses is associated with patient survival and response to immune checkpoint inhibitor treatments in 3,354 patients. We revealed differential spatial interaction patterns between γδ T cells and liver hepatocytes in healthy and cancerous contexts. Overall, spacia represents a notable step in advancing quantitative theories of cellular communications.

RESUMEN

During germination, the availability of sugars, oxygen, or cellular energy fluctuates under dynamic environmental conditions, likely affecting the global RNA profile of rice genes. Most genes that exhibit sugar-regulation in rice embryos under aerobic conditions are responsive to low energy and anaerobic conditions, indicating that sugar regulation is strongly associated with energy and anaerobic signaling. The interference pattern of sugar regulation by either anaerobic or low energy conditions indicates that induction is likely the more prevalent regulatory mechanism than repression for altering the expression of sugar-regulated genes. Among the aerobically sugar-regulated genes, limited genes exhibit sugar regulation under anaerobic conditions, indicating that anaerobic conditions strongly influence sugar regulated gene expression. Anaerobically responsive genes substantially overlap with low energy responsive genes. In particular, the expression levels of anaerobically downregulated genes are consistent with those provoked by low energy conditions, suggesting that anaerobic downregulation results from the prevention of aerobic respiration due to the absence of the final electron acceptor, i.e., molecular oxygen. It has been noted that abscisic acid (ABA) responsive genes are over representative of genes upregulated under low energy conditions, in contrast to downregulated genes. This suggests that either ABA itself or upstream signaling components of the ABA signaling pathway are likely to be involved in the signaling pathways activated by low energy conditions.

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RESUMEN

BACKGROUND: Improvement of additional immunization rate is indicated as an important factor for effective immunization of diseases. In this study, the relationship between retention of mother and child health handbook and additional immunization rate of Japanese encephalitis and tetanus was examined. METHODS: A survey via questionnaire was performed against parents of students of middle schools in Gwangmyeong-si, Gyeonggi-do, and elementary schools in Seoul. Among 350 copies of the questionnaire delivered via post mail, 261 copies were collected and used in the analysis. The questionnaire included general features of subjects and their children, retention of the mother and child health handbook, and recognition of additional immunization of the Japanese encephalitis and tetanus vaccine. RESULTS: It was found that 80.8% of subjects answered affirmative to retaining the mother and child health handbook, and the group retaining the handbook had higher recognition rate of the need for additional immunization than the group that did not, for the Japanese encephalitis vaccine (83.2% vs. 51.2%, P < 0.001) and for the tetanus vaccine (66.5% vs. 31.7%, P < 0.001). Although the group retaining the handbook had a significantly higher additional immunization rate of the tetanus vaccine of 48.6% vs. 17.1% (P = 0.001), the immunization rate of the Japanese encephalitis vaccine did not show a significant difference (P = 0.231). The group recognizing the need for additional immunization of the Japanese encephalitis and tetanus vaccine had a significantly higher additional immunization rate than the counterpart (P < 0.001). CONCLUSION: It was considered that retention of the mother and child health handbook was related to recognition and execution of additional immunizations.