Expression of transferrin receptor/TFRC protein in bladder cancer cell T24 and its role in inducing iron death in bladder cancer.

Bladder cancer (BC) is a very common malignant tumor in the urinary system. However, the incidence rate, recurrence rate, progression rate and metastasis rate of bladder cancer are still very high, leading to poor long-term prognosis of patients. This study was to investigate the expression of transferrin receptor/TFRC protein in bladder cancer tissue and its role in inducing iron death of T24 human bladder cancer cells. Based on the intersection of 259 FerrDb genes in the iron death database with GSE13507 and GSE13167 data sets, 54 genes related to iron death in bladder cancer were obtained. Analyzing 54 genes, KEGG enrichment analysis showed that the pathways involved were mainly focused on iron death, autophagy, and tumor center carbon metabolism. GO analysis found that the molecular functions mainly gather in ubiquitin like protein ligase binding, ubiquitin protein ligase binding, and antioxidant activity. In the cellular components, it is mainly distributed in pigment granules, melanosomes, and the basal lateral plasma membrane. In biological processes, it is enriched in nutrient level responses, responses to extracellular stimuli, and cellular redox homeostasis. Screen out the top 10 core genes. The 10 core genes are SLC2A1, TFRC, EGFR, KRAS, CAV1, HSPA5, NFE2L2, VEGFA, PIK3CA, and HRAS. Finally, TFRC was selected as the research object. TCGA analysis showed that the expression level in bladder cancer tissue was higher than that in normal tissue, and the difference was statistically significant (P < 0.001). Conclusion (1) TFRC is highly expressed in many kinds of tumors, and it is more highly expressed in bladder cancer than in normal bladder tissue. (2) TFRC has certain diagnostic and prognostic value in bladder cancer. (3) Erastin, an iron death inducer, induced the iron death of T24 human bladder cancer cells, knocked down the expression of TFRC in T24 human bladder cancer cells, and preliminarily verified that silencing TFRC could inhibit the iron death of T24 human bladder cancer cells.

Cytomegalovirus immunoglobulin therapy for CMV retinitis post hematopoietic stem cell transplantation.

PURPOSE: To report a case of cytomegalovirus (CMV) retinitis complicated with ganciclovir-related myelosuppression, which was successfully managed with intravenous (IV) ganciclovir and CMV immunoglobulin (CMVIG) therapy. METHODS: Observational case report. RESULTS: A 51-year-old male with follicular type non-Hodgkin lymphoma post hematopoietic stem cell transplantation (HSCT) developed vision-threatening retinitis. polymerase chain reaction (PCR) of the aqueous humour showed positive for CMV. Despite myelosuppression occurred during IV ganciclovir therapy, the retinitis resolved and intraocular CMV viral load significantly improved after CMVIG therapy. CONCLUSION: Combined IV ganciclovir treatment and CMVIG therapy can significantly improve visual outcome and reduce intraocular CMV viral load in vision-threatening CMV retinitis.

Spontaneous Closure of Cyclodialysis Cleft in a Case of Normal-Tension Glaucoma Post Ab-Interno Trabeculotomy.

A cyclodialysis cleft (CDC) is the detachment of longitudinal ciliary muscle from scleral spur, causing an unusual communication between anterior chamber and suprachoroidal space, resulting in possible hypotony. We report a case of a 63-year-old woman with normal-tension glaucoma (NTG), who developed a shallow anterior chamber with relatively low intraocular pressure (IOP, 6-8 mmHg) after combined ab-interno trabeculotomy and phacoemulsification. Her vision reached good (20/20) with the mild myopic shift. After detecting subtle signs of clinical hypotony, CDC was confirmed and monitored using anterior segment optical coherence tomography. Five months after surgery, she encountered an episode of eye pain, with transient IOP elevation and deepening of the anterior chamber. Spontaneous closure of CDC was suspected and confirmed gonioscopically. To the best of our knowledge, this is the first case to describe the clinical course of spontaneous CDC closure in a patient with NTG after ab-interno trabeculotomy. It is advisable to inform the patient about potential IOP spike after spontaneous closure once CDC is diagnosed.

RAGE mediates airway inflammation via the HDAC1 pathway in a toluene diisocyanate-induced murine asthma model.

BACKGROUND: Exposure to toluene diisocyanate (TDI) is a significant pathogenic factor for asthma. We previously reported that the receptor for advanced glycation end products (RAGE) plays a key role in TDI-induced asthma. Histone deacetylase (HDAC) has been reported to be important in asthmatic pathogenesis. However, its effect on TDI-induced asthma is not known. The aim of this study was to determine the role of RAGE and HDAC in regulating airway inflammation using a TDI-induced murine asthma model. METHODS: BALB/c mice were sensitized and challenged with TDI to establish an asthma model. FPS-ZM1 (RAGE inhibitor), JNJ-26482585 and romidepsin (HDAC inhibitors) were administered intraperitoneally before each challenge. In vitro, the human bronchial epithelial cell line 16HBE was stimulated with TDI-human serum albumin (TDI-HSA). RAGE knockdown cells were constructed and evaluated, and MK2006 (AKT inhibitor) was also used in the experiments. RESULTS: In TDI-induced asthmatic mice, the expression of RAGE, HDAC1, and p-AKT/t-AKT was upregulated, and these expressions were attenuated by FPS-ZM1. Airway reactivity, Th2 cytokine levels in lymph supernatant, IgE, airway inflammation, and goblet cell metaplasia were significantly increased in the TDI-induced asthmatic mice. These increases were suppressed by JNJ-26482585 and romidepsin. In addition, JNJ-26482585 and romidepsin ameliorated the redistribution of E-cadherin and ß-catenin in TDI-induced asthma. In TDI-HSA-stimulated 16HBE cells, knockdown of RAGE attenuated the upregulation of HDAC1 and phospho-AKT (p-AKT). Treatment with the AKT inhibitor MK2006 suppressed TDI-induced HDAC1 expression. CONCLUSIONS: These findings indicate that RAGE modulates HDAC1 expression via the PI3K/AKT pathway, and that inhibition of HDAC prevents TDI-induced airway inflammation.

Comprehensive analysis of the lncRNA-miRNA-mRNA regulatory network for bladder cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) are essential regulators for various human cancers. However, these lncRNAs need to be further classified for cancer. In the present study, we identified novel competing endogenous RNA (ceRNA) network for bladder cancer (BC) and explored the gene functions of the ceRNA regulatory network. METHODS: Differential gene expression analysis were performed on The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) datasets to identify differentially expressed messenger RNAs (mRNAs), lncRNAs, and microRNAs (miRNAs). Based on the competing endogenous RNA (ceRNA) hypothesis, a lncRNA-miRNA-mRNA network was constructed using the StarBase database and visualization by Cytoscape software. Functional enrichment analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed via R package ClusterProfiler. The protein-protein interaction network was constructed by STRING database and visualization by Cytoscape. Finally, we used CIBERSORT and the TIMER database to analyze the immune infiltrations for BC. RESULTS: The regulatory network was constructed via TCGA BLCA cohort. The differential expressions of lncRNA, miRNA, and mRNA were 186, 200, and 2,661, respectively. There were 106 lncRNA, miRNA, and mRNA included in the ceRNA network. In this network, Calcium Voltage-gated Channel Auxiliary Subunit Alpha2delta1 (CACNA2D1, P<0.001), domain containing engulfment adaptor1 (GULP1, P=0.001), latent transforming growth factor beta binding protein 1 (LTBP1, P=0.006), myosin light chain kinase (MYLK, P=0.001), serpin family E member 2 (SERPINE2, P=0.002), spectrin beta non-erythrocytic 2 (SPTBN2, P=0.047), and hsa-miR-590-3p (P<0.001) significantly affected the prognosis of BC patients. Functional enrichment analyses showed that the biological functions included negative regulation of protein phosphorylation, cell morphogenesis, and sensory organ morphogenesis. Important cancer pathways of KEGG included parathyroid hormone synthesis secretion action, the notch signaling pathway, MAPK signaling pathway, the Rap1 signaling pathway, signaling pathways regulating the pluripotency of stem cells, and the transforming growth factor-ß signaling pathway. Our findings demonstrated that the ceRNA network has important biological functions and a significant influence on the prognosis of BC. CONCLUSIONS: The lncRNA-miRNA-mRNA network constructed in the present study could provide useful insight into the underlying tumorigenesis of BC, and can determine new molecular biomarkers for the diagnosis and therapeutical treatment of BC.

The immune-related gene CD52 is a favorable biomarker for breast cancer prognosis.

BACKGROUND: An increasing number of studies have demonstrated a role for the tumor microenvironment in tumorigenesis, disease progression, and therapeutic response. This present study aimed to screen the significant immune-related genes and their possible role in the prognosis of breast cancer (BRCA). METHODS: The transcriptome data and clinical data of breast cancer were collected from The Cancer Genome Atlas (TCGA), and the immune scores and stromal scores were calculated by ESTIMATE algorithm. The differentially expressed genes were screened base on immune and stromal scores (high score vs. low score), than the intersected genes were used for subsequent functional enrichment analysis and protein-protein interaction (PPI) analysis. Furthermore, the key gene was identified by the intersection of the hub genes of PPI network and the prognostic genes of breast cancer. Finally, we explored the infiltration of immune cells of BRCA base on the CIBERSORT algorithm, and analysis the relationship between key gene and immune cells. RESULTS: High levels of CD52 expression were detected in the early stages of breast cancer and were associated with favorable prognosis. Overexpression of CD52 led to higher infiltrations of M1 macrophages, monocytes, T follicular helper cells, and resting memory CD4 T cells. Downregulation of CD52 resulted in high infiltrations of M2 macrophages. Therefore, high expression of CD52 may negatively regulate the infiltration of M2 macrophages but accelerate the infiltration of anti-cancer immune cells, and thus, high expression of CD52 may have a protective effect in breast cancer patients. CONCLUSIONS: CD52 can increase the infiltration of anti-cancer immune cells but inhibit the infiltration of M2 macrophages, thereby improving the prognosis of breast cancer patients.

A functional variant rs1464938 in the promoter of fibroblast growth factor 12 is associated with an increased risk of bladder transitional cell carcinoma.

Increasing evidence shows that inflammation plays critical roles in the tumorigenesis of bladder cancer. Fibroblast growth factor 12 (FGF12), a kind of inflammatory cytokine, is located in the region of 3q28 that has been demonstrated to be a bladder cancer risk locus by genome wide association study (GWAS). In this study, we aimed to investigate the association of GWAS signal rs710521 and rs884309 and rs1464938 in the promoter of FGF12 with the risk of bladder transitional cell carcinoma (TCC). The polymorphisms were analyzed by using a Taqman assay in 331 TCC patients and 516 age-, gender-, and ethnicity-matched controls. The expression levels of FGF12 mRNA were examined in TCC and non-cancerous normal tissues by using quantitative real-time PCR and the luciferase activity was determined by using the Dual-Luciferase Assay System. The rs1464938 AA genotype and A allele were associated with a significantly increased risk of TCC (AA vs. GG: adjusted OR = 2.54, 95% CI, 1.49-4.35, P < 0.001; AA vs. AG/GG: adjusted OR = 2.25, 95% CI, 1.36-3.71, P = 0.002; A vs. G: adjusted OR = 1.44, 95% CI, 1.15-1.80, P = 0.001, respectively). Haplotype analysis showed that rs884309G- rs1464938A haplotype was associated with an increased risk of TCC (OR = 1.61, 95% CI, 1.23-2.11, P = 0.001). Functional analysis showed that the rs1464938 AG/AA genotypes exhibited higher levels of FGF12 mRNA in TCC tissues and the rs1464938 A allele enhanced FGF12 promoter activity (P < 0.05). These findings suggest that the rs1464938 A allele at the 3q28 locus contribute to the development of TCC by regulating FGF12 expression levels.

[Lung sounds can be used as an indicator for assessing severity of chronic obstructive pulmonary disease at the initial diagnosis].

OBJECTIVE: To assess the value of pulmonary auscultation for evaluating the severity of chronic obstructive pulmonary disease (COPD) at the initial diagnosis. METHODS: The patients with newly diagnosed COPD in our hospital between May, 2016 and May, 2019 were enrolled in this study. According to the findings of pulmonary auscultation, the lung sounds were classified into 5 groups: normal breathing sounds, weakened breathing sounds, weakened breathing sounds with wheezing, obviously weakened breathing sounds, and obviously weakened breathing sounds with wheezing. The pulmonary function of the patients was graded according to GOLD guidelines, and the differential diagnosis of COPD from asthmatic asthma COPD overlap (ACO) was made based on the GOLD guidelines and the European Respiratory Criteria. RESULTS: A total of 1046 newly diagnosed COPD patients were enrolled, including 949 male and 97 female patients with a mean age of 62.6± 8.71. According to the GOLD criteria, 88.1% of the patients were identified to have moderate or above COPD, 50.0% to have severe or above COPD; a further diagnosis of ACO was made in 347 (33.2%) of the patients. ANOVA analysis showed significant differences in disease course, FEV1, FEV1%, FEV1/FVC, FVC, FVC% and mMRC among the 5 auscultation groups (P < 0.001), but FENO did not differ significantly among them (P=0.097). The percentage of patients with wheezing in auscultation was significantly greater in ACO group than in COPD group (P < 0.001). Spearman correlation analysis showed that lung sounds was significantly correlated with disease severity, FEV1, FEV1%, FVC and FVC% of the patients (P < 0.001); Multiple linear regression analysis showed that a longer disease course, a history of smoking and lung sounds were all associated with poorer lung functions and a greater disease severity. CONCLUSIONS: Lung sounds can be used as an indicator for assessing the severity of COPD at the initial diagnosis.

Prediction of clinical response to omalizumab in moderate-to-severe asthma patients using the change in total serum IgE level.

BACKGROUND: Omalizumab (OMA) is an effective anti-immunoglobulin E (IgE) treatment for moderate-to-severe asthma. However, predicting an individual's response is difficult. Monitoring change of total serum IgE may be useful for predicting the response to OMA. The purpose of this study was to determine if measuring the change in total IgE level could predict the response to OMA in patients with moderate-to-severe asthma. METHODS: This study included 25 patients (11 females and 14 males; mean age =46.1 years; mean pre-bronchodilator FEV1% =67.8%) with moderate-to-severe asthma. All patients were treated with OMA, and total IgE serum concentrations were measured at baseline before treatment (median baseline total serum IgE =210 IU/mL) and at 4 weeks after beginning treatment. Patients were divided into responders (i.e., excellent or good response) and non-responders (i.e., moderate or poor response) using the global treatment effectiveness (GETE) response method after 16 weeks of treatment. The characteristics of responders and non-responders were compared, and receiver operating characteristic (ROC) curve analysis was used to determine the ability of change in IgE level to predict treatment response. RESULTS: There were 20 responders (80%) and 5 non-responders (20%), and responders demonstrated better improvements of asthma control test (ACT) and asthma control questionnaire (ACQ) scores, and reduction of oral corticosteroid use as compared with non-responders. Twenty-one patients had a total serum IgE 4-week-to-baseline ratio ≥2, and 20 of the patients responded to OMA. The area under the ROC curve (AUC) for baseline IgE level for predicting treatment response was 0.53 (95% CI: 0.18-0.88), and that of the week 4 IgE level was 0.69 (95% CI: 0.42-0.96). Using a cutoff value of 2, the 4-week: baseline IgE ratio achieved the highest AUC of 0.87 (95% CI: 0.64-1), with a sensitivity and specificity of 100% and 80%, respectively, for predicting treatment response. CONCLUSIONS: A total week 4 serum IgE level:baseline level ratio ≥2 can predict the response to OMA in patients with moderate-to-severe asthma after 16 weeks of treatment with high likelihood. Monitoring changes of total IgE level in asthma patients treated OMA may be useful for predicting clinical response.

BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress.

The BH3-only pro-apoptotic protein BIK is regulated by the ubiquitin-proteasome system. However, the mechanism of this regulation and its physiological functions remain elusive. Here, we identify Cul5-ASB11 as the E3 ligase targeting BIK for ubiquitination and degradation. ER stress leads to the activation of ASB11 by XBP1s during the adaptive phase of the unfolded protein response, which stimulates BIK ubiquitination, interaction with p97/VCP, and proteolysis. This mechanism of BIK degradation contributes to ER stress adaptation by promoting cell survival. Conversely, genotoxic agents down-regulate this IRE1α-XBP1s-ASB11 axis and stabilize BIK, which contributes in part to the apoptotic response to DNA damage. We show that blockade of this BIK degradation pathway by an IRE1α inhibitor can stabilize a BIK active mutant and increase its anti-tumor activity. Our study reveals that different cellular stresses regulate BIK ubiquitination by ASB11 in opposing directions, which determines whether or not cells survive, and that blocking BIK degradation has the potential to be used as an anti-cancer strategy.

Fractional exhaled nitric oxide was not associated with the future risk of exacerbations in Chinese asthmatics: a non-interventional 1-year real-world study.

BACKGROUND: Exacerbations are recognized as the most relevant predictor of future risk in asthmatics. We aimed to evaluate the association between asthma exacerbations, fractional exhaled nitric oxide (FENO), spirometry indices, and other potential risk factors in a non-interventional, real-world study performed in Guangzhou, China. METHODS: We performed a prospective 12 months follow-up of Chinese asthmatics. Spirometry and FENO measurements were performed at baseline. Adherence to inhaled corticosteroids (ICS) use was divided into two categories (>80% and <80%). Patients were seen 4 times after the initial baseline visit. RESULTS: A total of 222 patients with asthma (49.1% males) completed the study, of which 51 (23.0%) experienced exacerbations during the study period. Of the patients, 117 (52.7%) had good compliance. We compared lung function indices between the patients with and without exacerbations. There was no difference of forced expiratory volume in 1 s (FEV1) predicted, forced vital capacity (FVC) predicted, and FEVI/FVC (all, P>0.05) between the groups. There was also no significant difference in FENO level between the two groups. Compared to those that had exacerbations, patients without exacerbations had better treatment compliance (P<0.001). Logistic regression analysis identified an association between asthma exacerbations, poor control of symptom [odds ratio (OR) =2.295; 95% confidence interval (CI): 1.130-4.663; P=0.022], and nonadherence to asthma medications (OR =4.718; 95% CI: 2.149-10.359; P<0.001). CONCLUSIONS: Poor adherence rather than baseline FENO and FEV1% predicted was associated with the future risk of exacerbations in Chinese asthmatics in real world.

[Delayed diagnosis is associated with greater disease severity of chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the association of the time of initial diagnosis with the severity of chronic obstructive pulmonary disease (COPD). METHODS: A total of 803 patients who were diagnosed to have COPD for the first time in our hospital between May 2015 to February 2018 were enrolled in this study.The diagnoses of COPD and asthma COPD overlap (ACO) were made according GOLD guidelines and european consensus definition.Lung function of the patients was graded according to the GOLD guidelines. RESULTS: The patients with COPD had a mean age of 61.8±9.9 years,including 726 male and 77 female patients.The course of the patients (defined as the time from symptom onset to the establishment of a diagnosis) was 3(0.5,8) years.Among these patients,85.2% had a moderate disease severity (FEV1%<80%),and 48.3% had severe or very severe conditions (FEV1%<50%);47.0% of them were positive for bronchial dilation test.In the overall patients,295(36.7%) were also diagnosed to have ACO,and the mean disease course of ACO[3(1,9) years]was similar to that of COPD[3(0.5,8) years](P>0.05).A significant correlation was found between the disease course and the lung function of the patients.Multiple linear regression analysis showed that an older age and a longer disease course were associated with poorer lung functions and a greater disease severity. CONCLUSIONS: The delay of the initial diagnosis is significantly related to the severity of COPD.

Glaucomatocyclitic Crises May Occur in Patients with Narrow or Closed Angles.

PURPOSE: To report cases of glaucomatocyclitic crises and discuss the possibility of occurrence in patients with narrow or closed angles. BACKGROUND: The prevalence of angle closure is much higher among Asians than among the Western population. Currently, there is no evidence for a direct relationship between the etiology and angle structure. DESIGN: A retrospective and observational case series. METHODS: We retrospectively collected data from nine adult patients (three males and six females) who were diagnosed with a glaucomatocyclitic crisis and a shallow anterior chamber over a 21-year period, from 1995 to 2016, at the Kaohsiung Medical University Hospital. A narrow angle was defined as a grade less than the Shaffer system grade II. Ophthalmic examinations, including anterior segment biomicroscopy, direct ophthalmoscopy, intraocular pressure measurements, anterior chamber reaction, visual field tests, and the grade of the anterior chamber angle according to the Shaffer system, were reviewed. RESULTS: These patients experienced at least one typical unilateral ocular hypertensive episode that fulfilled the criteria of a glaucomatocyclitic crisis without the angle feature. All patients had gonioscopically narrow or closed angles with or without peripheral anterior synechiae. CONCLUSIONS: The coexistence of narrow or closed angles and a glaucomatocyclitic crisis is possible, especially in patients of Asian descent. In patients with shallow anterior chambers, a glaucomatocyclitic crisis may be a cause of acute glaucoma episodes.

A Functional rs353293 Polymorphism in the Promoter of miR-143/145 Is Associated with a Reduced Risk of Bladder Cancer.

BACKGROUND AND OBJECTIVES: MicroRNA (miR)-143/145, known as tumor suppressors, can promote cell apoptosis and differentiation, and suppress cell proliferation, invasion and migration. We performed a case-control study to investigate the association of rs353293 in the promoter region of miR-143/145 with bladder cancer risk. METHODS: In total, 869 subjects including 333 cases and 536 controls were enrolled in this study, and the rs353293 polymorphism was genotyped by using a Taqman assay. The promoter activity was measured by the Dual-Luciferase Assay System. RESULTS: We calculated an adjusted odds ratio of 0.64 for the presence of either AA/AG genotypes (95% CI 0.46-0.90) and 0.64 (95% CI 0.47-0.87) for carrying at least one A allele in bladder cancer. Stratified analyses showed that the AA/AG genotypes and the A allele were less prevalent in patients with low grade tumors, compared to those harboring higher grade bladder cancers (adjusted OR = 0.53, 95% CI, 0.30-0.94, P = 0.03 and adjusted OR = 0.54, 95% CI, 0.32-0.92, P = 0.02, respectively). In vitro luciferase reporter analysis showed that rs353293A allele had a lower activity compared with the rs353293G allele (P < 0.001). CONCLUSION: These findings suggest that the functional rs353293 polymorphism may be a useful biomarker to predict the risk of bladder cancer.

Integrating data clustering and visualization for the analysis of 3D gene expression data.

The recent development of methods for extracting precise measurements of spatial gene expression patterns from three-dimensional (3D) image data opens the way for new analyses of the complex gene regulatory networks controlling animal development. We present an integrated visualization and analysis framework that supports user-guided data clustering to aid exploration of these new complex data sets. The interplay of data visualization and clustering-based data classification leads to improved visualization and enables a more detailed analysis than previously possible. We discuss 1) the integration of data clustering and visualization into one framework, 2) the application of data clustering to 3D gene expression data, 3) the evaluation of the number of clusters k in the context of 3D gene expression clustering, and 4) the improvement of overall analysis quality via dedicated postprocessing of clustering results based on visualization. We discuss the use of this framework to objectively define spatial pattern boundaries and temporal profiles of genes and to analyze how mRNA patterns are controlled by their regulatory transcription factors.

Coupling visualization and data analysis for knowledge discovery from multi-dimensional scientific data.

Knowledge discovery from large and complex scientific data is a challenging task. With the ability to measure and simulate more processes at increasingly finer spatial and temporal scales, the growing number of data dimensions and data objects presents tremendous challenges for effective data analysis and data exploration methods and tools. The combination and close integration of methods from scientific visualization, information visualization, automated data analysis, and other enabling technologies -such as efficient data management- supports knowledge discovery from multi-dimensional scientific data. This paper surveys two distinct applications in developmental biology and accelerator physics, illustrating the effectiveness of the described approach.

Visual exploration of three-dimensional gene expression using physical views and linked abstract views.

During animal development, complex patterns of gene expression provide positional information within the embryo. To better understand the underlying gene regulatory networks, the Berkeley Drosophila Transcription Network Project (BDTNP) has developed methods that support quantitative computational analysis of three-dimensional (3D) gene expression in early Drosophila embryos at cellular resolution. We introduce PointCloudXplore (PCX), an interactive visualization tool that supports visual exploration of relationships between different genes' expression using a combination of established visualization techniques. Two aspects of gene expression are of particular interest: 1) gene expression patterns defined by the spatial locations of cells expressing a gene and 2) relationships between the expression levels of multiple genes. PCX provides users with two corresponding classes of data views: 1) Physical Views based on the spatial relationships of cells in the embryo and 2) Abstract Views that discard spatial information and plot expression levels of multiple genes with respect to each other. Cell Selectors highlight data associated with subsets of embryo cells within a View. Using linking, these selected cells can be viewed in multiple representations. We describe PCX as a 3D gene expression visualization tool and provide examples of how it has been used by BDTNP biologists to generate new hypotheses.

A quantitative spatiotemporal atlas of gene expression in the Drosophila blastoderm.

To fully understand animal transcription networks, it is essential to accurately measure the spatial and temporal expression patterns of transcription factors and their targets. We describe a registration technique that takes image-based data from hundreds of Drosophila blastoderm embryos, each costained for a reference gene and one of a set of genes of interest, and builds a model VirtualEmbryo. This model captures in a common framework the average expression patterns for many genes in spite of significant variation in morphology and expression between individual embryos. We establish the method's accuracy by showing that relationships between a pair of genes' expression inferred from the model are nearly identical to those measured in embryos costained for the pair. We present a VirtualEmbryo containing data for 95 genes at six time cohorts. We show that known gene-regulatory interactions can be automatically recovered from this data set and predict hundreds of new interactions.