Bayesian hierarchical modeling for signaling pathway inference from single cell interventional data

Recent technological advances have made it possible to simultaneously measure multiple protein activities at the single cell level. With such data collected under different stimulatory or inhibitory conditions, it is possible to infer the causal relationships among proteins from single cell interventional data. In this article we propose a Bayesian hierarchical modeling framework to infer the signaling pathway based on the posterior distributions of parameters in the model. Under this framework, we consider network sparsity and model the existence of an association between two proteins both at the overall level across all experiments and at each individual experimental level. This allows us to infer the pairs of proteins that are associated with each other and their causal relationships. We also explicitly consider both intrinsic noise and measurement error. Markov chain Monte Carlo is implemented for statistical inference. We demonstrate that this hierarchical modeling can effectively pool information from different interventional experiments through simulation studies and real data analysis.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS425 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Blood Transcriptomics and Metabolomics for Mersonalized Medicine

Molecular analysis of blood samples is pivotal to clinical diagnosis and has been intensively investigated since the rise of systems biology. Recent developments have opened new opportunities to utilize transcriptomics and metabolomics for personalized and precision medicine. Efforts from human immunology have infused into this area exquisite characterizations of subpopulations of blood cells. It is now possible to infer from blood transcriptomics, with fine accuracy, the contribution of immune activation and of cell subpopulations. In parallel, high-resolution mass spectrometry has brought revolutionary analytical capability, detecting N10,000 metabolites, together with environmental exposure, dietary intake, microbial activity, and pharmaceutical drugs. Thus, the re-examination of blood chemicals by metabolomics is in order. Transcriptomics and metabolomics can be integrated to provide a more comprehensive understanding of the human biological states. We will review these new data and methods and discuss how they can contribute to personalized medicine

Number of Triangulations of a M\"obius Strip

Consider a M\"obius strip with $n$ chosen points on its edge. A triangulation is a maximal collection of arcs among these points and cuts the strip into triangles. In this paper, we proved the number of all triangulations that one can obtain from a M\"obius strip with $n$ chosen points on its edge is given by $4^{n-1}+\binom{2n-2}{n-1}$, then we made the connection with the number of clusters in the quasi-cluster algebra arising from the M\"obius strip

Glycogen synthase kinase-3β inhibition induces nuclear factor-κB-mediated apoptosis in pediatric acute lymphocyte leukemia cells

<p>Abstract</p> <p>Background</p> <p>Molecular therapies that target genetic abnormalities in leukemic cells and their affected signaling pathways have been emerging in pediatric acute lymphoblastic leukemia (ALL). Glycogen synthase kinase-3β (GSK-3β) has recently been found to positively regulate the activity of nuclear factor-κB (NF-κB). Here, we investigated the relationship between GSK-3β inhibition and NF-κB in apoptosis of pediatric primary leukemia cells obtained from 39 newly diagnosed ALL children in China.</p> <p>Methods</p> <p>Bone marrow mononuclear cells (BMMC) were isolated by density gradient centrifugation from the heparinized aspirates of children with ALL. We used immunofluorescence staining to detect nuclear GSK-3β in these cells. After treatment with chemically distinct GSK-3β inhibitors in vitro, NF-κB transcriptional activity was identified by means of western blotting and electrophoretic mobility shift assay (EMSA). NF-κB-mediated apoptosis was detected by Annexin V-PE/7-AAD double-staining flow cytometry. The expression level of the <it>survivin </it>gene was detected by reverse-transcriptase polymerase chain reaction (RT-PCR).</p> <p>Results</p> <p>GSK-3β significantly accumulates in the nuclei of ALL cells than in the nuclei of control cells. Cell death induced by GSK-3β inhibition in ALL cells was mediated by a downregulation of NF-κB p65 transcriptional activity. GSK-3β inhibition significantly decreased the expression of the NF-κB target gene <it>survivin</it>.</p> <p>Conclusions</p> <p>These results indicate that inhibition of GSK-3β downregulates the NF-κB activation pathway, leading to suppression of the expression of an NF-κB-regulated gene and promotion of apoptosis in ALL cells in vitro. Furthermore, our findings suggest that GSK-3β or NF-κB is a potential therapeutic target in the treatment of pediatric ALL.</p

Association Between Melanoma And Glioma: An Observaitonal Study In A Random Sample Of The Taiwanese Populaiton

Background: In a previous study, it was shown that melanoma patients have a greater incidence of glioma as compared to the general population in United States. Because glioma and melanoma do not have common environmental risk factors, this observation suggests a common genetic predisposition shared by glioma and melanoma that maybe used to lead future research of the specific genes and drug targets for both malignancies. However, this observation has to be confirmed in other populations. The aim of this study was to investigate the association between melanoma and glioma in Taiwanese population. Methods: We used claim data of Taiwan’s National Health Insurance Research Database (NHIRD) from year 1998 to 2010. The study population included 1,000,000 randomly selected men and women ages 20 and older from the NHIRD database. Glioma was defined by ICD-9-CM codes 191, 192.0-192.3, 192.8, 192.9, 225 and 237.5. Melanoma was defined by ICD-9-CM codes 172, 173, 190.0, 190.9, 192.1, 216.X (X=0, 3-7, 9), 224, 223.2, 235.1, 235.2, 237.6, 238.2, 238.3, 238.8. We excluded participants under ages 20 at 1998 and unknown gender (n=324,879). Cox\u27s proportional hazard regression analysis was conducted to estimate the association between the history of melanoma on glioma risk. Main results: The hazard ratio of developing glioma was significantly higher in patients with melanoma than in those without melanoma (hazard ratio (HR) = 6.18; 95% confidence interval (CI) = 5.57-6.85). The hazard ratio for developing glioma was lower in male patients than in female patients, with the hazard ratio of 0.77 (95% CI = 0.71-0.84), adjusted for melanoma and age. The hazard ratio increased with age peaking at age group age from 60 to 69 and decrease after 70 years and older. Conclusion: The present study showed that Taiwanese patients with melanoma are at a higher risk of developing glioma. The exact underlying etiologies require further investigation