Sub-population analysis based on temporal features of high content images

Background: High content screening techniques are increasingly used to understand the regulation and progression of cell motility. The demand of new platforms, coupled with availability of terabytes of data has challenged the traditional technique of identifying cell populations by manual methods and resulted in development of high-dimensional analytical methods. Results: In this paper, we present sub-populations analysis of cells at the tissue level by using dynamic features of the cells. We used active contour without edges for segmentation of cells, which preserves the cell morphology, and autoregressive modeling to model cell trajectories. The sub-populations were obtained by clustering static, dynamic and a combination of both features. We were able to identify three unique sub-populations in combined clustering. Conclusion: We report a novel method to identify sub-populations using kinetic features and demonstrate that these features improve sub-population analysis at the tissue level. These advances will facilitate the application of high content screening data analysis to new and complex biological problems.Computation and Systems Biology Programme of Singapore--Massachusetts Institute of Technology Allianc

Animal Models of Dengue Virus Infection

The development of animal models of dengue virus (DENV) infection and disease has been challenging, as epidemic DENV does not naturally infect non-human species. Non-human primates (NHPs) can sustain viral replication in relevant cell types and develop a robust immune response, but they do not develop overt disease. In contrast, certain immunodeficient mouse models infected with mouse-adapted DENV strains show signs of severe disease similar to the ‘vascular-leak’ syndrome seen in severe dengue in humans. Humanized mouse models can sustain DENV replication and show some signs of disease, but further development is needed to validate the immune response. Classically, immunocompetent mice infected with DENV do not manifest disease or else develop paralysis when inoculated intracranially; however, a new model using high doses of DENV has recently been shown to develop hemorrhagic signs after infection. Overall, each model has its advantages and disadvantages and is differentially suited for studies of dengue pathogenesis and immunopathogenesis and/or pre-clinical testing of antiviral drugs and vaccines

IIS-Mine: A new efficient method for mining frequent itemsets

A new approach to mine all frequent itemsets from a transaction database isproposed. The main features of this paper are as follows: (1) the proposed algorithmperforms database scanning only once to construct a data structure called an invertedindex structure (IIS); (2) the change in the minimum support threshold is not affected bythis structure, and as a result, a rescan of the database is not required; and (3) theproposed mining algorithm, IIS-Mine, uses an efficient property of an extendable itemset,which reduces the recursiveness of mining steps without generating candidate itemsets,allowing frequent itemsets to be found quickly. We have provided definitions, examples,and a theorem, the completeness and correctness of which is shown by mathematicalproof. We present experiments in which the run time, memory consumption and scalabilityare tested in comparison with a frequent-pattern (FP) growth algorithm when theminimum support threshold is varied. Both algorithms are evaluated by applying them tosynthetics and real-world datasets. The experimental results demonstrate that IIS-Mineprovides better performance than FP-growth in terms of run time and space consumptionand is effective when used on dense datasets

Fatal dengue hemorrhagic fever in adults during a dengue epidemic in Singapore.

BACKGROUND: Dengue fever has seen a significant re-emergence in Southeast Asia. Associated with the rise of dengue has been the increase in dengue-associated mortality. To better understand the predictors of mortality, we conducted a review of hospitalized adult dengue infections within our institution. METHODS: This was a retrospective case-control study of dengue-associated deaths at a large tertiary care hospital. RESULTS: In 2004, of 3186 cases of dengue fever (DF)/hemorrhagic dengue fever (DHF) admitted to our institution, there were 130 cases of DHF and seven dengue-associated deaths (case-fatality rate 5.4%). At least three of the seven fatal cases had serological evidence of primary dengue infection. All dengue-mortality cases had rapidly progressive clinical deterioration at an average of day 4 of fever with intensive care admission occurring on a mean of 5.6 days of fever. Adult respiratory distress syndrome, disseminated intravascular coagulopathy, and multi-organ failure were the most common causes of death despite early hospitalization, intravenous fluid, and blood-product support. CONCLUSION: Dengue is associated with severe disease, and deaths do occur despite current supportive management. Fatal DHF/dengue shock syndrome (DSS) does occur in adults and in primary dengue infection. Better early predictors of disease severity and clinical interventions are needed