Regardless of the advent of high-throughput sequencing, microarrays remain central in current biomedical research. Conventional microarray analysis pipelines apply data reduction before the estimation of differential expression, which is likely to render the estimates susceptible to noise from signal summarization and reduce statistical power. We present a probe-level framework, which capitalizes on the high number of concurrent measurements to provide more robust differential expression estimates. The framework naturally extends to various experimental designs and target categories (e.g. transcripts, genes, genomic regions) as well as small sample sizes. Benchmarking in relation to popular microarray and RNA-sequencing data-analysis pipelines indicated high and stable performance on the Microarray Quality Control dataset and in a cell-culture model of hypoxia. Experimental-data-exhibiting long-range epigenetic silencing of gene expression was used to demonstrate the efficacy of detecting differential expression of genomic regions, a level of analysis not embraced by conventional workflows. Finally, we designed and conducted an experiment to identify hypothermia-responsive genes in terms of monotonic time-response. As a novel insight, hypothermia-dependent up-regulation of multiple genes of two major antioxidant pathways was identified and verified by quantitative real-time PCR.
Abstract. Attack tree analysis is used to estimate different parameters of general security threats based on information available for atomic subthreats. We focus on estimating the expected gains of an adversary based on both the cost and likelihood of the subthreats. Such a multi-parameter analysis is considerably more complicated than separate probability or skill level estimation, requiring exponential time in general. However, this paper shows that under reasonable assumptions a completely different type of optimal substructure exists which can be harnessed into a linear-time algorithm for optimal gains estimation. More concretely, we use a decision-theoretic framework in which a rational adversary sequentially considers and performs the available attacks. The assumption of rationality serves as an upper bound as any irrational behavior will just hurt the end result of the adversary himself. We show that if the attacker considers the attacks in a goal-oriented way, his optimal expected gains can be computed in linear time. Our model places the least restrictions on adversarial behavior of all known attack tree models that analyze economic viability of an attack and, as such, provides for the best efficiently computable estimate for the potential reward.
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