Measuring reproducibility of high-throughput experiments

Reproducibility is essential to reliable scientific discovery in high-throughput experiments. In this work we propose a unified approach to measure the reproducibility of findings identified from replicate experiments and identify putative discoveries using reproducibility. Unlike the usual scalar measures of reproducibility, our approach creates a curve, which quantitatively assesses when the findings are no longer consistent across replicates. Our curve is fitted by a copula mixture model, from which we derive a quantitative reproducibility score, which we call the "irreproducible discovery rate" (IDR) analogous to the FDR. This score can be computed at each set of paired replicate ranks and permits the principled setting of thresholds both for assessing reproducibility and combining replicates. Since our approach permits an arbitrary scale for each replicate, it provides useful descriptive measures in a wide variety of situations to be explored. We study the performance of the algorithm using simulations and give a heuristic analysis of its theoretical properties. We demonstrate the effectiveness of our method in a ChIP-seq experiment.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS466 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Biasing the perception of ambiguous vocal affect: a TMS study on frontal asymmetry

Several sources of evidence point toward a link between asymmetry of prefrontal brain activity and approach–withdrawal tendencies. Here, we tested the causal nature of this link and examined if the categorization of an ambiguous approach- or withdrawal-related vocal signal can be biased by manipulating left and right frontal neural activity. We used voice morphing of affective non-verbal vocalizations to create individually tailored affectively ambiguous stimuli on an Anger–Fear continuum—two emotions that represent extremes on the approach–withdrawal dimension. We tested perception of these stimuli after 10 min of low-frequency repetitive transcranial magnetic stimulation over left or right dorsolateral prefrontal cortex or over the vertex (control), a technique that has transient inhibitory effects on the targeted brain region. As expected, ambiguous stimuli were more likely perceived as expressing Anger (approach) than Fear (withdrawal) after right prefrontal compared with left prefrontal or control stimulation. These results provide the first evidence that the manipulation of asymmetrical activity in prefrontal cortex can change the explicit categorization of ambiguous emotional signals

The perception of emotion in artificial agents

Given recent technological developments in robotics, artificial intelligence and virtual reality, it is perhaps unsurprising that the arrival of emotionally expressive and reactive artificial agents is imminent. However, if such agents are to become integrated into our social milieu, it is imperative to establish an understanding of whether and how humans perceive emotion in artificial agents. In this review, we incorporate recent findings from social robotics, virtual reality, psychology, and neuroscience to examine how people recognize and respond to emotions displayed by artificial agents. First, we review how people perceive emotions expressed by an artificial agent, such as facial and bodily expressions and vocal tone. Second, we evaluate the similarities and differences in the consequences of perceived emotions in artificial compared to human agents. Besides accurately recognizing the emotional state of an artificial agent, it is critical to understand how humans respond to those emotions. Does interacting with an angry robot induce the same responses in people as interacting with an angry person? Similarly, does watching a robot rejoice when it wins a game elicit similar feelings of elation in the human observer? Here we provide an overview of the current state of emotion expression and perception in social robotics, as well as a clear articulation of the challenges and guiding principles to be addressed as we move ever closer to truly emotional artificial agents

Distributed Control of Microscopic Robots in Biomedical Applications

Current developments in molecular electronics, motors and chemical sensors could enable constructing large numbers of devices able to sense, compute and act in micron-scale environments. Such microscopic machines, of sizes comparable to bacteria, could simultaneously monitor entire populations of cells individually in vivo. This paper reviews plausible capabilities for microscopic robots and the physical constraints due to operation in fluids at low Reynolds number, diffusion-limited sensing and thermal noise from Brownian motion. Simple distributed controls are then presented in the context of prototypical biomedical tasks, which require control decisions on millisecond time scales. The resulting behaviors illustrate trade-offs among speed, accuracy and resource use. A specific example is monitoring for patterns of chemicals in a flowing fluid released at chemically distinctive sites. Information collected from a large number of such devices allows estimating properties of cell-sized chemical sources in a macroscopic volume. The microscopic devices moving with the fluid flow in small blood vessels can detect chemicals released by tissues in response to localized injury or infection. We find the devices can readily discriminate a single cell-sized chemical source from the background chemical concentration, providing high-resolution sensing in both time and space. By contrast, such a source would be difficult to distinguish from background when diluted throughout the blood volume as obtained with a blood sample

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Neuromorphic analogue VLSI

Neuromorphic systems emulate the organization and function of nervous systems. They are usually composed of analogue electronic circuits that are fabricated in the complementary metal-oxide-semiconductor (CMOS) medium using very large-scale integration (VLSI) technology. However, these neuromorphic systems are not another kind of digital computer in which abstract neural networks are simulated symbolically in terms of their mathematical behavior. Instead, they directly embody, in the physics of their CMOS circuits, analogues of the physical processes that underlie the computations of neural systems. The significance of neuromorphic systems is that they offer a method of exploring neural computation in a medium whose physical behavior is analogous to that of biological nervous systems and that operates in real time irrespective of size. The implications of this approach are both scientific and practical. The study of neuromorphic systems provides a bridge between levels of understanding. For example, it provides a link between the physical processes of neurons and their computational significance. In addition, the synthesis of neuromorphic systems transposes our knowledge of neuroscience into practical devices that can interact directly with the real world in the same way that biological nervous systems do