SPECS: a non-parametric method to identify tissue-specific molecular features for unbalanced sample groups

Background To understand biology and differences among various tissues or cell types, one typically searches for molecular features that display characteristic abundance patterns. Several specificity metrics have been introduced to identify tissue-specific molecular features, but these either require an equal number of replicates per tissue or they can’t handle replicates at all. Results We describe a non-parametric specificity score that is compatible with unequal sample group sizes. To demonstrate its usefulness, the specificity score was calculated on all GTEx samples, detecting known and novel tissue-specific genes. A webtool was developed to browse these results for genes or tissues of interest. An example python implementation of SPECS is available at https://github.com/celineeveraert/SPECS. The precalculated SPECS results on the GTEx data are available through a user-friendly browser at specs.cmgg.be. Conclusions SPECS is a non-parametric method that identifies known and novel specific-expressed genes. In addition, SPECS could be adopted for other features and applications

Structure Learning in Nested Effects Models

Nested Effects Models (NEMs) are a class of graphical models introduced to analyze the results of gene perturbation screens. NEMs explore noisy subset relations between the high-dimensional outputs of phenotyping studies, e.g. the effects showing in gene expression profiles or as morphological features of the perturbed cell. In this paper we expand the statistical basis of NEMs in four directions: First, we derive a new formula for the likelihood function of a NEM, which generalizes previous results for binary data. Second, we prove model identifiability under mild assumptions. Third, we show that the new formulation of the likelihood allows to efficiently traverse model space. Fourth, we incorporate prior knowledge and an automated variable selection criterion to decrease the influence of noise in the data

Primary visual cortex as a saliency map: parameter-free prediction of behavior from V1 physiology

It has been hypothesized that neural activities in the primary visual cortex (V1) represent a saliency map of the visual field to exogenously guide attention. This hypothesis has so far provided only qualitative predictions and their confirmations. We report this hypothesis' first quantitative prediction, derived without free parameters, and its confirmation by human behavioral data. The hypothesis provides a direct link between V1 neural responses to a visual location and the saliency of that location to guide attention exogenously. In a visual input containing many bars, one of them saliently different from all the other bars which are identical to each other, saliency at the singleton's location can be measured by the shortness of the reaction time in a visual search task to find the singleton. The hypothesis predicts quantitatively the whole distribution of the reaction times to find a singleton unique in color, orientation, and motion direction from the reaction times to find other types of singletons. The predicted distribution matches the experimentally observed distribution in all six human observers. A requirement for this successful prediction is a data-motivated assumption that V1 lacks neurons tuned simultaneously to color, orientation, and motion direction of visual inputs. Since evidence suggests that extrastriate cortices do have such neurons, we discuss the possibility that the extrastriate cortices play no role in guiding exogenous attention so that they can be devoted to other functional roles like visual decoding or endogenous attention.Comment: 11 figures, 66 page

Growth rings in tropical trees : role of functional traits, environment, and phylogeny

Acknowledgments Financial support of the Centre National de la Recherche Scientifique (USR 3330), France, and from the Rufford Small Grants Foundation (UK) is acknowledged. We thank the private farmers and coffee plantation companies of Kodagu for providing permissions and logistical support for this project. We are grateful to N. Barathan for assistance with slide preparation and data entry, S. Aravajy for botanical assistance, S. Prasad and G. Orukaimoni for technical inputs, and A. Prathap, S. Shiva, B. Saravana, and P. Shiva for field assistance. The corresponding editor and three anonymous reviewers provided insightful comments that improved the manuscript.Peer reviewedPostprin

Evaluating Leniency with Missing Information on Undetected Cartels: Exploring Time-Varying Policy Impacts on Cartel Duration

This paper examines the effects of European Commission’s (EC) new leniency program on the EC’s capabilities in detecting and deterring cartels. As a supplementary analysis, the US leniency is studied. I discuss a dynamic model of cartel formation and dissolution to illustrate how changes in antitrust policies and economic conditions might affect cartel duration. Comparative statics results are then corroborated with empirical estimates of hazard functions adjusted to account for both the heterogeneity of cartels and the time-varying policy impacts suggested by theory. Contrary to earlier studies, my statistical tests are consistent with the theoretic predictions that following an efficacious leniency program, the average duration of discovered cartels rises in the short run and falls in the long run. The results shed light on the design of enforcement programs against cartels and other forms of conspiracy

Distribution of Mutual Information from Complete and Incomplete Data

Mutual information is widely used, in a descriptive way, to measure the stochastic dependence of categorical random variables. In order to address questions such as the reliability of the descriptive value, one must consider sample-to-population inferential approaches. This paper deals with the posterior distribution of mutual information, as obtained in a Bayesian framework by a second-order Dirichlet prior distribution. The exact analytical expression for the mean, and analytical approximations for the variance, skewness and kurtosis are derived. These approximations have a guaranteed accuracy level of the order O(1/n^3), where n is the sample size. Leading order approximations for the mean and the variance are derived in the case of incomplete samples. The derived analytical expressions allow the distribution of mutual information to be approximated reliably and quickly. In fact, the derived expressions can be computed with the same order of complexity needed for descriptive mutual information. This makes the distribution of mutual information become a concrete alternative to descriptive mutual information in many applications which would benefit from moving to the inductive side. Some of these prospective applications are discussed, and one of them, namely feature selection, is shown to perform significantly better when inductive mutual information is used.Comment: 26 pages, LaTeX, 5 figures, 4 table

Prosody-Based Automatic Segmentation of Speech into Sentences and Topics

A crucial step in processing speech audio data for information extraction, topic detection, or browsing/playback is to segment the input into sentence and topic units. Speech segmentation is challenging, since the cues typically present for segmenting text (headers, paragraphs, punctuation) are absent in spoken language. We investigate the use of prosody (information gleaned from the timing and melody of speech) for these tasks. Using decision tree and hidden Markov modeling techniques, we combine prosodic cues with word-based approaches, and evaluate performance on two speech corpora, Broadcast News and Switchboard. Results show that the prosodic model alone performs on par with, or better than, word-based statistical language models -- for both true and automatically recognized words in news speech. The prosodic model achieves comparable performance with significantly less training data, and requires no hand-labeling of prosodic events. Across tasks and corpora, we obtain a significant improvement over word-only models using a probabilistic combination of prosodic and lexical information. Inspection reveals that the prosodic models capture language-independent boundary indicators described in the literature. Finally, cue usage is task and corpus dependent. For example, pause and pitch features are highly informative for segmenting news speech, whereas pause, duration and word-based cues dominate for natural conversation.Comment: 30 pages, 9 figures. To appear in Speech Communication 32(1-2), Special Issue on Accessing Information in Spoken Audio, September 200

The reentry hypothesis: The putative interaction of the frontal eye field, ventrolateral prefrontal cortex, and areas V4, IT for attention and eye movement

Attention is known to play a key role in perception, including action selection, object recognition and memory. Despite findings revealing competitive interactions among cell populations, attention remains difficult to explain. The central purpose of this paper is to link up a large number of findings in a single computational approach. Our simulation results suggest that attention can be well explained on a network level involving many areas of the brain. We argue that attention is an emergent phenomenon that arises from reentry and competitive interactions. We hypothesize that guided visual search requires the usage of an object-specific template in prefrontal cortex to sensitize V4 and IT cells whose preferred stimuli match the target template. This induces a feature-specific bias and provides guidance for eye movements. Prior to an eye movement, a spatially organized reentry from occulomotor centers, specifically the movement cells of the frontal eye field, occurs and modulates the gain of V4 and IT cells. The processes involved are elucidated by quantitatively comparing the time course of simulated neural activity with experimental data. Using visual search tasks as an example, we provide clear and empirically testable predictions for the participation of IT, V4 and the frontal eye field in attention. Finally, we explain a possible physiological mechanism that can lead to non-flat search slopes as the result of a slow, parallel discrimination process