An efficient algorithm to perform multiple testing in epistasis screening

Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. Gene-gene interaction studies will require a memory proportional to the squared number of SNPs. A genome-wide epistasis search would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MBMDR-3.0.3. We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn’s disease. Results: In the case of a binary (affected/unaffected) trait, the parallel workflow of MBMDR-3.0.3 analyzes all gene-gene interactions with a dataset of 100,000 SNPs typed on 1000 individuals within 4 days and 9 hours, using 999 permutations of the trait to assess statistical significance, on a cluster composed of 10 blades, containing each four Quad-Core AMD Opteron(tm) Processor 2352 2.1 GHz. In the case of a continuous trait, a similar run takes 9 days. Our program found 14 SNP-SNP interactions with a multiple-testing corrected p-value of less than 0.05 on real-life Crohn’s disease (CD) data. Conclusions: Our software is the first implementation of the MB-MDR methodology able to solve large-scale SNP-SNP interactions problems within a few days, without using much memory, while adequately controlling the type I error rates. A new implementation to reach genome-wide epistasis screening is under construction. In the context of Crohn’s disease, MBMDR-3.0.3 could identify epistasis involving regions that are well known in the field and could be explained from a biological point of view. This demonstrates the power of our software to find relevant phenotype-genotype higher-order associations.

A Robust Multiple Feature Approach To Endpoint Detection In Car Environment Based On Advanced Classifiers

In this paper we propose an endpoint detection system based on the use of several features extracted from each speech frame, followed by a robust classifier (i.e Adaboost and Bagging of decision trees, and a multilayer perceptron) and a finite state automata (FSA). We present results for four different classifiers. The FSA module consisted of a 4-state decision logic that filtered false alarms and false positives. We compare the use of four different classifiers in this task. The look ahead of the method that we propose was of 7 frames, which are the number of frames that maximized the accuracy of the system. The system was tested with real signals recorded inside a car, with signal to noise ratio that ranged from 6 dB to 30dB. Finally we present experimental results demonstrating that the system yields robust endpoint detection.

Multiple processes regulate long-term population dynamics of sea urchins on Mediterranean rocky reefs

We annually monitored the abundance and size structure of herbivorous sea urchin populations (Paracentrotus lividus and Arbacia lixula) inside and outside a marine reserve in the Northwestern Mediterranean on two distinct habitats (boulders and vertical walls) over a period of 20 years, with the aim of analyzing changes at different temporal scales in relation to biotic and abiotic drivers. P. lividus exhibited significant variability in density over time on boulder bottoms but not on vertical walls, and temporal trends were not significantly different between the protection levels. Differences in densities were caused primarily by variance in recruitment, which was less pronounced inside the MPA and was correlated with adult density, indicating density-dependent recruitment under high predation pressure, as well as some positive feedback mechanisms that may facilitate higher urchin abundances despite higher predator abundance. Populations within the reserve were less variable in abundance and did not exhibit the hyper-abundances observed outside the reserve, suggesting that predation effects maybe more subtle than simply lowering the numbers of urchins in reserves. A. lixula densities were an order of magnitude lower than P. lividus densities and varied within sites and over time on boulder bottoms but did not differ between protection levels. In December 2008, an exceptionally violent storm reduced sea urchin densities drastically (by 50% to 80%) on boulder substrates, resulting in the lowest values observed over the entire study period, which remained at that level for at least two years (up to the present). Our results also showed great variability in the biological and physical processes acting at different temporal scales. This study highlights the need for appropriate temporal scales for studies to fully understand ecosystem functioning, the concepts of which are fundamental to successful conservation and management.

Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas

Multiple osteochondromas is an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped tumours. Two causal genes have been identified, EXT1 and EXT2, which account for 65% and 30% of cases, respectively. We have undertaken a mutation analysis of the EXT1 and EXT2 genes in 39 unrelated Spanish patients, most of them with moderate phenotype, and looked for genotype-phenotype correlations. We found the mutant allele in 37 patients, 29 in EXT1 and 8 in EXT2. Five of the EXT1 mutations were deletions identified by MLPA. Two cases of mosaicism were documented. We detected a lower number of exostoses in patients with missense mutation versus other kinds of mutations. In conclusion, we found a mutation in EXT1 or in EXT2 in 95% of the Spanish patients. Eighteen of the mutations were novel.

Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas

Multiple osteochondromas is an autosomal dominant skeletal disorder characterized by the formation of multiple cartilage-capped tumours. Two causal genes have been identified, EXT1 and EXT2, which account for 65% and 30% of cases, respectively. We have undertaken a mutation analysis of the EXT1 and EXT2 genes in 39 unrelated Spanish patients, most of them with moderate phenotype, and looked for genotype-phenotype correlations. We found the mutant allele in 37 patients, 29 in EXT1 and 8 in EXT2. Five of the EXT1 mutations were deletions identified by MLPA. Two cases of mosaicism were documented. We detected a lower number of exostoses in patients with missense mutation versus other kinds of mutations. In conclusion, we found a mutation in EXT1 or in EXT2 in 95% of the Spanish patients. Eighteen of the mutations were novel.

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters.

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters.

A novel semi-fragile forensic watermarking scheme for remote sensing images

Peer-reviewed

The building blocks of the full body ownership illusion

Previous work has reported that it is not difficult to give people the illusion of ownership over an artificial body, providing a powerful tool for the investigation of the neural and cognitive mechanisms underlying body perception and self consciousness. We present an experimental study that uses immersive virtual reality (IVR) focused on identifying the perceptual building blocks of this illusion. We systematically manipulated visuotactile and visual sensorimotor contingencies, visual perspective, and the appearance of the virtual body in order to assess their relative role and mutual interaction. Consistent results from subjective reports and physiological measures showed that a first person perspective over a fake humanoid body is essential for eliciting a body ownership illusion. We found that the illusion of ownership can be generated when the virtual body has a realistic skin tone and spatially substitutes the real body seen from a first person perspective. In this case there is no need for an additional contribution of congruent visuotactile or sensorimotor cues. Additionally, we found that the processing of incongruent perceptual cues can be modulated by the level of the illusion: when the illusion is strong, incongruent cues are not experienced as incorrect. Participants exposed to asynchronous visuotactile stimulation can experience the ownership illusion and perceive touch as originating from an object seen to contact the virtual body. Analogously, when the level of realism of the virtual body is not high enough and/or when there is no spatial overlap between the two bodies, then the contribution of congruent multisensory and/or sensorimotor cues is required for evoking the illusion. On the basis of these results and inspired by findings from neurophysiological recordings in the monkey, we propose a model that accounts for many of the results reported in the literature.

Proxemics with multiple dynamic characters in an immersive virtual environment

An experiment was carried out to examine the impact on electrodermal activity of people when approached by groups of one or four virtual characters at varying distances. It was premised on the basis of proxemics theory that the closer the approach of the virtual characters to the participant, the greater the level of physiological arousal. Physiological arousal was measured by the number of skin conductance responses within a short time period after the approach, and the maximum change in skin conductance level 5 s after the approach. The virtual characters were each either female or a cylinder of human size, and one or four characters approached each subject a total of 12 times. Twelve male subjects were recruited for the experiment. The results suggest that the number of skin conductance responses after the approach and the change in skin conductance level increased the closer the virtual characters approached toward the participants. Moreover, these response variables were inversely correlated with the number of visits, showing a typical adaptation effect. There was some evidence to suggest that the number of characters who simultaneously approached (one or four) was positively associated with the responses. Surprisingly there was no evidence of a difference in response between the humanoid characters and cylinders on the basis of this physiological data. It is suggested that the similarity in this quantitative arousal response to virtual characters and virtual objects might mask a profound difference in qualitative response, an interpretation supported by questionnaire and interview results. Overall the experiment supported the premise that people exhibit heightened physiological arousal the closer they are approached by virtual characters.

T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension

This article introduces a new interface for T-Coffee, a consistency-based multiple sequence alignment program. This interface provides an easy and intuitive access to the most popular functionality of the package. These include the default T-Coffee mode for protein and nucleic acid sequences, the M-Coffee mode that allows combining the output of any other aligners, and template-based modes of T-Coffee that deliver high accuracy alignments while using structural or homology derived templates. These three available template modes are Expresso for the alignment of protein with a known 3D-Structure, R-Coffee to align RNA sequences with conserved secondary structures and PSI-Coffee to accurately align distantly related sequences using homology extension. The new server benefits from recent improvements of the T-Coffee algorithm and can align up to 150 sequences as long as 10 000 residues and is available from both http://www.tcoffee.org and its main mirror http://tcoffee.crg.cat.

Analysis of vineyard differential management zones and relation to vine development, grape maturity and quality

The objective of research was to analyse the potential of Normalized Difference Vegetation Index (NDVI) maps from satellite images, yield maps and grapevine fertility and load variables to delineate zones with different wine grape properties for selective harvesting. Two vineyard blocks located in NE Spain (Cabernet Sauvignon and Syrah) were analysed. The NDVI was computed from a Quickbird-2 multi-spectral image at veraison (July 2005). Yield data was acquired by means of a yield monitor during September 2005. Other variables, such as the number of buds, number of shoots, number of wine grape clusters and weight of 100 berries were sampled in a 10 rows × 5 vines pattern and used as input variables, in combination with the NDVI, to define the clusters as alternative to yield maps. Two days prior to the harvesting, grape samples were taken. The analysed variables were probable alcoholic degree, pH of the juice, total acidity, total phenolics, colour, anthocyanins and tannins. The input variables, alone or in combination, were clustered (2 and 3 Clusters) by using the ISODATA algorithm, and an analysis of variance and a multiple rang test were performed. The results show that the zones derived from the NDVI maps are more effective to differentiate grape maturity and quality variables than the zones derived from the yield maps. The inclusion of other grapevine fertility and load variables did not improve the results.

Multiple processes regulate long-term population dynamics of sea urchins on Mediterranean rocky reefs

We annually monitored the abundance and size structure of herbivorous sea urchin populations (Paracentrotus lividus and Arbacia lixula) inside and outside a marine reserve in the Northwestern Mediterranean on two distinct habitats (boulders and vertical walls) over a period of 20 years, with the aim of analyzing changes at different temporal scales in relation to biotic and abiotic drivers. P. lividus exhibited significant variability in density over time on boulder bottoms but not on vertical walls, and temporal trends were not significantly different between the protection levels. Differences in densities were caused primarily by variance in recruitment, which was less pronounced inside the MPA and was correlated with adult density, indicating density-dependent recruitment under high predation pressure, as well as some positive feedback mechanisms that may facilitate higher urchin abundances despite higher predator abundance. Populations within the reserve were less variable in abundance and did not exhibit the hyper-abundances observed outside the reserve, suggesting that predation effects maybe more subtle than simply lowering the numbers of urchins in reserves. A. lixula densities were an order of magnitude lower than P. lividus densities and varied within sites and over time on boulder bottoms but did not differ between protection levels. In December 2008, an exceptionally violent storm reduced sea urchin densities drastically (by 50% to 80%) on boulder substrates, resulting in the lowest values observed over the entire study period, which remained at that level for at least two years (up to the present). Our results also showed great variability in the biological and physical processes acting at different temporal scales. This study highlights the need for appropriate temporal scales for studies to fully understand ecosystem functioning, the concepts of which are fundamental to successful conservation and management.

Multiple supernumerary teeth not associated with complex syndromes: a retrospective study

Objectives: To determine the epidemiology and describe the clinical and radiographic characteristics, the type of treatment, and the possible delayed appearance of new supernumerary teeth in patients with non-syndromic multiple hyperdontia. Patients and Methods: We conducted a small retrospective observational study of 8 patients diagnosed with nonsyndromic multiple hyperdontia. Multiple hyperdontia not associated to complex syndromes was defined as apparently generally healthy patients with one or more supernumerary teeth in two or more areas. Results: The average patient age was 16.23 years; males predominated (3:1). Multiple hyperodontia with a minimum of 2 and a maximum of 9 supernumerary teeth was found (total: 34 mean: 4.25). The most frequent location was the upper jaw (76.47%). Eumorphic teeth were seen at lower premolar level, while the rest were all heteromorphic. There was altered eruption of the contiguous teeth of 4 of the impacted supernumerary teeth all the rest being asymptomatic. Extraction was the treatment in all patients, and in one of them the delayed appearance of 4 supernumerary teeth was detected. Conclusions: Multiple hyperodontia rarely occurs without being associated with complex syndromes. Prophylactic surgical removal of the supernumerary teeth is generally the treatment of choice.

Multiple Myeloma with primary manifestation in the mandible: a case report

Multiple myeloma is a monoclonal malignant proliferation of plasma cells that causes osteolytic lesions in the vertebrae, ribs, pelvic bone, skull and jaw. We report on a clinical case of an 81-year-old male patient who presented with a tumefaction in the mandibular symphysis region, which had evolved over the previous seven months. In the radiographic examination, an extensive osteolytic lesion was observed in the region mentioned above. An incisional biopsy was performed and a histopathological study revealed a malignant hematopoietic neoplasm formed by plasmacytoid cells. During the bone gammagraphy a dissemination of the disease was detected in the scapula, clavicle and ribs. The diagnosis was multiple myeloma. Knowledge about the maxillofacial manifestations of multiple myeloma is important for the early diagnosis of the disease, since its primary form can manifest itself in the jaw. In the clinical case presented here, we highlight the interdisciplinarity needed to obtain a diagnosis and treatment of multiple myeloma