Single-Trial {MEG} Data Can Be Denoised Through Cross-Subject Predictive Modeling

A pervasive challenge in brain imaging is the presence of noise that hinders investigation of underlying neural processes, with Magnetoencephalography (MEG) in particular having very low Signal-to-Noise Ratio (SNR). The established strategy to increase MEG's SNR involves averaging multiple repetitions of data corresponding to the same stimulus. However, repetition of stimulus can be undesirable, because underlying neural activity has been shown to change across trials, and repeating stimuli limits the breadth of the stimulus space experienced by subjects. In particular, the rising popularity of naturalistic studies with a single viewing of a movie or story necessitates the discovery of new approaches to increase SNR. We introduce a simple framework to reduce noise in single-trial MEG data by leveraging correlations in neural responses across subjects as they experience the same stimulus. We demonstrate its use in a naturalistic reading comprehension task with 8 subjects, with MEG data collected while they read the same story a single time. We find that our procedure results in data with reduced noise and allows for better discovery of neural phenomena. As proof-of-concept, we show that the N400m's correlation with word surprisal, an established finding in literature, is far more clearly observed in the denoised data than the original data. The denoised data also shows higher decoding and encoding accuracy than the original data, indicating that the neural signals associated with reading are either preserved or enhanced after the denoising procedure

Outlier detection algorithms over fuzzy data with weighted least squares

In the classical leave-one-out procedure for outlier detection in regression analysis, we exclude an observation and then construct a model on the remaining data. If the difference between predicted and observed value is high we declare this value an outlier. As a rule, those procedures utilize single comparison testing. The problem becomes much harder when the observations can be associated with a given degree of membership to an underlying population, and the outlier detection should be generalized to operate over fuzzy data. We present a new approach for outlier detection that operates over fuzzy data using two inter-related algorithms. Due to the way outliers enter the observation sample, they may be of various order of magnitude. To account for this, we divided the outlier detection procedure into cycles. Furthermore, each cycle consists of two phases. In Phase 1, we apply a leave-one-out procedure for each non-outlier in the dataset. In Phase 2, all previously declared outliers are subjected to Benjamini–Hochberg step-up multiple testing procedure controlling the false-discovery rate, and the non-confirmed outliers can return to the dataset. Finally, we construct a regression model over the resulting set of non-outliers. In that way, we ensure that a reliable and high-quality regression model is obtained in Phase 1 because the leave-one-out procedure comparatively easily purges the dubious observations due to the single comparison testing. In the same time, the confirmation of the outlier status in relation to the newly obtained high-quality regression model is much harder due to the multiple testing procedure applied hence only the true outliers remain outside the data sample. The two phases in each cycle are a good trade-off between the desire to construct a high-quality model (i.e., over informative data points) and the desire to use as much data points as possible (thus leaving as much observations as possible in the data sample). The number of cycles is user defined, but the procedures can finalize the analysis in case a cycle with no new outliers is detected. We offer one illustrative example and two other practical case studies (from real-life thrombosis studies) that demonstrate the application and strengths of our algorithms. In the concluding section, we discuss several limitations of our approach and also offer directions for future research

Outlier detection algorithms over fuzzy data with weighted least squares

In the classical leave-one-out procedure for outlier detection in regression analysis, we exclude an observation and then construct a model on the remaining data. If the difference between predicted and observed value is high we declare this value an outlier. As a rule, those procedures utilize single comparison testing. The problem becomes much harder when the observations can be associated with a given degree of membership to an underlying population, and the outlier detection should be generalized to operate over fuzzy data. We present a new approach for outlier detection that operates over fuzzy data using two inter-related algorithms. Due to the way outliers enter the observation sample, they may be of various order of magnitude. To account for this, we divided the outlier detection procedure into cycles. Furthermore, each cycle consists of two phases. In Phase 1, we apply a leave-one-out procedure for each non-outlier in the dataset. In Phase 2, all previously declared outliers are subjected to Benjamini–Hochberg step-up multiple testing procedure controlling the false-discovery rate, and the non-confirmed outliers can return to the dataset. Finally, we construct a regression model over the resulting set of non-outliers. In that way, we ensure that a reliable and high-quality regression model is obtained in Phase 1 because the leave-one-out procedure comparatively easily purges the dubious observations due to the single comparison testing. In the same time, the confirmation of the outlier status in relation to the newly obtained high-quality regression model is much harder due to the multiple testing procedure applied hence only the true outliers remain outside the data sample. The two phases in each cycle are a good trade-off between the desire to construct a high-quality model (i.e., over informative data points) and the desire to use as much data points as possible (thus leaving as much observations as possible in the data sample). The number of cycles is user defined, but the procedures can finalize the analysis in case a cycle with no new outliers is detected. We offer one illustrative example and two other practical case studies (from real-life thrombosis studies) that demonstrate the application and strengths of our algorithms. In the concluding section, we discuss several limitations of our approach and also offer directions for future research

Ensembl Genomes 2013: scaling up access to genome-wide data

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species. The project exploits and extends technologies for genome annotation, analysis and dissemination, developed in the context of the vertebrate-focused Ensembl project, and provides a complementary set of resources for non-vertebrate species through a consistent set of programmatic and interactive interfaces. These provide access to data including reference sequence, gene models, transcriptional data, polymorphisms and comparative analysis. This article provides an update to the previous publications about the resource, with a focus on recent developments. These include the addition of important new genomes (and related data sets) including crop plants, vectors of human disease and eukaryotic pathogens. In addition, the resource has scaled up its representation of bacterial genomes, and now includes the genomes of over 9000 bacteria. Specific extensions to the web and programmatic interfaces have been developed to support users in navigating these large data sets. Looking forward, analytic tools to allow targeted selection of data for visualization and download are likely to become increasingly important in future as the number of available genomes increases within all domains of life, and some of the challenges faced in representing bacterial data are likely to become commonplace for eukaryotes in future

KIR gene content diversity in four Iranian populations

Killer cell immunoglobulin-like receptors (KIR) regulate natural killer cell response against infection and malignancy. KIR genes are variable in the number and type, thereby discriminating individuals and populations. Herein, we analyzed the KIR gene content diversity in four native populations of Iran. The KIR genomic diversity was comparable between Bakhtiari and Persian and displayed a balance of A and B KIR haplotypes, a trend reported in Caucasian and African populations. The KIR gene content profiles of Arab and Azeri were comparable and displayed a preponderance of B haplotypes, a scenario reported in the natives of America, India, and Australia. A majority of the B haplotype carriers of Azeri and Arab had a centromeric gene-cluster (KIR2DS2-2DL2-2DS3-2DL5). Remarkably, this cluster was totally absent from the American natives but occurred at highest frequencies in the natives of India and Australia in combination with another gene cluster at the telomeric region (KIR3DS1-2DL5-2DS5-2DS1). Therefore, despite having similar frequencies of B haplotypes, the occurrence of B haplotype-specific KIR genes, such as 2DL2, 2DL5, 3DS1, 2DS1, 2DS2, 2DS3, and 2DS5 in Azeri and Arab were substantially different from the natives of America, India, and Australia. In conclusion, each Iranian population exhibits distinct KIR gene content diversity, and the Indo-European KIR genetic signatures of the Iranians concur with geographic proximity, linguistic affinity, and human migrations

Getting aligned on representational alignment

Biological and artificial information processing systems form representations that they can use to categorize, reason, plan, navigate, and make decisions. How can we measure the extent to which the representations formed by these diverse systems agree? Do similarities in representations then translate into similar behavior? How can a system's representations be modified to better match those of another system? These questions pertaining to the study of representational alignment are at the heart of some of the most active research areas in cognitive science, neuroscience, and machine learning. For example, cognitive scientists measure the representational alignment of multiple individuals to identify shared cognitive priors, neuroscientists align fMRI responses from multiple individuals into a shared representational space for group-level analyses, and ML researchers distill knowledge from teacher models into student models by increasing their alignment. Unfortunately, there is limited knowledge transfer between research communities interested in representational alignment, so progress in one field often ends up being rediscovered independently in another. Thus, greater cross-field communication would be advantageous. To improve communication between these fields, we propose a unifying framework that can serve as a common language between researchers studying representational alignment. We survey the literature from all three fields and demonstrate how prior work fits into this framework. Finally, we lay out open problems in representational alignment where progress can benefit all three of these fields. We hope that our work can catalyze cross-disciplinary collaboration and accelerate progress for all communities studying and developing information processing systems. We note that this is a working paper and encourage readers to reach out with their suggestions for future revisions.Comment: Working paper, changes to be made in upcoming revision

Ensembl Genomes: an integrative resource for genome-scale data from non-vertebrate species

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrative resource for genome-scale data from non-vertebrate species. The project exploits and extends technology (for genome annotation, analysis and dissemination) developed in the context of the (vertebrate-focused) Ensembl project and provides a complementary set of resources for non-vertebrate species through a consistent set of programmatic and interactive interfaces. These provide access to data including reference sequence, gene models, transcriptional data, polymorphisms and comparative analysis. Since its launch in 2009, Ensembl Genomes has undergone rapid expansion, with the goal of providing coverage of all major experimental organisms, and additionally including taxonomic reference points to provide the evolutionary context in which genes can be understood. Against the backdrop of a continuing increase in genome sequencing activities in all parts of the tree of life, we seek to work, wherever possible, with the communities actively generating and using data, and are participants in a growing range of collaborations involved in the annotation and analysis of genomes

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved