2,684 research outputs found

    Neural manifold analysis of brain circuit dynamics in health and disease

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    Recent developments in experimental neuroscience make it possible to simultaneously record the activity of thousands of neurons. However, the development of analysis approaches for such large-scale neural recordings have been slower than those applicable to single-cell experiments. One approach that has gained recent popularity is neural manifold learning. This approach takes advantage of the fact that often, even though neural datasets may be very high dimensional, the dynamics of neural activity tends to traverse a much lower-dimensional space. The topological structures formed by these low-dimensional neural subspaces are referred to as “neural manifolds”, and may potentially provide insight linking neural circuit dynamics with cognitive function and behavioral performance. In this paper we review a number of linear and non-linear approaches to neural manifold learning, including principal component analysis (PCA), multi-dimensional scaling (MDS), Isomap, locally linear embedding (LLE), Laplacian eigenmaps (LEM), t-SNE, and uniform manifold approximation and projection (UMAP). We outline these methods under a common mathematical nomenclature, and compare their advantages and disadvantages with respect to their use for neural data analysis. We apply them to a number of datasets from published literature, comparing the manifolds that result from their application to hippocampal place cells, motor cortical neurons during a reaching task, and prefrontal cortical neurons during a multi-behavior task. We find that in many circumstances linear algorithms produce similar results to non-linear methods, although in particular cases where the behavioral complexity is greater, non-linear methods tend to find lower-dimensional manifolds, at the possible expense of interpretability. We demonstrate that these methods are applicable to the study of neurological disorders through simulation of a mouse model of Alzheimer’s Disease, and speculate that neural manifold analysis may help us to understand the circuit-level consequences of molecular and cellular neuropathology

    Advancing combined radiological and optical scanning for breast-conserving surgery margin guidance

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    Breast cancer is one of the most common types of cancer worldwide, and standard-of-care for early-stage disease typically involves a lumpectomy or breast-conserving surgery (BCS). BCS involves the local resection of cancerous tissue, while sparring as much healthy tissue as possible. State-of-the-art methods for intraoperatively evaluating BCS margins are limited. Approximately 20% of BCS cases result in a tissue resection with cancer at or near the resection surface (i.e., a positive margin). A two-fold increase in ipsilateral breast cancer recurrence is associated with the presence of one or more positive margins. Consequently, positive margins often necessitate costly re-excision procedures to achieve a curative outcome. X-ray micro-computed tomography (CT) is emerging as a powerful ex vivo specimen imaging technology, as it provides robust three-dimensional sensing of tumor morphology rapidly. However, X-ray attenuation lacks contrast between soft tissues that are important for surgical decision making during BCS. Optical structured light imaging, including spatial frequency domain imaging and active line scan imaging, can act as adjuvant tools to complement micro-CT, providing wide field-of-view, non-contact sensing of relevant breast tissue subtypes on resection margins that cannot be differentiated by micro-CT alone. This thesis is dedicated to multimodal imaging of BCS tissues to ultimately improve intraoperative BCS margin assessment, reducing the number of positive margins after initial surgeries and thereby reducing the need for costly follow-up procedures. Volumetric sensing of micro-CT is combined with surface-weighted, sub-diffuse optical reflectance derived from high spatial frequency structured light imaging. Sub-diffuse reflectance plays the key role of providing enhanced contrast to a suite of normal, abnormal benign, and malignant breast tissue subtypes. This finding is corroborated through clinical studies imaging BCS specimen slices post-operatively and is further investigated through an observational clinical trial focused on combined, intraoperative micro-CT and optical imaging of whole, freshly resected BCS tumors. The central thesis of this work is that combining volumetric X-ray imaging and sub-diffuse optical scanning provides a synergistic multimodal imaging solution to margin assessment, one that can be readily implemented or retrofitted in X-ray specimen imaging systems and that could meaningfully improve surgical guidance during initial BCS procedures

    Broadcasting Convolutional Network for Visual Relational Reasoning

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    In this paper, we propose the Broadcasting Convolutional Network (BCN) that extracts key object features from the global field of an entire input image and recognizes their relationship with local features. BCN is a simple network module that collects effective spatial features, embeds location information and broadcasts them to the entire feature maps. We further introduce the Multi-Relational Network (multiRN) that improves the existing Relation Network (RN) by utilizing the BCN module. In pixel-based relation reasoning problems, with the help of BCN, multiRN extends the concept of `pairwise relations' in conventional RNs to `multiwise relations' by relating each object with multiple objects at once. This yields in O(n) complexity for n objects, which is a vast computational gain from RNs that take O(n^2). Through experiments, multiRN has achieved a state-of-the-art performance on CLEVR dataset, which proves the usability of BCN on relation reasoning problems.Comment: Accepted paper at ECCV 2018. 24 page

    Analysis of large-scale molecular biological data using self-organizing maps

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    Modern high-throughput technologies such as microarrays, next generation sequencing and mass spectrometry provide huge amounts of data per measurement and challenge traditional analyses. New strategies of data processing, visualization and functional analysis are inevitable. This thesis presents an approach which applies a machine learning technique known as self organizing maps (SOMs). SOMs enable the parallel sample- and feature-centered view of molecular phenotypes combined with strong visualization and second-level analysis capabilities. We developed a comprehensive analysis and visualization pipeline based on SOMs. The unsupervised SOM mapping projects the initially high number of features, such as gene expression profiles, to meta-feature clusters of similar and hence potentially co-regulated single features. This reduction of dimension is attained by the re-weighting of primary information and does not entail a loss of primary information in contrast to simple filtering approaches. The meta-data provided by the SOM algorithm is visualized in terms of intuitive mosaic portraits. Sample-specific and common properties shared between samples emerge as a handful of localized spots in the portraits collecting groups of co-regulated and co-expressed meta-features. This characteristic color patterns reflect the data landscape of each sample and promote immediate identification of (meta-)features of interest. It will be demonstrated that SOM portraits transform large and heterogeneous sets of molecular biological data into an atlas of sample-specific texture maps which can be directly compared in terms of similarities and dissimilarities. Spot-clusters of correlated meta-features can be extracted from the SOM portraits in a subsequent step of aggregation. This spot-clustering effectively enables reduction of the dimensionality of the data in two subsequent steps towards a handful of signature modules in an unsupervised fashion. Furthermore we demonstrate that analysis techniques provide enhanced resolution if applied to the meta-features. The improved discrimination power of meta-features in downstream analyses such as hierarchical clustering, independent component analysis or pairwise correlation analysis is ascribed to essentially two facts: Firstly, the set of meta-features better represents the diversity of patterns and modes inherent in the data and secondly, it also possesses the better signal-to-noise characteristics as a comparable collection of single features. Additionally to the pattern-driven feature selection in the SOM portraits, we apply statistical measures to detect significantly differential features between sample classes. Implementation of scoring measurements supplements the basal SOM algorithm. Further, two variants of functional enrichment analyses are introduced which link sample specific patterns of the meta-feature landscape with biological knowledge and support functional interpretation of the data based on the ‘guilt by association’ principle. Finally, case studies selected from different ‘OMIC’ realms are presented in this thesis. In particular, molecular phenotype data derived from expression microarrays (mRNA, miRNA), sequencing (DNA methylation, histone modification patterns) or mass spectrometry (proteome), and also genotype data (SNP-microarrays) is analyzed. It is shown that the SOM analysis pipeline implies strong application capabilities and covers a broad range of potential purposes ranging from time series and treatment-vs.-control experiments to discrimination of samples according to genotypic, phenotypic or taxonomic classifications

    3D reconstruction of medical images from slices automatically landmarked with growing neural models

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    In this study, we utilise a novel approach to segment out the ventricular system in a series of high resolution T1-weighted MR images. We present a brain ventricles fast reconstruction method. The method is based on the processing of brain sections and establishing a fixed number of landmarks onto those sections to reconstruct the ventricles 3D surface. Automated landmark extraction is accomplished through the use of the self-organising network, the growing neural gas (GNG), which is able to topographically map the low dimensionality of the network to the high dimensionality of the contour manifold without requiring a priori knowledge of the input space structure. Moreover, our GNG landmark method is tolerant to noise and eliminates outliers. Our method accelerates the classical surface reconstruction and filtering processes. The proposed method offers higher accuracy compared to methods with similar efficiency as Voxel Grid

    Visual Search: finding similar images

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    Visual Search task focuses on finding visually similar images given a query image and returning the results in a ranked order where the most similar images ranked first. The main contributions of this thesis are implementing an end-toend system to perform the visual search that can be used in further research or applications, and conducting experiments on different types of feature extraction and dimensionality reduction methods to understand which ones are more likely to give better search relevance and quality results

    A survey of outlier detection methodologies

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    Outlier detection has been used for centuries to detect and, where appropriate, remove anomalous observations from data. Outliers arise due to mechanical faults, changes in system behaviour, fraudulent behaviour, human error, instrument error or simply through natural deviations in populations. Their detection can identify system faults and fraud before they escalate with potentially catastrophic consequences. It can identify errors and remove their contaminating effect on the data set and as such to purify the data for processing. The original outlier detection methods were arbitrary but now, principled and systematic techniques are used, drawn from the full gamut of Computer Science and Statistics. In this paper, we introduce a survey of contemporary techniques for outlier detection. We identify their respective motivations and distinguish their advantages and disadvantages in a comparative review
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