Santiago González

Three-Dimensional Spatial Distribution of Synapses in the Neocortex: A Dual-Beam Electron Microscopy Study

In the cerebral cortex, most synapses are found in the neuropil, but relatively little is known about their 3-dimensional organization. Using an automated dual-beam electron microscope that combines focused ion beam milling and scanning electron microscopy, we have been able to obtain 10 three-dimensional samples with an average volume of 180 µm3 from the neuropil of layer III of the young rat somatosensory cortex (hindlimb representation). We have used specific software tools to fully reconstruct 1695 synaptic junctions present in these samples and to accurately quantify the number of synapses per unit volume. These tools also allowed us to determine synapse position and to analyze their spatial distribution using spatial statistical methods. Our results indicate that the distribution of synaptic junctions in the neuropil is nearly random, only constrained by the fact that synapses cannot overlap in space. A theoretical model based on random sequential absorption, which closely reproduces the actual distribution of synapses, is also presented.

Synaptic Changes in the Dentate Gyrus of APP/PS1 Transgenic Mice Revealed by Electron Microscopy

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A methodology to compare Dimensionality Reduction algorithms in terms of loss of quality

Abstract Dimensionality Reduction (DR) is attracting more attention these days as a result of the increasing need to handle huge amounts of data effectively. DR methods allow the number of initial features to be reduced considerably until a set of them is found that allows the original properties of the data to be kept. However, their use entails an inherent loss of quality that is likely to affect the understanding of the data, in terms of data analysis. This loss of quality could be determinant when selecting a DR method, because of the nature of each method. In this paper, we propose a methodology that allows different DR methods to be analyzed and compared as regards the loss of quality produced by them. This methodology makes use of the concept of preservation of geometry (quality assessment criteria) to assess the loss of quality. Experiments have been carried out by using the most well-known DR algorithms and quality assessment criteria, based on the literature. These experiments have been applied on 12 real-world datasets. Results obtained so far show that it is possible to establish a method to select the most appropriate DR method, in terms of minimum loss of quality. Experiments have also highlighted some interesting relationships between the quality assessment criteria. Finally, the methodology allows the appropriate choice of dimensionality for reducing data to be established, whilst giving rise to a minimum loss of quality.

CliDaPa: A new approach to combining clinical data with DNA microarrays

Traditionally, clinical data have been used as the only source of information to diagnose diseases. Nowadays, other types of information, such as various forms of omics data (e.g. DNA microarrays), are taken into account to improve diagnosis and even prognosis in many diseases. This paper proposes a new approach, called CliDaPa, for efficiently combining both sources of information, namely clinical data and gene expressions, in order to further improve estimations. In this approach, patients are firstly divided into different clusters (represented as a decision tree) depending on their clinical information. Thus, different groups of patients with similar behaviors are identified. Each individual group can be studied and classified separately, using only gene expression data, with different supervised classification methods, such as decision trees, Bayesian networks or lazy induction learning. To validate this method, two datasets based on Breast Cancer, a high social impact disease, have been used. For the proposed approach, internal (0.632 Bootstrap) and external validations have been carried out. Results have shown improvements in accuracy in the internal and external validation compared with the standard methods with clinical data and gene expression data separately. Thus, the CliDaPa algorithm fulfills our proposed objectives.

New insights into the suitability of the third dimension for visualizing multivariate/multidimensional data: A study based on loss of quality quantification

Most visualization techniques have traditionally used two-dimensional, instead of three-dimensional representations to visualize multidimensional and multivariate data. In this article, a way to demonstrate the underlying superiority of three-dimensional, with respect to two-dimensional, representation is proposed. Specifically, it is based on the inevitable quality degradation produced when reducing the data dimensionality. The problem is tackled from two different approaches: a visual and an analytical approach. First, a set of statistical tests (point classification, distance perception, and outlier identification) using the two-dimensional and three-dimensional visualization are carried out on a group of 40 users. The results indicate that there is an improvement in the accuracy introduced by the inclusion of a third dimension; however, these results do not allow to obtain definitive conclusions on the superiority of three-dimensional representation. Therefore, in order to draw further conclusions, a deeper study based on an analytical approach is proposed. The aim is to quantify the real loss of quality produced when the data are visualized in two-dimensional and three-dimensional spaces, in relation to the original data dimensionality, to analyze the difference between them. To achieve this, a recently proposed methodology is used. The results obtained by the analytical approach reported that the loss of quality reaches significantly high values only when switching from three-dimensional to two-dimensional representation. The considerable quality degradation suffered in the two-dimensional visualization strongly suggests the suitability of the third dimension to visualize data.

EDA-Based Logistic Regression Applied to Biomarkers Selection in Breast Cancer

Logistic regression (LR) is a simple and efficient supervised learning algorithm for estimating the probability of an outcome variable. This algorithm is widely accepted and used in medicine for classification of diseases using DNA microarray data. Classical LR does not perform well for microarrays when applied directly, because the number of variables exceeds the number of samples. However, by reducing the number of genes and selecting specific variables (using filtering methods) great results can be obtained with this algorithm. On this contribution we propose a novel approach for fitting the (penalized) LR models based on EDAs. Breast Cancer dataset has been proposed to compare both accuracy and gene selection.

MedVir: An Interactive Representation System of Multidimensional Medical Data Applied to Traumatic Brain Injury’s Rehabilitation Prediction

Clinicians could model the brain injury of a patient through his brain activity. However, how this model is defined and how it changes when the patient is recovering are questions yet unanswered. In this paper, the use of MedVir framework is proposed with the aim of answering these questions. Based on complex data mining techniques, this provides not only the differentiation between TBI patients and control subjects (with a 72% of accuracy using 0.632 Bootstrap validation), but also the ability to detect whether a patient may recover or not, and all of that in a quick and easy way through a visualization technique which allows interaction.