Automated phenotyping of mouse social behavior

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2011.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (p. 66-68).Inspired by the connections between social behavior and intelligence, I have developed a trainable system to phenotype mouse social behavior. This system is of immediate interest to researchers studying mouse models of social disorders such as depression or autism. Mice studies provide a controlled environment to begin exploring the questions of how to best quantify social behavior. For the purposes of evaluating this system and to encourage further research, I introduce a new video dataset annotated with five social behaviors: nose-to-nose sniffing, nose-to-head sniffing, nose-to-anogenital sniffing, crawl under / crawl over, and upright head contact. These four behaviors are of particular importance to researchers characterizing mouse social avoidance [9]. To effectively phenotype mouse social behavior, the system incorporates a novel mice tracker, and modules to represent and to classify social behavior. The mice tracker addresses the challenging computer vision problem of tracking two identical, highly deformable mice through complex occlusions. The tracker maintains an ellipse model of both mice and leverages motion cues and shape priors to maintain tracks during occlusions. Using these tracks, the classification system represents behavior with 14 spatial features characterizing relative position, relative motion, and shape. A regularized least squares (RLS) classifier, trained over representative instances of each behavior, classifies the behavior present in each frame. This system demonstrates the enormous potential for building automated systems to quantitatively study mouse social behavior.by Nicholas Edelman.M.Eng

Asymptotic forms for hard and soft edge general β\beta conditional gap probabilities

An infinite log-gas formalism, due to Dyson, and independently Fogler and Shklovskii, is applied to the computation of conditioned gap probabilities at the hard and soft edges of random matrix $\beta$-ensembles. The conditioning is that there are $n$ eigenvalues in the gap, with $n \ll |t|$, $t$ denoting the end point of the gap. It is found that the entropy term in the formalism must be replaced by a term involving the potential drop to obtain results consistent with known asymptotic expansions in the case $n=0$. With this modification made for general $n$, the derived expansions - which are for the logarithm of the gap probabilities - are conjectured to be correct up to and including terms O$(\log|t|)$. They are shown to satisfy various consistency conditions, including an asymptotic duality formula relating $\beta$ to $4/\beta$.Comment: Replaces v2 which contains typographical errors arising from a previous unpublished draf

Trainable, vision-based automated home cage behavioral phenotyping

We describe a fully trainable computer vision system enabling the automated analysis of complex mouse behaviors. Our system computes a sequence of feature descriptors for each video sequence and a classifier is used to learn a mapping from these features to behaviors of interest. We collected a very large manually annotated video database of mouse behaviors for training and testing the system. Our system performs on par with human scoring, as measured from the ground-truth manual annotations of thousands of clips of freely behaving mice. As a validation of the system, we characterized the home cage behaviors of two standard inbred and two nonstandard mouse strains. From this data, we were able to predict the strain identity of individual mice with high accuracy.California Institute of Technology. Broad Fellows Program in Brain CircuitryNational Science Council of Taiwan (TMS-094-1-A032

The Embryonic Transcriptome Of The Red-Eared Slider Turtle (Trachemys Scripta)

The bony shell of the turtle is an evolutionary novelty not found in any other group of animals, however, research into its formation has suggested that it has evolved through modification of conserved developmental mechanisms. Although these mechanisms have been extensively characterized in model organisms, the tools for characterizing them in non-model organisms such as turtles have been limited by a lack of genomic resources. We have used a next generation sequencing approach to generate and assemble a transcriptome from stage 14 and 17 Trachemys scripta embryos, stages during which important events in shell development are known to take place. The transcriptome consists of 231,876 sequences with an N-50 of 1,166 bp. GO terms and EC codes were assigned to the 61,643 unique predicted proteins identified in the transcriptome sequences. All major GO categories and metabolic pathways are represented in the transcriptome. Transcriptome sequences were used to amplify several cDNA fragments designed for use as RNA in situ probes. One of these, BMP5, was hybridized to a T. scripta embryo and exhibits both conserved and novel expression patterns. The transcriptome sequences should be of broad use for understanding the evolution and development of the turtle shell and for annotating any future T. scripta genome sequences

State of the Tropics 2014 report

[Extract] Is life in the Tropics getting better? The landmark State of the Tropics 2014 Report addresses this nominally simple question. It provides the first in-depth, objective assessment of the Tropics as an environmental and geopolitical entity in its own right. Drawing on the knowledge, experience and diverse backgrounds of leading institutions across the Tropics the report assesses the state of the region and examines the implications of the immense changes the region is experiencing. The assessment demonstrates that nations in the Tropics have made extraordinary progress across a wide range of environmental, social and economic indicators in recent decades. Rapid population and economic growth mean its influence is set to rise dramatically in coming decades. The nature of this influence will depend on how the region addresses its many challenges, and whether it realises its potential and opportunities. The report provides a basis from which to work towards a prosperous, sustainable and equitable future for the Tropics and will be a valuable resource for policy makers, geopolitical analysts, researchers, students and other stakeholders interested in the Tropics

Cellular magnesium acquisition : an anomaly in embryonic cation homeostasis

Author Posting. © The Author(s), 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Experimental and Molecular Pathology 83 (2007): 224-240, doi:10.1016/j.yexmp.2007.03.007.The intracellular dominance of magnesium ion makes clinical assessment difficult despite the critical role of Mg++ in many key functions of cells and enzymes. There is general consensus that serum Mg++ levels are not representative of the growing number of conditions for which magnesium is known to be important. There is no consensus method or sample source for testing for clinical purposes. High intracellular Mg++ in vertebrate embryos results in part from interactions of cations which influence cell membrane transport systems. These are functionally competent from the earliest stages, at least transiently held over from the unfertilized ovum. Kinetic studies with radiotracer cations, osmolar variations, media lacking one or more of the four biological cations, Na+, Mg++, K+, and Ca++, and metabolic poison 0.05 mEq/L NaF, demonstrated: (1) all four cations influence the behavior of the others, and (2) energy is required for uptake and efflux on different time scales, some against gradient. Na+ uptake is energy dependent against an efflux gradient. The rate of K+ loss is equal with or without fluoride, suggesting a lack of an energy requirement at these stages. Ca++ efflux took twice as long in the presence of fluoride, likely due in part to intracellular binding. Mg++ is anomalous in that early teleost vertebrate embryos have an intracellular content exceeding the surrounding sea water, an isolated unaffected yolk compartment, and a clear requirement for energy for both uptake and efflux. The physiological, pathological, and therapeutic roles of magnesium are poorly understood. This will change: (1) when 28Mg is once again generally available at a reasonable cost for both basic research and clinical assessment, and (2) when serum or plasma levels are determined simultaneously with intracellular values, preferably as part of complete four cation profiles. Atomic absorption spectrophotometry, energy-dispersive x-ray analysis, and inductively coupled plasma emission spectroscopy on sublingual mucosal and peripheral blood samples are potential methods of value for coordinated assessments.AEC Grant No. 134

Phenotypic Consequences of Copy Number Variation: Insights from Smith-Magenis and Potocki-Lupski Syndrome Mouse Models

The characterization of mice with different number of copies of the same genomic segment shows that structural changes influence the phenotypic outcome independently of gene dosage

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery