Dataset Information

Localizing genes to cerebellar layers by classifying ISH images.

ABSTRACT: Gene expression controls how the brain develops and functions. Understanding control processes in the brain is particularly hard since they involve numerous types of neurons and glia, and very little is known about which genes are expressed in which cells and brain layers. Here we describe an approach to detect genes whose expression is primarily localized to a specific brain layer and apply it to the mouse cerebellum. We learn typical spatial patterns of expression from a few markers that are known to be localized to specific layers, and use these patterns to predict localization for new genes. We analyze images of in-situ hybridization (ISH) experiments, which we represent using histograms of local binary patterns (LBP) and train image classifiers and gene classifiers for four layers of the cerebellum: the Purkinje, granular, molecular and white matter layer. On held-out data, the layer classifiers achieve accuracy above 94% (AUC) by representing each image at multiple scales and by combining multiple image scores into a single gene-level decision. When applied to the full mouse genome, the classifiers predict specific layer localization for hundreds of new genes in the Purkinje and granular layers. Many genes localized to the Purkinje layer are likely to be expressed in astrocytes, and many others are involved in lipid metabolism, possibly due to the unusual size of Purkinje cells.

SUBMITTER: Kirsch L

PROVIDER: S-EPMC3527225 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Localizing genes to cerebellar layers by classifying ISH images.

Kirsch Lior L Liscovitch Noa N Chechik Gal G

PLoS computational biology 20121220 12

Gene expression controls how the brain develops and functions. Understanding control processes in the brain is particularly hard since they involve numerous types of neurons and glia, and very little is known about which genes are expressed in which cells and brain layers. Here we describe an approach to detect genes whose expression is primarily localized to a specific brain layer and apply it to the mouse cerebellum. We learn typical spatial patterns of expression from a few markers that are k ...[more]

PMID: 23284274

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Project description:Accurate inference of molecular and functional interactions among genes, especially in multicellular organisms such as Drosophila, often requires statistical analysis of correlations not only between the magnitudes of gene expressions, but also between their temporal-spatial patterns. The ISH (in-situ-hybridization)-based gene expression micro-imaging technology offers an effective approach to perform large-scale spatial-temporal profiling of whole-body mRNA abundance. However, analytical tools for discovering gene interactions from such data remain an open challenge due to various reasons, including difficulties in extracting canonical representations of gene activities from images, and in inference of statistically meaningful networks from such representations. In this paper, we present GINI, a machine learning system for inferring gene interaction networks from Drosophila embryonic ISH images. GINI builds on a computer-vision-inspired vector-space representation of the spatial pattern of gene expression in ISH images, enabled by our recently developed [Formula: see text] system; and a new multi-instance-kernel algorithm that learns a sparse Markov network model, in which, every gene (i.e., node) in the network is represented by a vector-valued spatial pattern rather than a scalar-valued gene intensity as in conventional approaches such as a Gaussian graphical model. By capturing the notion of spatial similarity of gene expression, and at the same time properly taking into account the presence of multiple images per gene via multi-instance kernels, GINI is well-positioned to infer statistically sound, and biologically meaningful gene interaction networks from image data. Using both synthetic data and a small manually curated data set, we demonstrate the effectiveness of our approach in network building. Furthermore, we report results on a large publicly available collection of Drosophila embryonic ISH images from the Berkeley Drosophila Genome Project, where GINI makes novel and interesting predictions of gene interactions. Software for GINI is available at http://sailing.cs.cmu.edu/Drosophila_ISH_images/

Project description:Camera trapping and solicitation of wildlife images through citizen science have become common tools in ecological research. Such studies collect many wildlife images for which correct species classification is crucial; even low misclassification rates can result in erroneous estimation of the geographic range or habitat use of a species, potentially hindering conservation or management efforts. However, some species are difficult to tell apart, making species classification challenging-but the literature on classification agreement rates among experts remains sparse. Here, we measure agreement among experts in distinguishing between images of two similar congeneric species, bobcats (Lynx rufus) and Canada lynx (Lynx canadensis). We asked experts to classify the species in selected images to test whether the season, background habitat, time of day, and the visible features of each animal (e.g., face, legs, tail) affected agreement among experts about the species in each image. Overall, experts had moderate agreement (Fleiss' kappa = 0.64), but experts had varying levels of agreement depending on these image characteristics. Most images (71%) had ?1 expert classification of "unknown," and many images (39%) had some experts classify the image as "bobcat" while others classified it as "lynx." Further, experts were inconsistent even with themselves, changing their classifications of numerous images when they were asked to reclassify the same images months later. These results suggest that classification of images by a single expert is unreliable for similar-looking species. Most of the images did obtain a clear majority classification from the experts, although we emphasize that even majority classifications may be incorrect. We recommend that researchers using wildlife images consult multiple species experts to increase confidence in their image classifications of similar sympatric species. Still, when the presence of a species with similar sympatrics must be conclusive, physical or genetic evidence should be required.

Dataset Information

Localizing genes to cerebellar layers by classifying ISH images.

Publications

Localizing genes to cerebellar layers by classifying ISH images.

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