Drosophila melanogaster has been established as a model organism for investigating the developmental gene interactions. The spatio-temporal gene expression patterns of Drosophila melanogaster can be visualized by in situ hybridization and documented as digital images. Automated and efficient tools for analyzing these expression images will provide biological insights into the gene functions, interactions, and networks. To facilitate pattern recognition and comparison, many web-based resources have been created to conduct comparative analysis based on the body part keywords and the associated images. With the fast accumulation of images from high-throughput techniques, manual inspection of images will impose a serious impediment on the pace of biological discovery. It is thus imperative to design an automated system for efficient image annotation and comparison.
Results
We present a computational framework to perform anatomical keywords annotation for Drosophila gene expression images. The spatial sparse coding approach is used to represent local patches of images in comparison with the well-known bag-of-words (BoW) method. Three pooling functions including max pooling, average pooling and Sqrt (square root of mean squared statistics) pooling are employed to transform the sparse codes to image features. Based on the constructed features, we develop both an image-level scheme and a group-level scheme to tackle the key challenges in annotating Drosophila gene expression pattern images automatically. To deal with the imbalanced data distribution inherent in image annotation tasks, the undersampling method is applied together with majority vote. Results on Drosophila embryonic expression pattern images verify the efficacy of our approach.
Conclusion
In our experiment, the three pooling functions perform comparably well in feature dimension reduction. The undersampling with majority vote is shown to be effective in tackling the problem of imbalanced data. Moreover, combining sparse coding and image-level scheme leads to consistent performance improvement in keywords annotation.
Multicellular organisms consist of cells of many different types that are established during development. Each type of cell is characterized by the unique combination of expressed gene products as a result of spatiotemporal gene regulation. Currently, a fundamental challenge in regulatory biology is to elucidate the gene expression controls that generate the complex body plans during development. Recent advances in high-throughput biotechnologies have generated spatiotemporal expression patterns for thousands of genes in the model organism fruit fly Drosophila melanogaster. Existing qualitative methods enhanced by a quantitative analysis based on computational tools we present in this paper would provide promising ways for addressing key scientific questions.
Results
We develop a set of computational methods and open source tools for identifying co-expressed embryonic domains and the associated genes simultaneously. To map the expression patterns of many genes into the same coordinate space and account for the embryonic shape variations, we develop a mesh generation method to deform a meshed generic ellipse to each individual embryo. We then develop a co-clustering formulation to cluster the genes and the mesh elements, thereby identifying co-expressed embryonic domains and the associated genes simultaneously. Experimental results indicate that the gene and mesh co-clusters can be correlated to key developmental events during the stages of embryogenesis we study. The open source software tool has been made available at http://compbio.cs.odu.edu/fly/.
Conclusions
Our mesh generation and machine learning methods and tools improve upon the flexibility, ease-of-use and accuracy of existing methods.
Friedrich Leopold August Weismann published Das
Keimplasma: eine Theorie der Vererbung (The Germ-Plasm: a
Theory of Heredity, hereafter The Germ-Plasm) while
working at the University of Freiburg in Freiburg, Germany in 1892.
William N. Parker, a professor in the University College of South
Wales and Monmouthshire in Cardiff, UK, translated The
Germ-Plasm into English in 1893. In The Germ-Plasm,
Weismann proposed a theory of heredity based on the concept of the
germ plasm, a substance in the germ cell that carries hereditary information. The
Germ-Plasm compiled Weismann's theoretical work and analyses of
other biologists' experimental work in the 1880s, and it provided a
framework to study development, evolution and heredity. Weismann
anticipated that the germ-plasm theory would enable researchers to
investigate the functions and material of hereditary substances.
Dizhou Tong, also called Ti Chou Tung, studied marine animals and helped introduce and organize experimental embryology in China during the twentieth century. He introduced cellular nuclear transfer technology to the Chinese biological community, developed methods to clone organisms from many marine species, and investigated the role of cytoplasm in early development. Tong's administrative and scientific leadership in the fields of marine, cellular, and developmental biology contributed to China's experimental embryology research programs.
Green fluorescent protein (GFP) is a protein in the jellyfish Aequorea Victoria that exhibits green fluorescence when exposed to light. The protein has 238 amino acids, three of them (Numbers 65 to 67) form a structure that emits visible green fluorescent light. In the jellyfish, GFP interacts with another protein, called aequorin, which emits blue light when added with calcium. Biologists use GFP to study cells in embryos and fetuses during developmental processes.
In 1868 in England, Charles Darwin proposed his pangenesis theory to describe the units of inheritance between parents and offspring and the processes by which those units control development in offspring. Darwin coined the concept of gemmules, which he said referred to hypothesized minute particles of inheritance thrown off by all cells of the body. The theory suggested that an organism's environment could modify the gemmules in any parts of the body, and that these modified gemmules would congregate in the reproductive organs of parents to be passed on to their offspring. Darwin's theory of pangenesis gradually lost popularity in the 1890s when biologists increasingly abandoned the theory of inheritance of acquired characteristics (IAC), on which the pangenesis theory partially relied. Around the turn of the twentieth century, biologists replaced the theory of pangenesis with germ plasm theory and then with chromosomal theories of inheritance, and they replaced the concept of gemmules with that of genes.
Muriel Wheldale Onslow studied flowers in England with genetic and biochemical techniques in the early twentieth century. Working with geneticist William Bateson, Onslow used Mendelian principles and biochemical analysis together to understand the inheritance of flower colors at the beginning of the twentieth century. Onslow's study of snapdragons, or Antirrhinum majus, resulted in her description of epistasis, a phenomenon in which the phenotypic effect of one gene is influenced by one or more other genes. She discovered several biochemicals related to color formation. Onslow's methodology also partly contributed to the establishment of the field of chemical genetics.
Oswald Theodore Avery studied strains of pneumococcus of the genus Streptococcus in the US in the first half of the twentieth century. This bacterium causes pneumonia, a common cause of death at the turn of the twentieth century. In a 1944 paper, Avery demonstrated with colleagues Colin Munro MacLeod and Maclyn McCarty that deoxyribonucleic acid, or DNA, instead of protein, formed the material of heritable transformation in bacteria. Avery helped untangle some of the relationships between genes and developmental processes.