FlyExpress: visual mining of spatiotemporal patterns for genes and publications in Drosophila embryogenesis.

SUMMARY: Images containing spatial expression patterns illuminate the roles of different genes during embryogenesis. In order to generate initial clues to regulatory interactions, biologists frequently need to know the set of genes expressed at the same time at specific locations in a developing embryo, as well as related research publications. However, text-based mining of image annotations and research articles cannot produce all relevant results, because the primary data are images that exist as graphical objects. We have developed a unique knowledge base (FlyExpress) to facilitate visual mining of images from Drosophila melanogaster embryogenesis. By clicking on specific locations in pictures of fly embryos from different stages of development and different visual projections, users can produce a list of genes and publications instantly. In FlyExpress, each queryable embryo picture is a heat-map that captures the expression patterns of more than 4500 genes and more than 2600 published articles. In addition, one can view spatial patterns for particular genes over time as well as find other genes with similar expression patterns at a given developmental stage. Therefore, FlyExpress is a unique tool for mining spatiotemporal expression patterns in a format readily accessible to the scientific community. AVAILABILITY: http://www.flyexpress.net CONTACT: s.kumar@asu.edu.

BING: biomedical informatics pipeline for Next Generation Sequencing.

High throughput parallel genomic sequencing (Next Generation Sequencing, NGS) shifts the bottleneck in sequencing processes from experimental data production to computationally intensive informatics-based data analysis. This manuscript introduces a biomedical informatics pipeline (BING) for the analysis of NGS data that offers several novel computational approaches to 1. image alignment, 2. signal correlation, compensation, separation, and pixel-based cluster registration, 3. signal measurement and base calling, 4. quality control and accuracy measurement. These approaches address many of the informatics challenges, including image processing, computational performance, and accuracy. These new algorithms are benchmarked against the Illumina Genome Analysis Pipeline. BING is the one of the first software tools to perform pixel-based analysis of NGS data. When compared to the Illumina informatics tool, BING's pixel-based approach produces a significant increase in the number of sequence reads, while reducing the computational time per experiment and error rate (<2%). This approach has the potential of increasing the density and throughput of NGS technologies.

Association of orthodenticle with natural variation for early embryonic patterning in Drosophila melanogaster.

Although it is well established that cis-acting regulatory variation contributes to morphological evolution between species, few concrete examples of polymorphism affecting developmental patterning within species have been demonstrated. Early embryogenesis in Drosophila is initiated by a gradient of Bicoid morphogen activity that results in differential expression of multiple target genes. In a screen for genetic variation affecting this process, we surveyed 96 wild-type lines of Drosophila melanogaster for polymorphisms in binding sites within 16 Bicoid cis-regulatory response elements. One common polymorphism in the orthodenticle (otd) early head enhancer is associated with a complex series of indels/substitutions that define two distinct haplotypes. The middle region of this enhancer exhibits an unusual pattern of nucleotide diversity that does not easily fit into standard models of selection and demography. Population Gene Expression Maps, generated by extracting binary expression profiles from normalized embryo images, revealed a ventral reduction of otd transcript abundance in one of the haplotypes that was recapitulated in expression of transgenic constructs containing the two alleles. We thus demonstrate that even a process as robust as early developmental patterning is affected by standing genetic variation, intriguingly involving otd, whose morphogenetic function bicoid is thought to have displaced during dipteran evolution.