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/

MOTIVATION: Microarray profiling of mRNA abundance is often ill suited for temporal-spatial analysis of gene expressions in multicellular organisms such as Drosophila. Recent progress in image-based genome-scale profiling of whole-body mRNA patterns via in situ hybridization (ISH) calls for development of accurate and automatic image analysis systems to facilitate efficient mining of complex temporal-spatial mRNA patterns, which will be essential for functional genomics and network inference in higher organisms. RESULTS: We present SPEX(2), an automatic system for embryonic ISH image processing, which can extract, transform, compare, classify and cluster spatial gene expression patterns in Drosophila embryos. Our pipeline for gene expression pattern extraction outputs the precise spatial locations and strengths of the gene expression. We performed experiments on the largest publicly available collection of Drosophila ISH images, and show that our method achieves excellent performance in automatic image annotation, and also finds clusters that are significantly enriched, both for gene ontology functional annotations, and for annotation terms from a controlled vocabulary used by human curators to describe these images. AVAILABILITY: Software will be available at http://www.sailing.cs.cmu.edu/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Population heterogeneity through admixing of different founder populations can produce spurious associations in genome-wide association studies that are linked to the population structure rather than the phenotype. Since samples from the same population generally co-evolve, different populations may or may not share the same genetic underpinnings for the seemingly common phenotype. Our goal is to develop a unified framework for detecting causal genetic markers through a joint association analysis of multiple populations. RESULTS: Based on a multi-task regression principle, we present a multi-population group lasso algorithm using L(1)/L(2)-regularized regression for joint association analysis of multiple populations that are stratified either via population survey or computational estimation. Our algorithm combines information from genetic markers across populations, to identify causal markers. It also implicitly accounts for correlations between the genetic markers, thus enabling better control over false positive rates. Joint analysis across populations enables the detection of weak associations common to all populations with greater power than in a separate analysis of each population. At the same time, the regression-based framework allows causal alleles that are unique to a subset of the populations to be correctly identified. We demonstrate the effectiveness of our method on HapMap-simulated and lactase persistence datasets, where we significantly outperform state of the art methods, with greater power for detecting weak associations and reduced spurious associations. AVAILABILITY: Software will be available at http://www.sailing.cs.cmu.edu/.

The EROCS technology automatically links unstructured data with relevant structured data from an external relational database. We demonstrate how EROCS can be used for enhancing business intelligence by allowing OLAP tools to analyze structured and unstructured data in a consolidated manner. Our demonstration showcases the use of EROCS in exploiting latent information in customer emails, which helps in building a complete view of the customer. This results in new insights about the business which are not possible with the existing state of the art.

We introduce a new, powerful class of text proximity queries: find an instance of a given "answer type" (person, place, distance) near "selector" tokens matching given literals or satisfying given ground predicates. An example query is type=distance NEAR Hamburg Munich. Nearness is defined as a flexible, trainable parameterized aggregation function of the selectors, their frequency in the corpus, and their distance from the candidate answer. Such queries provide a key data reduction step for information extraction, data integration, question answering, and other text-processing applications. We describe the architecture of a next-generation information retrieval engine for such applications, and investigate two key technical problems faced in building it. First, we propose a new algorithm that estimates a scoring function from past logs of queries and answer spans. Plugging the scoring function into the query processor gives high accuracy: typically, an answer is found at rank 2-4. Second, we exploit the skew in the distribution over types seen in query logs to optimize the space required by the new index structures required by our system. Extensive performance studies with a 10GB, 2-million document TREC corpus and several hundred TREC queries show both the accuracy and the efficiency of our system. From an initial 4.3GB index using 18,000 types from WordNet, we can discard 88% of the space, while inflating query times by a factor of only 1.9. Our final index overhead is only 20% of the total index space needed.