GWAS in a box: statistical and visual analytics of structured associations via GenAMap.

With the continuous improvement in genotyping and molecular phenotyping technology and the decreasing typing cost, it is expected that in a few years, more and more clinical studies of complex diseases will recruit thousands of individuals for pan-omic genetic association analyses. Hence, there is a great need for algorithms and software tools that could scale up to the whole omic level, integrate different omic data, leverage rich structure information, and be easily accessible to non-technical users. We present GenAMap, an interactive analytics software platform that 1) automates the execution of principled machine learning methods that detect genome- and phenome-wide associations among genotypes, gene expression data, and clinical or other macroscopic traits, and 2) provides new visualization tools specifically designed to aid in the exploration of association mapping results.

NP-MuScL: unsupervised global prediction of interaction networks from multiple data sources.

Inference of gene interaction networks from expression data usually focuses on either supervised or unsupervised edge prediction from a single data source. However, in many real world applications, multiple data sources, such as microarray and ISH (in situ hybridization) measurements of mRNA abundances, are available to offer multiview information about the same set of genes. We propose ISH to estimate a gene interaction network that is consistent with such multiple data sources, which are expected to reflect the same underlying relationships between the genes.

GINI: from ISH images to gene interaction networks.

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.

SPEX2: automated concise extraction of spatial gene expression patterns from Fly embryo 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.

Multi-population GWA mapping via multi-task regularized regression.

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.