Despite strides in characterizing human history from genetic polymorphism data, progress in identifying genetic signatures of recent demography has been limited. Here we identify very recent fine-scale population structure in North America from a network of over 500 million genetic (identity-by-descent, IBD) connections among 770,000 genotyped individuals of US origin. We detect densely connected clusters within the network and annotate these clusters using a database of over 20 million genealogical records. Recent population patterns captured by IBD clustering include immigrants such as Scandinavians and French Canadians; groups with continental admixture such as Puerto Ricans; settlers such as the Amish and Appalachians who experienced geographic or cultural isolation; and broad historical trends, including reduced north-south gene flow. Our results yield a detailed historical portrait of North America after European settlement and support substantial genetic heterogeneity in the United States beyond that uncovered by previous studies.

Motivation: Estimating gene regulatory networks over biological lineages is central to a deeper understanding of how cells evolve during development and differentiation. However, one challenge in estimating such evolving networks is that their host cells not only contiguously evolve, but also branch over time. For example, a stem cell evolves into two more specialized daughter cells at each division, forming a tree of networks. Another example is in a laboratory setting: a biologist may apply several different drugs individually to malignant cancer cells to analyze the effects of each drug on the cells; the cells treated by one drug may not be intrinsically similar to those treated by another, but rather to the malignant cancer cells they were derived from.Results: We propose a novel algorithm, Treegl, an ℓ1 plus total variation penalized linear regression method, to effectively estimate multiple gene networks corresponding to cell types related by a tree-genealogy, based on only a few samples from each cell type. Treegl takes advantage of the similarity between related networks along the biological lineage, while at the same time exposing sharp differences between the networks. We demonstrate that our algorithm performs significantly better than existing methods via simulation. Furthermore we explore an application to a breast cancer dataset, and show that our algorithm is able to produce biologically valid results that provide insight into the progression and reversion of breast cancer cells.Availability: Software will be available at http://www.sailing.cs.cmu.edu/.Contact: epxing@cs.cmu.edu

Association mapping studies promise to link DNA mutations to gene expression data, possibly leading to innovative treatments for diseases. One challenge in large-scale association mapping studies is exploring the results of the computational analysis to find relevant and interesting associations. Although many association mapping studies find associations from a genomewide collection of genomic data to hundreds or thousands of traits, current visualization software only allow these associations to be explored one trait at a time. The inability to explore the association of a genomic location to multiple traits hides the inherent interaction between traits in the analysis. Additionally, researchers must rely on collections of in-house scripts and multiple tools to perform an analysis, adding time and effort to find interesting associations. In this paper, we present a novel visual analytics system called GenAMap. GenAMap replaces the time-consuming analysis of large-scale association mapping studies with exploratory visualization tools that give geneticists an overview of the data and lead them to relevant information. We present the results of a preliminary evaluation that validated our basic approach.

epxing@cs.cmu.edu.