Neuroinformatics for genomics and anatomy

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The Pavlidis lab focuses on the analysis of the mammalian nervous system at the level of genes and gene regulation, and how this relates to brain development, normal brain function, and pathological processes. We also do basic genomics research that has broader impact beyond neuroscience. A common theme is that we reanalyze, curate and integrate large quantities of publicly-available data. In this proposal we are targeting two specific research projects that will provide insight into gene function and regulation, which is of fundamental importance to understanding organismal biology. The first specific project we propose is to analyze patterns of gene activity in a large body of curated gene expression data we have accumulated in "Gemma", a publicly-available and continually expanding database of curated and re-analyzed gene expression data (gemma.msl.ubc.ca, currently nearly 500,000 samples representing over 12,000 studies and over 30,000 unique experimental conditions). We have recently developed and validated an algorithm, "GemmaDE", for this purpose. We will create a network of conditions used in experiments (e.g. drugs, genetic modifications, disease, developmental stages, sex and others) based on the similarity of their gene expression patterns. Analysis of this network will reveal which of these thousands of diverse conditions resemble each other, yielding new insights into the architecture of gene regulation. The second project will focus on the relationship between gene activity within and across cell types and tissues across the mammalian body, extending recent work from our lab. We will examine correlations between genes (coexpression) with respect to known and inferred mediators and patterns of gene regulation, and compare coexpression networks to each other to elucidate what types of regulatory information is specifically uncovered by each data modality. This project will make extensive use of publicly-available single cell genomics data in combination with other data in Gemma and third-party sources. Integrating these results with the condition network will also be used to provide context in terms of candidate regulators related to conditions. Our research will improve our understanding of gene function and regulation, in ways that are directly useful to other researchers. Applications in neuroscience include improving basic understanding of brain function, cellular processes underlying brain development, as well as the etiology of neuropsychiatric diseases. Beyond the brain, our research will provide broadly applicable insight into modes and regulatory factors underlying gene activity in hundreds of cell types and thousands of experimental conditions. All of our data and resources are made available to the public though web sites, software and application programming interfaces.