Specific Expression Analysis (SEA) Recent advances have substantially increased the number of genes associated with complex genetic disorders of the CNS such as autism and schizophrenia. It is now clear that there are hundreds of distinct loci contributing to these disorders, underscoring a remarkable genetic heterogeneity. However, the commonality of symptoms across patients indicates there must be a functional convergence downstream of these loci upon the circuits mediating the affected behaviors. One possible mechanism for this convergence would be the selective expression of at least a subset of these genes in the cell types that comprise the circuit. Here, we have provided a simple web server implementing our approach of Cell-type Specific Expression Analysis (CSEA), for identifying candidate cell populations likely to be disrupted across a set of patients with diverse genetic lesions. This leverages a mouse transcriptomic profiling dataset to identify sets of transcripts specifically expressed in particular mouse cells. Though data from specific cell types in the brain is not available in humans, we have also analyzed human data from the Brainspan collection to provide a parallel analysis of transcripts enriched in particular human brain regions, and/or developmental windows.
Enter candidate gene symbols for specific expression analysis across cell types (CSEA): Candidate gene list from
Enter candidate gene symbols for SEA of adult brain regions: Candidate gene list from
Enter candidate gene symbols for SEA across brain regions and development: Candidate gene list from
The results will be shown in a page in about one minute... This server can accept as an input lists of gene symbols (as assigned by HUGO), and returns an enrichment analysis of their expression across the currently available cell types and regions (Table 1). Candidate genes lists that overlap with lists of transcripts enriched in a particular cell type or region are identified by Fisher's exact test with Benjamini-Hochberg correction. User input candidate gene lists may be from any source including, candidate gene lists from genetic analyses of psychiatric disorder, lists of genes with altered expression from RNA-seq or Microarray analysis from postmortem patient tissue, animal models, tumor samples, etc. To properly calculate expected overlap for Fisher's Test, user should indicate whether candidate list is from human or mouse data. For each cell type (mouse) or brain region (human), transcripts that are specifically expressed or enriched have been identified as described (Dougherty et al.) at Specificity Index thresholds (pSI) of varying stringency (e.g., pSI smaller than .01 identifies a larger number of relatively enriched transcripts, while those at pSI smaller than .0001 will be just the subset that is relatively specific). Results will appear for all thresholds. Sample results and explanation are here. Human data are from BrainSpan: Atlas of the Developing Human Brain [Internet]. Funded by ARRA Awards 1RC2MH089921-01, 1RC2MH090047-01, and 1RC2MH089929-01. Â© 2011. Available from here. Version 1.1: Updated 7/31/17 to address a bug fix in which layer 6 neurons and layer 5b neurons were swapped in the CSEA plot output.