Biology subjects

Shannon E Ellis

Publications and source records attributed to Shannon E Ellis.

3 recordsLinked to original sources

bioRxiv2016

Exaggerated CpH Methylation in the Autism-Affected Brain

The etiology of autism, a complex neurodevelopmental disorder, remains largely unexplained. Here, we explore the role of CpG and CpH (H=A, C, or T) methylation within autism-affected cortical brain tissue. While no individual site of methylation was significantly associated with autism after multi-test correction, methylated CpH di-nucleotides were markedly enriched in autism-affected brains (~2-fold enrichment at p <0.05 cut-off, p=0.002). These results further implicate epigenetic alterations in pathobiological mechanisms that underlie autism.

Genetics↗

bioRxiv2016

recount: A large-scale resource of analysis-ready RNA-seq expression data

recount is a resource of processed and summarized expression data spanning nearly 60,000 human RNA-seq samples from the Sequence Read Archive (SRA). The associated recount Bio-conductor package provides a convenient API for querying, downloading, and analyzing the data. Each processed study consists of meta/phenotype data, the expression levels of genes and their underlying exons and splice junctions, and corresponding genomic annotation. We also provide data summarization types for quantifying novel transcribed sequence including base-resolution coverage and potentially unannotated splice junctions. We present workflows illustrating how to use recount to perform differential expression analysis including meta-analysis, annotation-free base-level analysis, and replication of smaller studies using data from larger studies. recount provides a valuable and user-friendly resource of processed RNA-seq datasets to draw additional biological insights from existing public data. The resource is available at https://jhubiostatistics.shinyapps.io/recount/.

Genomics↗

bioRxiv2015

Transcriptome Analysis of Cortical Tissue Reveals Shared Sets of Down-Regulated Genes in Autism and Schizophrenia

Autism (AUT), Schizophrenia (SCZ), and bipolar disorder (BPD) are three highly heritable neuropsychiatric conditions. Clinical similarities and genetic overlap between the three disorders have been reported; however, the causes and the downstream effects of this overlap remain elusive. By analyzing transcriptomic RNA-Sequencing data generated from post-mortem cortical brain tissues from AUT, SCZ, BPD and control subjects, we have begun to characterize the extent of gene expression overlap between these disorders. We report that the AUT and SCZ transcriptomes are significantly correlated (p<0.001), while the other two cross disorder comparisons (AUT-BPD, SCZ-BPD) are not. Among AUT and SCZ, we find that the genes differentially expressed across disorders are involved in neurotransmission and synapse regulation. Despite lack of global transcriptomic overlap across all three disorders, we highlight two genes, IQSEC3 and COPS7A, which are significantly down-regulated compared to controls across all three disorders, suggesting either shared etiology or compensatory changes across these neuropsychiatric conditions. Finally, we tested for enrichment of genes differentially expressed across disorders in genetic association signals in AUT, SCZ or BPD, reporting lack of signal in any of the previously published GWAS. Together, these studies highlight the importance of examining gene expression from the primary tissue involved in neuropsychiatric conditions, cortical brain. We identify a shared role for altered neurotransmission and synapse regulation in AUT and SCZ, in addition to two genes that may more generally contribute to neurodevelopmental and neuropsychiatric conditions.

Genetics↗