Activities
Training, immediate access to processing pipelines, ePRS design, and support interpreting and communicating results.
Background
In 2017, Meaney, Pokhvisneva and Silveira created a novel approach to genomic profiling, informed by biological function, characterizing gene networks based on the levels of co-expression in a specific tissue, called expression-based polygenic risk score (ePRS).
As opposed to current GWAS/PRS techniques focused on predicting highly significant genetic effects of small magnitude, ePRS identifies cohesive, biologically relevant and tissue-specific gene networks, providing critical mechanistic insights as a complement to prediction.
The goal of the ePRS Cluster is to provide a faster solution to ePRS and traditional genomic needs through training, pipeline access, ePRS design, and results support.
Workshop Modules
- Designing ePRSs: GWAS and PRS technology, expression-based polygenic scores, tissue-specific co-expression gene networks, enrichment analysis, and visualization pipelines.
- Genotyping Quality Control: GenomeStudio usage, pre- and post-imputation QC, imputation, data formats, and HRC alignment.
- PRS/ePRS calculation: tools, commands, GWAS and GTEx reference data sets, and approaches for very large data sets.
- Genetically predicted gene expression tools such as PrediXcan.
- Ancestry considerations and principal components for genotyping data.
- Statistical analysis and model fitting, including ethnicity/PC adjustment and gene-environment interaction form.
References
- Miguel PM, Pereira LO, Barth B, et al. Prefrontal Cortex Dopamine Transporter Gene Network Moderates the Effect of Perinatal Hypoxic-Ischemic Conditions on Cognitive Flexibility and Brain Gray Matter Density in Children. Biol Psychiatry. 2019;86(8):621-630.
- Hari Dass SA, McCracken K, Pokhvisneva I, et al. A biologically-informed polygenic score identifies endophenotypes and clinical conditions associated with the insulin receptor function on specific brain regions. EBioMedicine. 2019;42:188-202.
- Silveira PP, Pokhvisneva I, Parent C, et al. Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes moderated by a biologically informed polygenetic score based on SLC6A4 gene expression. Dev Psychopathol. 2017;29(5):1601-1617.
- de Lima RMS, Barth B, Arcego DM, et al. Amygdala 5-HTT Gene Network Moderates the Effects of Postnatal Adversity on Attention Problems: Anatomo-Functional Correlation and Epigenetic Changes. Front Neurosci-Switz. 2020;14(198).