Identifying brain development DERs Fetal Infant Child Teen Adult 50+ 6 / group, N = 36 Discovery data Null: Alt: Models Initial results Jaffe et al, Nat. Neuroscience, 2015 50,650 DERs replicated 63,135 DERs Final results
Propor#on of Cells Expression changes across development may represent a changing neuronal phenotype Jaffe et al, Nat. Neuroscience, 2015 Estimation method: Houseman et al, BMC Bioinformatics, 2012
Common ChIP-seq analysis pipeline Sample 1 Sample 2 ... Sample N 1 call peaks call peaks call peaks U 11 U 12 U 1N Number of unique peaks Merge unique peaks Total peaks: U merged ≤ U 1 + U 2 Determine differentially bound peaks between groups 1 & 2 Total tests: U merged 1 Total: U 1 Sample 1 Sample 2 ... Sample N 2 call peaks call peaks call peaks U 21 U 22 U 2N Number of unique peaks 2 Total: U 2 Group 1 Group 2 (A) (A) (B) (C)
Mo#va#ng problem: iden#fy and validate regions of the genome that change expression during brain development 1. derfinder permits discovery of novel expressed & differen#ally bound regions 2. we iden#fied & validated gene expression changes in the developing brain 3. we have developed tools for reproducible shareable repor#ng 4. these tools can be easily be used to process 2,040 projects via recount
Acknowledgements Advisors Jeffrey Leek Andrew Jaffe Collaborators Alyssa Frazee Abhinav Nellore Michael Love Ben Langmead Rafael Irizarry EpiMap project Funding NIH LIBD JHU-Biostats CONACyT México Conference Support Harvard Health Policy Data Science Lab, SACNAS 2016