A myelin-related transcriptomic profile is shared by Pitt–Hopkins syndrome models and human autism spectrum disorder.

Citation

Phan, B.N., Bohlen, J.F., Davis, B.A. et al. A myelin-related transcriptomic profile is shared by Pitt–Hopkins syndrome models and human autism spectrum disorder. Nat Neurosci 23, 375–385 (2020). https://doi.org/10.1038/s41593-019-0578-x

Description of data & code

Github

The Rscripts and affiliated tables or Rdata objects in this github repositories contain roughly half of what files are required to analyze mouse transcriptomic signatures of PTHS and the relation to other mouse models of syndromic ASD and human idiopathic ASD. The github file size limits prevent uploading of larger file objects. For those larger files, please see the Globus part of this README.

1. Sample sheet describing files, genotype, sex, batch, etc between the 2 sets of RNA-seq from the Maher lab and Philpot lab. An aggregated phenotype table of these samples are at here

2. DEG analyses

• Maher lab Tcf4^+/tr mouse DEG
• Maher lab Tcf4^+/tr mouse DEG by age group
• Mega DEG analyses across multiple Tcf4^+/mut mouse models by age group

3. Cell type-specific Expression Analysis (CSEA)

• Across mega DEGs by age

4. CIBERSORT analyses Note: CIBERSORT cell type quantifications were estimated w/ the CIBERSORT web portal. These Rscripts only assess the group statistical differences in cell type abundance between animals and cohorts.

5. Comparison to MeCP2 and Pten mutant mouse models JHPCE path: /users/bphan/tcf4/PTHS_mouse

Globus

Intermediates and and larger genomic data files generated along the RNA-seq data processing pipelines for this paper are deposited on Globus. These Globus would contain the files that would be referenced in the GitHub Rscripts. To access Globus, a user would have to make a Globus ID and follow instructions to grab these data. Below are descriptions of the general file types for various subsets of data both orignally published in Phan, Bohlen et al. and referenced from other studies. The contents of each Globus roughly contains roughly the following:

• raw sequencing files within the FASTQ folder
• FastQC reports for each corresponding set of sequencing file with the FastQC folder
• alignment .bam files within HISAT2_out folder
• coverage .bw within Coverage folder
• featureCounts objects at the gene, exon, or junction levels in the Counts folder
• aggregated rawCount objects (# of times a unique mRNA fragment align to a gene)
• aggregated rpkmCount object (rawCounts normalized by gene size and sequencing depth).
• sample sheet: annotated_pd.csv
• mega RNA-seq counts--used in mega Tcf4 +/mut differential analyses: rawCounts_mega_dataset_nov14_n110.rda
• mega RNA-seq counts with Pten and Mecp2 mice--used in cross-syndrome analyses: rawCounts_mega_dataset_asd_mice_nov17_n141.rda

Maher lab Tcf4^+/tr mouse processed files:

• counts: rawCounts_mouse_tcf4_n36_rerun_paired_stranded.rda
• rpkm: rpkmCounts_mouse_tcf4_n36_rerun_paired_stranded.rda
• DESeq2 object from Maher lab Tcf4^+/tr mouse DEG analyses: mouse_tcf4_ages_DESeq2_svaAdj.rda
• DESeq2 object from Mega DEG analyses: mega_tcf4_ages_DESeq2_svaAdj.rda
• JHPCE path: /dcl01/lieber/ajaffe/Brady/mouseRNAseq
• Globus path: https://app.globus.org/file-manager?origin_id=9a91a5da-41c2-11ee-88f9-03dc0e0dcc45&origin_path=%2F
• Globus endpoint: 9a91a5da-41c2-11ee-88f9-03dc0e0dcc45

Note: the Mega DEG DESeq2 objects will contain gene counts from Maher, Philpot, and Sweatt lab mouse models of PTHS.

Other datasets that were reprocessed from other monogenetic mutant models of ASD are also contained in this Globus. Briefly they are listed below:

1. MeCP2 mutant mouse from Gabel et al. in the Rett folder
2. Pten mutant mouse from Tilot et al. in the TilotPTEN folder

Philpot lab Tcf4^+/mut mouse processed files to use:

• counts: rawCounts_philpot_OCT20_n58.rda
• rpkm: rpkmCounts_philpot_OCT20_n58.rda
• DESeq object of Tcf4 mutation: philpot_by_age_DESeq2_svaAdj.rda
• JHPCE path: /dcl01/lieber/ajaffe/Brady/philpot
• Globus path: https://app.globus.org/file-manager?origin_id=2a7e9dca-b1f3-11ed-a502-1f2a3a60e896&origin_path=%2F~%2F
• Globus endpoint: 2a7e9dca-b1f3-11ed-a502-1f2a3a60e896

Sweatt lab Tcf4^+/tr mouse processed files

• counts: rawCounts_sweatt_OCT20_n16.rda
• rpkm: rpkmCounts_sweatt_OCT20_n16.rda
• Globus path: https://app.globus.org/file-manager?origin_id=844a91d8-b1f3-11ed-a502-1f2a3a60e896&origin_path=%2F~%2F
• Globus endpoint: 844a91d8-b1f3-11ed-a502-1f2a3a60e896
• JHPCE path: /dcl01/lieber/ajaffe/Brady/sweatt

Note: these sequencing dataset were originally published in Cell Reports, 2016 by Kennedy et al., so usage and citation should be to this publication. We are grateful for access to these data for this publication.