Last updated: 2022-10-03

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Note that any generated files, e.g. HTML, png, CSS, etc., are not included in this status report because it is ok for generated content to have uncommitted changes.


These are the previous versions of the repository in which changes were made to the R Markdown (analysis/PTR_m6A.Rmd) and HTML (docs/PTR_m6A.html) files. If you’ve configured a remote Git repository (see ?wflow_git_remote), click on the hyperlinks in the table below to view the files as they were in that past version.

File Version Author Date Message
html a2a8fae Jing Gu 2022-10-01 explore MTSplice
html 05a3009 Jing Gu 2022-08-02 PTR_m6A

Backgrounds

Post-transcriptional regulatory (PTR) processes have been implicated in development and diseases, however, it is largely unknown how genetic variations are mediated through PTR processes. We propose to annotate GWAS variants using both experimental measurements and computational predictions. With this prior knowledge, we can further identify most likely causal variants through fine-mapping and then link them to genes.

Several post-transcriptonal features will be explored:

  • alternative splicing
  • RNA modification: m6A
  • RNA binding
  • Polyadenylation

Results

LDSC enrichment across multiple traits

Version Author Date
a2a8fae Jing Gu 2022-10-01
05a3009 Jing Gu 2022-08-02
Fig 1.1a Enrichment of tissue-level m6A peaks across traits via LDSC

Version Author Date
a2a8fae Jing Gu 2022-10-01
05a3009 Jing Gu 2022-08-02
Fig 1.1b Enrichment of tissue-level m6A peaks across traits via LDSC

Adjusting for transcript-level variations across tissues

We compared the enrichment estimates for m6A peaks in fetal tissues conditional on all coding regions or coding regions from differentially expressed genes in each tissue.

Fetal cell atlas for transcriptomics

Cao et al.Science 2020:A human cell atlas of fetal gene expression.

The list DE genes obtained from DEG analysis on pseudobulk transcriptomes, comparing the most expressed tissue and the second most expressed tissue.

For heart tissue, 1011 genes show significantly higher expression than that in the second mostly expressed tissue at FDR 0.05.

Version Author Date
a2a8fae Jing Gu 2022-10-01

Joint analysis via LDSC

The extended region of $$250 bp away from the coding regions was included to adjust for the unsure boundary.

Version Author Date
a2a8fae Jing Gu 2022-10-01
Fig 1.2 Enrichment estimates for m6A peaks called from fetal heart jointly run with all coding regions via LDSC

7.8% of GWAS SNPs are within coding and the extended regions.

Version Author Date
a2a8fae Jing Gu 2022-10-01
Fig 1.3 Enrichment estimates for m6A peaks called from fetal heart jointly run with coding and flanking regions of DEGs in fetal heart via LDSC

Only 0.2% of GWAS SNPs are within coding and flaking regions of DEGs in fetal heart.

Adjusted m6A enrichment estimates across traits

Fig 1.4 (a,b) Enrichment of m6A peaks obtained from heart or liver tissues adjusted by transcribed mRNA levels in the corresponding fetal tissues via LDSC.
Fig 1.5 Enrichment estimates for m6A peaks before and after adjustment with transcribed mRNA levels in the corresponding fetal tissues across traits.

Conditional on transcribed mRNA levels, m6A enrichment estimates are slightly increased across tissues. It seems the adjustment did not affect the m6A enrichment.


sessionInfo()
R version 4.2.0 (2022-04-22)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: CentOS Linux 7 (Core)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.3.13-el7-x86_64/lib/libopenblas_haswellp-r0.3.13.so

locale:
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 [4] LC_COLLATE=C         LC_MONETARY=C        LC_MESSAGES=C       
 [7] LC_PAPER=C           LC_NAME=C            LC_ADDRESS=C        
[10] LC_TELEPHONE=C       LC_MEASUREMENT=C     LC_IDENTIFICATION=C 

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] gridExtra_2.3     dplyr_1.0.9       data.table_1.14.2 ggplot2_3.3.6    

loaded via a namespace (and not attached):
 [1] Rcpp_1.0.8.3     highr_0.9        pillar_1.7.0     compiler_4.2.0  
 [5] bslib_0.3.1      later_1.3.0      jquerylib_0.1.4  git2r_0.30.1    
 [9] workflowr_1.7.0  tools_4.2.0      digest_0.6.29    gtable_0.3.0    
[13] jsonlite_1.8.0   evaluate_0.15    lifecycle_1.0.1  tibble_3.1.7    
[17] pkgconfig_2.0.3  rlang_1.0.2      DBI_1.1.2        cli_3.3.0       
[21] rstudioapi_0.13  yaml_2.3.5       xfun_0.30        fastmap_1.1.0   
[25] withr_2.5.0      stringr_1.4.0    knitr_1.39       generics_0.1.2  
[29] fs_1.5.2         vctrs_0.4.1      sass_0.4.1       tidyselect_1.1.2
[33] rprojroot_2.0.3  grid_4.2.0       glue_1.6.2       R6_2.5.1        
[37] fansi_1.0.3      rmarkdown_2.14   farver_2.1.0     purrr_0.3.4     
[41] magrittr_2.0.3   whisker_0.4      scales_1.2.0     promises_1.2.0.1
[45] ellipsis_0.3.2   htmltools_0.5.2  assertthat_0.2.1 colorspace_2.0-3
[49] httpuv_1.6.5     labeling_0.4.2   utf8_1.2.2       stringi_1.7.6   
[53] munsell_0.5.0    crayon_1.5.1