Last updated: 2023-05-22

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Knit directory: Cardiotoxicity/

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File Version Author Date Message
Rmd e2b3215 reneeisnowhere 2023-05-22 add Seoane data
html c3481d8 reneeisnowhere 2023-05-22 Build site.
Rmd acbd0a8 reneeisnowhere 2023-05-22 updates on GWAS enrichment
Rmd e8c82ec reneeisnowhere 2023-05-18 adding other_analysis and genes of interest log2cpm

Knowles Comparison data:

Determining the genetic basis of anthracycline-cardiotoxicity by molecular response QTL mapping in induced cardiomyocytes David A Knowles, Courtney K Burrows†, John D Blischak, Kristen M Patterson, Daniel J Serie, Nadine Norton, Carole Ober, Jonathan K Pritchard, Yoav Gilad

Knowles \(~~et~ al.~\) eLife 2018;7:e33480. DOI: https://doi.org/10.7554/eLife.33480 My first question was about transcription response at the 24 hour mark with my treatments. 3 hour RNA-seq had low levels of DEGs,so my focus is at 24 hours. This also happens to be when the Knowles paper collected their RNA-seq data

Supplementary 4 contains a list of 518 SNPs within 1 Mb of TSS, which had a detectable marginal effect on expression (5% FDR). When converted from ensembl gene id to entrez gene id, my list of unique Entrezgeneids = 521. I will call these meSNPs for marginal effect snps. In the meSNPs, 503 are within my DEG of 14084. Using an adj. P value of 0.05, There are 199/6864 in 24 hour daunorubicin, 184/6516 in 24 hour doxorubicin, 182/6202 in 24 hour epirubicin, 30/1327 in 24 hour mitoxantrone and 0 in Trastuzumb

Supplementary 5 contains a list of 376 response eQTLs (reQTLs). These are variants that were associated with modulation of transcriptomic response to doxorubicin treatment. After database name conversion, I have 377 unique Entregene ids. Of the reQTLs list, 374 are within my DEG of 14084. Using an adj. P value of 0.05, There are 187/6864 in 24 hour daunorubicin, 180/6516 in 24 hour doxorubicin, 176/6202 in 24 hour epirubicin, 40/1327 in 24 hour mitoxantrone and 0 in Trastuzumb.

Count of genes in each treatment by using adj. P value of <0.05
time id n K4 K5
24_hours Daunorubicin 6864 199 187
24_hours Doxorubicin 6516 184 180
24_hours Epirubicin 6202 172 176
24_hours Mitoxantrone 1327 30 40
Count of genes in each treatment by total expressed genes
time id n K4 K5
24_hours Daunorubicin 14084 503 374
24_hours Doxorubicin 14084 503 374
24_hours Epirubicin 14084 503 374
24_hours Mitoxantrone 14084 503 374
24_hours Trastuzumab 14084 503 374

Seone, Jose Chromatin gene comparison: comes from supp data NAT. MED 2019

Seaone 2019

ArrGWAS to 24 hour DEG genes p < 0.05

Significant (adj. P value of <0.05) and non-sig gene counts in Arrhythmia GWAS
id sigcount ARR ARRcount
Daunorubicin notsig no 7169
Daunorubicin notsig y 51
Daunorubicin sig no 6795
Daunorubicin sig y 69
Doxorubicin notsig no 7512
Doxorubicin notsig y 56
Doxorubicin sig no 6452
Doxorubicin sig y 64
Epirubicin notsig no 7827
Epirubicin notsig y 55
Epirubicin sig no 6137
Epirubicin sig y 65
Mitoxantrone notsig no 12650
Mitoxantrone notsig y 107
Mitoxantrone sig no 1314
Mitoxantrone sig y 13
Trastuzumab notsig no 13964
Trastuzumab notsig y 120

HFGWAS

Significant (adj. P value of <0.05) and non-sig gene counts in HFhythmia GWAS
id sigcount HF HFcount
Daunorubicin notsig no 7209
Daunorubicin notsig y 11
Daunorubicin sig no 6842
Daunorubicin sig y 22
Doxorubicin notsig no 7556
Doxorubicin notsig y 12
Doxorubicin sig no 6495
Doxorubicin sig y 21
Epirubicin notsig no 7868
Epirubicin notsig y 14
Epirubicin sig no 6183
Epirubicin sig y 19
Mitoxantrone notsig no 12728
Mitoxantrone notsig y 29
Mitoxantrone sig no 1323
Mitoxantrone sig y 4
Trastuzumab notsig no 14051
Trastuzumab notsig y 33

CAD GWAS

Significant (adj. P value of <0.05) and non-sig gene counts in CAD GWAS
id sigcount CAD CADcount
Daunorubicin notsig no 7107
Daunorubicin notsig y 113
Daunorubicin sig no 6748
Daunorubicin sig y 116
Doxorubicin notsig no 7447
Doxorubicin notsig y 121
Doxorubicin sig no 6408
Doxorubicin sig y 108
Epirubicin notsig no 7762
Epirubicin notsig y 120
Epirubicin sig no 6093
Epirubicin sig y 109
Mitoxantrone notsig no 12547
Mitoxantrone notsig y 210
Mitoxantrone sig no 1308
Mitoxantrone sig y 19
Trastuzumab notsig no 13855
Trastuzumab notsig y 229

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Platform: x86_64-w64-mingw32/x64 (64-bit)
Running under: Windows 10 x64 (build 19045)

Matrix products: default

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