Last updated: 2023-01-11

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Knit directory: Serreze-T1D_Workflow/

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    Untracked:  data/ici-sick.vs.ici-eoi_blup_sub_chr-8_peak.marker-UNCHS023592_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_blup_sub_chr-9_peak.marker-UNC16009822_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_blup_sub_chr-9_peak.marker-UNC17271730_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_blup_sub_chr-X_peak.marker-UNC31358512_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_blup_sub_chr-X_peak.marker-UNCHS049472_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-10_peak.marker-UNC18805053_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-10_peak.marker-UNCHS029427_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-11_peak.marker-UNCHS031753_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-11_peak.marker-UNCHS031790_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-11_peak.marker-UNCHS031802_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-12_peak.marker-JAX00326005_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-12_peak.marker-UNC20622785_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-12_peak.marker-UNC21995304_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-13_peak.marker-JAX00370189_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-13_peak.marker-UNCHS035661_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-13_peak.marker-UNCHS037125_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-14_peak.marker-UNC24597582_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-14_peak.marker-UNCHS039096_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-15_peak.marker-UNC25489755_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-15_peak.marker-UNCHS040614_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-16_peak.marker-UNCHS042686_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-17_peak.marker-UNCHS043775_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-17_peak.marker-UNCHS043777_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-17_peak.marker-UNCHS043880_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-18_peak.marker-UNC29296831_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-18_peak.marker-UNC29297751_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-19_peak.marker-UNC30069852_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-19_peak.marker-UNC30386742_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-1_peak.marker-UNCHS001121_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-1_peak.marker-UNCHS002308_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-2_peak.marker-UNC3990359_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-2_peak.marker-UNCHS006134_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-3_peak.marker-JAX00105915_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-3_peak.marker-UNC6020011_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-4_peak.marker-UNC8099452_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-4_peak.marker-UNC8161950_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-5_peak.marker-UNC9678100_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-5_peak.marker-UNC9678931_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-6_peak.marker-UNC12162881_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-6_peak.marker-backupUNC060363218_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-7_peak.marker-UNC12719038_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-7_peak.marker-UNCHS022024_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-8_peak.marker-UNC14948439_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-8_peak.marker-UNCHS023592_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-9_peak.marker-UNC16009822_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-9_peak.marker-UNC17271730_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-X_peak.marker-UNC31358512_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_genes_chr-X_peak.marker-UNCHS049472_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_gm_qtl_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_marker.freq_low.geno.freq.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_marker.freq_low.geno.freq.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/ici-sick.vs.ici-eoi_marker.freq_low.geno.freq.removed_sample.outliers.removed_geno.ratiov_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_marker.freq_low.geno.freq.removed_sample.outliers.removed_geno.ratiov_4.batches_myo_mis.csv
    Untracked:  data/ici-sick.vs.ici-eoi_marker.freq_low.probs.freq.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_marker.freq_low.probs.freq.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/ici-sick.vs.ici-eoi_marker.freq_low.probs.freq.removed_sample.outliers.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/ici-sick.vs.ici-eoi_marker.freq_low.probs.freq.removed_sample.outliers.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/ici.vs.pbs_gm_qtl_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/ici.vs.pbs_marker.freq_low.geno.freq.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/ici.vs.pbs_marker.freq_low.geno.freq.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/ici.vs.pbs_marker.freq_low.geno.freq.removed_sample.outliers.removed_geno.ratiov_4.batches_myo.csv
    Untracked:  data/ici.vs.pbs_marker.freq_low.geno.freq.removed_sample.outliers.removed_geno.ratiov_4.batches_myo_mis.csv
    Untracked:  data/ici.vs.pbs_marker.freq_low.probs.freq.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/ici.vs.pbs_marker.freq_low.probs.freq.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/ici.vs.pbs_marker.freq_low.probs.freq.removed_sample.outliers.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/ici.vs.pbs_marker.freq_low.probs.freq.removed_sample.outliers.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/myo-yes.vs.myo-no_marker.freq_low.geno.freq.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/myo-yes.vs.myo-no_marker.freq_low.geno.freq.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/myo-yes.vs.myo-no_marker.freq_low.geno.freq.removed_sample.outliers.removed_geno.ratiov_4.batches_myo.csv
    Untracked:  data/myo-yes.vs.myo-no_marker.freq_low.geno.freq.removed_sample.outliers.removed_geno.ratiov_4.batches_myo_mis.csv
    Untracked:  data/myo-yes.vs.myo-no_marker.freq_low.probs.freq.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/myo-yes.vs.myo-no_marker.freq_low.probs.freq.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/myo-yes.vs.myo-no_marker.freq_low.probs.freq.removed_sample.outliers.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/myo-yes.vs.myo-no_marker.freq_low.probs.freq.removed_sample.outliers.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/pbs-myo-yes.vs.pbs-myo-no_gm_qtl_snpsqc_dis_no-x_updated_4.batches_myo.csv
    Untracked:  data/pbs-myo-yes.vs.pbs-myo-no_marker.freq_low.geno.freq.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/pbs-myo-yes.vs.pbs-myo-no_marker.freq_low.geno.freq.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/pbs-myo-yes.vs.pbs-myo-no_marker.freq_low.geno.freq.removed_sample.outliers.removed_geno.ratiov_4.batches_myo.csv
    Untracked:  data/pbs-myo-yes.vs.pbs-myo-no_marker.freq_low.geno.freq.removed_sample.outliers.removed_geno.ratiov_4.batches_myo_mis.csv
    Untracked:  data/pbs-myo-yes.vs.pbs-myo-no_marker.freq_low.probs.freq.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/pbs-myo-yes.vs.pbs-myo-no_marker.freq_low.probs.freq.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/pbs-myo-yes.vs.pbs-myo-no_marker.freq_low.probs.freq.removed_sample.outliers.removed_geno.ratio_4.batches_myo.csv
    Untracked:  data/pbs-myo-yes.vs.pbs-myo-no_marker.freq_low.probs.freq.removed_sample.outliers.removed_geno.ratio_4.batches_myo_mis.csv
    Untracked:  data/percent_missing_id_4.batches_myo.RData
    Untracked:  data/percent_missing_marker_4.batches_myo.RData
    Untracked:  data/pheno_4.batches_myo.csv
    Untracked:  data/physical_map_4.batches_myo.csv
    Untracked:  data/physical_map_4.batches_myo_BC217.csv
    Untracked:  data/qc_info_bad_sample_4.batches_myo.RData
    Untracked:  data/sample_geno_AHB_4.batches_myo.csv
    Untracked:  data/sample_geno_AHB_4.batches_myo_BC217.csv
    Untracked:  data/sample_geno_bc_4.batches_myo.csv
    Untracked:  data/sample_geno_bc_4.batches_myo_BC217.csv
    Untracked:  data/sample_geno_raw_4.batches_myo_BC217.csv
    Untracked:  data/serreze_probs_4.batches_myo.rds
    Untracked:  data/serreze_probs_allqc_4.batches_myo.rds
    Untracked:  data/serreze_probs_allqc_4.batches_myo_mis.rds
    Untracked:  data/summary.cg_4.batches_myo.RData

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    Modified:   analysis/_site.yml

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Data Information

Loading Data

We will load the data and subset indivials out that are in the groups of interest.

load("data/gm_allqc_4.batches_myo.RData")

#gm_allqc
gm=gm_allqc
gm
Object of class cross2 (crosstype "bc")

Total individuals              208
No. genotyped individuals      208
No. phenotyped individuals     208
No. with both geno & pheno     208

No. phenotypes                   1
No. covariates                  11
No. phenotype covariates         0

No. chromosomes                 20
Total markers                32610

No. markers by chr:
   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
2498 2407 1748 1770 1649 1835 1544 1515 1773 1102 1744 1214 1442 1497 1109  835 
  17   18   19    X 
 674  813  940 4501 
#pr <- readRDS("data/serreze_probs_allqc.rds")
#pr <- readRDS("data/serreze_probs.rds")

##extracting animals with ici and pbs group status
#miceinfo <- covars[gm$covar$group == "PBS" | gm$covar$group == "ICI",]
#table(miceinfo$group)
#mice.ids <- rownames(miceinfo)

#gm <- gm[mice.ids]
#gm
#table(gm$covar$group)

#gm$covar$ici.myo.yes_vs_ici.myo.no <- ifelse(gm$covar$group == "PBS", 0, 1)
#gm.full <- gm

covars <- read_csv("data/covar_corrected_ici-myo-yes.vs.ici-myo-no_4.batches_myo.csv")
#removing any missing info
#covars <- subset(covars, covars$ici.myo.yes_vs_ici.myo.no!='')
nrow(covars)
[1] 93
table(covars$"Myocarditis Status")

 NO YES 
  7  86 
table(covars$"Murine MHC KO Status")

HOM 
 93 
table(covars$"Drug Treatment")

ICI 
 93 
table(covars$"clinical pheno")

 EOI SICK 
   7   86 
#keeping only informative mice
gm <- gm[covars$Mouse.ID]
gm
Object of class cross2 (crosstype "bc")

Total individuals               93
No. genotyped individuals       93
No. phenotyped individuals      93
No. with both geno & pheno      93

No. phenotypes                   1
No. covariates                  11
No. phenotype covariates         0

No. chromosomes                 20
Total markers                32610

No. markers by chr:
   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
2498 2407 1748 1770 1649 1835 1544 1515 1773 1102 1744 1214 1442 1497 1109  835 
  17   18   19    X 
 674  813  940 4501 
table(gm$covar$"Myocarditis Status")

 NO YES 
  7  86 
table(gm$covar$"Murine MHC KO Status")

HOM 
 93 
table(gm$covar$"Drug Treatment")

ICI 
 93 
table(gm$covar$"clinical pheno")

 EOI SICK 
   7   86 
#pr.qc.ids <- pr
#for (i in 1:20){pr.qc.ids[[i]] = pr.qc.ids[[i]][covars$Mouse.ID,,]}

##removing problmetic marker

#gm <- drop_markers(gm, "UNCHS013106")

##dropping monomorphic markers within the dataset

g <- do.call("cbind", gm$geno)

gf_mar <- t(apply(g, 2, function(a) table(factor(a, 1:2))/sum(a != 0)))
#gn_mar <- t(apply(g, 2, function(a) table(factor(a, 1:2))))

gf_mar <- gf_mar[gf_mar[,2] != "NaN",]

count <- rowSums(gf_mar <=0.05)
low_freq_df <- merge(as.data.frame(gf_mar),as.data.frame(count), by="row.names",all=T)
low_freq_df[is.na(low_freq_df)] <- ''
low_freq_df <- low_freq_df[low_freq_df$count == 1,]
rownames(low_freq_df) <- low_freq_df$Row.names

low_freq <- find_markerpos(gm, rownames(low_freq_df))
low_freq$id <- rownames(low_freq)

nrow(low_freq)
[1] 6555
low_freq_bad <- merge(low_freq,low_freq_df, by="row.names",all=T)
names(low_freq_bad)[1] <- c("marker")

gf_mar <- gf_mar[gf_mar[,2] != "NaN",]
MAF <- apply(gf_mar, 1, function(x) min(x))
MAF <- as.data.frame(MAF)
MAF$index <- 1:nrow(gf_mar)
gf_mar_maf <- merge(gf_mar,as.data.frame(MAF), by="row.names")
gf_mar_maf <- gf_mar_maf[order(gf_mar_maf$index),]

gfmar <- NULL
gfmar$gfmar_mar_0 <- sum(gf_mar_maf$MAF==0)
gfmar$gfmar_mar_1 <- sum(gf_mar_maf$MAF< 0.01)
gfmar$gfmar_mar_5 <- sum(gf_mar_maf$MAF< 0.05)
gfmar$gfmar_mar_10 <- sum(gf_mar_maf$MAF< 0.10)
gfmar$gfmar_mar_15 <- sum(gf_mar_maf$MAF< 0.15)
gfmar$gfmar_mar_25 <- sum(gf_mar_maf$MAF< 0.25)
gfmar$gfmar_mar_50 <- sum(gf_mar_maf$MAF< 0.50)
gfmar$total_snps <- nrow(as.data.frame(gf_mar_maf))

gfmar <- t(as.data.frame(gfmar))
gfmar <- as.data.frame(gfmar)
gfmar$count <- gfmar$V1

gfmar[c(2)] %>%
  kable(escape = F,align = c("ccccccccc"),linesep ="\\hline") %>%
  kable_styling(full_width = F) %>%
  kable_styling("striped", full_width = F)  %>%
  row_spec(8 ,bold=T,color= "white",background = "black")
count
gfmar_mar_0 4458
gfmar_mar_1 4458
gfmar_mar_5 6555
gfmar_mar_10 6792
gfmar_mar_15 6836
gfmar_mar_25 6895
gfmar_mar_50 32447
total_snps 32610 
gm_qc <- drop_markers(gm, low_freq_bad$marker)
gm_qc <- drop_nullmarkers(gm_qc)

gm_qc
Object of class cross2 (crosstype "bc")

Total individuals               93
No. genotyped individuals       93
No. phenotyped individuals      93
No. with both geno & pheno      93

No. phenotypes                   1
No. covariates                  11
No. phenotype covariates         0

No. chromosomes                 20
Total markers                26055

No. markers by chr:
   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
2293 2240 1575 1635 1508 1668 1433 1414 1637  945 1621 1087 1339 1385 1008  717 
  17   18   19    X 
 554  733  891  372 
## dropping disproportionate markers
dismark <- read.csv("data/ici-myo-yes.vs.ici-myo-no_marker.freq_low.geno.freq.removed_geno.ratio_4.batches_myo.csv")
nrow(dismark)
[1] 26055
names(dismark)[1] <- c("marker")
dismark <- dismark[!dismark$Include,]
nrow(dismark)
[1] 20489
gm_qc_dis <- drop_markers(gm_qc, dismark$marker)
gm_qc_dis <- drop_nullmarkers(gm_qc_dis)

gm = gm_qc_dis
gm
Object of class cross2 (crosstype "bc")

Total individuals              93
No. genotyped individuals      93
No. phenotyped individuals     93
No. with both geno & pheno     93

No. phenotypes                  1
No. covariates                 11
No. phenotype covariates        0

No. chromosomes                20
Total markers                5566

No. markers by chr:
  1   2   3   4   5   6   7   8   9  10  11  12  13  14  15  16  17  18  19   X 
408 803   5 842 317 436 144 114 588 615 209 230  52  23 377  14  80   5 303   1 
markers <- marker_names(gm)
gmapdf <- read.csv("data/genetic_map_4.batches_myo_BC217.csv")
pmapdf <- read.csv("data/physical_map_4.batches_myo_BC217.csv")
#mapdf <- merge(gmapdf,pmapdf, by=c("marker","chr"), all=T)
#rownames(mapdf) <- mapdf$marker
#mapdf <- mapdf[markers,]
#names(mapdf) <- c('marker','chr','gmapdf','pmapdf')
#mapdfnd <- mapdf[!duplicated(mapdf[c(2:3)]),]

pr.qc <- calc_genoprob(gm)

colnames(covars) <- gsub(" ", ".", colnames(covars))

Genome-wide scan

For each of the phenotype analyzed, permutations were used for each model to obtain genome-wide LOD significance threshold for p < 0.01, p < 0.05, p < 0.10, respectively, separately for X and automsomes (A).

The table shows the estimated significance thresholds from permutation test.

We also looked at the kinship to see how correlated each sample is. Kinship values between pairs of samples range between 0 (no relationship) and 1.0 (completely identical). The darker the colour the more indentical the pairs are.

#Xcovar <- get_x_covar(gm)
addcovar = model.matrix(~sex+Histology.Score, data = covars)[,-1]
covars$ici.myo.yes_vs_ici.myo.no= as.numeric(covars$ici.myo.yes_vs_ici.myo.no)

kinship <- calc_kinship(pr.qc)
heatmap(kinship)

operm <- scan1perm(pr.qc, covars["ici.myo.yes_vs_ici.myo.no"], model="binary", addcovar=addcovar, n_perm=1000)

summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01,  0.05, 0.1))))
names(summary_table) <- c("autosomes")
summary_table$X = summary_table$autosomes
summary_table$significance.level <- rownames(summary_table)

rownames(summary_table) <- NULL

summary_table[c(3,1:2)] %>%
  kable(escape = F,align = c("ccc")) %>%
  kable_styling("striped", full_width = T) %>%
  column_spec(1, bold=TRUE)
significance.level autosomes X
0.01 0 0
0.05 0 0
0.1 0 0

The figures below show QTL maps for each phenotype

#out <- scan1(pr.qc, covars["ici.myo.yes_vs_ici.myo.no"], Xcovar=Xcovar, model="binary")
out <- scan1(pr.qc, covars["ici.myo.yes_vs_ici.myo.no"], model="binary",addcovar=addcovar)

summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01,  0.05, 0.1))))


plot_lod<-function(out,map){
  for (i in 1:dim(out)[2]){
    #png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i],  "_lod.png"))
    
    ymx <- maxlod(out) # overall maximum LOD score
    plot(out, map, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
    #legend("topright", lwd=2, colnames(out)[i], bg="gray90")
    title(main = paste0(colnames(out)[i], " [positions in cM]"))
    add_threshold(map,  summary(operm,alpha=0.1), col = 'purple')
    add_threshold(map,  summary(operm, alpha=0.05), col = 'red')
    add_threshold(map,  summary(operm, alpha=0.01), col = 'blue')

    ##par(mar=c(5.1, 6.1, 1.1, 1.1))
    #ymx <- 11 # overall maximum LOD score
    #plot(out, map, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
    ##legend("topright", lwd=2, colnames(out)[i], bg="gray90")
    #title(main = paste0(colnames(out)[i], " [positions in cM] \n(using same scale as eoi vs ici for easier comparison)"))
    #add_threshold(map,  summary(operm, alpha=0.1), col = 'purple')
    #add_threshold(map,  summary(operm, alpha=0.05), col = 'red')
    #add_threshold(map,  summary(operm, alpha=0.01), col = 'blue')
    ##for (j in 1: dim(summary_table)[1]){
    ##  abline(h=summary_table[j, i],col="red")
    ##  text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
    ##}
    ##dev.off()
  }
}

plot_lod(out,gm$gmap)

LOD peaks

The table below shows QTL peaks associated with the phenotype. We use the 95% threshold from the permutations to find peaks.

Centimorgan (cM)

peaks <- find_peaks(out, gm$pmap, threshold=summary(operm,alpha=0.05), thresholdX = summary(operm,alpha=0.05), peakdrop=3, drop=1.5)

if(nrow(peaks) >0){
peaks$marker <- find_marker(gm$gmap, chr=peaks$chr,pos=peaks$pos)
names(peaks)[2] <- c("phenotype")
peaks <- peaks[-1]

rownames(peaks) <- NULL
print(kable(peaks, escape = F, align = c("cccccccc"), "html") 
  %>% kable_styling("striped", full_width = T)%>%
  column_spec(1, bold=TRUE)
  )

#plot only peak chromosomes

plot_lod_chr<-function(out,map,chrom){
  for (i in 1:dim(out)[2]){
    #png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i],  "_lod.png"))
    
    #par(mar=c(5.1, 6.1, 1.1, 1.1))
    ymx <- maxlod(out) # overall maximum LOD score
    plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
    #legend("topright", lwd=2, colnames(out)[i], bg="gray90")
    title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in cM]"))
    add_threshold(map,  summary(operm,alpha=0.1), col = 'purple')
    add_threshold(map,  summary(operm, alpha=0.05), col = 'red')
    add_threshold(map,  summary(operm, alpha=0.01), col = 'blue')
    #for (j in 1: dim(summary_table)[1]){
    #  abline(h=summary_table[j, i],col="red")
    #  text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
    #}
    #dev.off()

    
    #ymx <- 11
    #plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
    ##legend("topright", lwd=2, colnames(out)[i], bg="gray90")
    #title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in cM]\n(using same scale as eoi vs. ici for easier comparison)"))
    #add_threshold(map,  summary(operm,alpha=0.1), col = 'purple')
    #add_threshold(map,  summary(operm, alpha=0.05), col = 'red')
    #add_threshold(map,  summary(operm, alpha=0.01), col = 'blue')

  }
}


for(i in unique(peaks$chr)){
#for (i in 1:nrow(peaks)){
  #plot_lod_chr(out,gm$gmap, peaks$chr[i])
  plot_lod_chr(out,gm$gmap, i)
}

} else {
  print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05), " [autosomes & x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 0 [autosomes & x-chromosome]”

Megabase (MB)

print("peaks in MB positions")

[1] “peaks in MB positions”

peaks_mba <- find_peaks(out, gm$pmap, threshold=summary(operm,alpha=0.05), thresholdX = summary(operm,alpha=0.05), peakdrop=3, drop=1.5)

if(nrow(peaks) >0){
peaks_mba$marker <- find_marker(gm$pmap, chr=peaks_mba$chr,pos=peaks_mba$pos)
names(peaks_mba)[2] <- c("phenotype")
peaks_mba <- peaks_mba[-1]


rownames(peaks_mba) <- NULL
print(kable(peaks_mba, escape = F, align = c("cccccccc"), "html") 
  %>% kable_styling("striped", full_width = T)%>%
  column_spec(1, bold=TRUE)
  )

plot_lod_chr_mb<-function(out,map,chrom){
  for (i in 1:dim(out)[2]){
    #png(filename=paste0("/Users/chenm/Documents/qtl/Jai/",colnames(out)[i],  "_lod.png"))
    
    #par(mar=c(5.1, 6.1, 1.1, 1.1))
    ymx <- maxlod(out) # overall maximum LOD score
    plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
    #legend("topright", lwd=2, colnames(out)[i], bg="gray90")
    title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in MB]"))
    add_threshold(map,  summary(operm,alpha=0.1), col = 'purple')
    add_threshold(map,  summary(operm, alpha=0.05), col = 'red')
    add_threshold(map,  summary(operm, alpha=0.01), col = 'blue')
    #for (j in 1: dim(summary_table)[1]){
    #  abline(h=summary_table[j, i],col="red")
    #  text(x=400, y =summary_table[j, i]+0.12, labels = paste("p=", row.names(summary_table)[j]))
    #}
    #dev.off()

    #ymx <- 11
    #plot(out, map, chr = chrom, lodcolumn=i, col="slateblue", ylim=c(0, ymx+0.5))
    ##legend("topright", lwd=2, colnames(out)[i], bg="gray90")
    #title(main = paste0(colnames(out)[i], " - chr", chrom, " [positions in MB]\n(using same scale as eoi vs. ici for easier comparison)"))
    #add_threshold(map,  summary(operm,alpha=0.1), col = 'purple')
    #add_threshold(map,  summary(operm, alpha=0.05), col = 'red')
    #add_threshold(map,  summary(operm, alpha=0.01), col = 'blue')


  }
}

for(i in unique(peaks_mba$chr)){
#for (i in 1:nrow(peaks_mba)){
  #plot_lod_chr_mb(out,gm$pmap, peaks_mba$chr[i])
  plot_lod_chr_mb(out,gm$pmap,i)
}

} else {
  print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05), " [autosomes]/",summary(operm,alpha=0.05), " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 0 [autosomes]/0 [x-chromosome]”

QTL effects

For each peak LOD location we give a list of gene

query_variants <- create_variant_query_func("code/cc_variants.sqlite")
query_genes <- create_gene_query_func("code/mouse_genes_mgi.sqlite")

if(nrow(peaks) >0){
for (i in 1:nrow(peaks)){


  g <- maxmarg(pr.qc, gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i], return_char=TRUE)
  #png(filename=paste0("/Users/chenm/Documents/qtl/Jai/","qtl_effect_", i, ".png"))
  #par(mar=c(4.1, 4.1, 1.5, 0.6))
  plot_pxg(g, covars[,peaks$phenotype[i]], ylab=peaks$phenotype[i], sort=FALSE)
  title(main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," )"), line=0.2)
  ##dev.off()

  chr = peaks$chr[i]

# Plot 2
  pr_sub <- pull_genoprobint(pr.qc, gm$gmap, chr, c(peaks$ci_lo[i], peaks$ci_hi[i]))
  blup <- scan1blup(pr.qc[,chr], covars[peaks$phenotype[i]],addcovar = addcovar)
  blup_sub <- scan1blup(pr_sub[,chr], covars[peaks$phenotype[i]], addcovar = addcovar)

  write.csv(as.data.frame(blup_sub), paste0("data/ici-myo-yes.vs.ici-myo-no_blup_sub_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv"), quote=F)

  plot_coef(blup, 
       gm$gmap, columns=1:2,
       bgcolor="gray95", legend="bottomleft", 
       main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i]," [scan1blup; positions in cM])")
       )

  plot_coef(blup_sub, 
       gm$gmap, columns=1:2,
       bgcolor="gray95", legend="bottomleft", 
       main = paste0("chr: ", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$phenotype[i],"; 1.5 LOD drop interval [scan1blup; positions in cM])")
       )

  #Table 1
  chr = peaks_mba$chr[i]
  start=as.numeric(peaks_mba$ci_lo[i])
  end=as.numeric(peaks_mba$ci_hi[i])

  genesgss = query_genes(chr, start, end)

  write.csv(genesgss, file=paste0("data/ici-myo-yes.vs.ici-myo-no_genes_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_dis_no-x_updated_4.batches_myo.csv"), quote=F)

  rownames(genesgss) <- NULL
  genesgss$strand_old = genesgss$strand
  genesgss$strand[genesgss$strand=="+"] <- "positive"
  genesgss$strand[genesgss$strand=="-"] <- "negative"

  print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], "html") %>% kable_styling("striped", full_width = T))


}

} else {
  print(paste0("There are no peaks that have a LOD that reaches suggestive (p<0.05) level of ",summary(operm,alpha=0.05), " [autosomes]/",summary(operm,alpha=0.05), " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 0 [autosomes]/0 [x-chromosome]”

R/qtl

scanone


R version 4.0.3 (2020-10-10)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Ubuntu 20.04.5 LTS

Matrix products: default
BLAS:   /usr/lib/x86_64-linux-gnu/openblas-pthread/libblas.so.3
LAPACK: /usr/lib/x86_64-linux-gnu/openblas-pthread/liblapack.so.3

locale:
 [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
 [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
 [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
 [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
 [9] LC_ADDRESS=C               LC_TELEPHONE=C            
[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       

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

other attached packages:
 [1] abind_1.4-5       qtl2_0.22         reshape2_1.4.4    ggplot2_3.4.0    
 [5] tibble_3.1.8      psych_2.2.9       readxl_1.4.1      cluster_2.1.4    
 [9] dplyr_1.0.10      optparse_1.7.3    rhdf5_2.34.0      mclust_6.0.0     
[13] tidyr_1.2.1       data.table_1.14.6 knitr_1.41        kableExtra_1.3.4 
[17] workflowr_1.7.0  

loaded via a namespace (and not attached):
 [1] httr_1.4.4         sass_0.4.4         bit64_4.0.5        jsonlite_1.7.2    
 [5] viridisLite_0.4.1  bslib_0.4.2        assertthat_0.2.1   getPass_0.2-2     
 [9] highr_0.8          blob_1.2.1         cellranger_1.1.0   yaml_2.2.1        
[13] pillar_1.8.1       RSQLite_2.2.3      lattice_0.20-41    glue_1.6.2        
[17] digest_0.6.31      promises_1.1.1     rvest_1.0.3        colorspace_2.0-0  
[21] htmltools_0.5.4    httpuv_1.5.5       plyr_1.8.8         pkgconfig_2.0.3   
[25] purrr_0.3.4        scales_1.2.1       webshot_0.5.4      processx_3.8.0    
[29] svglite_2.1.0      whisker_0.4        getopt_1.20.3      later_1.1.0.1     
[33] git2r_0.28.0       generics_0.1.3     cachem_1.0.3       withr_2.5.0       
[37] cli_3.6.0          mnormt_2.1.1       magrittr_2.0.1     memoise_2.0.1     
[41] evaluate_0.19      ps_1.5.0           fs_1.5.2           fansi_0.4.2       
[45] nlme_3.1-149       xml2_1.3.3         tools_4.0.3        lifecycle_1.0.3   
[49] stringr_1.4.0      Rhdf5lib_1.12.1    munsell_0.5.0      callr_3.7.3       
[53] compiler_4.0.3     jquerylib_0.1.3    systemfonts_1.0.1  rlang_1.0.6       
[57] grid_4.0.3         rhdf5filters_1.2.1 rstudioapi_0.13    rmarkdown_2.19    
[61] gtable_0.3.0       DBI_1.1.1          R6_2.5.0           bit_4.0.4         
[65] fastmap_1.1.0      utf8_1.1.4         rprojroot_2.0.2    stringi_1.5.3     
[69] parallel_4.0.3     Rcpp_1.0.6         vctrs_0.5.1        tidyselect_1.2.0  
[73] xfun_0.36