Last updated: 2022-07-02

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Knit directory: Serreze-T1D_Workflow/

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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-17_peak.marker-UNCrs47191360_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008281_lod.drop-1.5_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008286_lod.drop-1.5_5.batches_0.csv
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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008409_lod.drop-1.5_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008432_lod.drop-1.5_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008487_lod.drop-1.5_snpsqc_5.batches_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008487_lod.drop-1.5_snpsqc_5.batches_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008487_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008487_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008487_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008487_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008511_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008511_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008609_lod.drop-1.5_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008613_lod.drop-1.5_5.batches_0.csv
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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008614_lod.drop-1.5_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008627_lod.drop-1.5_5.batches_mis_0.csv
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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008725_lod.drop-1.5_5.batches_mis_0.csv
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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS008815_lod.drop-1.5_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCHS009066_lod.drop-1.5_5.batches_52.csv
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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-UNCJPD001276_lod.drop-1.5_5.batches_mis_0.csv
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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-3_peak.marker-sanger2496q_lod.drop-1.5_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-4_peak.marker-UNC8250659_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-4_peak.marker-UNC8439633_lod.drop-1.5_snpsqc_5.batches_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-4_peak.marker-UNC8439633_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-4_peak.marker-UNCHS012955_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-6_peak.marker-UNC11108920_lod.drop-1.5_snpsqc_5.batches.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-6_peak.marker-UNC11108920_lod.drop-1.5_snpsqc_5.batches_mis.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-7_peak.marker-UNCHS020066_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-7_peak.marker-UNCHS020066_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-7_peak.marker-UNCHS020066_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-7_peak.marker-UNCHS020066_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-8_peak.marker-UNC15524531_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-8_peak.marker-UNC15524531_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-8_peak.marker-UNC15524531_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-8_peak.marker-UNC15524531_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-9_peak.marker-UNC17203597_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-9_peak.marker-UNC17203597_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-X_peak.marker-UNCHS048314_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-X_peak.marker-UNCHS048314_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-X_peak.marker-UNCHS048314_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_blup_sub_chr-X_peak.marker-UNCHS048314_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-JAX00020646_lod.drop-1.5_5.batches_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-JAX00292499_lod.drop-1.5_5.batches_52.csv
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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-JAX00294019_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18216614_lod.drop-1.5_5.batches_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18240977_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18311938_lod.drop-1.5_5.batches_0.csv
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    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18311938_lod.drop-1.5_snpsqc_5.batches_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18311938_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18343181_lod.drop-1.5_5.batches_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18363544_lod.drop-1.5_5.batches_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18363544_lod.drop-1.5_5.batches_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18363544_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNC18376338_lod.drop-1.5_snpsqc_5.batches_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNCHS028236_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNCHS028236_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNCHS028536_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-10_peak.marker-UNCHS028536_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-11_peak.marker-UNC19970181_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-11_peak.marker-UNC19970181_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-11_peak.marker-UNC20090524_lod.drop-1.5_snpsqc_5.batches_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-12_peak.marker-ICR499_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-12_peak.marker-ICR499_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-12_peak.marker-ICR499_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-13_peak.marker-UNCHS036773_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-13_peak.marker-UNCHS036773_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-14_peak.marker-UNC24056202_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-14_peak.marker-UNC24056202_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-15_peak.marker-UNC26070435_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-15_peak.marker-UNC26070435_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-17_peak.marker-UNCHS044241_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-17_peak.marker-UNCHS044241_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-17_peak.marker-UNCJPD006614_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-17_peak.marker-UNCrs47191360_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-18_peak.marker-UNCHS045343_lod.drop-1.5_snpsqc_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-18_peak.marker-UNCHS045343_lod.drop-1.5_snpsqc_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-2_peak.marker-UNC4609527_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_0.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-2_peak.marker-UNC4609527_lod.drop-1.5_snpsqc_dis_no-x_updated_5.batches_mis_52.csv
    Untracked:  data/ici.vs.eoi_age.of.onset-no.covariates_genes_chr-2_peak.marker-UNCHS008007_lod.drop-1.5_5.batches_mis.csv
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Unstaged changes:
    Modified:   analysis/4.1.1_qtl.analysis_binary_ici-early.vs.pbs_5.batches.Rmd
    Modified:   analysis/4.1.1_qtl.analysis_binary_ici-early.vs.pbs_5.batches_mis.Rmd
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    Modified:   analysis/4.1.1_qtl.analysis_binary_ici-early.vs.pbs_snpsqc_dis_no-x_updated_5.batches.Rmd
    Modified:   analysis/4.1.1_qtl.analysis_binary_ici-early.vs.pbs_snpsqc_dis_no-x_updated_5.batches_mis.Rmd
    Modified:   analysis/4.1.1_qtl.analysis_binary_ici.vs.eoi_snpsqc_dis_no-x_updated.Rmd
    Modified:   analysis/4.1.1_qtl.analysis_binary_ici.vs.pbs_snpsqc_dis_no-x_updated.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_pheno.corrected.cleaned_5.batches.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_pheno.corrected.cleaned_5.batches_mis.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
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    Modified:   analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_age_ici.vs.eoi_pheno.corrected.cleaned_5.batches.Rmd
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    Modified:   analysis/4.1.2_qtl.analysis_cont_age_ici.vs.pbs_pheno.corrected.cleaned_5.batches.Rmd
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    Modified:   analysis/4.1.2_qtl.analysis_cont_age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici-early.vs.pbs_pheno.corrected.cleaned_5.batches.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici-early.vs.pbs_pheno.corrected.cleaned_5.batches_mis.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici-early.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
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    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_pheno.corrected.cleaned_5.batches_mis.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_5.batches_mis.Rmd
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    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.eoi_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_pheno.corrected.cleaned_5.batches.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_pheno.corrected.cleaned_5.batches_mis.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_5.batches_mis.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches.Rmd
    Modified:   analysis/4.1.2_qtl.analysis_cont_rz.age_ici.vs.pbs_snpsqc_pheno.corrected.cleaned_dis_no-xk_5.batches_mis.Rmd
    Modified:   analysis/genotype.frequencies_ici.vs.eoi_5.batches.Rmd
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    Modified:   analysis/genotype.frequencies_ici.vs.pbs_5.batches_mis.Rmd
    Modified:   analysis/index_5.batches.Rmd
    Modified:   analysis/index_5.batches_additional.Rmd

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.


There are no past versions. Publish this analysis with wflow_publish() to start tracking its development.


Loading Data

We will load the data and subset indivials out that are in the groups of interest. We will create a binary phenotype from this (PBS ==0, ICI == 1).

load("data/gm_allqc_5.batches.RData")

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

Total individuals              308
No. genotyped individuals      308
No. phenotyped individuals     308
No. with both geno & pheno     308

No. phenotypes                   1
No. covariates                   6
No. phenotype covariates         0

No. chromosomes                 20
Total markers                34537

No. markers by chr:
   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
2643 2629 1857 1890 1774 1941 1672 1627 1878 1176 1871 1300 1549 1578 1257  935 
  17   18   19    X 
 501  913 1014 4532 
#pr <- readRDS("data/serreze_probs_allqc.rds")
#pr <- readRDS("data/serreze_probs.rds")

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

ICI PBS 
104  34 
mice.ids <- rownames(miceinfo)

gm <- gm[mice.ids]
gm
Object of class cross2 (crosstype "bc")

Total individuals              138
No. genotyped individuals      138
No. phenotyped individuals     138
No. with both geno & pheno     138

No. phenotypes                   1
No. covariates                   6
No. phenotype covariates         0

No. chromosomes                 20
Total markers                34537

No. markers by chr:
   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
2643 2629 1857 1890 1774 1941 1672 1627 1878 1176 1871 1300 1549 1578 1257  935 
  17   18   19    X 
 501  913 1014 4532 
#pr.qc <- pr
#for (i in 1:20){pr.qc[[i]] = pr.qc[[i]][mice.ids,,]}

#bin_pheno <- NULL
#bin_pheno$PBS <- ifelse(gm$covar$group == "PBS", 1, 0)
#bin_pheno$ICI <- ifelse(gm$covar$group == "ICI", 1, 0)
#bin_pheno <- as.data.frame(bin_pheno)
#rownames(bin_pheno) <- rownames(gm$covar)

gm$covar$ICI.vs.PBS <- ifelse(gm$covar$group == "PBS", 0, 1)
gm.full <- gm


##adding peaks as covariates: UNCHS008487, UNC8250659, UNC18240977

mar.covar <- pull_markers(gm, c("UNCHS008487", "UNC8250659", "UNC18240977"))
mar.covar.g <- do.call("cbind", mar.covar$geno)

covars <- merge(gm$covar, mar.covar.g, by='row.names', sort=F)
table(covars$group)

ICI PBS 
104  34 
rownames(covars) <- covars$Row.names
covars <- covars[-1]


##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] 7989
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 3814
gfmar_mar_1 4068
gfmar_mar_5 7989
gfmar_mar_10 8527
gfmar_mar_15 8598
gfmar_mar_25 9313
gfmar_mar_50 33753
total_snps 34537
gm_qc <- drop_markers(gm, low_freq_bad$marker)
gm_qc <- drop_nullmarkers(gm_qc)
 
gm = gm_qc
gm
Object of class cross2 (crosstype "bc")

Total individuals              138
No. genotyped individuals      138
No. phenotyped individuals     138
No. with both geno & pheno     138

No. phenotypes                   1
No. covariates                   7
No. phenotype covariates         0

No. chromosomes                 20
Total markers                26548

No. markers by chr:
   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
2374 2374 1623 1691 1568 1703 1464 1468 1685  974 1671 1134 1377 1411  876  751 
  17   18   19    X 
 330  770  920  384 
markers <- marker_names(gm)
gmapdf <- read.csv("/Users/corneb/Documents/MyJax/CS/Projects/Serreze/haplotype.reconstruction/output_5.batches/genetic_map.csv")
pmapdf <- read.csv("/Users/corneb/Documents/MyJax/CS/Projects/Serreze/haplotype.reconstruction/output_5.batches/physical_map.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)

Conditionaing on eoi vs. ici chr 3 peak (UNCHS008487)

Genome-wide scan

#gm

Xcovar <- get_x_covar(gm)
#addcovar = model.matrix(~Sex, data = covars)[,-1]

addcovar = model.matrix(~UNCHS008487, data = covars)[,-1]

#K <- calc_kinship(pr.qc, type = "loco")
#heatmap(K[[1]])
#K.overall <- calc_kinship(pr.qc, type = "overall")
#heatmap(K.overall)
kinship <- calc_kinship(pr.qc)
heatmap(kinship)

#operm <- scan1perm(pr.qc, gm$covar$phenos, Xcovar=Xcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, addcovar = addcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, n_perm=2000)
operm <- scan1perm(pr.qc, gm$covar["ICI.vs.PBS"], model="binary", n_perm=10, perm_Xsp=TRUE, chr_lengths=chr_lengths(gm$gmap), addcovar = addcovar)

summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01,  0.05, 0.1))))
names(summary_table) <- c("autosomes","X")
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 2.728945 4.014186
0.05 2.674651 3.303588
0.1 2.606618 2.374305

The figures below show QTL maps for each phenotype

out <- scan1(pr.qc, gm$covar["ICI.vs.PBS"], Xcovar=Xcovar, 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$gmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, 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, "html") 
#  %>% kable_styling("striped", full_width = T) %>%
#  column_spec(1, bold=TRUE)
#  )

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

#peaks[] %>%
#  kable(escape = F,align = c("cccccccc")) %>%
#  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)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.67465122006504 [autosomes]/3.30358811059369 [x-chromosome]”

Megabase (MB)

print("peaks in MB positions")

[1] “peaks in MB positions”

peaks_mba <- find_peaks(out, gm$pmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, 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]

#peaks_mbl <- list()
##corresponding info in Mb
#for(i in 1:nrow(peaks)){
#  #lodindex <- peaks$lodindex[i]
#  phenotype <- peaks$phenotype[i]
#  chr <- as.character(peaks$chr[i])
#  lod <- peaks$lod[i]
#  mark <- peaks$marker[i]
#  pos <- mapdf[mapdf$marker==mark,]$pmapdf
#  ci_lo <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_lo[i] & mapdfnd$chr == peaks$chr[i])]
#  ci_hi <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_hi[i] & mapdfnd$chr == peaks$chr[i])]
#  peaks_mb=as.data.frame(cbind(phenotype, chr, pos, lod, ci_lo, ci_hi, mark))
#  names(peaks_mb)[7] <- c("marker")
#  peaks_mbl[[i]] <- peaks_mb
#}
#peaks_mba2 <- do.call(rbind, peaks_mbl)
#peaks_mba2 <- as.data.frame(peaks_mba)
#peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")] <- sapply(peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")], as.numeric)

rownames(peaks_mba) <- NULL

#print(kable(peaks_mba, "html") 
#  %>% kable_styling("striped", full_width = T) %>%
#  column_spec(1, bold=TRUE)
#  )

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

#peaks_mba[] %>%
#  kable(escape = F,align = c("cccccccc")) %>%
#  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)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.67465122006504 [autosomes]/3.30358811059369 [x-chromosome]”

QTL effects

For each peak LOD location we give a list of gene

query_variants <- create_variant_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/cc_variants.sqlite")
query_genes <- create_gene_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/mouse_genes_mgi.sqlite")

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

  #marker = find_marker(gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i])
  #gp <- g[,marker]
  #gp[gp==1] <- "AA"
  #gp[gp==2] <- "AB"
  #gp[gp==0] <- NA
  #plot_pxg(gp, gm$covar[,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()

  g <- maxmarg(pr.qc, gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i], return_char=TRUE)
  #png(filename=paste0("/Users/chenm/Documents/qtl/Jai/","qtl_effect_", i, ".png"))
  #par(mar=c(4.1, 4.1, 1.5, 0.6))
  plot_pxg(g, gm$covar[,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$ci_hi[i]))
  #coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar)
  #coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], Xcovar=Xcovar)
  #coeff <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
  #coeff_sub <- scan1coef(pr_sub[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
  blup <- scan1blup(pr.qc[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)
  blup_sub <- scan1blup(pr_sub[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)

  write.csv(as.data.frame(blup_sub), paste0("data/ici.vs.pbs_blup_sub_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr3.csv"), quote=F)

  #plot_coef(coeff, 
  #     gm$gmap, columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i]," [scan1coeff; positions in cM])")
  #     )

  #plot_coef(coeff_sub, 
  #     gm$gmap, columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i],"; 1.5 LOD drop interval [scan1coeff; positions in cM] ) ")
  #     )


  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])")
       )


 # Plot 3
  #c2effB <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary", contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
  #c2effBb <- scan1blup(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
  ##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
  ##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]],Xcovar=Xcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
  #plot(c2effB, gm$gmap[chr], columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
  #     )
  #plot(c2effBb, gm$gmap[chr], columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
  #     )
  ##last_coef <- unclass(c2effB)[nrow(c2effB),2:3] # last two coefficients
  ##for(t in seq(along=last_coef))
  ##  axis(side=4, at=last_coef[t], names(last_coef)[t], tick=FALSE)


  #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.vs.pbs_genes_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr3.csv"), quote=F)

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

  #genesgss <- 
  #table <- 
  #genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")] %>%
  #kable(escape = F,align = c("ccccccccccc")) %>%
  #kable_styling("striped", full_width = T) #%>% 
  #cat #%>%
  #column_spec(1, bold=TRUE)
#
  #print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], escape = F,align = c("ccccccccccc")))

  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)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.67465122006504 [autosomes]/3.30358811059369 [x-chromosome]”

R/qtl

scanone

gm
Object of class cross2 (crosstype "bc")

Total individuals              138
No. genotyped individuals      138
No. phenotyped individuals     138
No. with both geno & pheno     138

No. phenotypes                   1
No. covariates                   7
No. phenotype covariates         0

No. chromosomes                 20
Total markers                26548

No. markers by chr:
   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
2374 2374 1623 1691 1568 1703 1464 1468 1685  974 1671 1134 1377 1411  876  751 
  17   18   19    X 
 330  770  920  384 
#detach("package:qtl2", unload=TRUE)
#library(qtl)

cross <- qtl::read.cross("csv", file = "data/ici.vs.pbs_gm_qtl_snpsqc_5.batches_mis_conditional_1-peak-chr3.csv",alleles=c("A","B"))
 --Read the following data:
     138  individuals
     26548  markers
     4  phenotypes
 --Cross type: bc 
cross <- qtl::jittermap(cross)

summary(cross)
    Backcross

    No. individuals:    138 

    No. phenotypes:     4 
    Percent phenotyped: 100 100 100 100 

    No. chromosomes:    20 
        Autosomes:      1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 
        X chr:          X 

    Total markers:      26548 
    No. markers:        2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671 
                        1134 1377 1411 876 751 330 770 920 384 
    Percent genotyped:  99.5 
    Genotypes (%):    
          Autosomes:    AA:54.4  AB:45.6 
       X chromosome:    AA:53.3  AB:46.7 
cross.probs <- qtl::calc.genoprob(cross)

print("method == hk")
[1] "method == hk"
add.covars = qtl::pull.pheno(cross.probs, c("UNCHS008487"))

scanone.hk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="hk", addcovar = add.covars)
operm.hk <- qtl::scanone(cross.probs, method = "hk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE, addcovar = add.covars)
plot(operm.hk)

print(summary(operm.hk, alpha=c(0.01,  0.05, 0.1)))
Autosome LOD thresholds (10 permutations)
     lod
1%  3.87
5%  3.37
10% 2.75

X chromosome LOD thresholds (186 permutations)
     lod
1%  3.24
5%  3.05
10% 2.79
#plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")  
#qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.1, col = 'purple')

ymx <- maxlod(out) # overall maximum LOD score
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]"))  
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.1, col = 'purple')

ymx <- 11
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]\n(using same scale as eoi vs ici for easier comparison)"))
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.1, col = 'purple')

print(as.data.frame(summary(scanone.hk, perms=operm.hk, pvalues=TRUE, format="allpeaks")))
            chr       pos       lod      pval
UNC163443     1  4.774075 1.3742470 1.0000000
UNC2987704    2 27.689343 0.8724495 1.0000000
JAX00521745   3 20.613263 0.7585338 1.0000000
JAX00556948   4 41.038578 0.7729973 1.0000000
JAX00585101   5 36.216736 0.8544324 1.0000000
UNC10923091   6 18.321248 0.7018820 1.0000000
JAX00657315   7 81.940339 0.7731087 1.0000000
UNCHS023364   8 35.540812 1.5630473 0.9116914
UNCHS026281   9 40.415965 0.5497421 1.0000000
UNCHS028001  10 21.783253 1.0219015 1.0000000
UNCHS030712  11 32.135777 0.8396617 1.0000000
UNC21787084  12 53.288083 0.7631460 1.0000000
UNC22384241  13 13.831342 1.6038654 0.9116914
UNCHS038350  14 30.005599 0.4749227 1.0000000
UNC25285746  15 12.031111 0.8983676 1.0000000
UNC26465114  16 13.431084 0.7730271 1.0000000
JAX00077123  17 31.150016 0.7729946 1.0000000
UNC29709766  18 55.191705 0.5543284 1.0000000
UNC29893228  19  8.029054 1.6298590 0.8166471
JAX00176908   X  4.172023 0.7731463 0.9999998
print("all peaks with a p-value less or equal to 0.05 (suggestive)")
[1] "all peaks with a p-value less or equal to 0.05 (suggestive)"
print(as.data.frame(summary(scanone.hk, perms=operm.hk, alpha=0.05, pvalues=TRUE, format="allpeaks")))
[1] chr pos lod
<0 rows> (or 0-length row.names)
#print("method == ehk")

#scanone.ehk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="ehk")
#operm.ehk <- qtl::scanone(cross.probs, method = "ehk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE)
#plot(operm.ehk)
#print(summary(operm.ehk, alpha=c(0.01,  0.05, 0.1)))

#plot(scanone.ehk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")  
#qtl::add.threshold(scanone.ehk,  perms= operm.ehk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.ehk,  perms= operm.ehk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.ehk,  perms= operm.ehk, alpha=0.1, col = 'purple')

#print(as.data.frame(summary(scanone.ehk)))
#print(as.data.frame(summary(scanone.ehk, perms=operm.ehk, alpha=0.05, pvalues=TRUE, format="allpeaks")))

Conditionaing on eoi vs. ici chr 4 peak (UNC8250659)

Genome-wide scan

#gm

Xcovar <- get_x_covar(gm)
#addcovar = model.matrix(~Sex, data = covars)[,-1]

addcovar = model.matrix(~UNC8250659, data = covars)[,-1]

#K <- calc_kinship(pr.qc, type = "loco")
#heatmap(K[[1]])
#K.overall <- calc_kinship(pr.qc, type = "overall")
#heatmap(K.overall)
kinship <- calc_kinship(pr.qc)
heatmap(kinship)

#operm <- scan1perm(pr.qc, gm$covar$phenos, Xcovar=Xcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, addcovar = addcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, n_perm=2000)
operm <- scan1perm(pr.qc, gm$covar["ICI.vs.PBS"], model="binary", n_perm=10, perm_Xsp=TRUE, chr_lengths=chr_lengths(gm$gmap), addcovar = addcovar)

summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01,  0.05, 0.1))))
names(summary_table) <- c("autosomes","X")
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 2.997095 2.614432
0.05 2.720357 2.589449
0.1 2.373590 2.556779

The figures below show QTL maps for each phenotype

out <- scan1(pr.qc, gm$covar["ICI.vs.PBS"], Xcovar=Xcovar, 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$gmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, 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, "html") 
#  %>% kable_styling("striped", full_width = T) %>%
#  column_spec(1, bold=TRUE)
#  )

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

#peaks[] %>%
#  kable(escape = F,align = c("cccccccc")) %>%
#  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)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.72035707026121 [autosomes]/2.58944938717251 [x-chromosome]”

Megabase (MB)

print("peaks in MB positions")

[1] “peaks in MB positions”

peaks_mba <- find_peaks(out, gm$pmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, 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]

#peaks_mbl <- list()
##corresponding info in Mb
#for(i in 1:nrow(peaks)){
#  #lodindex <- peaks$lodindex[i]
#  phenotype <- peaks$phenotype[i]
#  chr <- as.character(peaks$chr[i])
#  lod <- peaks$lod[i]
#  mark <- peaks$marker[i]
#  pos <- mapdf[mapdf$marker==mark,]$pmapdf
#  ci_lo <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_lo[i] & mapdfnd$chr == peaks$chr[i])]
#  ci_hi <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_hi[i] & mapdfnd$chr == peaks$chr[i])]
#  peaks_mb=as.data.frame(cbind(phenotype, chr, pos, lod, ci_lo, ci_hi, mark))
#  names(peaks_mb)[7] <- c("marker")
#  peaks_mbl[[i]] <- peaks_mb
#}
#peaks_mba2 <- do.call(rbind, peaks_mbl)
#peaks_mba2 <- as.data.frame(peaks_mba)
#peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")] <- sapply(peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")], as.numeric)

rownames(peaks_mba) <- NULL

#print(kable(peaks_mba, "html") 
#  %>% kable_styling("striped", full_width = T) %>%
#  column_spec(1, bold=TRUE)
#  )

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

#peaks_mba[] %>%
#  kable(escape = F,align = c("cccccccc")) %>%
#  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)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.72035707026121 [autosomes]/2.58944938717251 [x-chromosome]”

QTL effects

For each peak LOD location we give a list of gene

query_variants <- create_variant_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/cc_variants.sqlite")
query_genes <- create_gene_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/mouse_genes_mgi.sqlite")

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

  #marker = find_marker(gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i])
  #gp <- g[,marker]
  #gp[gp==1] <- "AA"
  #gp[gp==2] <- "AB"
  #gp[gp==0] <- NA
  #plot_pxg(gp, gm$covar[,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()

  g <- maxmarg(pr.qc, gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i], return_char=TRUE)
  #png(filename=paste0("/Users/chenm/Documents/qtl/Jai/","qtl_effect_", i, ".png"))
  #par(mar=c(4.1, 4.1, 1.5, 0.6))
  plot_pxg(g, gm$covar[,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$ci_hi[i]))
  #coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar)
  #coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], Xcovar=Xcovar)
  #coeff <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
  #coeff_sub <- scan1coef(pr_sub[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
  blup <- scan1blup(pr.qc[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)
  blup_sub <- scan1blup(pr_sub[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)

  write.csv(as.data.frame(blup_sub), paste0("data/ici.vs.pbs_blup_sub_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr4.csv"), quote=F)

  #plot_coef(coeff, 
  #     gm$gmap, columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i]," [scan1coeff; positions in cM])")
  #     )

  #plot_coef(coeff_sub, 
  #     gm$gmap, columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i],"; 1.5 LOD drop interval [scan1coeff; positions in cM] ) ")
  #     )


  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])")
       )


 # Plot 3
  #c2effB <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary", contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
  #c2effBb <- scan1blup(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
  ##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
  ##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]],Xcovar=Xcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
  #plot(c2effB, gm$gmap[chr], columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
  #     )
  #plot(c2effBb, gm$gmap[chr], columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
  #     )
  ##last_coef <- unclass(c2effB)[nrow(c2effB),2:3] # last two coefficients
  ##for(t in seq(along=last_coef))
  ##  axis(side=4, at=last_coef[t], names(last_coef)[t], tick=FALSE)


  #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.vs.pbs_genes_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr4.csv"), quote=F)

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

  #genesgss <- 
  #table <- 
  #genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")] %>%
  #kable(escape = F,align = c("ccccccccccc")) %>%
  #kable_styling("striped", full_width = T) #%>% 
  #cat #%>%
  #column_spec(1, bold=TRUE)
#
  #print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], escape = F,align = c("ccccccccccc")))

  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)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 2.72035707026121 [autosomes]/2.58944938717251 [x-chromosome]”

R/qtl

scanone

gm
Object of class cross2 (crosstype "bc")

Total individuals              138
No. genotyped individuals      138
No. phenotyped individuals     138
No. with both geno & pheno     138

No. phenotypes                   1
No. covariates                   7
No. phenotype covariates         0

No. chromosomes                 20
Total markers                26548

No. markers by chr:
   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
2374 2374 1623 1691 1568 1703 1464 1468 1685  974 1671 1134 1377 1411  876  751 
  17   18   19    X 
 330  770  920  384 
#detach("package:qtl2", unload=TRUE)
#library(qtl)

cross <- qtl::read.cross("csv", file = "data/ici.vs.pbs_gm_qtl_snpsqc_5.batches_mis_conditional_1-peak-chr4.csv",alleles=c("A","B"))
 --Read the following data:
     138  individuals
     26548  markers
     4  phenotypes
 --Cross type: bc 
cross <- qtl::jittermap(cross)

summary(cross)
    Backcross

    No. individuals:    138 

    No. phenotypes:     4 
    Percent phenotyped: 100 100 100 100 

    No. chromosomes:    20 
        Autosomes:      1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 
        X chr:          X 

    Total markers:      26548 
    No. markers:        2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671 
                        1134 1377 1411 876 751 330 770 920 384 
    Percent genotyped:  99.5 
    Genotypes (%):    
          Autosomes:    AA:54.4  AB:45.6 
       X chromosome:    AA:53.3  AB:46.7 
cross.probs <- qtl::calc.genoprob(cross)

print("method == hk")
[1] "method == hk"
add.covars = qtl::pull.pheno(cross.probs, c("UNC8250659"))

scanone.hk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="hk", addcovar = add.covars)
operm.hk <- qtl::scanone(cross.probs, method = "hk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE, addcovar = add.covars)
plot(operm.hk)

print(summary(operm.hk, alpha=c(0.01,  0.05, 0.1)))
Autosome LOD thresholds (10 permutations)
     lod
1%  2.62
5%  2.46
10% 2.26

X chromosome LOD thresholds (186 permutations)
     lod
1%  2.52
5%  2.41
10% 2.26
#plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")  
#qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.1, col = 'purple')

ymx <- maxlod(out) # overall maximum LOD score
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]"))  
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.1, col = 'purple')

ymx <- 11
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]\n(using same scale as eoi vs ici for easier comparison)"))
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.1, col = 'purple')

print(as.data.frame(summary(scanone.hk, perms=operm.hk, pvalues=TRUE, format="allpeaks")))
            chr       pos       lod      pval
UNC163443     1  4.774075 1.3742470 0.9116914
UNC2987704    2 27.689343 0.8724495 1.0000000
JAX00521745   3 20.613263 0.7585338 1.0000000
JAX00556948   4 41.038578 0.7729973 1.0000000
JAX00585101   5 36.216736 0.8544324 1.0000000
UNC10923091   6 18.321248 0.7018820 1.0000000
JAX00657315   7 81.940339 0.7731087 1.0000000
UNCHS023364   8 35.540812 1.5630473 0.7188828
UNCHS026281   9 40.415965 0.5497421 1.0000000
UNCHS028001  10 21.783253 1.0219015 1.0000000
UNCHS030712  11 32.135777 0.8396617 1.0000000
UNC21787084  12 53.288083 0.7631460 1.0000000
UNC22384241  13 13.831342 1.6038654 0.7188828
UNCHS038350  14 30.005599 0.4749227 1.0000000
UNC25285746  15 12.031111 0.8983676 1.0000000
UNC26465114  16 13.431084 0.7730271 1.0000000
JAX00077123  17 31.150016 0.7729946 1.0000000
UNC29709766  18 55.191705 0.5543284 1.0000000
UNC29893228  19  8.029054 1.6298590 0.7188828
JAX00176908   X  4.172023 0.7731463 0.9999829
print("all peaks with a p-value less or equal to 0.05 (suggestive)")
[1] "all peaks with a p-value less or equal to 0.05 (suggestive)"
print(as.data.frame(summary(scanone.hk, perms=operm.hk, alpha=0.05, pvalues=TRUE, format="allpeaks")))
[1] chr pos lod
<0 rows> (or 0-length row.names)
#print("method == ehk")

#scanone.ehk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="ehk")
#operm.ehk <- qtl::scanone(cross.probs, method = "ehk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE)
#plot(operm.ehk)
#print(summary(operm.ehk, alpha=c(0.01,  0.05, 0.1)))

#plot(scanone.ehk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")  
#qtl::add.threshold(scanone.ehk,  perms= operm.ehk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.ehk,  perms= operm.ehk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.ehk,  perms= operm.ehk, alpha=0.1, col = 'purple')

#print(as.data.frame(summary(scanone.ehk)))
#print(as.data.frame(summary(scanone.ehk, perms=operm.ehk, alpha=0.05, pvalues=TRUE, format="allpeaks")))

Conditionaing on eoi vs. ici chr 10 peak (UNC18240977)

Genome-wide scan

#gm

Xcovar <- get_x_covar(gm)
#addcovar = model.matrix(~Sex, data = covars)[,-1]

addcovar = model.matrix(~UNC18240977, data = covars)[,-1]

#K <- calc_kinship(pr.qc, type = "loco")
#heatmap(K[[1]])
#K.overall <- calc_kinship(pr.qc, type = "overall")
#heatmap(K.overall)
kinship <- calc_kinship(pr.qc)
heatmap(kinship)

#operm <- scan1perm(pr.qc, gm$covar$phenos, Xcovar=Xcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, addcovar = addcovar, n_perm=2000)
#operm <- scan1perm(pr.qc, gm$covar$phenos, n_perm=2000)
operm <- scan1perm(pr.qc, gm$covar["ICI.vs.PBS"], model="binary", n_perm=10, perm_Xsp=TRUE, chr_lengths=chr_lengths(gm$gmap), addcovar = addcovar)

summary_table<-data.frame(unclass(summary(operm, alpha=c(0.01,  0.05, 0.1))))
names(summary_table) <- c("autosomes","X")
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 3.179263 3.082049
0.05 3.107175 3.001548
0.1 3.016845 2.896273

The figures below show QTL maps for each phenotype

out <- scan1(pr.qc, gm$covar["ICI.vs.PBS"], Xcovar=Xcovar, 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$gmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, 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, "html") 
#  %>% kable_styling("striped", full_width = T) %>%
#  column_spec(1, bold=TRUE)
#  )

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

#peaks[] %>%
#  kable(escape = F,align = c("cccccccc")) %>%
#  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)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 3.10717507101817 [autosomes]/3.00154804082885 [x-chromosome]”

Megabase (MB)

print("peaks in MB positions")

[1] “peaks in MB positions”

peaks_mba <- find_peaks(out, gm$pmap, threshold=summary(operm,alpha=0.05)$A, thresholdX = summary(operm,alpha=0.05)$X, 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]

#peaks_mbl <- list()
##corresponding info in Mb
#for(i in 1:nrow(peaks)){
#  #lodindex <- peaks$lodindex[i]
#  phenotype <- peaks$phenotype[i]
#  chr <- as.character(peaks$chr[i])
#  lod <- peaks$lod[i]
#  mark <- peaks$marker[i]
#  pos <- mapdf[mapdf$marker==mark,]$pmapdf
#  ci_lo <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_lo[i] & mapdfnd$chr == peaks$chr[i])]
#  ci_hi <- mapdfnd$pmapdf[which(mapdfnd$gmapdf == peaks$ci_hi[i] & mapdfnd$chr == peaks$chr[i])]
#  peaks_mb=as.data.frame(cbind(phenotype, chr, pos, lod, ci_lo, ci_hi, mark))
#  names(peaks_mb)[7] <- c("marker")
#  peaks_mbl[[i]] <- peaks_mb
#}
#peaks_mba2 <- do.call(rbind, peaks_mbl)
#peaks_mba2 <- as.data.frame(peaks_mba)
#peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")] <- sapply(peaks_mba[,c("chr", "pos", "lod", "ci_lo", "ci_hi")], as.numeric)

rownames(peaks_mba) <- NULL

#print(kable(peaks_mba, "html") 
#  %>% kable_styling("striped", full_width = T) %>%
#  column_spec(1, bold=TRUE)
#  )

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

#peaks_mba[] %>%
#  kable(escape = F,align = c("cccccccc")) %>%
#  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)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 3.10717507101817 [autosomes]/3.00154804082885 [x-chromosome]”

QTL effects

For each peak LOD location we give a list of gene

query_variants <- create_variant_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/cc_variants.sqlite")
query_genes <- create_gene_query_func("/Users/corneb/Documents/MyJax/CS/Projects/support.files/qtl2/mouse_genes_mgi.sqlite")

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

  #marker = find_marker(gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i])
  #gp <- g[,marker]
  #gp[gp==1] <- "AA"
  #gp[gp==2] <- "AB"
  #gp[gp==0] <- NA
  #plot_pxg(gp, gm$covar[,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()

  g <- maxmarg(pr.qc, gm$gmap, chr=peaks$chr[i], pos=peaks$pos[i], return_char=TRUE)
  #png(filename=paste0("/Users/chenm/Documents/qtl/Jai/","qtl_effect_", i, ".png"))
  #par(mar=c(4.1, 4.1, 1.5, 0.6))
  plot_pxg(g, gm$covar[,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$ci_hi[i]))
  #coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar)
  #coeff <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], Xcovar=Xcovar)
  #coeff <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
  #coeff_sub <- scan1coef(pr_sub[,chr], gm$covar[peaks$lodcolumn[i]], model="binary")
  blup <- scan1blup(pr.qc[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)
  blup_sub <- scan1blup(pr_sub[,chr], gm$covar[peaks$phenotype[i]], addcovar = addcovar)

  write.csv(as.data.frame(blup_sub), paste0("data/ici.vs.pbs_blup_sub_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr10.csv"), quote=F)

  #plot_coef(coeff, 
  #     gm$gmap, columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i]," [scan1coeff; positions in cM])")
  #     )

  #plot_coef(coeff_sub, 
  #     gm$gmap, columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i],"; pos: ", peaks$pos[i], "cM /",peaks_mba$pos[i],"MB\n(",peaks$lodcolumn[i],"; 1.5 LOD drop interval [scan1coeff; positions in cM] ) ")
  #     )


  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])")
       )


 # Plot 3
  #c2effB <- scan1coef(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], model="binary", contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
  #c2effBb <- scan1blup(pr.qc[,chr], gm$covar[peaks$lodcolumn[i]], contrasts=cbind(a=c(-1, 0), d=c(0, -1)))
  ##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]], addcovar = addcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
  ##c2effB <- scan1coef(pr[,chr], cross$pheno[,peaks$lodcolumn[i]],Xcovar=Xcovar, contrasts=cbind(mu=c(1,1,1), a=c(-1, 0, 1), d=c(0, 1, 0)))
  #plot(c2effB, gm$gmap[chr], columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
  #     )
  #plot(c2effBb, gm$gmap[chr], columns=1:2,
  #     bgcolor="gray95", legend="bottomleft", 
  #     main = paste("chr", chr=peaks$chr[i], "pos", peaks$pos[i], "(",peaks$lodcolumn[i],")")
  #     )
  ##last_coef <- unclass(c2effB)[nrow(c2effB),2:3] # last two coefficients
  ##for(t in seq(along=last_coef))
  ##  axis(side=4, at=last_coef[t], names(last_coef)[t], tick=FALSE)


  #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.vs.pbs_genes_chr-",chr,"_peak.marker-",peaks$marker[i],"_lod.drop-1.5_snpsqc_5.batches_mis_conditional_1-peak-chr10.csv"), quote=F)

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

  #genesgss <- 
  #table <- 
  #genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")] %>%
  #kable(escape = F,align = c("ccccccccccc")) %>%
  #kable_styling("striped", full_width = T) #%>% 
  #cat #%>%
  #column_spec(1, bold=TRUE)
#
  #print(kable(genesgss[,c("chr","type","start","stop","strand","ID","Name","Dbxref","gene_id","mgi_type","description")], escape = F,align = c("ccccccccccc")))

  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)$A, " [autosomes]/",summary(operm,alpha=0.05)$X, " [x-chromosome]"))
}

[1] “There are no peaks that have a LOD that reaches suggestive (p<0.05) level of 3.10717507101817 [autosomes]/3.00154804082885 [x-chromosome]”

R/qtl

scanone

gm
Object of class cross2 (crosstype "bc")

Total individuals              138
No. genotyped individuals      138
No. phenotyped individuals     138
No. with both geno & pheno     138

No. phenotypes                   1
No. covariates                   7
No. phenotype covariates         0

No. chromosomes                 20
Total markers                26548

No. markers by chr:
   1    2    3    4    5    6    7    8    9   10   11   12   13   14   15   16 
2374 2374 1623 1691 1568 1703 1464 1468 1685  974 1671 1134 1377 1411  876  751 
  17   18   19    X 
 330  770  920  384 
#detach("package:qtl2", unload=TRUE)
#library(qtl)

cross <- qtl::read.cross("csv", file = "data/ici.vs.pbs_gm_qtl_snpsqc_5.batches_mis_conditional_1-peak-chr10.csv",alleles=c("A","B"))
 --Read the following data:
     138  individuals
     26548  markers
     4  phenotypes
 --Cross type: bc 
cross <- qtl::jittermap(cross)

summary(cross)
    Backcross

    No. individuals:    138 

    No. phenotypes:     4 
    Percent phenotyped: 100 100 100 100 

    No. chromosomes:    20 
        Autosomes:      1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 
        X chr:          X 

    Total markers:      26548 
    No. markers:        2374 2374 1623 1691 1568 1703 1464 1468 1685 974 1671 
                        1134 1377 1411 876 751 330 770 920 384 
    Percent genotyped:  99.5 
    Genotypes (%):    
          Autosomes:    AA:54.4  AB:45.6 
       X chromosome:    AA:53.3  AB:46.7 
cross.probs <- qtl::calc.genoprob(cross)

print("method == hk")
[1] "method == hk"
add.covars = qtl::pull.pheno(cross.probs, c("UNC18240977"))

scanone.hk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="hk", addcovar = add.covars)
operm.hk <- qtl::scanone(cross.probs, method = "hk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE, addcovar = add.covars)
plot(operm.hk)

print(summary(operm.hk, alpha=c(0.01,  0.05, 0.1)))
Autosome LOD thresholds (10 permutations)
     lod
1%  2.71
5%  2.63
10% 2.53

X chromosome LOD thresholds (186 permutations)
     lod
1%  2.79
5%  2.67
10% 2.52
#plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")  
#qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.1, col = 'purple')

ymx <- maxlod(out) # overall maximum LOD score
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]"))  
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.1, col = 'purple')

ymx <- 11
plot(scanone.hk, bandcol = "grey90",lty=1, cex=1, col = "slateblue", ylim=c(0, ymx+0.5))
title(main = paste0(colnames(out), " [positions in cM]\n(using same scale as eoi vs ici for easier comparison)"))
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.01, col = 'blue')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.05, col = 'red')
qtl::add.threshold(scanone.hk,  perms= operm.hk, alpha=0.1, col = 'purple')

print(as.data.frame(summary(scanone.hk, perms=operm.hk, pvalues=TRUE, format="allpeaks")))
            chr       pos       lod      pval
UNC163443     1  4.774075 1.3742470 1.0000000
UNC2987704    2 27.689343 0.8724495 1.0000000
JAX00521745   3 20.613263 0.7585338 1.0000000
JAX00556948   4 41.038578 0.7729973 1.0000000
JAX00585101   5 36.216736 0.8544324 1.0000000
UNC10923091   6 18.321248 0.7018820 1.0000000
JAX00657315   7 81.940339 0.7731087 1.0000000
UNCHS023364   8 35.540812 1.5630473 0.8166471
UNCHS026281   9 40.415965 0.5497421 1.0000000
UNCHS028001  10 21.783253 1.0219015 1.0000000
UNCHS030712  11 32.135777 0.8396617 1.0000000
UNC21787084  12 53.288083 0.7631460 1.0000000
UNC22384241  13 13.831342 1.6038654 0.8166471
UNCHS038350  14 30.005599 0.4749227 1.0000000
UNC25285746  15 12.031111 0.8983676 1.0000000
UNC26465114  16 13.431084 0.7730271 1.0000000
JAX00077123  17 31.150016 0.7729946 1.0000000
UNC29709766  18 55.191705 0.5543284 1.0000000
UNC29893228  19  8.029054 1.6298590 0.8166471
JAX00176908   X  4.172023 0.7731463 0.9999829
print("all peaks with a p-value less or equal to 0.05 (suggestive)")
[1] "all peaks with a p-value less or equal to 0.05 (suggestive)"
print(as.data.frame(summary(scanone.hk, perms=operm.hk, alpha=0.05, pvalues=TRUE, format="allpeaks")))
[1] chr pos lod
<0 rows> (or 0-length row.names)
#print("method == ehk")

#scanone.ehk <-qtl::scanone(cross.probs, pheno.col="ICI.vs.PBS" , model="binary", method="ehk")
#operm.ehk <- qtl::scanone(cross.probs, method = "ehk", pheno.col="ICI.vs.PBS", n.perm = 10, perm.Xsp = TRUE, model="binary", verbose=FALSE)
#plot(operm.ehk)
#print(summary(operm.ehk, alpha=c(0.01,  0.05, 0.1)))

#plot(scanone.ehk, bandcol = "grey90",lty=1, cex=1, col = "steelblue")  
#qtl::add.threshold(scanone.ehk,  perms= operm.ehk, alpha=0.01, col = 'blue')
#qtl::add.threshold(scanone.ehk,  perms= operm.ehk, alpha=0.05, col = 'red')
#qtl::add.threshold(scanone.ehk,  perms= operm.ehk, alpha=0.1, col = 'purple')

#print(as.data.frame(summary(scanone.ehk)))
#print(as.data.frame(summary(scanone.ehk, perms=operm.ehk, alpha=0.05, pvalues=TRUE, format="allpeaks")))

R version 3.5.1 (2018-07-02)
Platform: x86_64-apple-darwin15.6.0 (64-bit)
Running under: macOS  10.15.7

Matrix products: default
BLAS: /Library/Frameworks/R.framework/Versions/3.5/Resources/lib/libRblas.0.dylib
LAPACK: /Library/Frameworks/R.framework/Versions/3.5/Resources/lib/libRlapack.dylib

locale:
[1] en_AU.UTF-8/en_AU.UTF-8/en_AU.UTF-8/C/en_AU.UTF-8/en_AU.UTF-8

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

other attached packages:
 [1] abind_1.4-5       qtl2_0.22         reshape2_1.4.3    ggplot2_3.3.6    
 [5] tibble_3.1.7      psych_2.2.5       readxl_1.4.0      cluster_2.0.7-1  
 [9] dplyr_1.0.9       optparse_1.6.6    rhdf5_2.26.2      mclust_5.4.5     
[13] tidyr_1.2.0       data.table_1.14.2 knitr_1.29        kableExtra_1.3.4 
[17] workflowr_1.6.2  

loaded via a namespace (and not attached):
 [1] httr_1.4.3        bit64_0.9-7       viridisLite_0.3.0 assertthat_0.2.1 
 [5] highr_0.8         blob_1.2.1        cellranger_1.1.0  yaml_2.2.1       
 [9] gdtools_0.2.1     pillar_1.7.0      RSQLite_2.2.0     backports_1.1.5  
[13] lattice_0.20-35   glue_1.6.2        digest_0.6.25     promises_1.1.0   
[17] rvest_1.0.2       colorspace_1.4-1  htmltools_0.5.2   httpuv_1.5.2     
[21] plyr_1.8.6        pkgconfig_2.0.3   purrr_0.3.4       scales_1.1.1     
[25] webshot_0.5.3     svglite_1.2.3     qtl_1.46-2        getopt_1.20.3    
[29] later_1.0.0       git2r_0.26.1      generics_0.0.2    ellipsis_0.3.2   
[33] withr_2.5.0       cli_3.3.0         mnormt_1.5-6      magrittr_2.0.3   
[37] crayon_1.5.1      memoise_1.1.0     evaluate_0.14     fs_1.3.2         
[41] fansi_0.4.1       nlme_3.1-137      xml2_1.3.2        tools_3.5.1      
[45] lifecycle_1.0.1   stringr_1.4.0     Rhdf5lib_1.4.3    munsell_0.5.0    
[49] compiler_3.5.1    systemfonts_0.1.1 rlang_1.0.3       grid_3.5.1       
[53] rstudioapi_0.13   rmarkdown_2.3     gtable_0.3.0      DBI_1.1.0        
[57] R6_2.4.1          fastmap_1.1.0     bit_1.1-15.2      utf8_1.1.4       
[61] rprojroot_1.3-2   stringi_1.4.6     parallel_3.5.1    Rcpp_1.0.4.6     
[65] vctrs_0.4.1       tidyselect_1.1.2  xfun_0.15