ROSMAP PCC alternative splicing QTL#

Religious Orders Study (ROS) or the Rush Memory and Aging Project (MAP) PCC alternative splicing.

Please refer to this document for an overview of the ROSMAP project.

Contact#

Frank Grenn

Study Overview#

In progress

Sample information: ####/####_sample_attributes.csv.
Lab protocol: ####/####_lab_protocol.csv.
Computational protocol: ####/####_computational_protocol.csv.
QTL summary statistics output: ####/####.qtl_results.csv.
Fine-mapping results individual level data model: ####/####.susie.csv.
Fine-mapping results summary statistics model: ####/####.susie_rss.csv.
Colocalization with AD GWAS: ####/####.susie_coloc.csv.

Analysis Status#

TransQTL association: Need to be performed.

Dataset Details#

Path(s) to genotype matrix#

Zhang Lab, /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.plink_files_list.txt

$ head ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.plink_files_list.txt
#id     dir
1       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.1.bed
2       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.2.bed
3       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.3.bed
4       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.4.bed
5       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.5.bed
6       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.6.bed
7       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.7.bed
8       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.8.bed
9       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/genotype/genotype_partition/ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.9.bed

$ ls -lh *.{bim,bed,fam} | head
-rw-r--r-- 1 fgrennjr casa  91M Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.1.bed
-rw-r--r-- 1 fgrennjr casa  33M Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.1.bim
-rw-r--r-- 1 fgrennjr casa 8.7K Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.1.fam
-rw-r--r-- 1 fgrennjr casa  59M Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.10.bed
-rw-r--r-- 1 fgrennjr casa  23M Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.10.bim
-rw-r--r-- 1 fgrennjr casa 8.7K Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.10.fam
-rw-r--r-- 1 fgrennjr casa  57M Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.11.bed
-rw-r--r-- 1 fgrennjr casa  22M Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.11.bim
-rw-r--r-- 1 fgrennjr casa 8.7K Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.11.fam
-rw-r--r-- 1 fgrennjr casa  56M Mar 17 14:03 ROSMAP_NIA_WGS.leftnorm.filtered.unrelated.filtered.12.bed

Path(s) to omics-data matrix#

Zhang Lab, /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom.recipe

$ ls -lh batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.txt
-rw-r--r-- 1 fgrennjr casa 3.1G Mar  6 14:06 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.txt

Path(s) to covariate data matrix#

Zhang Lab, /restricted/projectnb/casa/skandoi/ROSMAP_PCC/reference_data/ROSMAP_xqtl_covariates_sex_death_pmi_study.tsv

$ head batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom.recipe
#id     #dir
5       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr5.bed.gz
18      /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr18.bed.gz
7       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr7.bed.gz
10      /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr10.bed.gz
8       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr8.bed.gz
Y       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chrY.bed.gz
11      /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr11.bed.gz
13      /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr13.bed.gz
9       /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/PDP_leafcutter/batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr9.bed.gz

$ ls -lh *bed.gz | head
-rw-r--r-- 1 fgrennjr casa 125M Mar  8 16:08 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr1.bed.gz
-rw-r--r-- 1 fgrennjr casa  56M Mar  8 16:07 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr10.bed.gz
-rw-r--r-- 1 fgrennjr casa  67M Mar  8 16:07 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr11.bed.gz
-rw-r--r-- 1 fgrennjr casa  69M Mar  8 16:07 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr12.bed.gz
-rw-r--r-- 1 fgrennjr casa  26M Mar  8 16:07 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr13.bed.gz
-rw-r--r-- 1 fgrennjr casa  43M Mar  8 16:07 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr14.bed.gz
-rw-r--r-- 1 fgrennjr casa  50M Mar  8 16:07 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr15.bed.gz
-rw-r--r-- 1 fgrennjr casa  58M Mar  8 16:07 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr16.bed.gz
-rw-r--r-- 1 fgrennjr casa  74M Mar  8 16:07 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr17.bed.gz
-rw-r--r-- 1 fgrennjr casa  22M Mar  8 16:07 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.chr18.bed.gz

Path(s) to QTL results#

Zhang Lab, /restricted/projectnb/casa/frank/xqtl_project/ROSMAP_PCC/TensorQTL/sQTL

$ ls -lh | head
total 27G
-rw-r--r-- 1 fgrennjr casa 374M Mar 24 11:42 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom_leafcutter.pcc_batch_all.ROSMAP_covariates.ROSMAP_NIA_WGS.pca.PEER.txt.1.cis_qtl_pairs.1.parquet
-rw-r--r-- 1 fgrennjr casa  285 Mar 24 22:12 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom_leafcutter.pcc_batch_all.ROSMAP_covariates.ROSMAP_NIA_WGS.pca.PEER.txt.1.cis_qtl_pairs.1.parquet.stderr
-rw-r--r-- 1 fgrennjr casa 138K Mar 24 22:12 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom_leafcutter.pcc_batch_all.ROSMAP_covariates.ROSMAP_NIA_WGS.pca.PEER.txt.1.cis_qtl_pairs.1.parquet.stdout
-rw-r--r-- 1 fgrennjr casa 433K Mar 24 22:12 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom_leafcutter.pcc_batch_all.ROSMAP_covariates.ROSMAP_NIA_WGS.pca.PEER.txt.1.emprical.cis_sumstats.txt
-rw-r--r-- 1 fgrennjr casa 2.2G Mar 24 11:44 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom_leafcutter.pcc_batch_all.ROSMAP_covariates.ROSMAP_NIA_WGS.pca.PEER.txt.1.norminal.cis_long_table.txt
-rw-r--r-- 1 fgrennjr casa 180M Mar 24 11:28 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom_leafcutter.pcc_batch_all.ROSMAP_covariates.ROSMAP_NIA_WGS.pca.PEER.txt.10.cis_qtl_pairs.10.parquet
-rw-r--r-- 1 fgrennjr casa  285 Mar 24 16:48 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom_leafcutter.pcc_batch_all.ROSMAP_covariates.ROSMAP_NIA_WGS.pca.PEER.txt.10.cis_qtl_pairs.10.parquet.stderr
-rw-r--r-- 1 fgrennjr casa  58K Mar 24 16:48 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom_leafcutter.pcc_batch_all.ROSMAP_covariates.ROSMAP_NIA_WGS.pca.PEER.txt.10.cis_qtl_pairs.10.parquet.stdout
-rw-r--r-- 1 fgrennjr casa 187K Mar 24 16:48 batch_all_bam_no_ext_no_outlier_intron_usage_perind.counts.gz_raw_data.qqnorm.formated.bed.per_chrom_leafcutter.pcc_batch_all.ROSMAP_covariates.ROSMAP_NIA_WGS.pca.PEER.txt.10.emprical.cis_sumstats.txt

Links to QTL analysis notebooks for LeafCutter2#

See notebooks in:

https://github.com/cumc/xqtl-analysis/tree/main/analysis/Wang_Columbia/ROSMAP/sQTL/PCC

The notebooks in this folder contain the commands and data wrangling codes for analysis of the eQTL and sQTL data in ROSMAP. (data wrangling exist because not all data are processed using the xqtl-pipeline from the beginning and need to be reformatted to fit one intermediate step of the pipeline). Since the sQTL phenotype pre-processing used eQTL STAR alignment output, some of the early stage code are shared.

Association data preprocessing#

LeafCutter2_QC shows the commands used for quality control of the LeafCutter2 results.
genotype_preprocessing.ipynb shows the commands used for genotype processing and preparation steps.all QTLs in one cohort have the same genotype_preprocessing procedure.
phenotype_preprocessing.ipynb shows the commands used for the phenotype data processing and preparation steps.
covariate_preprocessing.ipynb shows the commands used for the covariate data processing and preparation steps.

Association scan using TensorQTL and summary statistics standardization#

TensorQTL.ipynb provides the pipeline to generate TensorQTL cis association results for all QTLs.
ROSMAP_sQTL_LeafCutter2_commands provides information about the input files for AC/DLPFC/PCC TensorQTL cis association in the base_params variable in [generate_command_1].

output of TensorQTL.ipynb

s3://statfungen/ftp_fgc_xqtl/analysis_result/cis_association/ROSMAP/sQTL/PCC/leafcutter2/