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Thank you for your interest!! Here, I will briefly describe my analysis in the paper "Contribution of CRISPRable DNA on human complex traits" where we investigated the 21 Cas enriched genomic regions' contribution to human complex traits and diseases.

Count PAMs on 22 chromosomes

We used the GRCh37 assembly of the human genome, which can be found here. Briefly, run fecth.py can get the position of the PAM sequence. Taking GG for example,

python fecth.py human_g1k_v37_bk.fasta GG > GG_hg19_pos.tsv

can get GG positions into GG_hg19_pos.tsv file.

Considering the reverse strand, we also run

python fecth.py human_g1k_v37_bk.fasta CC > CC_hg19_pos.tsv

to get reversing GG positions.

Then, using make_bed_PAM.R, we split GG positions into 22 files for 22 chromosomes.

Cut the genome into 20,000 segments

We simply think of the 22 chromosomes as one. Then we cut it into 20,000 segments and count the number of PAM sequences in each segment. Next, we get segments that contain the largest number of PAM sequences, and save those segments' locations in one Top10.bed file for LDSC. See PAMs_top10.R.

Running LDSC

The code in make_annot_with_bed.R is modified from the LD Score Estimation Tutorial to compute LD scores for all 22 chromosomes. Partitioning heritability of 28 human complex traits also followed the instructions from Partitioned Heritability of LDSC software.