Home

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.

Heritability enrichment analysis

First, we count the number of PAM in the 22 autosomes. We used the GRCh37 assembly of the human genome, which can be found here. Briefly, running 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.

Analysis of the human genome was based on the GRCh37 assembly. To simplify the process, we considered 22 autosomal chromosomes end to end as one single piece with a total of 2,881,033,286 bases. We cut the entire piece into 20,000 segments, resulting in about 144,052 bases per segment.

Running S-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.