diff --git a/cre.gemini.variant_impacts.vcf2db.sh b/cre.gemini.variant_impacts.vcf2db.sh index 99deadf..44aaa6f 100755 --- a/cre.gemini.variant_impacts.vcf2db.sh +++ b/cre.gemini.variant_impacts.vcf2db.sh @@ -3,10 +3,9 @@ # database schema: https://gemini.readthedocs.io/en/latest/content/database_schema.html#the-variants-table # by default bcbio writes PASS only variants to the database -#PBS -l walltime=1:00:00,nodes=1:ppn=1 -#PBS -joe . -#PBS -d . -#PBS -l vmem=10g,mem=10g +#SBATCH --time=1:00:00 +#SBATCH --ntasks-per-node=1 +#SBATCH --mem=10G if [ -z $file ] then @@ -81,7 +80,7 @@ fi initialQuery=$sQuery" from variants v,variant_impacts i" #store field selection -sQuery=$initialQuery" where "$severity_filter" v.gnomad_af_popmax <= "$max_af" and \ +sQuery=$initialQuery" where "$severity_filter" v.gnomad_fafmax_faf95_max <= "$max_af" and \ v.variant_id=i.variant_id "$caller_filter"" s_gt_filter='' @@ -111,13 +110,13 @@ else # grab the clinvar variants cQuery=$initialQuery # everything that has a clinvar_sig value - cQuery=$cQuery" where v.gnomad_af_popmax <= ${max_af} and v.variant_id=i.variant_id and v.clinvar_status <> '' "$caller_filter" " - #cQuery=$cQuery" where gnomad_af_popmax <= ${max_af} and v.variant_id=i.variant_id and clinvar_sig <> ''" + cQuery=$cQuery" where v.gnomad_fafmax_faf95_max <= ${max_af} and v.variant_id=i.variant_id and v.clinvar_status <> '' "$caller_filter" " + #cQuery=$cQuery" where gnomad_af_grpax <= ${max_af} and v.variant_id=i.variant_id and clinvar_sig <> ''" # only get variants where AD >= 1 (any sample with an alternate read) s_gt_filter="(gt_alt_depths).(*).(>=1).(any) or (gt_alt_depths).(*).(==-1).(all)" gemini query -q "$cQuery" --gt-filter "$s_gt_filter" $file # add variants where gnomad freq is > 1%, Clinvar is pathogenic, likely pathogenic or conflicting and any status except no assertion cQuery=$initialQuery - cQuery=$cQuery" where v.gnomad_af_popmax > ${max_af} and v.variant_id=i.variant_id and v.clinvar_status != 'no_assertion_criteria_provided' and Clinvar in ('Pathogenic', 'Likely_pathogenic', 'Conflicting_interpretations_of_pathogenicity') "$caller_filter"" + cQuery=$cQuery" where v.gnomad_fafmax_faf95_max > ${max_af} and v.variant_id=i.variant_id and v.clinvar_status != 'no_assertion_criteria_provided' and Clinvar in ('Pathogenic', 'Likely_pathogenic', 'Conflicting_interpretations_of_pathogenicity') "$caller_filter"" gemini query -q "$cQuery" $file fi diff --git a/cre.gemini2txt.vcf2db.sh b/cre.gemini2txt.vcf2db.sh index 29b876d..1eb3b4c 100755 --- a/cre.gemini2txt.vcf2db.sh +++ b/cre.gemini2txt.vcf2db.sh @@ -8,10 +8,9 @@ # when using vcfanno/vcfdb loader some fields are different # for some reason \n in the query string does not work here -#PBS -l walltime=1:00:00,nodes=1:ppn=1 -#PBS -joe . -#PBS -d . -#PBS -l vmem=10g,mem=10g +#SBATCH --time=1:00:00 +#SBATCH --ntasks-per-node=1 +#SBATCH --mem=10G if [ -z $file ] then @@ -79,10 +78,12 @@ sQuery="select \ domains as Protein_domains,\ rs_ids as rsIDs,\ gnomad_af as Gnomad_af,\ - gnomad_af_popmax as Gnomad_af_popmax,\ + gnomad_af_grpmax as Gnomad_af_grpmax,\ gnomad_ac as Gnomad_ac,\ gnomad_hom as Gnomad_hom,\ - gnomad_male_ac as Gnomad_male_ac, \ + gnomad_male_ac as Gnomad_male_ac, \ + gnomad_fafmax_faf95_max as Gnomad_fafmax_faf95_max, \ + gnomad_filter as Gnomad_filter, \ sift_score as Sift_score,\ polyphen_score as Polyphen_score,\ cadd_phred as Cadd_score,\ @@ -131,7 +132,7 @@ initialQuery=$sQuery # keep the field selection part for later use #max_aaf_all frequency is from gemini.conf and does not include gnomad WGS frequencing, gnomad WES only #gnomad_af includes gnomad WGS -sQuery=$sQuery" where gnomad_af_popmax <= "${max_af}" "$caller_filter""${severity_filter}"" +sQuery=$sQuery" where gnomad_fafmax_faf95_max <= "${max_af}" "$caller_filter""${severity_filter}"" s_gt_filter='' # denovo 0/1 is exported in cre.sh @@ -163,14 +164,14 @@ else # also get the clinvar variants (duplicates will be removed later) cQuery=$initialQuery - cQuery=$cQuery" where gnomad_af_popmax <= ${max_af} "$caller_filter" and Clinvar <> ''" + cQuery=$cQuery" where gnomad_fafmax_faf95_max <= ${max_af} "$caller_filter" and Clinvar <> ''" # only get variants where AD >= 1 (any sample with an alternate read) c_gt_filter="(gt_alt_depths).(*).(>=1).(any) or (gt_alt_depths).(*).(==-1).(all)" gemini query -q "$cQuery" --gt-filter "$c_gt_filter" $file # if allele frequency is > 1% and Clinvar is pathogenic, likely pathogenic or conflicting and any status except for no assertion cQuery=$initialQuery - cQuery=$cQuery" where gnomad_af_popmax > ${max_af} "$caller_filter" and Clinvar_status != 'no_assertion_criteria_provided' and Clinvar in ('Pathogenic', 'Likely_pathogenic', 'Conflicting_interpretations_of_pathogenicity')" + cQuery=$cQuery" where gnomad_fafmax_faf95_max > ${max_af} "$caller_filter" and Clinvar_status != 'no_assertion_criteria_provided' and Clinvar in ('Pathogenic', 'Likely_pathogenic', 'Conflicting_interpretations_of_pathogenicity')" gemini query -q "$cQuery" $file fi diff --git a/cre.gnomad_scores_v4.1.py b/cre.gnomad_scores_v4.1.py new file mode 100644 index 0000000..ff026c3 --- /dev/null +++ b/cre.gnomad_scores_v4.1.py @@ -0,0 +1,65 @@ +import pandas as pd + +""" +This script processes the gnomAD v4.1 constraint scores present here /hpf/largeprojects/ccmbio/ajain/crg2_hg38/gnomad_v4.1/constraint_metrics/gnomad.v4.1.constraint_metrics.tsv +to retain only Ensemble mane select genes. + +Final processed file is located in ~/cre/data/gnomad_scores_v4.1.csv + +Script written by Anjali Jain +Date: Aug 27, 2024 +""" + +# Read in the constraints file that was downloaded from gnomAD: https://storage.googleapis.com/gcp-public-data--gnomad/release/4.1/constraint/gnomad.v4.1.constraint_metrics.tsv +constraints = pd.read_csv( + "/hpf/largeprojects/ccmbio/ajain/crg2_hg38/gnomad_v4.1/constraint_metrics/gnomad.v4.1.constraint_metrics.tsv", + sep="\t", +) + +# Filtering for the Ensembl canonical transcript +constraints = constraints[ + constraints["gene_id"].str.startswith("ENSG") & constraints["mane_select"] == True +] + +# Check if there are any duplicates +if len(constraints["gene_id"]) == len(set(constraints["gene_id"])): + print( + f"There are no duplicates in this dataframe. There are {len(constraints['gene_id'])} unique ensembl mane select genes" + ) +else: + print("Duplicates found!") + +# Keeping columns that are relevant +constraints = constraints[ + [ + "gene_id", + "transcript", + "lof.oe", + "lof.oe_ci.lower", + "lof.oe_ci.upper", + "lof.pLI", + "lof.pNull", + "lof.pRec", + "mis.oe", + "mis.z_score", + ] +] + +# renaming the columns +constraints = constraints.rename( + columns={ + "gene_id": "Ensembl_gene_id", + "transcript": "Ensembl_transcript_id", + "lof.oe": "Gnomad_oe_lof_score", + "lof.oe_ci.lower": "Gnomad_oe_ci_lower", + "lof.oe_ci.upper": "Gnomad_oe_ci_upper", + "lof.pLI": "Gnomad_pLI_score", + "lof.pNull": "Gnomad_pnull_score", + "lof.pRec": "Gnomad_prec_score", + "mis.oe": "Gnomad_oe_mis_score", + "mis.z_score": "Gnomad_mis_z_score", + } +) + +# Write the constraints score to ~/cre/data/gnomad_scores_v4.1.csv +constraints.to_csv("~/cre/data/gnomad_scores_v4.1.csv", index=False) diff --git a/cre.vcf2db.R b/cre.vcf2db.R index 6d83aba..6bb489c 100644 --- a/cre.vcf2db.R +++ b/cre.vcf2db.R @@ -87,7 +87,7 @@ create_report <- function(family, samples, type){ # Column3 = GNOMAD_Link variants$GNOMAD_POS <- with(variants, paste(Chrom,Pos,Ref,Alt, sep='-')) sGNOMAD1 <- "=HYPERLINK(\"http://gnomad.broadinstitute.org/variant/" - sGNOMAD2 <- "?dataset=gnomad_r3" + sGNOMAD2 <- "?dataset=gnomad_r4" sGNOMAD3 <- "\",\"GNOMAD_link\")" variants$GNOMAD_Link <- with(variants, paste(sGNOMAD1, GNOMAD_POS, sGNOMAD2, sGNOMAD3, sep = '')) @@ -270,12 +270,19 @@ create_report <- function(family, samples, type){ # population frequencies # Column34 = Gnomad_af - # Column35 = Gnomad_af_popmax + # Column35 = gnomad_af_grpmax # Gnomad gene constraint scores # Column36 = Gnomad_oe_lof_score # Column37 = Gnomad_oe_mis_score - gnomad_scores_file <- paste0(default_tables_path, "/gnomad_scores.csv") + # Column = Ensembl_transcript_id + # Column = Gnomad_oe_ci_lower + # Column = Gnomad_oe_ci_upper + # Column = Gnomad_pLI_score + # Column = Gnomad_pnull_score + # Column = Gnomad_prec_score + # Column = Gnomad_mis_z_score + gnomad_scores_file <- paste0(default_tables_path, "/gnomad_scores_v4.1.csv") gnomad_scores <- read.csv(gnomad_scores_file, stringsAsFactors = F) variants <- merge(variants, gnomad_scores, all.x = T, all.y = F) @@ -411,7 +418,7 @@ create_report <- function(family, samples, type){ # Column 57: ENH_cellline_tissue # replace -1 with 0 - for (field in c("Trio_coverage", "Gnomad_af", "Gnomad_af_popmax")){ + for (field in c("Trio_coverage", "Gnomad_af", "Gnomad_af_grpmax")){ variants[,field] <- with(variants, gsub("-1", "0", get(field), fixed = T)) variants[,field] <- with(variants, gsub("None", "0", get(field), fixed = T)) } @@ -453,13 +460,13 @@ select_and_write2 <- function(variants, samples, prefix, type) "C4R_WES_counts", "C4R_WES_samples"), wgs_counts, c("HGMD_id", "HGMD_gene", "HGMD_tag", "HGMD_ref", - "Gnomad_af_popmax", "Gnomad_af", "Gnomad_ac", "Gnomad_hom", + "Gnomad_af_grpmax", "Gnomad_af", "Gnomad_ac", "Gnomad_hom","Gnomad_male_ac","Gnomad_fafmax_faf95_max", "Gnomad_filter", "Ensembl_transcript_id", "AA_position", "Exon", "Protein_domains", "rsIDs", - "Gnomad_oe_lof_score", "Gnomad_oe_mis_score", "Exac_pli_score", "Exac_prec_score", "Exac_pnull_score", + "Gnomad_oe_lof_score", "Gnomad_oe_ci_lower","Gnomad_oe_ci_upper","Gnomad_oe_mis_score", "Gnomad_mis_z_score","Gnomad_pLI_score","Gnomad_pnull_score","Gnomad_prec_score", "Conserved_in_30_mammals", "SpliceAI_impact", "SpliceAI_score", "Sift_score", "Polyphen_score", "Cadd_score", "Vest4_score", "Revel_score", "Gerp_score", "AlphaMissense"), noncoding_scores, - c("Imprinting_status", "Imprinting_expressed_allele", "Pseudoautosomal", "Gnomad_male_ac", - "Number_of_callers", "Old_multiallelic", "UCE_100bp", "UCE_200bp"), noncoding_cols)] + c("Imprinting_status", "Imprinting_expressed_allele", "Pseudoautosomal", + "Number_of_callers", "Old_multiallelic", "UCE_100bp", "UCE_200bp"), noncoding_cols)] variants <- variants[order(variants$Position),] @@ -828,15 +835,15 @@ clinical_report <- function(project,samples,type){ # for clinical, only keep variants where one of the alt depths was >= 20 full_report <- dplyr::filter_at(full_report, paste0("Alt_depths.",samples), any_vars(as.integer(.) >= 20)) filtered_report <- subset(full_report, - Quality > 1000 & Gnomad_af_popmax < 0.005 & C4R_WES_counts < 6, + Quality > 1000 & Gnomad_af_grpmax < 0.005 & C4R_WES_counts < 6, select = c("Position", "GNOMAD_Link", "Ref", "Alt", "Gene", paste0("Zygosity.", samples), paste0("Burden.",samples), paste0("Alt_depths.",samples), "Variation", "Info", "Refseq_change", "omim_phenotype", "omim_inheritance", "Orphanet", "Clinvar", "C4R_WES_counts", - "Gnomad_af_popmax", "Gnomad_af", "Gnomad_ac", "Gnomad_hom", + "Gnomad_af_grpmax", "Gnomad_af", "Gnomad_ac", "Gnomad_hom","Gnomad_male_ac","Gnomad_fafmax_faf95_max","Gnomad_filter", "Sift_score", "Polyphen_score", "Cadd_score", "Vest4_score", "Revel_score", - "Imprinting_status", "Pseudoautosomal", "Gnomad_male_ac", "UCE_100bp","UCE_200bp") + "Imprinting_status", "Pseudoautosomal", "UCE_100bp","UCE_200bp") ) # recalculate burden using the filtered report @@ -860,9 +867,9 @@ clinical_report <- function(project,samples,type){ paste0("Burden.", samples), "Variation", "Info", "Refseq_change", "omim_phenotype", "omim_inheritance", "Orphanet", "Clinvar", "C4R_WES_counts", - "Gnomad_af_popmax", "Gnomad_af", "Gnomad_ac", "Gnomad_hom", + "Gnomad_af_grpmax", "Gnomad_af", "Gnomad_ac", "Gnomad_hom", "Gnomad_male_ac","Gnomad_fafmax_faf95_max","Gnomad_filter", "Sift_score", "Polyphen_score", "Cadd_score", "Vest4_score", "Revel_score", - "Imprinting_status", "Pseudoautosomal", "Gnomad_male_ac", "UCE_100bp", "UCE_200bp")] + "Imprinting_status", "Pseudoautosomal", "UCE_100bp", "UCE_200bp")] write.csv(filtered_report, paste0(project, ".clinical.", type, ".", datetime, ".csv"), row.names = F) } diff --git a/data/gnomad_scores_v4.1.csv b/data/gnomad_scores_v4.1.csv new file mode 100644 index 0000000..4d7d7f7 --- /dev/null +++ b/data/gnomad_scores_v4.1.csv @@ -0,0 +1,17482 @@ +Ensembl_gene_id,Ensembl_transcript_id,Gnomad_oe_lof_score,Gnomad_oe_ci_lower,Gnomad_oe_ci_upper,Gnomad_pLI_score,Gnomad_pnull_score,Gnomad_prec_score,Gnomad_oe_mis_score,Gnomad_mis_z_score +ENSG00000121410,ENST00000263100,1.05,0.8220000000000001,1.34,1.77e-16,0.843,0.157,1.09,-0.861 +ENSG00000148584,ENST00000373997,0.643,0.506,0.825,7.66e-10,0.00196,0.998,0.8759999999999999,1.24 +ENSG00000175899,ENST00000318602,0.645,0.546,0.765,9.76e-20,9.69e-06,1.0,0.813,2.76 +ENSG00000166535,ENST00000299698,0.83,0.725,0.953,1.71e-40,0.10099999999999999,0.899,0.893,1.66 +ENSG00000184389,ENST00000442999,1.02,0.698,1.53,1.02e-06,0.425,0.575,1.57,-4.08 +ENSG00000128274,ENST00000642412,0.616,0.302,1.39,0.0755,0.126,0.7979999999999999,1.03,-0.278 +ENSG00000118017,ENST00000236709,0.701,0.38299999999999995,1.38,0.0191,0.14400000000000002,0.8370000000000001,0.861,1.06 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