Bgen input with an error caused by an incorrect variable invocation.

[1511878618]

A bug for --geno is a bgen file with code like below:

python /home/xutingfeng/github_code/others/polyfun/finemapper.py --geno data.bgen --sumstats polyfun_sumstats.tsv --chr 1 --start 15333350 --verbose --allow-missing \
--end 15833356 \
--method susie \
--max-num-causal 5 \
--out output/test.gz \
--n 383290 \
--non-funct \
--ldstore2 $(which ldstore2) \
--sample-file data.sample --threads 4 --memory 10240

and the error is :

bug source

the bug is caused by compute_ld_bgen at df_snp = df_z.query('SNP == "%s"'%(rsid))

 def compute_ld_bgen(self, locus_start, locus_end, verbose=False):
    
        #create df_z
        df_z = self.df_sumstats_locus[['SNP', 'CHR', 'BP', 'A1', 'A2']].copy()
        
        #add leading zeros to chromosome numbers if needed
        try:
            import bgen
        except (ImportError, ModuleNotFoundError):
            raise ValueError('\n\nPlease install the bgen package (using "pip install bgen")')
        from bgen.reader import BgenFile
        bfile = BgenFile(self.genotypes_file)
        bgen_chromosomes = bfile.chroms()
        if bgen_chromosomes[0].startswith('0'):
            df_z['CHR'] = '0' + df_z['CHR'].astype(str)
            
            
        #sync the order of the alleles between the sumstats and the bgen file
        list_bgen = []
        #rsids = bfile.rsids()
        #small change reduces the time for bgen processing
        #the previous implementation would iterate through all the SNPs in the bgen file
        #this implementation loops over just the snps in the locus
        rsids = bfile.fetch(self.chr, locus_start, locus_end)
        for snp_i, rsid in enumerate(rsids):
#             if rsid not in df_z['SNP'].values: continue
#             snp_alleles = bfile[snp_i].alleles
#             snp_chrom = bfile[snp_i].chrom
#             snp_pos = bfile[snp_i].pos
            if rsid.rsid not in df_z['SNP'].values: continue
            snp_alleles = rsid.alleles
            snp_chrom = rsid.chrom
            snp_pos = rsid.pos
            assert len(snp_alleles) == 2, 'cannot handle SNPs with more than two alleles'
            df_snp = df_z.query('SNP == "%s"'%(rsid)) # NOTE: bug is here 
            assert df_snp.shape[0]==1
            a1, a2 = df_snp['A1'].iloc[0], df_snp['A2'].iloc[0]
            snp_a1, snp_a2 = snp_alleles[0], snp_alleles[1]
            if set([a1,a2]) != set([snp_a1, snp_a2]):
                raise ValueError('The alleles for SNP %s are different in the sumstats and in the bgen file:\n \
                                 bgen:     A1=%s  A2=%s\n \
                                 sumstats: A1=%s  A2=%s \
                                '%(rsid, snp_alleles[0], snp_alleles[1], a1, a2))
            d = {'SNP':rsid, 'CHR':snp_chrom, 'BP':snp_pos, 'A1':snp_a1, 'A2':snp_a2}
            list_bgen.append(d)
        df_bgen = pd.DataFrame(list_bgen)
        df_bgen = set_snpid_index(df_bgen, allow_swapped_indel_alleles=self.allow_swapped_indel_alleles)
        df_z = set_snpid_index(df_z, allow_swapped_indel_alleles=self.allow_swapped_indel_alleles)
        df_z = df_z[[]].merge(df_bgen, left_index=True, right_index=True)
        df_z = df_z[['SNP', 'CHR', 'BP', 'A1', 'A2']]
            
        
        #rename columns
        df_z.rename(columns={'SNP':'rsid', 'CHR':'chromosome', 'BP':'position', 'A1':'allele1', 'A2':'allele2'}, inplace=True)
                
        #Create LDstore input files
        temp_dir = tempfile.mkdtemp()    
        incl_file = os.path.join(temp_dir, 'incl.incl')
        master_file = os.path.join(temp_dir, 'master.master')
        z_file = os.path.join(temp_dir, 'chr%s.%s_%s.z'%(self.chr, locus_start, locus_end))
        dose_file = os.path.join(temp_dir, 'dosages.bdose')
        df_z.to_csv(z_file, sep=' ', index=False)
        
        #find number of samples
        if self.incl_samples is None:
            num_samples = pd.read_table(self.sample_file).shape[0]-1
        else:
            num_samples = pd.read_table(self.incl_samples, header=None).shape[0]
            
        #get output file name
        bcor_file = self.get_ld_output_file_prefix(locus_start, locus_end, temp_dir) + '.bcor'
        
        #Create LDstore master file
        df_master = pd.DataFrame(columns=['z','bgen','bgi','bcor','dose','sample','n_samples'])
        df_master['z'] = [z_file]
        df_master['bgen'] = [self.genotypes_file]
        df_master['bgi'] = [self.genotypes_file+'.bgi']
        df_master['bcor'] = [bcor_file]
        df_master['bdose'] = [dose_file]
        df_master['sample'] = [self.sample_file]
        df_master['n_samples'] = num_samples
        if self.incl_samples is not None:
            df_master['incl'] = self.incl_samples
        df_master.to_csv(master_file, sep=';', header=True, index=False)    
        
        #run LDstore
        ldstore_cmd = [self.ldstore_exe, '--in-files', master_file, '--write-bcor', '--write-bdose', '--bdose-version', '1.0']
        if self.memory is not None:
            ldstore_cmd += ['--memory', str(self.memory)]
        if self.n_threads is not None:
            ldstore_cmd += ['--n-threads', str(self.n_threads)]
        run_executable(ldstore_cmd, 'LDStore', measure_time=True, show_output=verbose, show_command=verbose)
        
        if not os.path.exists(bcor_file):
            raise IOError('Could not find output BCOR file')
            
        return bcor_file

the reason is
rsid is kind of BgenVar("", "1:15333718:C:T", "1", 15333718, ['C', 'T']) ;while the truth variable should used here is rsid.rsid (which is correct used at above code, but not used at below).

SOLUTION

Let rsid = rsid.rsid or change the variable Name can solve the problem. code like below

test_polyfun.py doesn't have a test code for bgen file input

[omerwe]

@1511878618 thanks for the bug report! Would you mind submitting a pull request with the fix you suggested? I'll be happy to merge it into the main branch. Thanks!

[1511878618]

@1511878618 thanks for the bug report! Would you mind submitting a pull request with the fix you suggested? I'll be happy to merge it into the main branch. Thanks!

Sure, I've made a lot of changes in the finemapper.py, some of which may not be particularly good, but I'm submitting them now for you to review. After that, you can decide which ones to merge into the main branch (I will show you the contents in the PR)