gsMap 1.67__py3-none-any.whl → 1.70__py3-none-any.whl

gsMap/format_sumstats.py

@@ -1,407 +1,407 @@
-import numpy as np
-import logging
-import re
-
-import math
-import numpy as np
-import pandas as pd
-from scipy.stats import chi2
-
-from gsMap.config import FormatSumstatsConfig
-
-VALID_SNPS = {'AC', 'AG', 'CA', 'CT', 'GA', 'GT', 'TC', 'TG'}
-logger = logging.getLogger(__name__)
-
-default_cnames = {
-    # RS NUMBER
-    'SNP': 'SNP',
-    'RS': 'SNP',
-    'RSID': 'SNP',
-    'RS_NUMBER': 'SNP',
-    'RS_NUMBERS': 'SNP',
-    # P-VALUE
-    'P': 'P',
-    'PVALUE': 'P',
-    'P_VALUE': 'P',
-    'PVAL': 'P',
-    'P_VAL': 'P',
-    'GC_PVALUE': 'P',
-    'p': 'P',
-    # EFFECT_ALLELE (A1)
-    'A1': 'A1',
-    'ALLELE1': 'A1',
-    'ALLELE_1': 'A1',
-    'EFFECT_ALLELE': 'A1',
-    'REFERENCE_ALLELE': 'A1',
-    'INC_ALLELE': 'A1',
-    'EA': 'A1',
-    # NON_EFFECT_ALLELE (A2)
-    'A2': 'A2',
-    'ALLELE2': 'A2',
-    'ALLELE_2': 'A2',
-    'OTHER_ALLELE': 'A2',
-    'NON_EFFECT_ALLELE': 'A2',
-    'DEC_ALLELE': 'A2',
-    'NEA': 'A2',
-    # N
-    'N': 'N',
-    'NCASE': 'N_CAS',
-    'CASES_N': 'N_CAS',
-    'N_CASE': 'N_CAS',
-    'N_CASES': 'N_CAS',
-    'N_CONTROLS': 'N_CON',
-    'N_CAS': 'N_CAS',
-    'N_CON': 'N_CON',
-    'N_CASE': 'N_CAS',
-    'NCONTROL': 'N_CON',
-    'CONTROLS_N': 'N_CON',
-    'N_CONTROL': 'N_CON',
-    'WEIGHT': 'N',
-    # SIGNED STATISTICS
-    'ZSCORE': 'Z',
-    'Z-SCORE': 'Z',
-    'GC_ZSCORE': 'Z',
-    'Z': 'Z',
-    'OR': 'OR',
-    'B': 'BETA',
-    'BETA': 'BETA',
-    'LOG_ODDS': 'LOG_ODDS',
-    'EFFECTS': 'BETA',
-    'EFFECT': 'BETA',
-    'b': 'BETA',
-    'beta': 'BETA',
-    # SE
-    'se': 'SE',
-    # INFO
-    'INFO': 'INFO',
-    'Info': 'INFO',
-    # MAF
-    'EAF': 'FRQ',
-    'FRQ': 'FRQ',
-    'MAF': 'FRQ',
-    'FRQ_U': 'FRQ',
-    'F_U': 'FRQ',
-    'frq_A1': 'FRQ',
-    'frq': 'FRQ',
-    'freq': 'FRQ'
-}
-
-
-def get_compression(fh):
-    '''
-    Read filename suffixes and figure out whether it is gzipped,bzip2'ed or not compressed
-    '''
-    if fh.endswith('gz'):
-        compression = 'gzip'
-    elif fh.endswith('bz2'):
-        compression = 'bz2'
-    else:
-        compression = None
-
-    return compression
-
-
-def gwas_checkname(gwas, config):
-    '''
-    Iterpret column names of gwas
-    '''
-    old_name = gwas.columns
-    mapped_cnames = {}
-    for col in gwas.columns:
-        mapped_cnames[col] = default_cnames.get(col, col)
-    gwas.columns = list(mapped_cnames.values())
-
-    # When column names are provided by users
-    name_updates = {'SNP': config.snp, 'A1': config.a1, 'A2': config.a2, 'INFO': config.info,
-                    'BETA': config.beta, 'SE': config.se, 'P': config.p, 'FRQ': config.frq, 'N': config.n,
-                    'Z': config.z, 'Chr': config.chr, 'Pos': config.pos, 'OR': config.OR, 'SE_OR': config.se_OR}
-
-    for key, value in name_updates.items():
-        if value is not None and value in gwas.columns:
-            gwas.rename(columns={value: key}, inplace=True)
-    new_name = gwas.columns
-    # check the name duplication
-    for head in new_name:
-        numc = list(new_name).count(head)
-        if numc > 1:
-            raise ValueError(f"Found {numc} different {head} columns, please check your {head} column.")
-
-    name_dict = {new_name[i]: old_name[i] for i in range(len(new_name))}
-
-    # When at OR scale
-    if 'OR' in new_name and 'SE_OR' in new_name:
-        gwas['BETA'] = gwas.OR.apply(lambda x: math.log(x) if x > 0 else None)
-        gwas['SE'] = gwas.SE_OR.apply(lambda x: math.log(x) if x > 0 else None)
-
-    interpreting = {
-        "SNP": 'Variant ID (e.g., rs number).',
-        "A1": 'Allele 1, interpreted as the effect allele for signed sumstat.',
-        "A2": 'Allele 2, interpreted as the non-effect allele for signed sumstat.',
-        "BETA": '[linear/logistic] regression coefficient (0 → no effect; above 0 → A1 is trait/risk increasing).',
-        "SE": 'Standard error of the regression coefficient.',
-        "OR": 'Odds ratio, will be transferred to linear scale.',
-        "SE_OR": 'Standard error of the odds ratio, will be transferred to linear scale.',
-        "P": 'P-Value.',
-        "Z": 'Z-Value.',
-        "N": 'Sample size.',
-        "INFO": 'INFO score (imputation quality; higher → better imputation).',
-        "FRQ": 'Allele frequency of A1.',
-        "Chr": 'Chromsome.',
-        'Pos': 'SNP positions.'
-    }
-
-    logger.info(f'\nIterpreting column names as follows:')
-    for key, value in interpreting.items():
-        if key in new_name:
-            logger.info(f'{name_dict[key]}: {interpreting[key]}')
-
-    return gwas
-
-
-def gwas_checkformat(gwas, config):
-    '''
-    Check column names required for different format
-    '''
-    if config.format == 'gsMap':
-        condition1 = np.any(np.isin(['P', 'Z'], gwas.columns))
-        condition2 = np.all(np.isin(['BETA', 'SE'], gwas.columns))
-        if not (condition1 or condition2):
-            raise ValueError(
-                'To munge GWAS data into gsMap format, either P or Z values, or both BETA and SE values, are required.')
-        else:
-            if 'Z' in gwas.columns:
-                pass
-            elif 'P' in gwas.columns:
-                gwas['Z'] = np.sqrt(chi2.isf(gwas.P, 1)) * np.where(gwas['BETA'] < 0, -1, 1)
-            else:
-                gwas['Z'] = gwas.BETA / gwas.SE
-
-    elif config.format == 'COJO':
-        condition = np.all(np.isin(['A1', 'A2', 'FRQ', 'BETA', 'SE', 'P', 'N'], gwas.columns))
-        if not condition:
-            raise ValueError('To munge GWAS data into COJO format, either A1|A2|FRQ|BETA|SE|P|N, are required.')
-        else:
-            gwas['Z'] = np.sqrt(chi2.isf(gwas.P, 1)) * np.where(gwas['BETA'] < 0, -1, 1)
-
-    return gwas
-
-
-def filter_info(info, config):
-    '''Remove INFO < args.info_min (default 0.9) and complain about out-of-bounds INFO.'''
-    if type(info) is pd.Series:  # one INFO column
-        jj = ((info > 2.0) | (info < 0)) & info.notnull()
-        ii = info >= config.info_min
-    elif type(info) is pd.DataFrame:  # several INFO columns
-        jj = (((info > 2.0) & info.notnull()).any(axis=1) | (
-                (info < 0) & info.notnull()).any(axis=1))
-        ii = (info.sum(axis=1) >= config.info_min * (len(info.columns)))
-    else:
-        raise ValueError('Expected pd.DataFrame or pd.Series.')
-
-    bad_info = jj.sum()
-    if bad_info > 0:
-        msg = 'WARNING: {N} SNPs had INFO outside of [0,1.5]. The INFO column may be mislabeled.'
-        logger.warning(msg.format(N=bad_info))
-
-    return ii
-
-
-def filter_frq(frq, config):
-    '''
-    Filter on MAF. Remove MAF < args.maf_min and out-of-bounds MAF.
-    '''
-    jj = (frq < 0) | (frq > 1)
-    bad_frq = jj.sum()
-    if bad_frq > 0:
-        msg = 'WARNING: {N} SNPs had FRQ outside of [0,1]. The FRQ column may be mislabeled.'
-        logger.warning(msg.format(N=bad_frq))
-
-    frq = np.minimum(frq, 1 - frq)
-    ii = frq > config.maf_min
-    return ii & ~jj
-
-
-def filter_pvals(P, config):
-    '''Remove out-of-bounds P-values'''
-    ii = (P > 0) & (P <= 1)
-    bad_p = (~ii).sum()
-    if bad_p > 0:
-        msg = 'WARNING: {N} SNPs had P outside of (0,1]. The P column may be mislabeled.'
-        logger.warning(msg.format(N=bad_p))
-
-    return ii
-
-
-def filter_alleles(a):
-    '''Remove alleles that do not describe strand-unambiguous SNPs'''
-    return a.isin(VALID_SNPS)
-
-
-def gwas_qc(gwas, config):
-    '''
-    Filter out SNPs based on INFO, FRQ, MAF, N, and Genotypes. 
-    '''
-    old = len(gwas)
-    logger.info(f'\nFiltering SNPs as follows:')
-    # filter: SNPs with missing values
-    drops = {'NA': 0, 'P': 0, 'INFO': 0, 'FRQ': 0, 'A': 0, 'SNP': 0, 'Dup': 0, 'N': 0}
-
-    gwas = gwas.dropna(axis=0, how="any", subset=filter(
-        lambda x: x != 'INFO', gwas.columns)).reset_index(drop=True)
-
-    drops['NA'] = old - len(gwas)
-    logger.info(f'Removed {drops["NA"]} SNPs with missing values.')
-
-    # filter: SNPs with Info < 0.9
-    if 'INFO' in gwas.columns:
-        old = len(gwas)
-        gwas = gwas.loc[filter_info(gwas['INFO'], config)]
-        drops['INFO'] = old - len(gwas)
-        logger.info(f'Removed {drops["INFO"]} SNPs with INFO <= 0.9.')
-
-    # filter: SNPs with MAF <= 0.01
-    if 'FRQ' in gwas.columns:
-        old = len(gwas)
-        gwas = gwas.loc[filter_frq(gwas['FRQ'], config)]
-        drops['FRQ'] += old - len(gwas)
-        logger.info(f'Removed {drops["FRQ"]} SNPs with MAF <= 0.01.')
-
-    # filter: P-value that out-of-bounds [0,1]
-    if 'P' in gwas.columns:
-        old = len(gwas)
-        gwas = gwas.loc[filter_pvals(gwas['P'], config)]
-        drops['P'] += old - len(gwas)
-        logger.info(f'Removed {drops["P"]} SNPs with out-of-bounds p-values.')
-
-    # filter: Variants that are strand-ambiguous
-    if 'A1' in gwas.columns and 'A2' in gwas.columns:
-        gwas.A1 = gwas.A1.str.upper()
-        gwas.A2 = gwas.A2.str.upper()
-        gwas = gwas.loc[filter_alleles(gwas.A1 + gwas.A2)]
-        drops['A'] += old - len(gwas)
-        logger.info(f'Removed {drops["A"]} variants that were not SNPs or were strand-ambiguous.')
-
-    # filter: Duplicated rs numbers
-    if 'SNP' in gwas.columns:
-        old = len(gwas)
-        gwas = gwas.drop_duplicates(subset='SNP').reset_index(drop=True)
-        drops['Dup'] += old - len(gwas)
-        logger.info(f'Removed {drops["Dup"]} SNPs with duplicated rs numbers.')
-
-    # filter:Sample size
-    n_min = gwas.N.quantile(0.9) / 1.5
-    old = len(gwas)
-    gwas = gwas[gwas.N >= n_min].reset_index(drop=True)
-    drops['N'] += old - len(gwas)
-    logger.info(f'Removed {drops["N"]} SNPs with N < {n_min}.')
-
-    return gwas
-
-
-def variant_to_rsid(gwas, config):
-    '''
-    Convert variant id (Chr, Pos) to rsid
-    '''
-    logger.info("\nConverting the SNP position to rsid. This process may take some time.")
-    unique_ids = set(gwas['id'])
-    chr_format = gwas['Chr'].unique().astype(str)
-    chr_format = [re.sub(r'\d+', '', value) for value in chr_format][1]
-
-    dtype = {'chr': str, 'pos': str, 'ref': str, 'alt': str, 'dbsnp': str}
-    chunk_iter = pd.read_csv(config.dbsnp, chunksize=config.chunksize, sep="\t", skiprows=1,
-                             dtype=dtype, names=['chr', 'pos', 'ref', 'alt', 'dbsnp'])
-
-    # Iterate over chunks
-    matching_id = pd.DataFrame()
-    for chunk in chunk_iter:
-        chunk['id'] = chr_format + chunk["chr"] + "_" + chunk["pos"]
-        matching_id = pd.concat([matching_id, chunk[chunk['id'].isin(unique_ids)][['dbsnp', 'id']]])
-
-    matching_id = matching_id.drop_duplicates(subset='dbsnp').reset_index(drop=True)
-    matching_id = matching_id.drop_duplicates(subset='id').reset_index(drop=True)
-    matching_id.index = matching_id.id
-    return matching_id
-
-
-def clean_SNP_id(gwas, config):
-    '''
-    Clean SNP id
-    '''
-    old = len(gwas)
-    condition1 = 'SNP' in gwas.columns
-    condition2 = np.all(np.isin(['Chr', 'Pos'], gwas.columns))
-
-    if not (condition1 or condition2):
-        raise ValueError('Either SNP rsid, or both SNP chromosome and position, are required.')
-    elif condition1:
-        pass
-    elif condition2:
-        if config.dbsnp is None:
-            raise ValueError('To Convert SNP positions to rsid, dbsnp reference is required.')
-        else:
-            gwas['id'] = gwas["Chr"].astype(str) + "_" + gwas["Pos"].astype(str)
-            gwas = gwas.drop_duplicates(subset='id').reset_index(drop=True)
-            gwas.index = gwas.id
-
-            matching_id = variant_to_rsid(gwas, config)
-            gwas = gwas.loc[matching_id.id]
-            gwas['SNP'] = matching_id.dbsnp
-            num_fail = old - len(gwas)
-            logger.info(f'Removed {num_fail} SNPs that did not convert to rsid.')
-
-    return gwas
-
-
-def gwas_metadata(gwas, config):
-    '''
-    Report key features of GWAS data
-    '''
-    logger.info('\nSummary of GWAS data:')
-    CHISQ = (gwas.Z ** 2)
-    mean_chisq = CHISQ.mean()
-    logger.info('Mean chi^2 = ' + str(round(mean_chisq, 3)))
-    if mean_chisq < 1.02:
-        logger.warning("Mean chi^2 may be too small.")
-
-    logger.info('Lambda GC = ' + str(round(CHISQ.median() / 0.4549, 3)))
-    logger.info('Max chi^2 = ' + str(round(CHISQ.max(), 3)))
-    logger.info('{N} Genome-wide significant SNPs (some may have been removed by filtering).'.format(N=(CHISQ > 29).sum()))
-
-
-def gwas_format(config: FormatSumstatsConfig):
-    '''
-    Format GWAS data
-    '''
-    logger.info(f'------Formating gwas data for {config.sumstats}...')
-    compression_type = get_compression(config.sumstats)
-    gwas = pd.read_csv(config.sumstats, delim_whitespace=True, header=0, compression=compression_type,
-                       na_values=['.', 'NA'])
-    logger.info(f'Read {len(gwas)} SNPs from {config.sumstats}.')
-
-    # Check name and format
-    gwas = gwas_checkname(gwas, config)
-    gwas = gwas_checkformat(gwas, config)
-    # Clean the snp id
-    gwas = clean_SNP_id(gwas, config)
-    # QC
-    gwas = gwas_qc(gwas, config)
-    # Meta
-    gwas_metadata(gwas, config)
-
-    # Saving the data
-    if config.format == 'COJO':
-        keep = ['SNP', 'A1', 'A2', 'FRQ', 'BETA', 'SE', 'P', 'N']
-        appendix = '.cojo'
-    elif config.format == 'gsMap':
-        keep = ["SNP", "A1", "A2", "Z", "N"]
-        appendix = '.sumstats'
-
-    if 'Chr' in gwas.columns and 'Pos' in gwas.columns and config.keep_chr_pos is True:
-        keep = keep + ['Chr', 'Pos']
-
-    gwas = gwas[keep]
-    out_name = config.out + appendix + '.gz'
-
-    logger.info(f'\nWriting summary statistics for {len(gwas)} SNPs to {out_name}.')
-    gwas.to_csv(out_name, sep="\t", index=False,
-                float_format='%.3f', compression='gzip')
+import numpy as np
+import logging
+import re
+
+import math
+import numpy as np
+import pandas as pd
+from scipy.stats import chi2
+
+from gsMap.config import FormatSumstatsConfig
+
+VALID_SNPS = {'AC', 'AG', 'CA', 'CT', 'GA', 'GT', 'TC', 'TG'}
+logger = logging.getLogger(__name__)
+
+default_cnames = {
+    # RS NUMBER
+    'SNP': 'SNP',
+    'RS': 'SNP',
+    'RSID': 'SNP',
+    'RS_NUMBER': 'SNP',
+    'RS_NUMBERS': 'SNP',
+    # P-VALUE
+    'P': 'P',
+    'PVALUE': 'P',
+    'P_VALUE': 'P',
+    'PVAL': 'P',
+    'P_VAL': 'P',
+    'GC_PVALUE': 'P',
+    'p': 'P',
+    # EFFECT_ALLELE (A1)
+    'A1': 'A1',
+    'ALLELE1': 'A1',
+    'ALLELE_1': 'A1',
+    'EFFECT_ALLELE': 'A1',
+    'REFERENCE_ALLELE': 'A1',
+    'INC_ALLELE': 'A1',
+    'EA': 'A1',
+    # NON_EFFECT_ALLELE (A2)
+    'A2': 'A2',
+    'ALLELE2': 'A2',
+    'ALLELE_2': 'A2',
+    'OTHER_ALLELE': 'A2',
+    'NON_EFFECT_ALLELE': 'A2',
+    'DEC_ALLELE': 'A2',
+    'NEA': 'A2',
+    # N
+    'N': 'N',
+    'NCASE': 'N_CAS',
+    'CASES_N': 'N_CAS',
+    'N_CASE': 'N_CAS',
+    'N_CASES': 'N_CAS',
+    'N_CONTROLS': 'N_CON',
+    'N_CAS': 'N_CAS',
+    'N_CON': 'N_CON',
+    'N_CASE': 'N_CAS',
+    'NCONTROL': 'N_CON',
+    'CONTROLS_N': 'N_CON',
+    'N_CONTROL': 'N_CON',
+    'WEIGHT': 'N',
+    # SIGNED STATISTICS
+    'ZSCORE': 'Z',
+    'Z-SCORE': 'Z',
+    'GC_ZSCORE': 'Z',
+    'Z': 'Z',
+    'OR': 'OR',
+    'B': 'BETA',
+    'BETA': 'BETA',
+    'LOG_ODDS': 'LOG_ODDS',
+    'EFFECTS': 'BETA',
+    'EFFECT': 'BETA',
+    'b': 'BETA',
+    'beta': 'BETA',
+    # SE
+    'se': 'SE',
+    # INFO
+    'INFO': 'INFO',
+    'Info': 'INFO',
+    # MAF
+    'EAF': 'FRQ',
+    'FRQ': 'FRQ',
+    'MAF': 'FRQ',
+    'FRQ_U': 'FRQ',
+    'F_U': 'FRQ',
+    'frq_A1': 'FRQ',
+    'frq': 'FRQ',
+    'freq': 'FRQ'
+}
+
+
+def get_compression(fh):
+    '''
+    Read filename suffixes and figure out whether it is gzipped,bzip2'ed or not compressed
+    '''
+    if fh.endswith('gz'):
+        compression = 'gzip'
+    elif fh.endswith('bz2'):
+        compression = 'bz2'
+    else:
+        compression = None
+
+    return compression
+
+
+def gwas_checkname(gwas, config):
+    '''
+    Iterpret column names of gwas
+    '''
+    old_name = gwas.columns
+    mapped_cnames = {}
+    for col in gwas.columns:
+        mapped_cnames[col] = default_cnames.get(col, col)
+    gwas.columns = list(mapped_cnames.values())
+
+    # When column names are provided by users
+    name_updates = {'SNP': config.snp, 'A1': config.a1, 'A2': config.a2, 'INFO': config.info,
+                    'BETA': config.beta, 'SE': config.se, 'P': config.p, 'FRQ': config.frq, 'N': config.n,
+                    'Z': config.z, 'Chr': config.chr, 'Pos': config.pos, 'OR': config.OR, 'SE_OR': config.se_OR}
+
+    for key, value in name_updates.items():
+        if value is not None and value in gwas.columns:
+            gwas.rename(columns={value: key}, inplace=True)
+    new_name = gwas.columns
+    # check the name duplication
+    for head in new_name:
+        numc = list(new_name).count(head)
+        if numc > 1:
+            raise ValueError(f"Found {numc} different {head} columns, please check your {head} column.")
+
+    name_dict = {new_name[i]: old_name[i] for i in range(len(new_name))}
+
+    # When at OR scale
+    if 'OR' in new_name and 'SE_OR' in new_name:
+        gwas['BETA'] = gwas.OR.apply(lambda x: math.log(x) if x > 0 else None)
+        gwas['SE'] = gwas.SE_OR.apply(lambda x: math.log(x) if x > 0 else None)
+
+    interpreting = {
+        "SNP": 'Variant ID (e.g., rs number).',
+        "A1": 'Allele 1, interpreted as the effect allele for signed sumstat.',
+        "A2": 'Allele 2, interpreted as the non-effect allele for signed sumstat.',
+        "BETA": '[linear/logistic] regression coefficient (0 → no effect; above 0 → A1 is trait/risk increasing).',
+        "SE": 'Standard error of the regression coefficient.',
+        "OR": 'Odds ratio, will be transferred to linear scale.',
+        "SE_OR": 'Standard error of the odds ratio, will be transferred to linear scale.',
+        "P": 'P-Value.',
+        "Z": 'Z-Value.',
+        "N": 'Sample size.',
+        "INFO": 'INFO score (imputation quality; higher → better imputation).',
+        "FRQ": 'Allele frequency of A1.',
+        "Chr": 'Chromsome.',
+        'Pos': 'SNP positions.'
+    }
+
+    logger.info(f'\nIterpreting column names as follows:')
+    for key, value in interpreting.items():
+        if key in new_name:
+            logger.info(f'{name_dict[key]}: {interpreting[key]}')
+
+    return gwas
+
+
+def gwas_checkformat(gwas, config):
+    '''
+    Check column names required for different format
+    '''
+    if config.format == 'gsMap':
+        condition1 = np.any(np.isin(['P', 'Z'], gwas.columns))
+        condition2 = np.all(np.isin(['BETA', 'SE'], gwas.columns))
+        if not (condition1 or condition2):
+            raise ValueError(
+                'To munge GWAS data into gsMap format, either P or Z values, or both BETA and SE values, are required.')
+        else:
+            if 'Z' in gwas.columns:
+                pass
+            elif 'P' in gwas.columns:
+                gwas['Z'] = np.sqrt(chi2.isf(gwas.P, 1)) * np.where(gwas['BETA'] < 0, -1, 1)
+            else:
+                gwas['Z'] = gwas.BETA / gwas.SE
+
+    elif config.format == 'COJO':
+        condition = np.all(np.isin(['A1', 'A2', 'FRQ', 'BETA', 'SE', 'P', 'N'], gwas.columns))
+        if not condition:
+            raise ValueError('To munge GWAS data into COJO format, either A1|A2|FRQ|BETA|SE|P|N, are required.')
+        else:
+            gwas['Z'] = np.sqrt(chi2.isf(gwas.P, 1)) * np.where(gwas['BETA'] < 0, -1, 1)
+
+    return gwas
+
+
+def filter_info(info, config):
+    '''Remove INFO < args.info_min (default 0.9) and complain about out-of-bounds INFO.'''
+    if type(info) is pd.Series:  # one INFO column
+        jj = ((info > 2.0) | (info < 0)) & info.notnull()
+        ii = info >= config.info_min
+    elif type(info) is pd.DataFrame:  # several INFO columns
+        jj = (((info > 2.0) & info.notnull()).any(axis=1) | (
+                (info < 0) & info.notnull()).any(axis=1))
+        ii = (info.sum(axis=1) >= config.info_min * (len(info.columns)))
+    else:
+        raise ValueError('Expected pd.DataFrame or pd.Series.')
+
+    bad_info = jj.sum()
+    if bad_info > 0:
+        msg = 'WARNING: {N} SNPs had INFO outside of [0,1.5]. The INFO column may be mislabeled.'
+        logger.warning(msg.format(N=bad_info))
+
+    return ii
+
+
+def filter_frq(frq, config):
+    '''
+    Filter on MAF. Remove MAF < args.maf_min and out-of-bounds MAF.
+    '''
+    jj = (frq < 0) | (frq > 1)
+    bad_frq = jj.sum()
+    if bad_frq > 0:
+        msg = 'WARNING: {N} SNPs had FRQ outside of [0,1]. The FRQ column may be mislabeled.'
+        logger.warning(msg.format(N=bad_frq))
+
+    frq = np.minimum(frq, 1 - frq)
+    ii = frq > config.maf_min
+    return ii & ~jj
+
+
+def filter_pvals(P, config):
+    '''Remove out-of-bounds P-values'''
+    ii = (P > 0) & (P <= 1)
+    bad_p = (~ii).sum()
+    if bad_p > 0:
+        msg = 'WARNING: {N} SNPs had P outside of (0,1]. The P column may be mislabeled.'
+        logger.warning(msg.format(N=bad_p))
+
+    return ii
+
+
+def filter_alleles(a):
+    '''Remove alleles that do not describe strand-unambiguous SNPs'''
+    return a.isin(VALID_SNPS)
+
+
+def gwas_qc(gwas, config):
+    '''
+    Filter out SNPs based on INFO, FRQ, MAF, N, and Genotypes. 
+    '''
+    old = len(gwas)
+    logger.info(f'\nFiltering SNPs as follows:')
+    # filter: SNPs with missing values
+    drops = {'NA': 0, 'P': 0, 'INFO': 0, 'FRQ': 0, 'A': 0, 'SNP': 0, 'Dup': 0, 'N': 0}
+
+    gwas = gwas.dropna(axis=0, how="any", subset=filter(
+        lambda x: x != 'INFO', gwas.columns)).reset_index(drop=True)
+
+    drops['NA'] = old - len(gwas)
+    logger.info(f'Removed {drops["NA"]} SNPs with missing values.')
+
+    # filter: SNPs with Info < 0.9
+    if 'INFO' in gwas.columns:
+        old = len(gwas)
+        gwas = gwas.loc[filter_info(gwas['INFO'], config)]
+        drops['INFO'] = old - len(gwas)
+        logger.info(f'Removed {drops["INFO"]} SNPs with INFO <= 0.9.')
+
+    # filter: SNPs with MAF <= 0.01
+    if 'FRQ' in gwas.columns:
+        old = len(gwas)
+        gwas = gwas.loc[filter_frq(gwas['FRQ'], config)]
+        drops['FRQ'] += old - len(gwas)
+        logger.info(f'Removed {drops["FRQ"]} SNPs with MAF <= 0.01.')
+
+    # filter: P-value that out-of-bounds [0,1]
+    if 'P' in gwas.columns:
+        old = len(gwas)
+        gwas = gwas.loc[filter_pvals(gwas['P'], config)]
+        drops['P'] += old - len(gwas)
+        logger.info(f'Removed {drops["P"]} SNPs with out-of-bounds p-values.')
+
+    # filter: Variants that are strand-ambiguous
+    if 'A1' in gwas.columns and 'A2' in gwas.columns:
+        gwas.A1 = gwas.A1.str.upper()
+        gwas.A2 = gwas.A2.str.upper()
+        gwas = gwas.loc[filter_alleles(gwas.A1 + gwas.A2)]
+        drops['A'] += old - len(gwas)
+        logger.info(f'Removed {drops["A"]} variants that were not SNPs or were strand-ambiguous.')
+
+    # filter: Duplicated rs numbers
+    if 'SNP' in gwas.columns:
+        old = len(gwas)
+        gwas = gwas.drop_duplicates(subset='SNP').reset_index(drop=True)
+        drops['Dup'] += old - len(gwas)
+        logger.info(f'Removed {drops["Dup"]} SNPs with duplicated rs numbers.')
+
+    # filter:Sample size
+    n_min = gwas.N.quantile(0.9) / 1.5
+    old = len(gwas)
+    gwas = gwas[gwas.N >= n_min].reset_index(drop=True)
+    drops['N'] += old - len(gwas)
+    logger.info(f'Removed {drops["N"]} SNPs with N < {n_min}.')
+
+    return gwas
+
+
+def variant_to_rsid(gwas, config):
+    '''
+    Convert variant id (Chr, Pos) to rsid
+    '''
+    logger.info("\nConverting the SNP position to rsid. This process may take some time.")
+    unique_ids = set(gwas['id'])
+    chr_format = gwas['Chr'].unique().astype(str)
+    chr_format = [re.sub(r'\d+', '', value) for value in chr_format][1]
+
+    dtype = {'chr': str, 'pos': str, 'ref': str, 'alt': str, 'dbsnp': str}
+    chunk_iter = pd.read_csv(config.dbsnp, chunksize=config.chunksize, sep="\t", skiprows=1,
+                             dtype=dtype, names=['chr', 'pos', 'ref', 'alt', 'dbsnp'])
+
+    # Iterate over chunks
+    matching_id = pd.DataFrame()
+    for chunk in chunk_iter:
+        chunk['id'] = chr_format + chunk["chr"] + "_" + chunk["pos"]
+        matching_id = pd.concat([matching_id, chunk[chunk['id'].isin(unique_ids)][['dbsnp', 'id']]])
+
+    matching_id = matching_id.drop_duplicates(subset='dbsnp').reset_index(drop=True)
+    matching_id = matching_id.drop_duplicates(subset='id').reset_index(drop=True)
+    matching_id.index = matching_id.id
+    return matching_id
+
+
+def clean_SNP_id(gwas, config):
+    '''
+    Clean SNP id
+    '''
+    old = len(gwas)
+    condition1 = 'SNP' in gwas.columns
+    condition2 = np.all(np.isin(['Chr', 'Pos'], gwas.columns))
+
+    if not (condition1 or condition2):
+        raise ValueError('Either SNP rsid, or both SNP chromosome and position, are required.')
+    elif condition1:
+        pass
+    elif condition2:
+        if config.dbsnp is None:
+            raise ValueError('To Convert SNP positions to rsid, dbsnp reference is required.')
+        else:
+            gwas['id'] = gwas["Chr"].astype(str) + "_" + gwas["Pos"].astype(str)
+            gwas = gwas.drop_duplicates(subset='id').reset_index(drop=True)
+            gwas.index = gwas.id
+
+            matching_id = variant_to_rsid(gwas, config)
+            gwas = gwas.loc[matching_id.id]
+            gwas['SNP'] = matching_id.dbsnp
+            num_fail = old - len(gwas)
+            logger.info(f'Removed {num_fail} SNPs that did not convert to rsid.')
+
+    return gwas
+
+
+def gwas_metadata(gwas, config):
+    '''
+    Report key features of GWAS data
+    '''
+    logger.info('\nSummary of GWAS data:')
+    CHISQ = (gwas.Z ** 2)
+    mean_chisq = CHISQ.mean()
+    logger.info('Mean chi^2 = ' + str(round(mean_chisq, 3)))
+    if mean_chisq < 1.02:
+        logger.warning("Mean chi^2 may be too small.")
+
+    logger.info('Lambda GC = ' + str(round(CHISQ.median() / 0.4549, 3)))
+    logger.info('Max chi^2 = ' + str(round(CHISQ.max(), 3)))
+    logger.info('{N} Genome-wide significant SNPs (some may have been removed by filtering).'.format(N=(CHISQ > 29).sum()))
+
+
+def gwas_format(config: FormatSumstatsConfig):
+    '''
+    Format GWAS data
+    '''
+    logger.info(f'------Formating gwas data for {config.sumstats}...')
+    compression_type = get_compression(config.sumstats)
+    gwas = pd.read_csv(config.sumstats, delim_whitespace=True, header=0, compression=compression_type,
+                       na_values=['.', 'NA'])
+    logger.info(f'Read {len(gwas)} SNPs from {config.sumstats}.')
+
+    # Check name and format
+    gwas = gwas_checkname(gwas, config)
+    gwas = gwas_checkformat(gwas, config)
+    # Clean the snp id
+    gwas = clean_SNP_id(gwas, config)
+    # QC
+    gwas = gwas_qc(gwas, config)
+    # Meta
+    gwas_metadata(gwas, config)
+
+    # Saving the data
+    if config.format == 'COJO':
+        keep = ['SNP', 'A1', 'A2', 'FRQ', 'BETA', 'SE', 'P', 'N']
+        appendix = '.cojo'
+    elif config.format == 'gsMap':
+        keep = ["SNP", "A1", "A2", "Z", "N"]
+        appendix = '.sumstats'
+
+    if 'Chr' in gwas.columns and 'Pos' in gwas.columns and config.keep_chr_pos is True:
+        keep = keep + ['Chr', 'Pos']
+
+    gwas = gwas[keep]
+    out_name = config.out + appendix + '.gz'
+
+    logger.info(f'\nWriting summary statistics for {len(gwas)} SNPs to {out_name}.')
+    gwas.to_csv(out_name, sep="\t", index=False,
+                float_format='%.3f', compression='gzip')