geney 1.2.19__py2.py3-none-any.whl → 1.2.21__py2.py3-none-any.whl

geney/analyzers/survival.py

@@ -1,144 +0,0 @@
-import pandas as pd
-import numpy as np
-import matplotlib.pyplot as plt
-from pathlib import Path
-from scipy.integrate import trapz
-from geney.utils import unload_pickle, unload_json, contains
-from lifelines.exceptions import ConvergenceError
-from lifelines import KaplanMeierFitter
-from lifelines.statistics import logrank_test
-from lifelines import CoxPHFitter
-
-pd.set_option('display.max_columns', None)
-pd.options.mode.chained_assignment = None
-
-# epistasis_tracker = unload_pickle('epistasis2case_tracker.pkl')
-# mutation_tracker = unload_pickle('mutation2case_tracker.pkl')
-
-def prepare_clinical_data():
-    CLINICAL_DATA_FILE = Path('/tamir2/yoramzar/Projects/Cancer_mut/Explore_data/reports/df_p_all.pkl')
-    df = unload_pickle(CLINICAL_DATA_FILE)
-    df.rename(columns={'patient_uuid': 'case_id'}, inplace=True)
-    cols = list(df.columns)
-    cols_days_to_followup = [col for col in cols if 'days_to_followup' in col] + [col for col in cols if 'days_to_last_followup' in col]
-    cols_days_to_know_alive = [col for col in cols if 'days_to_know_alive' in col] + [col for col in cols if 'days_to_last_known_alive' in col]
-    cols_days_to_death = [col for col in cols if 'days_to_death' in col]
-    cols_duration = cols_days_to_followup + cols_days_to_know_alive + cols_days_to_death
-    col_vital_status = 'days_to_death'
-    event_col_label = 'event'
-    duration_col_label = 'duration'
-    df.insert(1, event_col_label, df.apply(lambda x: int(not np.isnan(x[col_vital_status])), axis=1))
-    df.insert(1, duration_col_label, df.apply(lambda x: max([x[col] for col in cols_duration if not np.isnan(x[col])], default=-1), axis=1))
-    df[duration_col_label] /= 365
-    df = df.query(f"{duration_col_label}>=0.0")[['duration', 'event', 'case_id', 'chemotherapy', 'hormone_therapy', 'immunotherapy', 'targeted_molecular_therapy', 'Proj_name']]
-    df.to_csv('/tamir2/nicolaslynn/data/tcga_metadata/tcga_clinical_data.csv')
-    return df
-
-
-class SurvivalAnalysis:
-    def __init__(self, clindf):
-        self.clindf = clindf
-        self.treatment_features = ['chemotherapy', 'hormone_therapy', 'immunotherapy', 'targeted_molecular_therapy']
-
-    def prepare_data(self, case_dict):
-        df1 = self.clindf.query(f"case_id in {case_dict['affected']}")
-        df2 = self.clindf.query(f"case_id in {case_dict['na1']}")
-        df3 = self.clindf.query(f"case_id in {case_dict['na2']}")
-        df1['group'] = 0
-        df2['group'] = 1
-        df3['group'] = 1
-        df = pd.concat([df1, df2, df3])
-        core_features = ['duration', 'event', 'group']
-        treatment_features = ['chemotherapy', 'hormone_therapy', 'immunotherapy', 'targeted_molecular_therapy']
-        df = df[treatment_features + core_features]
-        df.fillna(0, inplace=True)
-
-        cap_time = min([df[df.group == 0].duration.max(), df[df.group == 1].duration.max()])
-        df['duration'] = df['duration'].clip(upper=cap_time)
-
-        for col in treatment_features:
-            df.loc[df[col] > 0, col] = 1
-
-        df = df[core_features + [col for col in treatment_features if
-                                 df[col].nunique() > 1 and df[col].value_counts(normalize=True).min() >= 0.01]]
-        return df
-
-    def perform_cox_analysis(self, df):
-        return CoxPHFitter().fit(df, 'duration', 'event')
-
-    def get_km_fits(self, df, feature):
-        group_A = df[df[feature] == 0]
-        group_B = df[df[feature] == 1]
-
-        # Create Kaplan-Meier fitter instances
-        kmf_A = KaplanMeierFitter()
-        kmf_B = KaplanMeierFitter()
-
-        # Fit the data
-        if len(group_A) < 5 or len(group_B) < 5:
-            return 0, 0
-        label1, label2 = f'Epistasis ({len(group_A)})', f'CVs Only ({len(group_B)})'
-        self.label1, self.label2 = label1, label2
-        kmf_A.fit(group_A['duration'], group_A['event'], label=self.label1)
-        kmf_B.fit(group_B['duration'], group_B['event'], label=self.label2)
-        return kmf_A, kmf_B
-
-    def get_km_aucs(self, kmf_A, kmf_B):
-        surv_func_A = kmf_A.survival_function_
-        surv_func_B = kmf_B.survival_function_
-
-        # Numerical integration using Trapezoidal rule
-        auc_A = trapz(surv_func_A[self.label1], surv_func_A.index)
-        auc_B = trapz(surv_func_B[self.label2], surv_func_B.index)
-        return auc_A, auc_B
-
-    def plot_km_curve(self, kmf_A, kmf_B):
-        # Plot the survival curves
-        ax = kmf_A.plot()
-        kmf_B.plot(ax=ax)
-
-        # Add labels and title
-        p_value = 0.01
-        ax.text(0.5, 0.85, f'p-value: {p_value:.4f}', transform=ax.transAxes, fontsize=12, horizontalalignment='center')
-        # ax.text(0.45, 0.85, f'AUCe: {auc_A:.4f}', transform=ax.transAxes, fontsize=12, horizontalalignment='center')
-        # ax.text(0.45, 0.85, f'AUCc: {auc_B:.4f}', transform=ax.transAxes, fontsize=12, horizontalalignment='center')
-
-        plt.title('Kaplan-Meier Survival Curves')
-        plt.xlabel('Time')
-        plt.ylabel('Survival Probability')
-        plt.show()
-        return self
-
-    def log_rank(self, df, column):
-        group1, group2 = df[df[column] == 0], df[df[column] == 1]
-        result = logrank_test(group1['duration'], group2['duration'],
-                              event_observed_A=group1['event'],
-                              event_observed_B=group2['event'])
-        return result.p_value
-
-    def run_analysis(self, dict1, event_name):
-        try:
-            df = self.prepare_data(dict1)
-            if len(df[df.group == 0]) < 2 or len(df[df.group == 1]) < 2:
-                return None
-
-            elif len(df[df.group == 0]) < 10 or len(df[df.group == 1]) < 10:
-                temp = pd.Series()
-                temp['mut_id'] = event_name
-                for column in [c for c in df.columns if c != 'duration' and c != 'event']:
-                    temp[column] = self.log_rank(df, column)
-
-            else:
-                auca, aucb = self.get_km_aucs(*self.get_km_fits(df, 'group'))
-                cph = self.perform_cox_analysis(df)
-                temp = cph.summary.p
-                temp.name = ''
-                temp.index.name = ''
-                temp['auc_diff'] = auca - aucb
-                temp['mut_id'] = event_name
-            return temp
-
-        except ConvergenceError:
-            return None
-
-

geney/analyzers/tcga_annotations.py

@@ -1,194 +0,0 @@
-
-# CLINICAL_DATA_FILE = Path('/tamir2/nicolaslynn/data/TCGA/cancer_reports/new_df_p_proc.pkl')
-# CLINICAL_DATA_FILE = Path('/tamir2/yoramzar/Projects/Cancer_mut/Explore_data/reports/df_p_all.pkl')
-# CANCER_DATA_PATH = Path('/tamir2/cancer_proj/gdc_db/data/filtered_feb_2021/AllGenes')
-# MAF_FILE_NAME = 'GeneMutTble.txt'
-# CASE_TRACKER = pd.read_csv('/tamir2/nicolaslynn/projects/TCGAParsed/case2proj.csv', index_col=0)
-# PROJ_COUNTS = CASE_TRACKER.proj.value_counts()
-# OKGP_DATA_FILE = Path('/tamir2/nicolaslynn/projects/1000GenomesProjMutations/parsed_1kgp_mutations_in_target_genes.csv')
-# MUTATION_FREQ_DF = pd.read_csv(OKGP_DATA_FILE, index_col=0)
-# PROTEIN_ANNOTATIONS = pd.read_csv('/tamir2/nicolaslynn/data/BioMart/protein_annotations.csv').rename(columns={'Interpro start': 'start', 'Interpro end': 'end', 'Interpro Short Description': 'name'})[['Gene stable ID', 'Transcript stable ID', 'start', 'end', 'name']]
-# PROTEIN_ANNOTATIONS['length'] = PROTEIN_ANNOTATIONS.apply(lambda row: abs(row.start - row.end), axis=1)
-
-def prepare_gene_sets():
-    # gene_annotations_file = Path('/tamir2/nicolaslynn/data/COSMIC/cancer_gene_roles.csv')
-    # GENE_DF = pd.read_csv(gene_annotations_file, index_col=0)
-    # all_oncogenes = GENE_DF[GENE_DF.OG==True].index.tolist()
-    # all_oncogenes = list(set(all_oncogenes))
-    return [], [], []
-
-CLIN_DF = prepare_clinical_data()
-TSGS, ONCOGENES, CANCER_GENES = prepare_gene_sets()
-
-
-def generate_survival_quantitative(affected_df, nonaffected_df):
-    if affected_df.empty or nonaffected_df.empty:
-        return np.nan, np.nan, np.nan
-    results = logrank_test(affected_df['duration'], nonaffected_df['duration'],
-                           event_observed_A=affected_df['event'],
-                           event_observed_B=nonaffected_df['event'])
-    p_value = results.p_value
-    kmf = KaplanMeierFitter()
-    kmf.fit(affected_df['duration'], affected_df['event'], label=f'With Epistasis ({len(affected_df)})')
-    times, surv_probs = kmf.survival_function_.index.values, kmf.survival_function_.values.flatten()
-    auc1 = np.trapz(surv_probs, times)
-    kmf.fit(nonaffected_df['duration'], nonaffected_df['event'], label=f'Without Epistasis ({len(nonaffected_df)})')
-    times, surv_probs = kmf.survival_function_.index.values, kmf.survival_function_.values.flatten()
-    auc2 = np.trapz(surv_probs, times)
-    return p_value, auc1, auc2
-
-def generate_survival_pvalue(affected_df, unaffected_df):
-    results = logrank_test(affected_df['duration'], unaffected_df['duration'],
-                           event_observed_A=affected_df['event'],
-                           event_observed_B=unaffected_df['event'])
-
-    p_value = results.p_value
-    kmf = KaplanMeierFitter()
-    # Fit data
-    kmf.fit(affected_df['duration'], affected_df['event'], label=f'Without Epistasis ({len(affected_df)})')
-    ax = kmf.plot()
-
-    kmf.fit(unaffected_df['duration'], unaffected_df['event'], label=f'With Epistasis ({len(unaffected_df)})')
-    kmf.plot(ax=ax)
-    plt.text(5, 0.95, f'pval: {p_value:.3e}')
-    plt.show()
-    return p_value
-
-def get_project_prevalence(cases_affected):
-    ca = [c for c in cases_affected if c in CASE_TRACKER.index]
-    prevalences = CASE_TRACKER.loc[ca].proj.value_counts() / PROJ_COUNTS
-    prevalences.fillna(0, inplace=True)
-    prevalences = prevalences[[i for i in prevalences.index if 'TCGA' in i]]
-    prevalences.index = [s.replace('TCGA', 'prev') for s in prevalences.index]
-    return prevalences
-
-def get_project_counts(cases_affected):
-    ca = [c for c in cases_affected if c in CASE_TRACKER.index]
-    prevalences = CASE_TRACKER.loc[ca].proj.value_counts()
-    prevalences = prevalences[[i for i in prevalences.index if 'TCGA' in i]]
-    prevalences.index = [s.replace('TCGA_', '') for s in prevalences.index]
-    return prevalences
-
-def get_event_consequence(df):
-    assert df.Transcript_ID.nunique() == 1, 'Too many transcripts to return a single consequenc.'
-    return df.iloc[0].Consequence
-
-def get_dbSNP_id(df):
-    return df.iloc[0].dbSNP_RS
-
-def load_variant_file(gene):
-    df = pd.read_csv(CANCER_DATA_PATH / gene / MAF_FILE_NAME, low_memory=False)
-    df['mut_id'] = df.apply(lambda row: f"{row.Gene_name}:{row.Chromosome.replace('chr', '')}:{row.Start_Position}:{row.Reference_Allele}:{row.Tumor_Seq_Allele2}", axis=1)
-    return df
-
-def find_event_data(event):
-    df = load_variant_file(event.gene)
-    if df.empty:
-        return None
-
-    df = df.query \
-        ('Chromosome == @event.chromosome & Start_Position == @event.start & Reference_Allele == @event.ref & Tumor_Seq_Allele2 == @event.alt')
-
-    if df.empty:
-        return None
-
-    if event.transcript_id is not None:
-        df = df[df.Transcript_ID == event.transcript_id]
-    df['mut_id'] = event.event_id
-    return df
-
-
-class GEvent:
-    def __init__(self, event_id, transcript_id=None):
-        self.gene, self.chromosome, self.start, self.ref, self.alt = event_id.split(':')
-        self.transcript_id = transcript_id
-        self.chromosome = f'chr{self.chromosome}'
-        self.start = int(self.start)
-        self.event_id = event_id
-
-
-
-def get_okgp_mutation_frequency(mut_id):
-    if mut_id in MUTATION_FREQ_DF.index:
-        return MUTATION_FREQ_DF.loc[mut_id].cases_affected
-    else:
-        return 0
-
-def get_df_filter_info(df):
-    filter_artifact_values: list = ["oxog", "bPcr", "bSeq"]
-    MuTect2_filters: list = ['Germline risk', 't_lod_fstar', 'alt_allele_in_normal', 'panel_of_normals', 'clustered_events',
-                             'str_contraction', 'multi_event_alt_allele_in_normal', 'homologous_mapping_event', 'triallelic_site']
-    filter_col_name: str = "FILTER_info"  # column name to add to the dataframe
-    filter_info_list: list = []
-    f_cnr_info = {}
-
-    for j, (prj, df_prj) in enumerate(df.groupby('Proj_name')):
-        filter_vals = list(df_prj['FILTER'])
-        num_pass, num_artifacts, num_mutect2_filters = 0, 0, 0
-        for filter_val in filter_vals:
-            num_pass += ('PASS' in filter_val)
-            num_artifacts += any([x in filter_val for x in filter_artifact_values])
-            num_mutect2_filters += any([x in filter_val for x in MuTect2_filters])
-        num_rest = max(0, (len(filter_vals) - num_pass - num_artifacts - num_mutect2_filters))
-        f_cnr_info[str(prj)[5:]] = (num_pass, num_mutect2_filters, num_artifacts, num_rest)
-    return f_cnr_info
-
-def yoram_mutid(row):
-    return f'{row.Gene_name}:{row.Chromosome}:{row.Consequence}:{row.Start_Position}:{row.Reference_Allele}:{row.Tumor_Seq_Allele2}'
-
-
-def annotate_level_two(mut_id, tid):
-    mut = GEvent(mut_id, tid)
-    df = find_event_data(mut)
-
-    if df.empty or df is None:
-        return None
-
-    patients_affected = df.cases_affected.unique().tolist()
-    p_val, auc_a, auc_n = generate_survival_quantitative(CLIN_DF[CLIN_DF.case_id.isin(patients_affected)], CLIN_DF[~CLIN_DF.case_id.isin(patients_affected)])
-    project_prevalences = get_project_prevalence(patients_affected)
-    prev_dict = project_prevalences.to_dict().sort()
-    project_counts = get_project_counts(patients_affected)
-
-    s = pd.Series({
-        'mut_id': mut_id,
-        'yoram_mut_id': yoram_mutid(df.iloc[0]),
-        'transcript_id': tid,
-        'affected_cases': len(patients_affected),
-        'dbSNP_id': get_dbSNP_id(df),
-        'consequence': get_event_consequence(df),
-        'survival_p_value': p_val,
-        'auc_affected': auc_a,
-        'auc_nonaffected': auc_n,
-        'TSG': contains(TSGS, mut.gene),
-        'oncogene': contains(ONCOGENES, mut.gene),
-        'cases_1kgp': get_okgp_mutation_frequency(mut.event_id),
-        'filter_inf': get_df_filter_info(df),
-        'strand': df.Strand.unique().tolist()[0],
-        'prevalences': prev_dict
-    })
-
-    s['max_prev'] = project_prevalences.max()
-    s['rel_proj'] = ','.join([c.split('_')[-1] for c in project_prevalences[project_prevalences == project_prevalences.max()].index.tolist()])
-    s = pd.concat([s, project_prevalences, project_counts])
-    del df
-    return s
-
-def get_mut_counts():
-    cases = unload_json('/tamir2/nicolaslynn/projects/TCGAParsed/recurring_single_muts_tcga.json')
-    cases = pd.Series(cases)
-    cases.name = 'num_cases'
-    cases.index.name = 'mut_id'
-    cases = cases.to_frame()
-    cases.reset_index(inplace=True)
-    return cases
-
-
-def create_mut_id(row):
-    return f"{row.Gene_name}:{row['Chromosome']}:{row['Start_Position']}:{row['Reference_Allele']}:{row['Tumor_Seq_Allele2']}"
-
-
-def is_in_exon(mut_id, tid):
-    from geney.Gene import Gene
-    transcript = Gene(mut_id.split(':')[0]).generate_transcript(tid)
-    return int(mut_id.split(':')[2]) in transcript.exonic_indices