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

gsMap/diagnosis.py

@@ -1,273 +1,273 @@
-import logging
-import warnings
-from pathlib import Path
-
-import numpy as np
-import pandas as pd
-import scanpy as sc
-from scipy.stats import norm
-
-from gsMap.config import DiagnosisConfig
-from gsMap.utils.manhattan_plot import ManhattanPlot
-from gsMap.visualize import draw_scatter, load_st_coord, estimate_point_size_for_plot
-
-
-warnings.filterwarnings("ignore", category=FutureWarning)
-logger = logging.getLogger(__name__)
-
-
-def convert_z_to_p(gwas_data):
-    """Convert Z-scores to P-values."""
-    gwas_data['P'] = norm.sf(abs(gwas_data['Z'])) * 2
-    min_p_value = 1e-300
-    gwas_data['P'] = gwas_data['P'].clip(lower=min_p_value)
-    return gwas_data
-
-
-def load_ldsc(ldsc_input_file):
-    """Load LDSC data and calculate logp."""
-    ldsc = pd.read_csv(ldsc_input_file, compression='gzip')
-    ldsc['spot'] = ldsc['spot'].astype(str).replace('\.0', '', regex=True)
-    ldsc.set_index('spot', inplace=True)
-    ldsc['logp'] = -np.log10(ldsc['p'])
-    return ldsc
-
-
-def load_gene_diagnostic_info(config:DiagnosisConfig):
-    """Load or compute gene diagnostic info."""
-    gene_diagnostic_info_save_path = config.get_gene_diagnostic_info_save_path(config.trait_name)
-    if gene_diagnostic_info_save_path.exists():
-        logger.info(f'Loading gene diagnostic information from {gene_diagnostic_info_save_path}...')
-        return pd.read_csv(gene_diagnostic_info_save_path)
-    else:
-        logger.info('Gene diagnostic information not found. Calculating gene diagnostic information...')
-        return compute_gene_diagnostic_info(config)
-
-
-def compute_gene_diagnostic_info(config: DiagnosisConfig):
-    """Calculate gene diagnostic info and save it to adata."""
-    logger.info('Loading ST data and LDSC results...')
-    # adata = sc.read_h5ad(config.hdf5_with_latent_path, backed='r')
-    mk_score = pd.read_feather(config.mkscore_feather_path)
-    mk_score.set_index('HUMAN_GENE_SYM', inplace=True)
-    mk_score = mk_score.T
-    trait_ldsc_result = load_ldsc(config.get_ldsc_result_file(config.trait_name))
-
-    # Align marker scores with trait LDSC results
-    mk_score = mk_score.loc[trait_ldsc_result.index]
-    mk_score = mk_score.loc[:, mk_score.sum(axis=0) != 0]
-
-    logger.info('Calculating correlation between gene marker scores and trait logp-values...')
-    corr = mk_score.corrwith(trait_ldsc_result['logp'])
-    corr.name = 'PCC'
-
-    grouped_mk_score = mk_score.groupby(adata.obs[config.annotation]).median()
-    max_annotations = grouped_mk_score.idxmax()
-
-    high_GSS_Gene_annotation_pair = pd.DataFrame({
-        'Gene': max_annotations.index,
-        'Annotation': max_annotations.values,
-        'Median_GSS': grouped_mk_score.max().values
-    })
-
-    # Filter based on median GSS score
-    high_GSS_Gene_annotation_pair = high_GSS_Gene_annotation_pair[high_GSS_Gene_annotation_pair['Median_GSS'] >= 1.0]
-    high_GSS_Gene_annotation_pair = high_GSS_Gene_annotation_pair.merge(corr, left_on='Gene', right_index=True)
-
-    # Prepare the final gene diagnostic info dataframe
-    gene_diagnostic_info_cols = ['Gene', 'Annotation', 'Median_GSS', 'PCC']
-    gene_diagnostic_info = high_GSS_Gene_annotation_pair[gene_diagnostic_info_cols].drop_duplicates().dropna(
-        subset=['Gene'])
-    gene_diagnostic_info.sort_values('PCC', ascending=False, inplace=True)
-
-    # Save gene diagnostic info to a file
-    gene_diagnostic_info_save_path = config.get_gene_diagnostic_info_save_path(config.trait_name)
-    gene_diagnostic_info.to_csv(gene_diagnostic_info_save_path, index=False)
-    logger.info(f'Gene diagnostic information saved to {gene_diagnostic_info_save_path}.')
-
-    # Save to adata.var with the trait_name prefix
-    logger.info('Saving gene diagnostic info to adata.var...')
-    gene_diagnostic_info.set_index('Gene', inplace=True)  # Use 'Gene' as the index to align with adata.var
-    adata.var[f'{config.trait_name}_Annotation'] = gene_diagnostic_info['Annotation']
-    adata.var[f'{config.trait_name}_Median_GSS'] = gene_diagnostic_info['Median_GSS']
-    adata.var[f'{config.trait_name}_PCC'] = gene_diagnostic_info['PCC']
-
-    # Save trait_ldsc_result to adata.obs
-    logger.info(f'Saving trait LDSC results to adata.obs as gsMap_{config.trait_name}_p_value...')
-    adata.obs[f'gsMap_{config.trait_name}_p_value'] = trait_ldsc_result['p']
-    adata.write(config.hdf5_with_latent_path, )
-
-    return gene_diagnostic_info.reset_index()
-
-
-def load_gwas_data(config:DiagnosisConfig):
-    """Load and process GWAS data."""
-    logger.info('Loading and processing GWAS data...')
-    gwas_data = pd.read_csv(config.sumstats_file, compression='gzip', sep='\t')
-    return convert_z_to_p(gwas_data)
-
-
-def load_snp_gene_pairs(config:DiagnosisConfig):
-    """Load SNP-gene pairs from multiple chromosomes."""
-    ldscore_save_dir = Path(config.ldscore_save_dir)
-    return pd.concat([
-        pd.read_feather(ldscore_save_dir / f'SNP_gene_pair/SNP_gene_pair_chr{chrom}.feather')
-        for chrom in range(1, 23)
-    ])
-
-
-def filter_snps(gwas_data_with_gene_annotation_sort, SUBSAMPLE_SNP_NUMBER):
-    """Filter the SNPs based on significance levels."""
-    pass_suggestive_line_mask = gwas_data_with_gene_annotation_sort['P'] < 1e-5
-    pass_suggestive_line_number = pass_suggestive_line_mask.sum()
-
-    if pass_suggestive_line_number > SUBSAMPLE_SNP_NUMBER:
-        snps2plot = gwas_data_with_gene_annotation_sort[pass_suggestive_line_mask].SNP
-        logger.info(f'To reduce the number of SNPs to plot, only {snps2plot.shape[0]} SNPs with P < 1e-5 are plotted.')
-    else:
-        snps2plot = gwas_data_with_gene_annotation_sort.head(SUBSAMPLE_SNP_NUMBER).SNP
-        logger.info(
-            f'To reduce the number of SNPs to plot, only {SUBSAMPLE_SNP_NUMBER} SNPs with the smallest P-values are plotted.')
-
-    return snps2plot
-
-
-def generate_manhattan_plot(config: DiagnosisConfig):
-    """Generate Manhattan plot."""
-    report_save_dir = config.get_report_dir(config.trait_name)
-    gwas_data = load_gwas_data(config)
-    snp_gene_pair = load_snp_gene_pairs(config)
-    gwas_data_with_gene = snp_gene_pair.merge(gwas_data, on='SNP', how='inner').rename(columns={'gene_name': 'GENE'})
-    gene_diagnostic_info = load_gene_diagnostic_info(config)
-    gwas_data_with_gene_annotation = gwas_data_with_gene.merge(gene_diagnostic_info, left_on='GENE', right_on='Gene',
-                                                               how='left')
-
-    gwas_data_with_gene_annotation = gwas_data_with_gene_annotation[
-        ~gwas_data_with_gene_annotation['Annotation'].isna()]
-    gwas_data_with_gene_annotation_sort = gwas_data_with_gene_annotation.sort_values('P')
-
-    snps2plot = filter_snps(gwas_data_with_gene_annotation_sort, SUBSAMPLE_SNP_NUMBER=100_000)
-    gwas_data_to_plot = gwas_data_with_gene_annotation[
-        gwas_data_with_gene_annotation['SNP'].isin(snps2plot)].reset_index(drop=True)
-    gwas_data_to_plot['Annotation_text'] = 'PCC: ' + gwas_data_to_plot['PCC'].round(2).astype(
-        str) + '<br>' + 'Annotation: ' + gwas_data_to_plot['Annotation'].astype(str)
-
-    fig = ManhattanPlot(
-        dataframe=gwas_data_to_plot,
-        title='gsMap Diagnosis Manhattan Plot',
-        point_size=3,
-        highlight_gene_list=config.selected_genes or gene_diagnostic_info.Gene.iloc[:config.top_corr_genes].tolist(),
-        suggestiveline_value=-np.log10(1e-5),
-        annotation='Annotation_text',
-    )
-
-    save_manhattan_plot_path = config.get_manhattan_html_plot_path(config.trait_name)
-    fig.write_html(save_manhattan_plot_path)
-    logger.info(f'Diagnostic Manhattan Plot saved to {save_manhattan_plot_path}.')
-
-
-def generate_GSS_distribution(config: DiagnosisConfig):
-    """Generate GSS distribution plots."""
-    # logger.info('Loading ST data...')
-    # adata = sc.read_h5ad(config.hdf5_with_latent_path)
-    mk_score = pd.read_feather(config.mkscore_feather_path).set_index('HUMAN_GENE_SYM').T
-
-    plot_genes = config.selected_genes or load_gene_diagnostic_info(config).Gene.iloc[:config.top_corr_genes].tolist()
-    if config.selected_genes is not None:
-        logger.info(f'Generating GSS & Expression distribution plot for selected genes: {plot_genes}...')
-    else:
-        logger.info(f'Generating GSS & Expression distribution plot for top {config.top_corr_genes} correlated genes...')
-
-    if config.customize_fig:
-        pixel_width, pixel_height, point_size = config.fig_width, config.fig_height, config.point_size
-    else:
-        (pixel_width, pixel_height), point_size = estimate_point_size_for_plot(adata.obsm['spatial'])
-    sub_fig_save_dir = config.get_GSS_plot_dir(config.trait_name)
-
-    # save plot gene list
-    config.get_GSS_plot_select_gene_file(config.trait_name).write_text('\n'.join(plot_genes))
-
-    for selected_gene in plot_genes:
-        expression_series = pd.Series(adata[:, selected_gene].X.toarray().flatten(), index=adata.obs.index,name='Expression')
-        threshold = np.quantile(expression_series,0.9999)
-        expression_series[expression_series > threshold] = threshold
-        generate_and_save_plots(adata, mk_score, expression_series, selected_gene, point_size, pixel_width,
-                                pixel_height, sub_fig_save_dir, config.sample_name, config.annotation)
-
-
-def generate_and_save_plots(adata, mk_score, expression_series, selected_gene, point_size, pixel_width, pixel_height,
-                            sub_fig_save_dir, sample_name, annotation):
-    """Generate and save the plots."""
-    select_gene_expression_with_space_coord = load_st_coord(adata, expression_series, annotation)
-    sub_fig_1 = draw_scatter(select_gene_expression_with_space_coord, title=f'{selected_gene} (Expression)',
-                             annotation='annotation', color_by='Expression', point_size=point_size, width=pixel_width,
-                             height=pixel_height)
-    save_plot(sub_fig_1, sub_fig_save_dir, sample_name, selected_gene, 'Expression')
-
-    select_gene_GSS_with_space_coord = load_st_coord(adata, mk_score[selected_gene].rename('GSS'), annotation)
-    sub_fig_2 = draw_scatter(select_gene_GSS_with_space_coord, title=f'{selected_gene} (GSS)', annotation='annotation',
-                             color_by='GSS', point_size=point_size, width=pixel_width, height=pixel_height)
-    save_plot(sub_fig_2, sub_fig_save_dir, sample_name, selected_gene, 'GSS')
-
-    # combined_fig = make_subplots(rows=1, cols=2,
-    #                              subplot_titles=(f'{selected_gene} (Expression)', f'{selected_gene} (GSS)'))
-    # for trace in sub_fig_1.data:
-    #     combined_fig.add_trace(trace, row=1, col=1)
-    # for trace in sub_fig_2.data:
-    #     combined_fig.add_trace(trace, row=1, col=2)
-    #
-
-def save_plot(sub_fig, sub_fig_save_dir, sample_name, selected_gene, plot_type):
-    """Save the plot to HTML and PNG."""
-    save_sub_fig_path = sub_fig_save_dir / f'{sample_name}_{selected_gene}_{plot_type}_Distribution.html'
-    # sub_fig.write_html(str(save_sub_fig_path))
-    sub_fig.update_layout(showlegend=False)
-    sub_fig.write_image(str(save_sub_fig_path).replace('.html', '.png'))
-
-
-def generate_gsMap_plot(config: DiagnosisConfig):
-    """Generate gsMap plot."""
-    logger.info('Creating gsMap plot...')
-
-    trait_ldsc_result = load_ldsc(config.get_ldsc_result_file(config.trait_name))
-    space_coord_concat = load_st_coord(adata, trait_ldsc_result, annotation=config.annotation)
-
-    if config.customize_fig:
-        pixel_width, pixel_height, point_size = config.fig_width, config.fig_height, config.point_size
-    else:
-        (pixel_width, pixel_height), point_size = estimate_point_size_for_plot(adata.obsm['spatial'])
-    fig = draw_scatter(space_coord_concat,
-                       title=f'{config.trait_name} (gsMap)',
-                       point_size=point_size,
-                       width=pixel_width,
-                       height=pixel_height,
-                       annotation=config.annotation
-                       )
-
-    output_dir = config.get_gsMap_plot_save_dir(config.trait_name)
-    output_file_html = config.get_gsMap_html_plot_save_path(config.trait_name)
-    output_file_png = output_file_html.with_suffix('.png')
-    output_file_csv = output_file_html.with_suffix('.csv')
-
-    fig.write_html(output_file_html)
-    fig.write_image(output_file_png)
-    space_coord_concat.to_csv(output_file_csv)
-
-    logger.info(f'gsMap plot created and saved in {output_dir}.')
-
-
-def run_Diagnosis(config: DiagnosisConfig):
-    """Main function to run the diagnostic plot generation."""
-    global adata
-    adata = sc.read_h5ad(config.hdf5_with_latent_path)
-    if 'log1p' not in adata.uns.keys() and adata.X.max() > 14: 
-        sc.pp.normalize_total(adata, target_sum=1e4)
-        sc.pp.log1p(adata)
-
-    if config.plot_type in ['manhattan', 'all']:
-        generate_manhattan_plot(config)
-    if config.plot_type in ['GSS', 'all']:
-        generate_GSS_distribution(config)
-    if config.plot_type in ['gsMap', 'all']:
-        generate_gsMap_plot(config)
-
+import logging
+import warnings
+from pathlib import Path
+
+import numpy as np
+import pandas as pd
+import scanpy as sc
+from scipy.stats import norm
+
+from gsMap.config import DiagnosisConfig
+from gsMap.utils.manhattan_plot import ManhattanPlot
+from gsMap.visualize import draw_scatter, load_st_coord, estimate_point_size_for_plot
+
+
+warnings.filterwarnings("ignore", category=FutureWarning)
+logger = logging.getLogger(__name__)
+
+
+def convert_z_to_p(gwas_data):
+    """Convert Z-scores to P-values."""
+    gwas_data['P'] = norm.sf(abs(gwas_data['Z'])) * 2
+    min_p_value = 1e-300
+    gwas_data['P'] = gwas_data['P'].clip(lower=min_p_value)
+    return gwas_data
+
+
+def load_ldsc(ldsc_input_file):
+    """Load LDSC data and calculate logp."""
+    ldsc = pd.read_csv(ldsc_input_file, compression='gzip')
+    ldsc['spot'] = ldsc['spot'].astype(str).replace('\.0', '', regex=True)
+    ldsc.set_index('spot', inplace=True)
+    ldsc['logp'] = -np.log10(ldsc['p'])
+    return ldsc
+
+
+def load_gene_diagnostic_info(config:DiagnosisConfig):
+    """Load or compute gene diagnostic info."""
+    gene_diagnostic_info_save_path = config.get_gene_diagnostic_info_save_path(config.trait_name)
+    if gene_diagnostic_info_save_path.exists():
+        logger.info(f'Loading gene diagnostic information from {gene_diagnostic_info_save_path}...')
+        return pd.read_csv(gene_diagnostic_info_save_path)
+    else:
+        logger.info('Gene diagnostic information not found. Calculating gene diagnostic information...')
+        return compute_gene_diagnostic_info(config)
+
+
+def compute_gene_diagnostic_info(config: DiagnosisConfig):
+    """Calculate gene diagnostic info and save it to adata."""
+    logger.info('Loading ST data and LDSC results...')
+    # adata = sc.read_h5ad(config.hdf5_with_latent_path, backed='r')
+    mk_score = pd.read_feather(config.mkscore_feather_path)
+    mk_score.set_index('HUMAN_GENE_SYM', inplace=True)
+    mk_score = mk_score.T
+    trait_ldsc_result = load_ldsc(config.get_ldsc_result_file(config.trait_name))
+
+    # Align marker scores with trait LDSC results
+    mk_score = mk_score.loc[trait_ldsc_result.index]
+    mk_score = mk_score.loc[:, mk_score.sum(axis=0) != 0]
+
+    logger.info('Calculating correlation between gene marker scores and trait logp-values...')
+    corr = mk_score.corrwith(trait_ldsc_result['logp'])
+    corr.name = 'PCC'
+
+    grouped_mk_score = mk_score.groupby(adata.obs[config.annotation]).median()
+    max_annotations = grouped_mk_score.idxmax()
+
+    high_GSS_Gene_annotation_pair = pd.DataFrame({
+        'Gene': max_annotations.index,
+        'Annotation': max_annotations.values,
+        'Median_GSS': grouped_mk_score.max().values
+    })
+
+    # Filter based on median GSS score
+    high_GSS_Gene_annotation_pair = high_GSS_Gene_annotation_pair[high_GSS_Gene_annotation_pair['Median_GSS'] >= 1.0]
+    high_GSS_Gene_annotation_pair = high_GSS_Gene_annotation_pair.merge(corr, left_on='Gene', right_index=True)
+
+    # Prepare the final gene diagnostic info dataframe
+    gene_diagnostic_info_cols = ['Gene', 'Annotation', 'Median_GSS', 'PCC']
+    gene_diagnostic_info = high_GSS_Gene_annotation_pair[gene_diagnostic_info_cols].drop_duplicates().dropna(
+        subset=['Gene'])
+    gene_diagnostic_info.sort_values('PCC', ascending=False, inplace=True)
+
+    # Save gene diagnostic info to a file
+    gene_diagnostic_info_save_path = config.get_gene_diagnostic_info_save_path(config.trait_name)
+    gene_diagnostic_info.to_csv(gene_diagnostic_info_save_path, index=False)
+    logger.info(f'Gene diagnostic information saved to {gene_diagnostic_info_save_path}.')
+
+    # Save to adata.var with the trait_name prefix
+    logger.info('Saving gene diagnostic info to adata.var...')
+    gene_diagnostic_info.set_index('Gene', inplace=True)  # Use 'Gene' as the index to align with adata.var
+    adata.var[f'{config.trait_name}_Annotation'] = gene_diagnostic_info['Annotation']
+    adata.var[f'{config.trait_name}_Median_GSS'] = gene_diagnostic_info['Median_GSS']
+    adata.var[f'{config.trait_name}_PCC'] = gene_diagnostic_info['PCC']
+
+    # Save trait_ldsc_result to adata.obs
+    logger.info(f'Saving trait LDSC results to adata.obs as gsMap_{config.trait_name}_p_value...')
+    adata.obs[f'gsMap_{config.trait_name}_p_value'] = trait_ldsc_result['p']
+    adata.write(config.hdf5_with_latent_path, )
+
+    return gene_diagnostic_info.reset_index()
+
+
+def load_gwas_data(config:DiagnosisConfig):
+    """Load and process GWAS data."""
+    logger.info('Loading and processing GWAS data...')
+    gwas_data = pd.read_csv(config.sumstats_file, compression='gzip', sep='\t')
+    return convert_z_to_p(gwas_data)
+
+
+def load_snp_gene_pairs(config:DiagnosisConfig):
+    """Load SNP-gene pairs from multiple chromosomes."""
+    ldscore_save_dir = Path(config.ldscore_save_dir)
+    return pd.concat([
+        pd.read_feather(ldscore_save_dir / f'SNP_gene_pair/SNP_gene_pair_chr{chrom}.feather')
+        for chrom in range(1, 23)
+    ])
+
+
+def filter_snps(gwas_data_with_gene_annotation_sort, SUBSAMPLE_SNP_NUMBER):
+    """Filter the SNPs based on significance levels."""
+    pass_suggestive_line_mask = gwas_data_with_gene_annotation_sort['P'] < 1e-5
+    pass_suggestive_line_number = pass_suggestive_line_mask.sum()
+
+    if pass_suggestive_line_number > SUBSAMPLE_SNP_NUMBER:
+        snps2plot = gwas_data_with_gene_annotation_sort[pass_suggestive_line_mask].SNP
+        logger.info(f'To reduce the number of SNPs to plot, only {snps2plot.shape[0]} SNPs with P < 1e-5 are plotted.')
+    else:
+        snps2plot = gwas_data_with_gene_annotation_sort.head(SUBSAMPLE_SNP_NUMBER).SNP
+        logger.info(
+            f'To reduce the number of SNPs to plot, only {SUBSAMPLE_SNP_NUMBER} SNPs with the smallest P-values are plotted.')
+
+    return snps2plot
+
+
+def generate_manhattan_plot(config: DiagnosisConfig):
+    """Generate Manhattan plot."""
+    report_save_dir = config.get_report_dir(config.trait_name)
+    gwas_data = load_gwas_data(config)
+    snp_gene_pair = load_snp_gene_pairs(config)
+    gwas_data_with_gene = snp_gene_pair.merge(gwas_data, on='SNP', how='inner').rename(columns={'gene_name': 'GENE'})
+    gene_diagnostic_info = load_gene_diagnostic_info(config)
+    gwas_data_with_gene_annotation = gwas_data_with_gene.merge(gene_diagnostic_info, left_on='GENE', right_on='Gene',
+                                                               how='left')
+
+    gwas_data_with_gene_annotation = gwas_data_with_gene_annotation[
+        ~gwas_data_with_gene_annotation['Annotation'].isna()]
+    gwas_data_with_gene_annotation_sort = gwas_data_with_gene_annotation.sort_values('P')
+
+    snps2plot = filter_snps(gwas_data_with_gene_annotation_sort, SUBSAMPLE_SNP_NUMBER=100_000)
+    gwas_data_to_plot = gwas_data_with_gene_annotation[
+        gwas_data_with_gene_annotation['SNP'].isin(snps2plot)].reset_index(drop=True)
+    gwas_data_to_plot['Annotation_text'] = 'PCC: ' + gwas_data_to_plot['PCC'].round(2).astype(
+        str) + '<br>' + 'Annotation: ' + gwas_data_to_plot['Annotation'].astype(str)
+
+    fig = ManhattanPlot(
+        dataframe=gwas_data_to_plot,
+        title='gsMap Diagnosis Manhattan Plot',
+        point_size=3,
+        highlight_gene_list=config.selected_genes or gene_diagnostic_info.Gene.iloc[:config.top_corr_genes].tolist(),
+        suggestiveline_value=-np.log10(1e-5),
+        annotation='Annotation_text',
+    )
+
+    save_manhattan_plot_path = config.get_manhattan_html_plot_path(config.trait_name)
+    fig.write_html(save_manhattan_plot_path)
+    logger.info(f'Diagnostic Manhattan Plot saved to {save_manhattan_plot_path}.')
+
+
+def generate_GSS_distribution(config: DiagnosisConfig):
+    """Generate GSS distribution plots."""
+    # logger.info('Loading ST data...')
+    # adata = sc.read_h5ad(config.hdf5_with_latent_path)
+    mk_score = pd.read_feather(config.mkscore_feather_path).set_index('HUMAN_GENE_SYM').T
+
+    plot_genes = config.selected_genes or load_gene_diagnostic_info(config).Gene.iloc[:config.top_corr_genes].tolist()
+    if config.selected_genes is not None:
+        logger.info(f'Generating GSS & Expression distribution plot for selected genes: {plot_genes}...')
+    else:
+        logger.info(f'Generating GSS & Expression distribution plot for top {config.top_corr_genes} correlated genes...')
+
+    if config.customize_fig:
+        pixel_width, pixel_height, point_size = config.fig_width, config.fig_height, config.point_size
+    else:
+        (pixel_width, pixel_height), point_size = estimate_point_size_for_plot(adata.obsm['spatial'])
+    sub_fig_save_dir = config.get_GSS_plot_dir(config.trait_name)
+
+    # save plot gene list
+    config.get_GSS_plot_select_gene_file(config.trait_name).write_text('\n'.join(plot_genes))
+
+    for selected_gene in plot_genes:
+        expression_series = pd.Series(adata[:, selected_gene].X.toarray().flatten(), index=adata.obs.index,name='Expression')
+        threshold = np.quantile(expression_series,0.9999)
+        expression_series[expression_series > threshold] = threshold
+        generate_and_save_plots(adata, mk_score, expression_series, selected_gene, point_size, pixel_width,
+                                pixel_height, sub_fig_save_dir, config.sample_name, config.annotation)
+
+
+def generate_and_save_plots(adata, mk_score, expression_series, selected_gene, point_size, pixel_width, pixel_height,
+                            sub_fig_save_dir, sample_name, annotation):
+    """Generate and save the plots."""
+    select_gene_expression_with_space_coord = load_st_coord(adata, expression_series, annotation)
+    sub_fig_1 = draw_scatter(select_gene_expression_with_space_coord, title=f'{selected_gene} (Expression)',
+                             annotation='annotation', color_by='Expression', point_size=point_size, width=pixel_width,
+                             height=pixel_height)
+    save_plot(sub_fig_1, sub_fig_save_dir, sample_name, selected_gene, 'Expression')
+
+    select_gene_GSS_with_space_coord = load_st_coord(adata, mk_score[selected_gene].rename('GSS'), annotation)
+    sub_fig_2 = draw_scatter(select_gene_GSS_with_space_coord, title=f'{selected_gene} (GSS)', annotation='annotation',
+                             color_by='GSS', point_size=point_size, width=pixel_width, height=pixel_height)
+    save_plot(sub_fig_2, sub_fig_save_dir, sample_name, selected_gene, 'GSS')
+
+    # combined_fig = make_subplots(rows=1, cols=2,
+    #                              subplot_titles=(f'{selected_gene} (Expression)', f'{selected_gene} (GSS)'))
+    # for trace in sub_fig_1.data:
+    #     combined_fig.add_trace(trace, row=1, col=1)
+    # for trace in sub_fig_2.data:
+    #     combined_fig.add_trace(trace, row=1, col=2)
+    #
+
+def save_plot(sub_fig, sub_fig_save_dir, sample_name, selected_gene, plot_type):
+    """Save the plot to HTML and PNG."""
+    save_sub_fig_path = sub_fig_save_dir / f'{sample_name}_{selected_gene}_{plot_type}_Distribution.html'
+    # sub_fig.write_html(str(save_sub_fig_path))
+    sub_fig.update_layout(showlegend=False)
+    sub_fig.write_image(str(save_sub_fig_path).replace('.html', '.png'))
+
+
+def generate_gsMap_plot(config: DiagnosisConfig):
+    """Generate gsMap plot."""
+    logger.info('Creating gsMap plot...')
+
+    trait_ldsc_result = load_ldsc(config.get_ldsc_result_file(config.trait_name))
+    space_coord_concat = load_st_coord(adata, trait_ldsc_result, annotation=config.annotation)
+
+    if config.customize_fig:
+        pixel_width, pixel_height, point_size = config.fig_width, config.fig_height, config.point_size
+    else:
+        (pixel_width, pixel_height), point_size = estimate_point_size_for_plot(adata.obsm['spatial'])
+    fig = draw_scatter(space_coord_concat,
+                       title=f'{config.trait_name} (gsMap)',
+                       point_size=point_size,
+                       width=pixel_width,
+                       height=pixel_height,
+                       annotation=config.annotation
+                       )
+
+    output_dir = config.get_gsMap_plot_save_dir(config.trait_name)
+    output_file_html = config.get_gsMap_html_plot_save_path(config.trait_name)
+    output_file_png = output_file_html.with_suffix('.png')
+    output_file_csv = output_file_html.with_suffix('.csv')
+
+    fig.write_html(output_file_html)
+    fig.write_image(output_file_png)
+    space_coord_concat.to_csv(output_file_csv)
+
+    logger.info(f'gsMap plot created and saved in {output_dir}.')
+
+
+def run_Diagnosis(config: DiagnosisConfig):
+    """Main function to run the diagnostic plot generation."""
+    global adata
+    adata = sc.read_h5ad(config.hdf5_with_latent_path)
+    if 'log1p' not in adata.uns.keys() and adata.X.max() > 14: 
+        sc.pp.normalize_total(adata, target_sum=1e4)
+        sc.pp.log1p(adata)
+
+    if config.plot_type in ['manhattan', 'all']:
+        generate_manhattan_plot(config)
+    if config.plot_type in ['GSS', 'all']:
+        generate_GSS_distribution(config)
+    if config.plot_type in ['gsMap', 'all']:
+        generate_gsMap_plot(config)
+