gsMap 1.62__py3-none-any.whl → 1.63__py3-none-any.whl

gsMap/spatial_ldsc_multiple_sumstats.py

@@ -1,19 +1,19 @@
-import os
-import numpy as np
-import pandas as pd
-
-import argparse
+import gc
 import logging
-import multiprocessing
+import os
 from collections import defaultdict
 from pathlib import Path
 
+import anndata as ad
+import numpy as np
+import pandas as pd
+import zarr
 from scipy.stats import norm
-from tqdm.contrib.concurrent import process_map
+from tqdm.contrib.concurrent import thread_map
 
-import gsMap.jackknife as jk
-from gsMap.config import add_spatial_ldsc_args, SpatialLDSCConfig
-from gsMap.regression_read import _read_sumstats, _read_w_ld, _read_ref_ld_v2, _read_M_v2
+import gsMap.utils.jackknife as jk
+from gsMap.config import SpatialLDSCConfig
+from gsMap.utils.regression_read import _read_sumstats, _read_w_ld, _read_ref_ld_v2
 
 logger = logging.getLogger(__name__)
 
@@ -21,7 +21,8 @@ logger = logging.getLogger(__name__)
 # %%
 def _coef_new(jknife):
     # return coef[0], coef_se[0], z[0]]
-    est_ = jknife.est[0, 0] / Nbar
+    # est_ = jknife.est[0, 0] / Nbar
+    est_ = jknife.jknife_est[0, 0] / Nbar
     se_ = jknife.jknife_se[0, 0] / Nbar
     return est_, se_
 
@@ -68,16 +69,19 @@ def weights(ld, w_ld, N, M, hsq, intercept=1):
 
 def jackknife_for_processmap(spot_id):
     # calculate the initial weight for each spot
+    spot_spatial_annotation = spatial_annotation[:, spot_id]
+    spot_x_tot_precomputed = spot_spatial_annotation + ref_ld_baseline_column_sum
     initial_w = (
-        get_weight_optimized(sumstats, x_tot_precomputed_common_snp[:, spot_id], 10000, w_ld_common_snp, intercept=1)
+        get_weight_optimized(sumstats, x_tot_precomputed=spot_x_tot_precomputed,
+                             M_tot=10000, w_ld=w_ld_common_snp, intercept=1)
         .astype(np.float32)
         .reshape((-1, 1)))
 
     # apply the weight to baseline annotation, spatial annotation and CHISQ
     initial_w_scaled = initial_w / np.sum(initial_w)
     baseline_annotation_spot = baseline_annotation * initial_w_scaled
-    spatial_annotation_spot = spatial_annotation.iloc[:, spot_id].values.reshape((-1, 1)) * initial_w_scaled
-    CHISQ = sumstats.chisq.to_numpy(dtype=np.float32).reshape((-1, 1)).copy()
+    spatial_annotation_spot = spot_spatial_annotation.reshape((-1, 1)) * initial_w_scaled
+    CHISQ = sumstats.chisq.values.reshape((-1, 1))
     y = CHISQ * initial_w_scaled
 
     # run the jackknife
@@ -113,6 +117,9 @@ def _preprocess_sumstats(trait_name, sumstat_file_path, baseline_and_w_ld_common
         logger.warning(f'WARNING: number of SNPs less than 200k; for {trait_name} this is almost always bad.')
 
     sumstats = sumstats.loc[common_snp]
+
+    # get the common index position of baseline_and_w_ld_common_snp for quick access
+    sumstats['common_index_pos'] = pd.Index(baseline_and_w_ld_common_snp).get_indexer(sumstats.index)
     return sumstats
 
 
@@ -132,8 +139,77 @@ def _get_sumstats_from_sumstats_dict(sumstats_config_dict: dict, baseline_and_w_
     return sumstats_cleaned_dict
 
 
+class S_LDSC_Boost_with_pre_calculate_SNP_Gene_weight_matrix:
+    def __init__(self, config: SpatialLDSCConfig, common_snp_among_all_sumstats_pos):
+        self.config = config
+        mk_score = pd.read_feather(config.mkscore_feather_path).set_index('HUMAN_GENE_SYM')
+        mk_score_genes = mk_score.index
+
+        snp_gene_weight_adata = ad.read_h5ad(config.snp_gene_weight_adata_path)
+        common_genes = mk_score_genes.intersection(snp_gene_weight_adata.var.index)
+        common_snps = snp_gene_weight_adata.obs.index
+        # self.snp_gene_weight_adata = snp_gene_weight_adata[common_snp_among_all_sumstats:, common_genes.to_list()]
+        self.snp_gene_weight_matrix = snp_gene_weight_adata[common_snp_among_all_sumstats_pos, common_genes.to_list()].X
+        self.mk_score_common = mk_score.loc[common_genes]
+
+        # calculate the chunk number
+        self.chunk_starts = list(range(0, self.mk_score_common.shape[1], self.config.spots_per_chunk_quick_mode))
+
+    def fetch_ldscore_by_chunk(self, chunk_index):
+        chunk_start = self.chunk_starts[chunk_index]
+        mk_score_chunk = self.mk_score_common.iloc[:,
+                         chunk_start:chunk_start + self.config.spots_per_chunk_quick_mode]
+        ldscore_chunk = self.calculate_ldscore_use_SNP_Gene_weight_matrix_by_chunk(
+            mk_score_chunk,
+            drop_dummy_na=False,
+        )
+
+        spots_name = self.mk_score_common.columns[chunk_start:chunk_start + self.config.spots_per_chunk_quick_mode]
+        return ldscore_chunk, spots_name
+
+    def calculate_ldscore_use_SNP_Gene_weight_matrix_by_chunk(self,
+                                                              mk_score_chunk,
+                                                              drop_dummy_na=True,
+                                                              ):
+
+        if drop_dummy_na:
+            ldscore_chr_chunk = self.snp_gene_weight_matrix[:, :-1] @ mk_score_chunk
+        else:
+            ldscore_chr_chunk = self.snp_gene_weight_matrix @ mk_score_chunk
+
+        return ldscore_chr_chunk
+
+
+def _get_sumstats_with_common_snp_from_sumstats_dict(sumstats_config_dict: dict, baseline_and_w_ld_common_snp: pd.Index,
+                                                     chisq_max=None):
+    # first validate if all sumstats file exists
+    logger.info('Validating sumstats files...')
+    for trait_name, sumstat_file_path in sumstats_config_dict.items():
+        if not os.path.exists(sumstat_file_path):
+            raise FileNotFoundError(f'{sumstat_file_path} not found')
+    # then load all sumstats
+    sumstats_cleaned_dict = {}
+    for trait_name, sumstat_file_path in sumstats_config_dict.items():
+        sumstats_cleaned_dict[trait_name] = _preprocess_sumstats(trait_name, sumstat_file_path,
+                                                                 baseline_and_w_ld_common_snp, chisq_max)
+    # get the common snps among all sumstats
+    common_snp_among_all_sumstats = None
+    for trait_name, sumstats in sumstats_cleaned_dict.items():
+        if common_snp_among_all_sumstats is None:
+            common_snp_among_all_sumstats = sumstats.index
+        else:
+            common_snp_among_all_sumstats = common_snp_among_all_sumstats.intersection(sumstats.index)
+
+    # filter the common snps among all sumstats
+    for trait_name, sumstats in sumstats_cleaned_dict.items():
+        sumstats_cleaned_dict[trait_name] = sumstats.loc[common_snp_among_all_sumstats]
+
+    logger.info(f'!Common SNPs among all sumstats: {len(common_snp_among_all_sumstats)}')
+    return sumstats_cleaned_dict, common_snp_among_all_sumstats
+
+
 def run_spatial_ldsc(config: SpatialLDSCConfig):
-    global spatial_annotation, baseline_annotation, n_blocks, Nbar, sumstats, x_tot_precomputed_common_snp, w_ld_common_snp
+    global spatial_annotation, baseline_annotation, n_blocks, Nbar, sumstats, ref_ld_baseline_column_sum, w_ld_common_snp
     # config
     n_blocks = config.n_blocks
     sample_name = config.sample_name
@@ -144,72 +220,107 @@ def run_spatial_ldsc(config: SpatialLDSCConfig):
     w_ld_cname = w_ld.columns[1]
     w_ld.set_index('SNP', inplace=True)
 
-    # Load the baseline annotations
-    ld_file_baseline = f'{config.ldscore_input_dir}/baseline/baseline.'
+    ld_file_baseline = f'{config.ldscore_save_dir}/baseline/baseline.'
+
     ref_ld_baseline = _read_ref_ld_v2(ld_file_baseline)
-    n_annot_baseline = len(ref_ld_baseline.columns)
-    M_annot_baseline = _read_M_v2(ld_file_baseline, n_annot_baseline, config.not_M_5_50)
+    # n_annot_baseline = len(ref_ld_baseline.columns)
+    # M_annot_baseline = _read_M_v2(ld_file_baseline, n_annot_baseline, config.not_M_5_50)
 
     # common snp between baseline and w_ld
     baseline_and_w_ld_common_snp = ref_ld_baseline.index.intersection(w_ld.index)
-    if len(baseline_and_w_ld_common_snp) < 200000:
-        logger.warning(f'WARNING: number of SNPs less than 200k; for {sample_name} this is almost always bad.')
-    ref_ld_baseline = ref_ld_baseline.loc[baseline_and_w_ld_common_snp]
+    baseline_and_w_ld_common_snp_pos = pd.Index(ref_ld_baseline.index).get_indexer(baseline_and_w_ld_common_snp)
+
+    # Clean the sumstats
+    sumstats_cleaned_dict, common_snp_among_all_sumstats = _get_sumstats_with_common_snp_from_sumstats_dict(
+        config.sumstats_config_dict, baseline_and_w_ld_common_snp,
+        chisq_max=config.chisq_max)
+    common_snp_among_all_sumstats_pos = ref_ld_baseline.index.get_indexer(common_snp_among_all_sumstats)
+
+    # insure the order is monotonic
+    assert pd.Series(
+        common_snp_among_all_sumstats_pos).is_monotonic_increasing, 'common_snp_among_all_sumstats_pos is not monotonic increasing'
+
+    if len(common_snp_among_all_sumstats) < 200000:
+        logger.warning(
+            f'!!!!! WARNING: number of SNPs less than 200k; for {sample_name} this is almost always bad. Please check the sumstats files.')
+
+    ref_ld_baseline = ref_ld_baseline.loc[common_snp_among_all_sumstats]
+    w_ld = w_ld.loc[common_snp_among_all_sumstats]
 
     # load additional baseline annotations
     if config.use_additional_baseline_annotation:
-        ld_file_baseline_additional = f'{config.ldscore_input_dir}/additional_baseline/baseline.'
+        print('Using additional baseline annotations')
+        ld_file_baseline_additional = f'{config.ldscore_save_dir}/additional_baseline/baseline.'
         ref_ld_baseline_additional = _read_ref_ld_v2(ld_file_baseline_additional)
         n_annot_baseline_additional = len(ref_ld_baseline_additional.columns)
         logger.info(f'{len(ref_ld_baseline_additional.columns)} additional baseline annotations loaded')
         # M_annot_baseline_additional = _read_M_v2(ld_file_baseline_additional, n_annot_baseline_additional,
         #                                             config.not_M_5_50)
-        ref_ld_baseline_additional = ref_ld_baseline_additional.loc[baseline_and_w_ld_common_snp]
+        ref_ld_baseline_additional = ref_ld_baseline_additional.loc[common_snp_among_all_sumstats]
         ref_ld_baseline = pd.concat([ref_ld_baseline, ref_ld_baseline_additional], axis=1)
         del ref_ld_baseline_additional
 
-    w_ld = w_ld.loc[baseline_and_w_ld_common_snp]
-
-    # Clean the sumstats
-    sumstats_cleaned_dict = _get_sumstats_from_sumstats_dict(config.sumstats_config_dict, baseline_and_w_ld_common_snp,
-                                                             chisq_max=config.chisq_max)
+    # Detect available chunk files
+    if config.ldscore_save_format == 'quick_mode':
+        s_ldsc = S_LDSC_Boost_with_pre_calculate_SNP_Gene_weight_matrix(config, common_snp_among_all_sumstats_pos)
+        total_chunk_number_found = len(s_ldsc.chunk_starts)
+        print(f'Split data into {total_chunk_number_found} chunks')
+    else:
+        all_file = os.listdir(config.ldscore_save_dir)
+        total_chunk_number_found = sum('chunk' in name for name in all_file)
+        print(f'Find {total_chunk_number_found} chunked files in {config.ldscore_save_dir}')
 
-    # Detect avalable chunk files
-    all_file = os.listdir(config.ldscore_input_dir)
     if config.all_chunk is None:
-        all_chunk = sum('chunk' in name for name in all_file)
-        print(f'\t')
-        print(f'Find {all_chunk} chunked files')
+        if config.chunk_range is not None:
+            assert config.chunk_range[0] >= 1 and config.chunk_range[
+                1] <= total_chunk_number_found, 'Chunk range out of bound. It should be in [1, all_chunk]'
+            print(
+                f'chunk range provided, using chunked files from {config.chunk_range[0]} to {config.chunk_range[1]}')
+            start_chunk, end_chunk = config.chunk_range
+        else:
+            start_chunk, end_chunk = 1, total_chunk_number_found
     else:
         all_chunk = config.all_chunk
         print(f'using {all_chunk} chunked files by provided argument')
         print(f'\t')
         print(f'Input {all_chunk} chunked files')
+        start_chunk, end_chunk = 1, all_chunk
+
+    running_chunk_number = end_chunk - start_chunk + 1
 
     # Process each chunk
     output_dict = defaultdict(list)
-    for chunk_index in range(1, all_chunk + 1):
-        print(f'------Processing chunk-{chunk_index}')
-
-        # Load the spatial annotations for this chunk
-        ld_file_spatial = f'{config.ldscore_input_dir}/{sample_name}_chunk{chunk_index}/{sample_name}.'
-        ref_ld_spatial = _read_ref_ld_v2(ld_file_spatial)
-        ref_ld_spatial = ref_ld_spatial.loc[baseline_and_w_ld_common_snp]
-        ref_ld_spatial = ref_ld_spatial.astype(np.float32, copy=False)
+    zarr_path = Path(config.ldscore_save_dir) / f'{config.sample_name}.ldscore.zarr'
+    if config.ldscore_save_format == 'zarr':
+        assert zarr_path.exists(), f'{zarr_path} not found, which is required for zarr format'
+        zarr_file = zarr.open(str(zarr_path))
+        spots_name = zarr_file.attrs['spot_names']
+
+    for chunk_index in range(start_chunk, end_chunk + 1):
+        if config.ldscore_save_format == 'feather':
+            ref_ld_spatial, spatial_annotation_cnames = load_ldscore_chunk_from_feather(chunk_index,
+                                                                                        common_snp_among_all_sumstats_pos,
+                                                                                        config,
+                                                                                        )
+        elif config.ldscore_save_format == 'zarr':
+            ref_ld_spatial = zarr_file.blocks[:, chunk_index - 1][common_snp_among_all_sumstats_pos]
+            start_spot = (chunk_index - 1) * zarr_file.chunks[1]
+            ref_ld_spatial = ref_ld_spatial.astype(np.float32, copy=False)
+            spatial_annotation_cnames = spots_name[start_spot:start_spot + zarr_file.chunks[1]]
+        elif config.ldscore_save_format == 'quick_mode':
+            ref_ld_spatial, spatial_annotation_cnames = s_ldsc.fetch_ldscore_by_chunk(chunk_index - 1)
+        else:
+            raise ValueError(f'Invalid ld score save format: {config.ldscore_save_format}')
 
         # get the x_tot_precomputed matrix by adding baseline and spatial annotation
-        x_tot_precomputed = ref_ld_spatial + ref_ld_baseline.sum(axis=1).values.reshape((-1, 1))
+        ref_ld_baseline_column_sum = ref_ld_baseline.sum(axis=1).values
+        # x_tot_precomputed = ref_ld_spatial + ref_ld_baseline_column_sum
 
         for trait_name, sumstats in sumstats_cleaned_dict.items():
-            logger.info(f'Processing {trait_name}...')
 
-            # filter ldscore by common snp
-            common_snp = sumstats.index
-            spatial_annotation = ref_ld_spatial.loc[common_snp].astype(np.float32, copy=False)
-            spatial_annotation_cnames = spatial_annotation.columns
-            baseline_annotation = ref_ld_baseline.loc[common_snp].astype(np.float32, copy=False)
-            w_ld_common_snp = w_ld.loc[common_snp].astype(np.float32, copy=False)
-            x_tot_precomputed_common_snp = x_tot_precomputed.loc[common_snp].values
+            spatial_annotation = ref_ld_spatial.astype(np.float32, copy=False)
+            baseline_annotation = ref_ld_baseline.copy().astype(np.float32, copy=False)
+            w_ld_common_snp = w_ld.astype(np.float32, copy=False)
 
             # weight the baseline annotation by N
             baseline_annotation = baseline_annotation * sumstats.N.values.reshape((-1, 1)) / sumstats.N.mean()
@@ -219,10 +330,11 @@ def run_spatial_ldsc(config: SpatialLDSCConfig):
             # Run the jackknife
             Nbar = sumstats.N.mean()
             chunk_size = spatial_annotation.shape[1]
-            out_chunk = process_map(jackknife_for_processmap, range(chunk_size),
-                                    max_workers=config.num_processes,
-                                    chunksize=10,
-                                    desc=f'LDSC chunk-{chunk_index}: {trait_name}')
+            out_chunk = thread_map(jackknife_for_processmap, range(chunk_size),
+                                   max_workers=config.num_processes,
+                                   chunksize=10,
+                                   desc=f'Chunk-{chunk_index}/Total-chunk-{running_chunk_number} for {trait_name}',
+                                   )
 
             # cache the results
             out_chunk = pd.DataFrame.from_records(out_chunk,
@@ -230,7 +342,8 @@ def run_spatial_ldsc(config: SpatialLDSCConfig):
                                                   index=spatial_annotation_cnames)
             # get the spots with nan
             nan_spots = out_chunk[out_chunk.isna().any(axis=1)].index
-            logger.info(f'Nan spots: {nan_spots} in chunk-{chunk_index} for {trait_name}. They are removed.')
+            if len(nan_spots) > 0:
+                logger.info(f'Nan spots: {nan_spots} in chunk-{chunk_index} for {trait_name}. They are removed.')
             # drop the nan
             out_chunk = out_chunk.dropna()
 
@@ -238,70 +351,32 @@ def run_spatial_ldsc(config: SpatialLDSCConfig):
             out_chunk['p'] = norm.sf(out_chunk['z'])
             output_dict[trait_name].append(out_chunk)
 
-            # garbage collection
-            del spatial_annotation
+        del ref_ld_spatial, spatial_annotation, baseline_annotation, w_ld_common_snp
+        gc.collect()
 
     # Save the results
-    out_dir = Path(config.ldsc_save_dir)
-    out_dir.mkdir(parents=True, exist_ok=True, mode=0o777)
+    out_dir = config.ldsc_save_dir
     for trait_name, out_chunk_list in output_dict.items():
         out_all = pd.concat(out_chunk_list, axis=0)
-        out_file_name = out_dir / f'{sample_name}_{trait_name}.csv.gz'
+        if running_chunk_number == total_chunk_number_found:
+            out_file_name = out_dir / f'{sample_name}_{trait_name}.csv.gz'
+        else:
+            out_file_name = out_dir / f'{sample_name}_{trait_name}_chunk{start_chunk}-{end_chunk}.csv.gz'
         out_all['spot'] = out_all.index
         out_all = out_all[['spot', 'beta', 'se', 'z', 'p']]
         out_all.to_csv(out_file_name, compression='gzip', index=False)
+
         logger.info(f'Output saved to {out_file_name} for {trait_name}')
     logger.info(f'------Spatial LDSC for {sample_name} finished!')
 
 
-# %%
-if __name__ == '__main__':
-    # Main function of analysis
-    parser = argparse.ArgumentParser(
-        description="Run Spatial LD Score Regression (LDSC) analysis for GWAS and spatial transcriptomic data."
-    )
-    parser = add_spatial_ldsc_args(parser)
-    TEST = True
-    if TEST:
-        gwas_root = "/storage/yangjianLab/songliyang/GWAS_trait/LDSC"
-        gwas_trait = "/storage/yangjianLab/songliyang/GWAS_trait/GWAS_Public_Use_MaxPower.csv"
-        root = "/storage/yangjianLab/songliyang/SpatialData/Data/Brain/Human/Nature_Neuroscience_2021/processed/h5ad"
-
-        name = 'Cortex_151507'
-        spe_name = name
-        # ld_pth = f"/storage/yangjianLab/songliyang/SpatialData/Data/Brain/Human/Nature_Neuroscience_2021/annotation/{spe_name}/snp_annotation"
-        ld_pth = f"/storage/yangjianLab/chenwenhao/projects/202312_gsMap/data/gsMap_test/Nature_Neuroscience_2021/snake_workdir/{name}/generate_ldscore"
-        out_pth = f"/storage/yangjianLab/chenwenhao/projects/202312_gsMap/data/gsMap_test/Nature_Neuroscience_2021/snake_workdir/{name}/ldsc"
-        gwas_file = "ADULT1_ADULT2_ONSET_ASTHMA"
-        # Prepare the arguments list using f-strings
-        args_list = [
-            "--h2", f"{gwas_root}/{gwas_file}.sumstats.gz",
-            "--w_file", "/storage/yangjianLab/sharedata/LDSC_resource/LDSC_SEG_ldscores/weights_hm3_no_hla/weights.",
-            "--sample_name", spe_name,
-            "--num_processes", '4',
-            "--ldscore_input_dir", ld_pth,
-            "--ldsc_save_dir", out_pth,
-            '--trait_name', 'adult1_adult2_onset_asthma'
-        ]
-        # args = parser.parse_args(args_list)
-    else:
-        args = parser.parse_args()
-
-    os.chdir('/storage/yangjianLab/chenwenhao/tmp/gsMap_Height_debug')
-    TASK_ID = 16
-    spe_name = f'E{TASK_ID}.5_E1S1'
-    config = SpatialLDSCConfig(**{'all_chunk': None,
-                                  'chisq_max': None,
-                                  # 'sumstats_file': '/storage/yangjianLab/songliyang/GWAS_trait/LDSC/GIANT_EUR_Height_2022_Nature.sumstats.gz',
-                                  'ldsc_save_dir': f'{spe_name}/ldsc_results_three_row_sum_sub_config_traits',
-                                  'ldscore_input_dir': '/storage/yangjianLab/songliyang/SpatialData/Data/Embryo/Mice/Cell_MOSTA/annotation/E16.5_E1S1/generate_ldscore_new',
-                                  'n_blocks': 200,
-                                  'not_M_5_50': False,
-                                  'num_processes': 15,
-                                  'sample_name': spe_name,
-                                  # 'trait_name': 'GIANT_EUR_Height_2022_Nature',
-                                  'sumstats_config_file': '/storage/yangjianLab/chenwenhao/projects/202312_gsMap/src/gsMap/example/sumstats_config_sub.yaml',
-                                  'w_file': '/storage/yangjianLab/sharedata/LDSC_resource/LDSC_SEG_ldscores/weights_hm3_no_hla/weights.'
-                                  })
-    # config = SpatialLDSCConfig(**vars(args))
-    run_spatial_ldsc(config)
+def load_ldscore_chunk_from_feather(chunk_index, common_snp_among_all_sumstats_pos, config, ):
+    # Load the spatial annotations for this chunk
+    sample_name = config.sample_name
+    ld_file_spatial = f'{config.ldscore_save_dir}/{sample_name}_chunk{chunk_index}/{sample_name}.'
+    ref_ld_spatial = _read_ref_ld_v2(ld_file_spatial)
+    ref_ld_spatial = ref_ld_spatial.iloc[common_snp_among_all_sumstats_pos]
+    ref_ld_spatial = ref_ld_spatial.astype(np.float32, copy=False)
+
+    spatial_annotation_cnames = ref_ld_spatial.columns
+    return ref_ld_spatial.values, spatial_annotation_cnames

gsMap/templates/report_template.html

@@ -0,0 +1,198 @@
+<!DOCTYPE html>
+<html lang="en">
+<head>
+    <meta charset="UTF-8">
+    <title>{{ title }}</title>
+    <meta name="viewport" content="width=device-width, initial-scale=1">
+    <!-- Bootstrap CSS -->
+    <link href="https://cdn.jsdelivr.net/npm/bootstrap@5.3.0/dist/css/bootstrap.min.css" rel="stylesheet">
+    <!-- Custom Styles -->
+    <style>
+        body {
+            padding: 20px;
+            font-family: 'Helvetica Neue', Helvetica, Arial, sans-serif;
+        }
+        .plot-container {
+            margin-bottom: 50px;
+        }
+        .section-description {
+            color: #6c757d;
+            font-size: 0.95rem;
+            margin-bottom: 20px;
+        }
+        .scrollable-table {
+            max-height: 400px;
+            overflow-y: auto;
+        }
+        .table thead th {
+            position: sticky;
+            top: 0;
+            background-color: #f8f9fa;
+        }
+        img {
+            max-width: 100%;
+            height: auto;
+            border: 1px solid #dee2e6;
+            border-radius: 5px;
+        }
+        .gene-select-label {
+            font-weight: bold;
+            margin-bottom: 10px;
+        }
+        .collapse-toggle {
+            cursor: pointer;
+            color: #0d6efd;
+            text-decoration: underline;
+        }
+    </style>
+</head>
+<body>
+    <div class="container-fluid">
+        <h1 class="mb-4">{{ title }}</h1>
+
+        <!-- Genetic Spatial Mapping Plot -->
+        <div class="plot-container">
+            <h2>Genetic Spatial Mapping Plot</h2>
+            <p class="section-description">This plot shows the spatial genetic mapping results across different tissues.</p>
+            <div class="border rounded p-3">
+                {{ genetic_mapping_plot|safe }}
+            </div>
+        </div>
+
+        <!-- Cauchy Combination Result Table -->
+        <div class="plot-container">
+            <h2>Cauchy Combination Result</h2>
+            <p class="section-description">This table presents the results of the Cauchy combination test, summarizing the genetic associations.</p>
+            <div class="scrollable-table">
+                <table class="table table-hover table-bordered">
+                    <thead class="table-light">
+                        <tr>
+                            <th>Annotation</th>
+                            <th>P Cauchy</th>
+                            <th>P Median</th>
+                        </tr>
+                    </thead>
+                    <tbody>
+                        {% for row in cauchy_table %}
+                        <tr>
+                            <td>{{ row.annotation }}</td>
+                            <td>{{ "%.4e"|format(row.p_cauchy) }}</td>
+                            <td>{{ "%.4e"|format(row.p_median) }}</td>
+                        </tr>
+                        {% endfor %}
+                    </tbody>
+                </table>
+            </div>
+        </div>
+
+        <!-- Manhattan Plot -->
+        <div class="plot-container">
+            <h2>Diagnosis Manhattan Plot</h2>
+            <p class="section-description">The Manhattan plot shows the association of SNPs with the top associated gene across the genome.</p>
+            <div class="border rounded p-3">
+                {{ manhattan_plot|safe }}
+            </div>
+        </div>
+
+        <!-- Gene Expression and GSS Distribution -->
+        <div class="plot-container">
+            <h2>Gene Expression and GSS Distribution</h2>
+            <p class="section-description">Select a gene to view its expression distribution and gene specificity score (GSS).</p>
+            <label for="geneSelect" class="gene-select-label">Select a gene:</label>
+            <select id="geneSelect" class="form-select mb-4">
+                {% for gene in gene_plots %}
+                <option value="{{ gene.name }}">{{ gene.name }}</option>
+                {% endfor %}
+            </select>
+            <div id="genePlots" class="row">
+                <div class="col-md-6 mb-4">
+                    <h5>Expression Distribution</h5>
+                    <img src="{{ gene_plots[0].expression_plot }}" alt="{{ gene_plots[0].name }} Expression Distribution" id="expressionPlotImg" class="img-fluid">
+                </div>
+                <div class="col-md-6 mb-4">
+                    <h5>Gene Specificity Score (GSS)</h5>
+                    <img src="{{ gene_plots[0].gss_plot }}" alt="{{ gene_plots[0].name }} GSS Distribution" id="gssPlotImg" class="img-fluid">
+                </div>
+            </div>
+        </div>
+
+        <!-- Gene Diagnostic Info Table -->
+        <div class="plot-container">
+            <h2>Top 50 Gene Diagnostic Info</h2>
+            <p class="section-description">This table lists the top 50 genes based on diagnostic criteria, including the gene specificity score (GSS) and PCC.</p>
+            <div class="scrollable-table">
+                <table class="table table-hover table-bordered">
+                    <thead class="table-light">
+                        <tr>
+                            <th>Gene</th>
+                            <th>Annotation</th>
+                            <th>Median GSS</th>
+                            <th>PCC</th>
+                        </tr>
+                    </thead>
+                    <tbody>
+                        {% for row in gene_diagnostic_info %}
+                        <tr>
+                            <td>{{ row.Gene }}</td>
+                            <td>{{ row.Annotation }}</td>
+                            <td>{{ "%.4f"|format(row.Median_GSS) }}</td>
+                            <td>{{ "%.4f"|format(row.PCC) }}</td>
+                        </tr>
+                        {% endfor %}
+                    </tbody>
+                </table>
+            </div>
+        </div>
+
+        <!-- Running Info (collapsible) -->
+        <div class="plot-container">
+            <h2>Running Info</h2>
+            <p class="section-description">Click to view detailed run information and parameters.</p>
+            <p class="collapse-toggle" data-bs-toggle="collapse" href="#runningInfo" role="button" aria-expanded="false" aria-controls="runningInfo">
+                Show/Hide Running Info
+            </p>
+            <div class="collapse" id="runningInfo">
+                <div class="card card-body">
+                    <p><strong>gsMap Version:</strong> {{ gsmap_version }}</p>
+                    <p><strong>Parameters:</strong></p>
+                    <ul class="mb-0">
+                        {% for key, value in parameters.items() %}
+                        <li><strong>{{ key }}:</strong> {{ value }}</li>
+                        {% endfor %}
+                    </ul>
+                </div>
+            </div>
+        </div>
+    </div>
+
+    <!-- JavaScript for Gene Plots -->
+    <script src="https://cdn.jsdelivr.net/npm/bootstrap@5.3.0/dist/js/bootstrap.bundle.min.js"></script>
+    <script>
+        (function() {
+            const geneSelect = document.getElementById('geneSelect');
+            const expressionPlotImg = document.getElementById('expressionPlotImg');
+            const gssPlotImg = document.getElementById('gssPlotImg');
+
+            const genePlots = {
+                {% for gene in gene_plots %}
+                "{{ gene.name }}": {
+                    expression_plot: "{{ gene.expression_plot }}",
+                    gss_plot: "{{ gene.gss_plot }}"
+                }{% if not loop.last %},{% endif %}
+                {% endfor %}
+            };
+
+            geneSelect.addEventListener('change', function() {
+                const selectedGene = this.value;
+                const selectedGenePlots = genePlots[selectedGene];
+
+                // Update images
+                expressionPlotImg.src = selectedGenePlots.expression_plot;
+                expressionPlotImg.alt = `${selectedGene} Expression Distribution`;
+                gssPlotImg.src = selectedGenePlots.gss_plot;
+                gssPlotImg.alt = `${selectedGene} GSS Distribution`;
+            });
+        })();
+    </script>
+</body>
+</html>

gsMap/{generate_r2_matrix.py → utils/generate_r2_matrix.py}

@@ -69,7 +69,7 @@ def ID_List_Factory(colnames, keepcol, fname_end, header=None, usecols=None):
                 raise ValueError('{f} filename must end in {f}'.format(f=end))
             comp = get_compression(fname)
             self.df = pd.read_csv(fname, header=self.header, usecols=self.usecols,
-                                  delim_whitespace=True, compression=comp)
+                                  sep='\s+', compression=comp)
             if self.colnames:
                 self.df.columns = self.colnames
             if self.keepcol is not None:
@@ -733,11 +733,3 @@ def generate_r2_matrix_cache(bfile_prefix, chromosome_list, r2_cache_dir, ld_win
                                      ld_wind_cm=ld_wind_cm,
                                      output_cache_file_dir=output_cache_file_prefix)
         print(f'Compute r2 matrix for chr{chr} done!')
-
-
-if __name__ == '__main__':
-    bfile_prefix = '/storage/yangjianLab/sharedata/LDSC_resource/1000G_EUR_Phase3_plink/1000G.EUR.QC'
-    chromosome_list = range(1, 22)
-    r2_cache_dir = Path('/storage/yangjianLab/chenwenhao/projects/202312_gsMap/data/gsMap_test/r2_matrix')
-    ld_wind_cm = 1
-    generate_r2_matrix_cache(bfile_prefix, chromosome_list, r2_cache_dir, ld_wind_cm)