Oncodrive3D 1.0.4__py3-none-any.whl
This diff represents the content of publicly available package versions that have been released to one of the supported registries. The information contained in this diff is provided for informational purposes only and reflects changes between package versions as they appear in their respective public registries.
- oncodrive3d-1.0.4.dist-info/METADATA +333 -0
- oncodrive3d-1.0.4.dist-info/RECORD +36 -0
- oncodrive3d-1.0.4.dist-info/WHEEL +4 -0
- oncodrive3d-1.0.4.dist-info/entry_points.txt +5 -0
- oncodrive3d-1.0.4.dist-info/licenses/LICENSE +15 -0
- scripts/__init__.py +2 -0
- scripts/clustering_3d.code-workspace +7 -0
- scripts/datasets/__init__.py +0 -0
- scripts/datasets/af_merge.py +344 -0
- scripts/datasets/build_datasets.py +125 -0
- scripts/datasets/get_pae.py +78 -0
- scripts/datasets/get_structures.py +107 -0
- scripts/datasets/model_confidence.py +97 -0
- scripts/datasets/parse_pae.py +64 -0
- scripts/datasets/prob_contact_maps.py +258 -0
- scripts/datasets/seq_for_mut_prob.py +900 -0
- scripts/datasets/utils.py +394 -0
- scripts/globals.py +169 -0
- scripts/main.py +650 -0
- scripts/plotting/__init__.py +0 -0
- scripts/plotting/build_annotations.py +102 -0
- scripts/plotting/chimerax_plot.py +251 -0
- scripts/plotting/pdb_tool.py +149 -0
- scripts/plotting/pfam.py +94 -0
- scripts/plotting/plot.py +2484 -0
- scripts/plotting/stability_change.py +184 -0
- scripts/plotting/uniprot_feat.py +276 -0
- scripts/plotting/utils.py +594 -0
- scripts/run/__init__.py +0 -0
- scripts/run/clustering.py +749 -0
- scripts/run/communities.py +53 -0
- scripts/run/miss_mut_prob.py +206 -0
- scripts/run/mutability.py +289 -0
- scripts/run/pvalues.py +91 -0
- scripts/run/score_and_simulations.py +155 -0
- scripts/run/utils.py +461 -0
scripts/plotting/plot.py
ADDED
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import pandas as pd
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import daiquiri
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import logging
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import numpy as np
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from matplotlib import pyplot as plt
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import seaborn as sns
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import os
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import json
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import colorcet as cc
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import warnings
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from sklearn.preprocessing import StandardScaler
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import statsmodels.api as sm
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from statsmodels.tools.sm_exceptions import ConvergenceWarning
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from adjustText import adjust_text
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from matplotlib.axes._axes import Axes
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from scripts.plotting.utils import get_broad_consequence, save_annotated_result
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from scripts.plotting.utils import get_enriched_result, filter_o3d_result, subset_genes_and_ids, load_o3d_result
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from scripts import __logger_name__
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logger = daiquiri.getLogger(__logger_name__ + ".plotting.plot")
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logging.getLogger('matplotlib.font_manager').setLevel(logging.WARNING)
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# Summary plots
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# =============
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def get_summary_counts(gene_result, pos_result, seq_df):
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"""
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Get dataframes including the counts required to generate the summary plots.
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"""
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# Df with mut count
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count_mut_gene_hit = gene_result[["Gene", "Clust_mut"]].rename(columns={"Clust_mut" : "Mut_in_gene"})
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count_mut_gene_hit["C"] = "Mutations in clusters"
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count_mut_gene_not = pd.DataFrame({"Gene" : count_mut_gene_hit["Gene"].values,
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"Mut_in_gene" : gene_result.apply(lambda x: x["Mut_in_gene"] - x["Clust_mut"], axis=1)})
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count_mut_gene_not["C"] = "Mutations not in clusters"
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count_mut_gene = gene_result[["Gene", "Mut_in_gene"]].copy()
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count_mut_gene["C"] = "Total mutations"
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count_mut_gene_df = pd.concat((count_mut_gene_hit, count_mut_gene_not, count_mut_gene)).sort_values("Gene").rename(columns={"Mut_in_gene" : "Count"})
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count_mut_gene_df = count_mut_gene_df.sort_values(["C", "Count"], ascending=False).reset_index(drop=True)
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# Df with pos count
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pos_result_not = pos_result[pos_result["C"] == 0]
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if len(pos_result_not) > 0:
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pos_result_not = pos_result_not.groupby("Gene").apply(len)
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pos_result_not = pos_result_not.reset_index().rename(columns={0 : "Count"})
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pos_result_not["C"] = "Residues not in clusters"
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else:
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pos_result_not = pd.DataFrame(columns=["Gene", "Count", "C"])
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pos_result_hit = pos_result[pos_result["C"] == 1]
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if len(pos_result_hit) > 0:
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pos_result_hit = pos_result_hit.groupby("Gene").apply(len)
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pos_result_hit = pos_result_hit.reset_index().rename(columns={0 : "Count"})
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pos_result_hit["C"] = "Residues in clusters"
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else:
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pos_result_hit = pd.DataFrame(columns=["Gene", "Count", "C"])
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pos_result_total = pd.DataFrame(seq_df.apply(lambda x: (x.Gene, len(x.Seq)), axis=1).to_list())
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pos_result_total.columns = "Gene", "Count"
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pos_result_total["C"] = "Protein length"
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count_pos_df = pd.concat((pos_result_total, pos_result_hit, pos_result_not)).sort_values("Gene")
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count_pos_df = count_pos_df.sort_values("C", ascending=False).reset_index(drop=True)
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# Df with cluster count
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cluster_df = pos_result.groupby("Gene").max("Clump").Clump.reset_index()
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cluster_df["Clump"] = cluster_df["Clump"] + 1
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return count_mut_gene_df, count_pos_df, cluster_df
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def summary_plot(gene_result,
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pos_result,
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count_mut_gene_df,
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count_pos_df,
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cluster_df,
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output_dir,
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cohort,
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plot_pars,
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save_plot=True,
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show_plot=False,
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title=None):
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# Init
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h_ratios = plot_pars["summary_h_ratios"]
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tracks = list(h_ratios.keys())
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# Plot
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fsize_x, fsize_y = plot_pars["summary_figsize"]
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if len(gene_result) < 6:
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fsize_x = 3
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else:
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fsize_x = fsize_x * len(gene_result)
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fig, axes = plt.subplots(len(h_ratios), 1,
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figsize=(fsize_x, fsize_y),
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sharex=True,
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gridspec_kw={'hspace': 0.1,
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'height_ratios': h_ratios.values()})
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if "score" in tracks:
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ax = tracks.index("score")
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pos_result = pos_result.copy()
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pos_result["C"] = pos_result.C.map({1 : "Volume in clusters", 0 : "Volume not in clusters"})
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hue_order = ['Volume in clusters', 'Volume not in clusters']
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sns.boxplot(x='Gene', y='Score_obs_sim', data=pos_result, order=gene_result.Gene, color=sns.color_palette("pastel")[7], showfliers=False, ax=axes[ax])
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sns.stripplot(x='Gene', y='Score_obs_sim', data=pos_result, hue="C" ,jitter=True, size=6, alpha=plot_pars["summary_alpha"], order=gene_result.Gene.values,
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palette=sns.color_palette("tab10", n_colors=2), hue_order=hue_order, ax=axes[ax])
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axes[ax].set_ylabel('Clustering\nscore\n(obs/sim)', fontsize=12)
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axes[ax].legend(fontsize=9.5, loc="upper right")
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axes[ax].set_xlabel(None)
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if "miss_count" in tracks:
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ax = tracks.index("miss_count")
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hue_order = ['Total mutations', 'Mutations in clusters']
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custom_palette = [sns.color_palette("pastel")[7], sns.color_palette("pastel")[0]]
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sns.barplot(x='Gene', y='Count', data=count_mut_gene_df[count_mut_gene_df["C"] != "Mutations not in clusters"],
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order=gene_result.Gene, ax=axes[ax], hue="C", palette=custom_palette, hue_order=hue_order, ec="black", lw=0.5)
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axes[ax].set_ylabel('Missense\nmut count', fontsize=12)
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axes[ax].legend(fontsize=9.5, loc="upper right")
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axes[ax].set_xlabel(None)
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if "res_count" in tracks:
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ax = tracks.index("res_count")
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hue_order = ['Protein length', 'Residues in clusters']
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sns.barplot(x='Gene', y='Count', data=count_pos_df[count_pos_df["C"] != "Residues not in clusters"], order=gene_result.Gene, hue="C", ax=axes[ax],
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palette=custom_palette, hue_order=hue_order, ec="black", lw=0.5)
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axes[ax].set_ylabel('Residues\ncount', fontsize=12)
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axes[ax].legend(fontsize=9.5, loc="upper right")
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axes[ax].set_xlabel(None)
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if "res_clust_mut" in tracks:
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ax = tracks.index("res_clust_mut")
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count_mut_clusters = count_mut_gene_df[count_mut_gene_df["C"] == "Mutations in clusters"].drop(columns="C").rename(columns={"Count" : "Mut_count"})
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count_res_clusters = count_pos_df[count_pos_df["C"] == "Residues in clusters"].drop(columns="C").rename(columns={"Count" : "Res_count"})
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count_mut_res_clusters = count_mut_clusters.merge(count_res_clusters, on="Gene")
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count_mut_res_clusters["Per_res_mut"] = np.round(count_mut_res_clusters["Mut_count"] / count_mut_res_clusters["Res_count"], 2)
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sns.barplot(x='Gene', y='Per_res_mut', data=count_mut_res_clusters, order=gene_result.Gene, ax=axes[ax], color=sns.color_palette("pastel")[0], ec="black", lw=0.5)
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axes[ax].set_ylabel('Per-residue\nmut\nin clusters', fontsize=12)
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axes[ax].set_xlabel(None)
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if "clusters" in tracks:
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ax = tracks.index("clusters")
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sns.barplot(x='Gene', y='Clump', data=cluster_df, order=gene_result.Gene, ax=axes[ax], color=sns.color_palette("pastel")[0], ec="black", lw=0.5)
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axes[ax].set_ylabel('Clumps', fontsize=12)
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axes[ax].set_xlabel(None)
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# Details
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if title:
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fig.suptitle(f"{title} summary", fontsize=14)
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else:
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fig.suptitle(f"O3D analysis summary", fontsize=14)
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xticks_labels = [ r'$\mathbf{*}$ ' + gene if gene_result.loc[gene_result["Gene"] == gene, "C_gene"].values[0] == 1 else gene for gene in gene_result.Gene]
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axes[len(axes)-1].set_xticklabels(xticks_labels, rotation=45, rotation_mode="anchor", ha='right', fontsize=12)
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plt.xticks(rotation=45, rotation_mode="anchor", ha='right', fontsize=12)
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plt.subplots_adjust(top=0.94)
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# Save
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filename = f"{cohort}.summary_plot.png"
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output_path = os.path.join(output_dir, filename)
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if save_plot:
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plt.savefig(output_path, dpi=300, bbox_inches='tight')
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logger.debug(f"Saved {output_path}")
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if show_plot:
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plt.show()
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plt.close()
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# Gene plots
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# ==========
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def check_near_feat(uni_feat_gene, feat, dist_thr=0.05):
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"""
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Check if two domains could be closer to each other
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than allowed threshold (ratio of protein size).
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"""
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near_feat = False
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uni_feat_gene = uni_feat_gene.copy()
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if feat == "domain" or feat == "pfam":
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uni_feat_gene = uni_feat_gene[uni_feat_gene["Type"] == "DOMAIN"]
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if feat == "pfam":
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uni_feat_gene = uni_feat_gene[uni_feat_gene["Evidence"] == "Pfam"]
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else:
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uni_feat_gene = uni_feat_gene[uni_feat_gene["Evidence"] != "Pfam"]
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uni_feat_gene = uni_feat_gene.drop_duplicates(subset='Description', keep='first')
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elif feat == "motif":
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uni_feat_gene = uni_feat_gene[uni_feat_gene["Type"] == "MOTIF"]
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uni_feat_gene = uni_feat_gene.drop_duplicates(subset='Full_description', keep='first')
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mid_pos = (uni_feat_gene.Begin + uni_feat_gene.End) / 2
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mid_pos_norm = (mid_pos / mid_pos.max()).values
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for i in range(len(mid_pos_norm)):
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for j in range(i + 1, len(mid_pos_norm)):
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diff = abs(mid_pos_norm[i] - mid_pos_norm[j])
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if diff < dist_thr:
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near_feat = True
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return near_feat
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def get_gene_arg(pos_result_gene, plot_pars, uni_feat_gene, maf_nonmiss=None):
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"""
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Adjust the height ratio of tracks to include in the plot.
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"""
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h_ratios = plot_pars["h_ratios"].copy()
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plot_pars = plot_pars.copy()
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track = "maf_nonmiss"
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if track in h_ratios and not maf_nonmiss:
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del h_ratios[track]
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track = "maf_nonmiss_2"
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if track in h_ratios and not maf_nonmiss:
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del h_ratios[track]
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track = "ddg"
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if track in h_ratios and pos_result_gene["DDG"].isna().all():
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del h_ratios[track]
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track = "pae"
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if track in h_ratios and np.isnan(pos_result_gene["PAE_vol"]).all():
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del h_ratios[track]
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track = "ptm"
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if track in h_ratios:
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if len(uni_feat_gene[uni_feat_gene["Type"] == "PTM"]) == 0:
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del h_ratios[track]
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else:
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stracks = len(uni_feat_gene[uni_feat_gene["Type"] == "PTM"].Description.unique())
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h_ratios[track] = h_ratios[track] * stracks
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track = "site"
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if track in h_ratios:
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if len(uni_feat_gene[uni_feat_gene["Type"] == "SITE"]) == 0:
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del h_ratios[track]
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else:
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stracks = len(uni_feat_gene[uni_feat_gene["Type"] == "SITE"].Description.unique())
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h_ratios[track] = h_ratios[track] * stracks
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track = "pfam"
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if track in h_ratios:
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+
if len(uni_feat_gene[(uni_feat_gene["Type"] == "DOMAIN") & (uni_feat_gene["Evidence"] == "pfam")]) == 1:
|
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251
|
+
del h_ratios[track]
|
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252
|
+
near_pfam = False
|
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253
|
+
else:
|
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254
|
+
near_pfam = check_near_feat(uni_feat_gene, feat=track, dist_thr=plot_pars["dist_thr"])
|
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255
|
+
if near_pfam:
|
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256
|
+
h_ratios[track] = h_ratios[track] * 2
|
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257
|
+
|
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258
|
+
track = "prosite"
|
|
259
|
+
if track in h_ratios:
|
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260
|
+
if len(uni_feat_gene[(uni_feat_gene["Type"] == "DOMAIN") & (uni_feat_gene["Evidence"] != "Pfam")]) == 0:
|
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261
|
+
del h_ratios[track]
|
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262
|
+
near_prosite = False
|
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263
|
+
else:
|
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264
|
+
near_prosite = check_near_feat(uni_feat_gene, feat="domain", dist_thr=plot_pars["dist_thr"])
|
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265
|
+
if near_prosite:
|
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266
|
+
h_ratios[track] = h_ratios[track] * 2
|
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267
|
+
|
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268
|
+
track = "membrane"
|
|
269
|
+
if track in h_ratios:
|
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270
|
+
if len(uni_feat_gene[uni_feat_gene["Type"] == "MEMBRANE"]) == 0:
|
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271
|
+
del h_ratios[track]
|
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272
|
+
else:
|
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273
|
+
stracks = len(uni_feat_gene[uni_feat_gene["Type"] == "MEMBRANE"].Description.unique())
|
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274
|
+
h_ratios[track] = h_ratios[track] * stracks
|
|
275
|
+
|
|
276
|
+
track = "motif"
|
|
277
|
+
if track in h_ratios:
|
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278
|
+
if len(uni_feat_gene[uni_feat_gene["Type"] == "MOTIF"]) == 0:
|
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279
|
+
del h_ratios[track]
|
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280
|
+
near_motif = False
|
|
281
|
+
else:
|
|
282
|
+
near_motif = check_near_feat(uni_feat_gene, feat="motif", dist_thr=0.1)
|
|
283
|
+
if near_motif:
|
|
284
|
+
h_ratios[track] = h_ratios[track] * 1.8
|
|
285
|
+
|
|
286
|
+
h_ratios = {k:v/sum(h_ratios.values()) for k,v in h_ratios.items()}
|
|
287
|
+
|
|
288
|
+
return h_ratios, near_pfam, near_prosite, near_motif
|
|
289
|
+
|
|
290
|
+
|
|
291
|
+
def filter_non_processed_mut(maf, pos_result):
|
|
292
|
+
"""
|
|
293
|
+
Get rid of mutations of the input file that were not processed.
|
|
294
|
+
"""
|
|
295
|
+
# TO DO: In this way, I am not getting rid of the mismatches ones.. I should think about something else for these ones
|
|
296
|
+
len_maf = len(maf)
|
|
297
|
+
maf = maf[maf.apply(lambda x: f"{x.Gene}_{x.Pos}", axis=1).isin(pos_result.apply(lambda x: f"{x.Gene}_{x.Pos}", axis=1))]
|
|
298
|
+
logger.debug(f"Filtered out {len_maf - len(maf)} ({(len_maf - len(maf))/len_maf*100:.2f}%) mutations out of {len_maf} not processed during 3D-clustering analysis!")
|
|
299
|
+
|
|
300
|
+
return maf
|
|
301
|
+
|
|
302
|
+
|
|
303
|
+
def capitalize(string):
|
|
304
|
+
words = string.split("_")
|
|
305
|
+
words[0] = words[0].capitalize()
|
|
306
|
+
|
|
307
|
+
return ' '.join(words)
|
|
308
|
+
|
|
309
|
+
|
|
310
|
+
def get_nonmiss_mut(path_to_maf):
|
|
311
|
+
"""
|
|
312
|
+
Get non missense mutations from MAF file.
|
|
313
|
+
"""
|
|
314
|
+
try:
|
|
315
|
+
maf_nonmiss = pd.read_csv(path_to_maf, sep="\t", dtype={'Chromosome': str})
|
|
316
|
+
maf_nonmiss = maf_nonmiss[maf_nonmiss["Protein_position"] != "-"] ## TODO: Fix it for alternative MAF (see cancer)
|
|
317
|
+
maf_nonmiss = maf_nonmiss[~(maf_nonmiss['Consequence'].str.contains('Missense_Mutation')
|
|
318
|
+
| maf_nonmiss['Consequence'].str.contains('missense_variant'))]
|
|
319
|
+
maf_nonmiss = maf_nonmiss[["SYMBOL",
|
|
320
|
+
"Consequence",
|
|
321
|
+
"Protein_position"]].rename(
|
|
322
|
+
columns={"SYMBOL" : "Gene",
|
|
323
|
+
"Protein_position" : "Pos"}).reset_index(drop=True)
|
|
324
|
+
|
|
325
|
+
# Parse the consequence with multiple elements and get broader categories
|
|
326
|
+
maf_nonmiss["Consequence"] = get_broad_consequence(maf_nonmiss["Consequence"])
|
|
327
|
+
|
|
328
|
+
return maf_nonmiss
|
|
329
|
+
|
|
330
|
+
except Exception as e:
|
|
331
|
+
logger.warning("Can't parse non-missense mutation from MAF file: The track will not be included...")
|
|
332
|
+
logger.warning(f"{e}")
|
|
333
|
+
|
|
334
|
+
|
|
335
|
+
def avg_per_pos_ddg(pos_result_gene, ddg_prot, maf_gene):
|
|
336
|
+
"""
|
|
337
|
+
Compute per-position average stability change upon mutations (DDG).
|
|
338
|
+
"""
|
|
339
|
+
|
|
340
|
+
ddg_vec = np.repeat(0., len(pos_result_gene))
|
|
341
|
+
for pos, group in maf_gene.groupby('Pos'):
|
|
342
|
+
pos = str(pos)
|
|
343
|
+
obs_mut = group.Mut
|
|
344
|
+
if pos in ddg_prot:
|
|
345
|
+
ddg_pos = ddg_prot[pos]
|
|
346
|
+
ddg_pos = np.mean([ddg_pos[mut] for mut in obs_mut])
|
|
347
|
+
ddg_vec[int(pos)-1] = ddg_pos
|
|
348
|
+
|
|
349
|
+
return ddg_vec
|
|
350
|
+
|
|
351
|
+
|
|
352
|
+
def parse_pos_result_for_genes_plot(pos_result_gene, c_ext=True):
|
|
353
|
+
"""
|
|
354
|
+
Get mut count and score divided by Oncodriv3D
|
|
355
|
+
result: significant, not significant, significant extended
|
|
356
|
+
(mutation in a non-significant residue that contribute to
|
|
357
|
+
mutations in the volume of a significant one/s).
|
|
358
|
+
"""
|
|
359
|
+
|
|
360
|
+
pos_result_gene = pos_result_gene.copy()
|
|
361
|
+
pos_result_gene = pos_result_gene[["Pos", "Mut_in_res", "Mut_in_vol", "Score_obs_sim", "C", "C_ext", "pval", "Clump", "PAE_vol"]]
|
|
362
|
+
if not c_ext:
|
|
363
|
+
pos_result_gene["C"] = pos_result_gene.apply(
|
|
364
|
+
lambda x: 1 if (x["C"] == 1) & (x["C_ext"] == 0) else 2 if (x["C"] == 1) & (x["C_ext"] == 1) else 0, axis=1)
|
|
365
|
+
max_mut = np.max(pos_result_gene["Mut_in_res"].values)
|
|
366
|
+
|
|
367
|
+
return pos_result_gene, max_mut
|
|
368
|
+
|
|
369
|
+
|
|
370
|
+
def get_count_for_genes_plot(maf, maf_nonmiss, gene, non_missense_count=False):
|
|
371
|
+
"""
|
|
372
|
+
Get missense and non-missense mutations count.
|
|
373
|
+
"""
|
|
374
|
+
|
|
375
|
+
mut_count = maf.value_counts("Pos").reset_index()
|
|
376
|
+
mut_count = mut_count.rename(columns={0 : "Count"})
|
|
377
|
+
if non_missense_count:
|
|
378
|
+
maf_nonmiss_gene = maf_nonmiss[maf_nonmiss["Gene"] == gene]
|
|
379
|
+
mut_count_nonmiss = maf_nonmiss_gene.groupby("Consequence").value_counts("Pos").reset_index()
|
|
380
|
+
mut_count_nonmiss = mut_count_nonmiss.rename(columns={0 : "Count"})
|
|
381
|
+
# If there is more than one position affected, take the first one
|
|
382
|
+
ix_more_than_one_pos = mut_count_nonmiss.apply(lambda x: len(x["Pos"].split("-")), axis=1) > 1
|
|
383
|
+
mut_count_nonmiss.loc[ix_more_than_one_pos, "Pos"] = mut_count_nonmiss.loc[ix_more_than_one_pos].apply(lambda x: x["Pos"].split("-")[0], axis=1)
|
|
384
|
+
# Filter non-numerical Pos and get count
|
|
385
|
+
mut_count_nonmiss = mut_count_nonmiss[mut_count_nonmiss["Pos"].apply(lambda x: x.isdigit() or x.isnumeric())]
|
|
386
|
+
mut_count_nonmiss["Pos"] = mut_count_nonmiss["Pos"].astype(int)
|
|
387
|
+
else:
|
|
388
|
+
mut_count_nonmiss = None
|
|
389
|
+
|
|
390
|
+
return mut_count, mut_count_nonmiss
|
|
391
|
+
|
|
392
|
+
|
|
393
|
+
def get_score_for_genes_plot(pos_result_gene, mut_count, prob_vec):
|
|
394
|
+
"""
|
|
395
|
+
Add any non-mutated position to the pos_result df, get
|
|
396
|
+
per-position score and normalized score.
|
|
397
|
+
"""
|
|
398
|
+
|
|
399
|
+
pos_result_gene = pos_result_gene.copy()
|
|
400
|
+
score_vec = []
|
|
401
|
+
for pos in range(1, len(prob_vec)+1):
|
|
402
|
+
|
|
403
|
+
# Mut count
|
|
404
|
+
if pos in mut_count.Pos.values:
|
|
405
|
+
if pos not in pos_result_gene.Pos.values:
|
|
406
|
+
logger.error("Position in MAF not found in position-level O3D result: Check that MAF and O3D result are matching!")
|
|
407
|
+
score = pos_result_gene.loc[pos_result_gene["Pos"] == pos, "Score_obs_sim"].values[0]
|
|
408
|
+
else:
|
|
409
|
+
score = 0
|
|
410
|
+
row_gene = pd.DataFrame({'Pos': [pos], 'Mut_in_res': [0], 'Score_obs_sim': [np.nan], 'C': [np.nan]})
|
|
411
|
+
pos_result_gene = pd.concat([pos_result_gene, row_gene])
|
|
412
|
+
|
|
413
|
+
score_vec.append(score)
|
|
414
|
+
|
|
415
|
+
pos_result_gene = pos_result_gene.sort_values("Pos").reset_index(drop=True)
|
|
416
|
+
|
|
417
|
+
# Normalize score
|
|
418
|
+
if np.isnan(score_vec).any():
|
|
419
|
+
score_vec = pd.Series(score_vec).fillna(max(score_vec)).values
|
|
420
|
+
score_norm_vec = np.array(score_vec) / sum(score_vec)
|
|
421
|
+
|
|
422
|
+
return pos_result_gene, score_vec, score_norm_vec
|
|
423
|
+
|
|
424
|
+
|
|
425
|
+
def get_id_annotations(uni_id, pos_result_gene, maf_gene, annotations_dir, disorder, pdb_tool, uniprot_feat):
|
|
426
|
+
"""
|
|
427
|
+
Get the annotations for a specific protein ID.
|
|
428
|
+
"""
|
|
429
|
+
|
|
430
|
+
pos_result_gene = pos_result_gene.copy()
|
|
431
|
+
disorder_gene = disorder[disorder["Uniprot_ID"] == uni_id].reset_index(drop=True)
|
|
432
|
+
pdb_tool_gene = pdb_tool[pdb_tool["Uniprot_ID"] == uni_id].reset_index(drop=True)
|
|
433
|
+
uni_feat_gene = uniprot_feat[uniprot_feat["Uniprot_ID"] == uni_id].reset_index(drop=True)
|
|
434
|
+
ddg_path = os.path.join(annotations_dir, "stability_change", f"{uni_id}_ddg.json")
|
|
435
|
+
if os.path.isfile(ddg_path):
|
|
436
|
+
ddg = json.load(open(ddg_path))
|
|
437
|
+
ddg_vec = avg_per_pos_ddg(pos_result_gene, ddg, maf_gene)
|
|
438
|
+
pos_result_gene["DDG"] = ddg_vec
|
|
439
|
+
else:
|
|
440
|
+
pos_result_gene["DDG"] = np.nan
|
|
441
|
+
logger.debug(f"Stability change of {uni_id} not found. Path {ddg_path} doesn't exist: Skipping..")
|
|
442
|
+
|
|
443
|
+
# Avoid duplicates (Uniprot IDs mapping to the different gene names)
|
|
444
|
+
uni_feat_gene = uni_feat_gene.drop(columns=["Gene", "Ens_Transcr_ID", "Ens_Gene_ID"]).drop_duplicates()
|
|
445
|
+
|
|
446
|
+
return pos_result_gene, disorder_gene, pdb_tool_gene, uni_feat_gene
|
|
447
|
+
|
|
448
|
+
|
|
449
|
+
def get_site_pos(site_df):
|
|
450
|
+
|
|
451
|
+
positions = []
|
|
452
|
+
for begin, end in zip(site_df['Begin'], site_df['End']):
|
|
453
|
+
positions.extend(np.arange(begin, end + 1))
|
|
454
|
+
|
|
455
|
+
return np.array(positions)
|
|
456
|
+
|
|
457
|
+
|
|
458
|
+
def genes_plots(gene_result,
|
|
459
|
+
pos_result,
|
|
460
|
+
seq_df,
|
|
461
|
+
maf,
|
|
462
|
+
maf_nonmiss,
|
|
463
|
+
miss_prob_dict,
|
|
464
|
+
output_dir,
|
|
465
|
+
cohort,
|
|
466
|
+
annotations_dir,
|
|
467
|
+
disorder,
|
|
468
|
+
uniprot_feat,
|
|
469
|
+
pdb_tool,
|
|
470
|
+
plot_pars,
|
|
471
|
+
save_plot=True,
|
|
472
|
+
show_plot=False,
|
|
473
|
+
title=None,
|
|
474
|
+
c_ext=True):
|
|
475
|
+
"""
|
|
476
|
+
Generate a diagnostic plot for each gene showing Oncodrive3D
|
|
477
|
+
results and annotated features.
|
|
478
|
+
"""
|
|
479
|
+
|
|
480
|
+
annotated_result_lst = []
|
|
481
|
+
uni_feat_result_lst = []
|
|
482
|
+
for j, gene in enumerate(gene_result["Gene"].values):
|
|
483
|
+
|
|
484
|
+
|
|
485
|
+
# Load and parse
|
|
486
|
+
# ==============
|
|
487
|
+
|
|
488
|
+
# IDs
|
|
489
|
+
uni_id = seq_df[seq_df["Gene"] == gene].Uniprot_ID.values[0]
|
|
490
|
+
af_f = seq_df[seq_df["Gene"] == gene].F.values[0]
|
|
491
|
+
gene_len = len(seq_df[seq_df["Gene"] == gene].Seq.values[0])
|
|
492
|
+
maf_gene = maf[maf["Gene"] == gene]
|
|
493
|
+
|
|
494
|
+
# Parse
|
|
495
|
+
pos_result_gene = pos_result[pos_result["Gene"] == gene].sort_values("Pos").reset_index(drop=True)
|
|
496
|
+
|
|
497
|
+
if len(pos_result_gene) > 0:
|
|
498
|
+
|
|
499
|
+
pos_result_gene = pos_result_gene[["Pos", "Mut_in_res", "Mut_in_vol",
|
|
500
|
+
"Score_obs_sim", "C", "C_ext",
|
|
501
|
+
"pval", "Clump", "PAE_vol"]]
|
|
502
|
+
pos_result_gene, max_mut = parse_pos_result_for_genes_plot(pos_result_gene, c_ext=c_ext)
|
|
503
|
+
|
|
504
|
+
# Counts
|
|
505
|
+
mut_count, mut_count_nonmiss = get_count_for_genes_plot(maf_gene,
|
|
506
|
+
maf_nonmiss,
|
|
507
|
+
gene,
|
|
508
|
+
non_missense_count="nonmiss_count" in plot_pars["h_ratios"])
|
|
509
|
+
|
|
510
|
+
# Get prob vec
|
|
511
|
+
prob_vec = miss_prob_dict[f"{uni_id}-F{af_f}"] # TODO: If none, use uniform <-------------------------- TODO
|
|
512
|
+
|
|
513
|
+
# Get per-pos score and normalize score
|
|
514
|
+
pos_result_gene, score_vec, score_norm_vec = get_score_for_genes_plot(pos_result_gene,
|
|
515
|
+
mut_count,
|
|
516
|
+
prob_vec)
|
|
517
|
+
|
|
518
|
+
# Get annotations
|
|
519
|
+
pos_result_gene, disorder_gene, pdb_tool_gene, uni_feat_gene = get_id_annotations(uni_id,
|
|
520
|
+
pos_result_gene,
|
|
521
|
+
maf_gene,
|
|
522
|
+
annotations_dir,
|
|
523
|
+
disorder,
|
|
524
|
+
pdb_tool,
|
|
525
|
+
uniprot_feat)
|
|
526
|
+
|
|
527
|
+
|
|
528
|
+
# Generate plot
|
|
529
|
+
# =============
|
|
530
|
+
|
|
531
|
+
h_ratios, near_pfam, near_prosite, near_motif = get_gene_arg(pos_result_gene, plot_pars, uni_feat_gene, maf_nonmiss=maf_nonmiss)
|
|
532
|
+
annotations = list(h_ratios.keys())
|
|
533
|
+
fig, axes = plt.subplots(len(h_ratios), 1,
|
|
534
|
+
figsize=(24,12),
|
|
535
|
+
sharex=True,
|
|
536
|
+
gridspec_kw={'hspace': 0.1,
|
|
537
|
+
'height_ratios': h_ratios.values()})
|
|
538
|
+
|
|
539
|
+
|
|
540
|
+
# Plot for Non-missense mut track
|
|
541
|
+
# -------------------------------
|
|
542
|
+
if "nonmiss_count" in annotations:
|
|
543
|
+
ax = annotations.index("nonmiss_count")
|
|
544
|
+
if len(mut_count_nonmiss.Consequence.unique()) > 6:
|
|
545
|
+
ncol = 3
|
|
546
|
+
else:
|
|
547
|
+
ncol = 2
|
|
548
|
+
i = 0
|
|
549
|
+
axes[ax].vlines(mut_count_nonmiss["Pos"], ymin=0, ymax=mut_count_nonmiss["Count"],
|
|
550
|
+
color="gray", lw=0.7, zorder=0, alpha=0.5) # To cover the overlapping needle top part
|
|
551
|
+
axes[ax].scatter(mut_count_nonmiss["Pos"], mut_count_nonmiss["Count"], color='white', zorder=4, lw=plot_pars["s_lw"])
|
|
552
|
+
for cnsq in mut_count_nonmiss.Consequence.unique():
|
|
553
|
+
count_cnsq = mut_count_nonmiss[mut_count_nonmiss["Consequence"] == cnsq]
|
|
554
|
+
if cnsq == "synonymous_variant":
|
|
555
|
+
order = 1
|
|
556
|
+
else:
|
|
557
|
+
order = 2
|
|
558
|
+
if cnsq in plot_pars["color_cnsq"]:
|
|
559
|
+
color = plot_pars["color_cnsq"][cnsq]
|
|
560
|
+
else:
|
|
561
|
+
color=sns.color_palette("tab10")[i]
|
|
562
|
+
i+=1
|
|
563
|
+
axes[ax].scatter(count_cnsq.Pos.values, count_cnsq.Count.values, label=capitalize(cnsq),
|
|
564
|
+
color=color, zorder=order, alpha=0.7, lw=plot_pars["s_lw"], ec="black") # ec="black",
|
|
565
|
+
axes[ax].legend(fontsize=11.5, ncol=ncol, framealpha=0.75)
|
|
566
|
+
axes[ax].set_ylabel('Non\nmissense\nmutations', fontsize=13.5, rotation=0, va='center')
|
|
567
|
+
axes[ax].set_ylim(-0.5, mut_count_nonmiss["Count"].max()+0.5)
|
|
568
|
+
axes[ax].set_ylim(0, max(mut_count_nonmiss["Count"])*1.1)
|
|
569
|
+
|
|
570
|
+
|
|
571
|
+
# Plot for Missense Mut_in_res track
|
|
572
|
+
# ----------------------------------
|
|
573
|
+
if "miss_count" in annotations:
|
|
574
|
+
ax = annotations.index("miss_count")
|
|
575
|
+
|
|
576
|
+
axes[ax].vlines(mut_count["Pos"], ymin=0, ymax=mut_count["Count"], color="gray", lw=0.7, zorder=1, alpha=0.5)
|
|
577
|
+
|
|
578
|
+
mut_pos = pos_result_gene[pos_result_gene["Mut_in_res"] > 0].Pos.values
|
|
579
|
+
mut_res_pos = pos_result_gene[pos_result_gene["Mut_in_res"] > 0].Mut_in_res.values
|
|
580
|
+
# mut_vol_pos = pos_result_gene[pos_result_gene["Mut_in_res"] > 0].Mut_in_vol.values
|
|
581
|
+
|
|
582
|
+
axes[ax].scatter(mut_pos, mut_res_pos, color='white', zorder=3, lw=plot_pars["s_lw"], ec="white") # To cover the overlapping needle top part
|
|
583
|
+
axes[ax].scatter(mut_pos, mut_res_pos, color='gray', zorder=4, alpha=0.7, lw=plot_pars["s_lw"], ec="black", s=60)
|
|
584
|
+
|
|
585
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, max_mut, where=(pos_result_gene['C'] == 1),
|
|
586
|
+
color='skyblue', alpha=0.3, label='Position in cluster', zorder=0, lw=2)
|
|
587
|
+
# axes[ax].fill_between(pos_result_gene['Pos'], 0, max_mut, where=((pos_result_gene["C"] == 0) | (pos_result_gene["C"] == 2)),
|
|
588
|
+
# color='#ffd8b1', alpha=0.6, label='Mutated not *', zorder=0)
|
|
589
|
+
axes[ax].legend(fontsize=11.5, ncol=2, framealpha=0.75)
|
|
590
|
+
axes[ax].set_ylabel('Missense\nmutations', fontsize=13.5, rotation=0, va='center')
|
|
591
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
592
|
+
axes[ax].set_ylim(0-(max(mut_res_pos)*0.04), max(mut_res_pos)*1.1)
|
|
593
|
+
|
|
594
|
+
|
|
595
|
+
legend = axes[ax].legend(fontsize=11.5, ncol=1, framealpha=0.75, bbox_to_anchor=(0.97, 1.5), borderaxespad=0.)
|
|
596
|
+
legend.set_title("Global legend")
|
|
597
|
+
legend.get_title().set_fontsize(12)
|
|
598
|
+
|
|
599
|
+
# Plot for Miss prob track
|
|
600
|
+
# ----------------------------------
|
|
601
|
+
if "miss_prob" in annotations:
|
|
602
|
+
ax = annotations.index("miss_prob")
|
|
603
|
+
|
|
604
|
+
max_value = np.max(prob_vec)
|
|
605
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, max_value, where=(pos_result_gene['C'] == 1),
|
|
606
|
+
color='skyblue', alpha=0.3, label='Position in cluster', zorder=0, lw=2)
|
|
607
|
+
|
|
608
|
+
# axes[ax].hlines(0, xmin=0, xmax=gene_len, color="gray", lw=0.6, zorder=1)
|
|
609
|
+
axes[ax].plot(range(1, len(prob_vec)+1), prob_vec, zorder=3, color="C2", lw=1)
|
|
610
|
+
axes[ax].set_ylabel('Missense\nmut prob', fontsize=13.5, rotation=0, va='center')
|
|
611
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
612
|
+
|
|
613
|
+
# Plot for Score track
|
|
614
|
+
# ----------------------------------
|
|
615
|
+
if "score" in annotations:
|
|
616
|
+
ax = annotations.index("score")
|
|
617
|
+
|
|
618
|
+
max_value = np.max(score_vec)
|
|
619
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, max_value, where=(pos_result_gene['C'] == 1),
|
|
620
|
+
color='skyblue', alpha=0.3, label='Position in cluster', zorder=0)
|
|
621
|
+
|
|
622
|
+
# axes[ax].hlines(0, xmin=0, xmax=gene_len, color="gray", lw=0.7, zorder=1)
|
|
623
|
+
axes[ax].plot(range(1, len(score_vec)+1), score_vec, zorder=2, color="C2", lw=1)
|
|
624
|
+
|
|
625
|
+
# handles, labels = axes[ax].get_legend_handles_labels()
|
|
626
|
+
# axes[ax].legend(fontsize=11.5, framealpha=0.75, ncol=2)
|
|
627
|
+
axes[ax].set_ylabel('Clustering\nscore\n(obs/sim)', fontsize=13.5, rotation=0, va='center')
|
|
628
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
629
|
+
|
|
630
|
+
|
|
631
|
+
# Plot annotations
|
|
632
|
+
# ================
|
|
633
|
+
|
|
634
|
+
# Plot PAE
|
|
635
|
+
# ----------------------------------
|
|
636
|
+
if "pae" in annotations:
|
|
637
|
+
ax = annotations.index("pae")
|
|
638
|
+
|
|
639
|
+
max_value = np.max(pos_result_gene["PAE_vol"])
|
|
640
|
+
# axes[ax+3].fill_between(pos_result_gene['Pos'], 0, max_value, where=((pos_result_gene["C"] == 0) | (pos_result_gene["C"] == 2)),
|
|
641
|
+
# color='#ffd8b1', alpha=0.6)
|
|
642
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, max_value, where=(pos_result_gene['C'] == 1),
|
|
643
|
+
color='white', lw=2)
|
|
644
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, max_value, where=(pos_result_gene['C'] == 1),
|
|
645
|
+
color='skyblue', alpha=0.3, lw=2)
|
|
646
|
+
axes[ax].fill_between(pos_result_gene["Pos"], 0, pos_result_gene["PAE_vol"].fillna(0),
|
|
647
|
+
zorder=2, color="white")
|
|
648
|
+
axes[ax].fill_between(pos_result_gene["Pos"], 0, pos_result_gene["PAE_vol"].fillna(0),
|
|
649
|
+
zorder=2, color=sns.color_palette("pastel")[4], alpha=0.6)
|
|
650
|
+
axes[ax].plot(pos_result_gene['Pos'], pos_result_gene["PAE_vol"].fillna(0),
|
|
651
|
+
label="Confidence", zorder=3, color=sns.color_palette("tab10")[4], lw=0.5)
|
|
652
|
+
axes[ax].set_ylabel('Predicted\naligned error\n(Å)', fontsize=13.5, rotation=0, va='center')
|
|
653
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
654
|
+
|
|
655
|
+
# Plot disorder
|
|
656
|
+
# -------------
|
|
657
|
+
if "disorder" in annotations:
|
|
658
|
+
ax = annotations.index("disorder")
|
|
659
|
+
|
|
660
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, 100, where=(pos_result_gene['C'] == 1),
|
|
661
|
+
color='white', lw=2)
|
|
662
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, 100, where=(pos_result_gene['C'] == 1),
|
|
663
|
+
color='skyblue', alpha=0.4, label='Mutated *', lw=2)
|
|
664
|
+
|
|
665
|
+
axes[ax].fill_between(disorder_gene["Pos"], 0, disorder_gene["Confidence"].fillna(0),
|
|
666
|
+
zorder=2, color="white")
|
|
667
|
+
axes[ax].fill_between(disorder_gene["Pos"], 0, disorder_gene["Confidence"].fillna(0),
|
|
668
|
+
zorder=2, color=sns.color_palette("pastel")[4], alpha=0.6)
|
|
669
|
+
|
|
670
|
+
|
|
671
|
+
axes[ax].plot(disorder_gene["Pos"], disorder_gene["Confidence"],
|
|
672
|
+
label="Confidence", zorder=3, color=sns.color_palette("tab10")[4], lw=0.5)
|
|
673
|
+
axes[ax].set_ylabel('pLDDT\n(disorder)', fontsize=13.5, rotation=0, va='center')
|
|
674
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
675
|
+
axes[ax].set_ylim(-10, 110)
|
|
676
|
+
|
|
677
|
+
# Plot pACC
|
|
678
|
+
# ---------
|
|
679
|
+
if "pacc" in annotations:
|
|
680
|
+
ax = annotations.index("pacc")
|
|
681
|
+
|
|
682
|
+
# axes[ax+5].fill_between(pos_result_gene['Pos'], 0, 100, where=((pos_result_gene["C"] == 0) | (pos_result_gene["C"] == 2)),
|
|
683
|
+
# color='#ffd8b1', alpha=0.6)
|
|
684
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, 100, where=(pos_result_gene['C'] == 1),
|
|
685
|
+
color='white', lw=2)
|
|
686
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, 100, where=(pos_result_gene['C'] == 1),
|
|
687
|
+
color='skyblue', alpha=0.4, lw=2)
|
|
688
|
+
axes[ax].fill_between(pdb_tool_gene["Pos"], 0, pdb_tool_gene["pACC"].fillna(0),
|
|
689
|
+
zorder=2, color="white")
|
|
690
|
+
axes[ax].fill_between(pdb_tool_gene["Pos"], 0, pdb_tool_gene["pACC"].fillna(0),
|
|
691
|
+
zorder=2, color=sns.color_palette("pastel")[4], alpha=0.6)
|
|
692
|
+
axes[ax].plot(pdb_tool_gene['Pos'], pdb_tool_gene["pACC"].fillna(0),
|
|
693
|
+
label="pACC", zorder=3, color=sns.color_palette("tab10")[4], lw=0.5)
|
|
694
|
+
axes[ax].set_ylabel('Solvent\naccessibility', fontsize=13.5, rotation=0, va='center')
|
|
695
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
696
|
+
axes[ax].set_ylim(-10, 110)
|
|
697
|
+
|
|
698
|
+
# Plot stability change
|
|
699
|
+
# ---------------------
|
|
700
|
+
if "ddg" in annotations:
|
|
701
|
+
ax = annotations.index("ddg")
|
|
702
|
+
|
|
703
|
+
max_value, min_value = pos_result_gene["DDG"].max(), pos_result_gene["DDG"].min()
|
|
704
|
+
# axes[ax+6].fill_between(pos_result_gene['Pos'], min_value, max_value, where=((pos_result_gene["C"] == 0) | (pos_result_gene["C"] == 2)),
|
|
705
|
+
# color='#ffd8b1', alpha=0.6)
|
|
706
|
+
if sum(pos_result_gene['C'] == 1) > 0:
|
|
707
|
+
axes[ax].fill_between(pos_result_gene['Pos'], min_value, max_value, where=(pos_result_gene['C'] == 1),
|
|
708
|
+
color='white', lw=2)
|
|
709
|
+
axes[ax].fill_between(pos_result_gene['Pos'], min_value, max_value, where=(pos_result_gene['C'] == 1),
|
|
710
|
+
color='skyblue', alpha=0.4, lw=2)
|
|
711
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, pos_result_gene["DDG"], zorder=1,
|
|
712
|
+
color="white")
|
|
713
|
+
axes[ax].fill_between(pos_result_gene['Pos'], 0, pos_result_gene["DDG"], zorder=1,
|
|
714
|
+
color=sns.color_palette("pastel")[4], alpha=0.6)
|
|
715
|
+
axes[ax].plot(pos_result_gene['Pos'], pos_result_gene["DDG"],
|
|
716
|
+
label="Stability change", zorder=2, color=sns.color_palette("tab10")[4], lw=0.5)
|
|
717
|
+
axes[ax].set_ylabel('ΔΔG (kcal/mol)', fontsize=13.5, rotation=0, va='center')
|
|
718
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
719
|
+
|
|
720
|
+
# PTM
|
|
721
|
+
# --------------
|
|
722
|
+
if "ptm" in annotations:
|
|
723
|
+
ax = annotations.index("ptm")
|
|
724
|
+
|
|
725
|
+
ptm_gene = uni_feat_gene[uni_feat_gene["Type"] == "PTM"]
|
|
726
|
+
ptm_names = ptm_gene["Description"].unique()
|
|
727
|
+
sb_width = 0.5
|
|
728
|
+
max_value = (len(ptm_names) * sb_width) - 0.2
|
|
729
|
+
min_value = - 0.3
|
|
730
|
+
|
|
731
|
+
# axes[ax].fill_between(pos_result_gene['Pos'], min_value, max_value, where=((pos_result_gene["C"] == 0) | (pos_result_gene["C"] == 2)),
|
|
732
|
+
# color='#ffd8b1', alpha=0.6, label='Mutated not *')
|
|
733
|
+
axes[ax].fill_between(pos_result_gene['Pos'], min_value, max_value, where=(pos_result_gene['C'] == 1),
|
|
734
|
+
color='white', lw=2)
|
|
735
|
+
axes[ax].fill_between(pos_result_gene['Pos'], min_value, max_value, where=(pos_result_gene['C'] == 1),
|
|
736
|
+
color='skyblue', alpha=0.4, label='Mutated *', lw=2)
|
|
737
|
+
|
|
738
|
+
for n, name in enumerate(ptm_names):
|
|
739
|
+
c = sns.color_palette("tab10")[n]
|
|
740
|
+
ptm = ptm_gene[ptm_gene["Description"] == name]
|
|
741
|
+
ptm_pos = ptm.Begin.values
|
|
742
|
+
axes[ax].scatter(ptm_pos, np.repeat(n*sb_width, len(ptm_pos)), label=name, alpha=0.7, color=c) #label=name
|
|
743
|
+
axes[ax].hlines(y=n*sb_width, xmin=0, xmax=gene_len, linewidth=1, color='lightgray', alpha=0.7, zorder=0)
|
|
744
|
+
|
|
745
|
+
axes[ax].set_ylim(min_value, max_value)
|
|
746
|
+
y_ticks_positions = sb_width * np.arange(len(ptm_names))
|
|
747
|
+
axes[ax].set_yticks(y_ticks_positions)
|
|
748
|
+
axes[ax].set_yticklabels(ptm_names)
|
|
749
|
+
axes[ax].set_ylabel(' PTM ', fontsize=13.5, rotation=0, va='center')
|
|
750
|
+
|
|
751
|
+
# SITES
|
|
752
|
+
# --------------
|
|
753
|
+
if "site" in annotations:
|
|
754
|
+
ax = annotations.index("site")
|
|
755
|
+
|
|
756
|
+
site_gene = uni_feat_gene[uni_feat_gene["Type"] == "SITE"]
|
|
757
|
+
site_names = site_gene["Description"].unique()
|
|
758
|
+
sb_width = 0.5
|
|
759
|
+
max_value = (len(site_names) * sb_width) - 0.2
|
|
760
|
+
min_value = - 0.3
|
|
761
|
+
|
|
762
|
+
# axes[ax+8].fill_between(pos_result_gene['Pos'], min_value, max_value, where=((pos_result_gene["C"] == 0) | (pos_result_gene["C"] == 2)),
|
|
763
|
+
# color='#ffd8b1', alpha=0.6, label='Mutated not *')
|
|
764
|
+
axes[ax].fill_between(pos_result_gene['Pos'], min_value, max_value, where=(pos_result_gene['C'] == 1),
|
|
765
|
+
color='white', lw=2)
|
|
766
|
+
axes[ax].fill_between(pos_result_gene['Pos'], min_value, max_value, where=(pos_result_gene['C'] == 1),
|
|
767
|
+
color='skyblue', alpha=0.4, label='Mutated *', lw=2)
|
|
768
|
+
|
|
769
|
+
for n, name in enumerate(site_names):
|
|
770
|
+
c = sns.color_palette("tab10")[n]
|
|
771
|
+
site_df = site_gene[site_gene["Description"] == name]
|
|
772
|
+
site_pos = get_site_pos(site_df)
|
|
773
|
+
axes[ax].scatter(site_pos, np.repeat(n*sb_width, len(site_pos)), label=name, alpha=0.7, color=c)
|
|
774
|
+
axes[ax].hlines(y=n*sb_width, xmin=0, xmax=gene_len, linewidth=1, color='lightgray', alpha=0.7, zorder=0)
|
|
775
|
+
|
|
776
|
+
axes[ax].set_ylim(min_value, max_value)
|
|
777
|
+
y_ticks_positions = sb_width * np.arange(len(site_names))
|
|
778
|
+
axes[ax].set_yticks(y_ticks_positions)
|
|
779
|
+
axes[ax].set_yticklabels(site_names)
|
|
780
|
+
axes[ax].set_ylabel('Site ', fontsize=13.5, rotation=0, va='center')
|
|
781
|
+
|
|
782
|
+
# Clusters label
|
|
783
|
+
# --------------
|
|
784
|
+
if "clusters" in annotations:
|
|
785
|
+
ax = annotations.index("clusters")
|
|
786
|
+
|
|
787
|
+
clusters_label = pos_result_gene.Clump.dropna().unique()
|
|
788
|
+
palette = sns.color_palette(cc.glasbey, n_colors=len(clusters_label))
|
|
789
|
+
for i, cluster in enumerate(clusters_label):
|
|
790
|
+
axes[ax].fill_between(pos_result_gene['Pos'], -0.5, 0.46,
|
|
791
|
+
where=((pos_result_gene['Clump'] == cluster) & (pos_result_gene['C'] == 1)),
|
|
792
|
+
color=palette[i], lw=0.4) # alpha=0.6
|
|
793
|
+
axes[ax].set_ylabel('Clumps', fontsize=13.5, rotation=0, va='center')
|
|
794
|
+
axes[ax].set_yticks([])
|
|
795
|
+
axes[ax
|
|
796
|
+
].set_yticklabels([], fontsize=12)
|
|
797
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
798
|
+
|
|
799
|
+
# Secondary structure
|
|
800
|
+
# -------------------
|
|
801
|
+
if "sse" in annotations:
|
|
802
|
+
ax = annotations.index("sse")
|
|
803
|
+
|
|
804
|
+
for i, sse in enumerate(['Helix', 'Ladder', 'Coil']):
|
|
805
|
+
c = 0+i
|
|
806
|
+
ya, yb = c-plot_pars["sse_fill_width"], c+plot_pars["sse_fill_width"]
|
|
807
|
+
axes[ax].fill_between(pdb_tool_gene["Pos"].values, ya, yb, where=(pdb_tool_gene["SSE"] == sse),
|
|
808
|
+
color=sns.color_palette("tab10")[7+i], label=sse)
|
|
809
|
+
axes[ax].set_yticks([0, 1, 2])
|
|
810
|
+
axes[ax].set_yticklabels(['Helix', 'Ladder', 'Coil'], fontsize=10)
|
|
811
|
+
axes[ax].set_ylabel('SSE', fontsize=13.5, rotation=0, va='center')
|
|
812
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
813
|
+
|
|
814
|
+
# Pfam
|
|
815
|
+
# ----
|
|
816
|
+
if "pfam" in annotations:
|
|
817
|
+
ax = annotations.index("pfam")
|
|
818
|
+
|
|
819
|
+
pfam_gene = uni_feat_gene[(uni_feat_gene["Type"] == "DOMAIN") & (uni_feat_gene["Evidence"] == "Pfam")]
|
|
820
|
+
pfam_gene = pfam_gene.sort_values("Begin").reset_index(drop=True)
|
|
821
|
+
pfam_color_dict = {}
|
|
822
|
+
|
|
823
|
+
for n, name in enumerate(pfam_gene["Description"].unique()):
|
|
824
|
+
pfam_color_dict[name] = f"C{n}"
|
|
825
|
+
|
|
826
|
+
n = 0
|
|
827
|
+
added_pfam = []
|
|
828
|
+
for i, row in pfam_gene.iterrows():
|
|
829
|
+
if pd.Series([row["Description"], row["Begin"], row["End"]]).isnull().any():
|
|
830
|
+
continue
|
|
831
|
+
|
|
832
|
+
name = row["Description"]
|
|
833
|
+
start = int(row["Begin"])
|
|
834
|
+
end = int(row["End"])
|
|
835
|
+
axes[ax].fill_between(range(start, end+1), -0.45, 0.45, alpha=0.5, color=pfam_color_dict[name])
|
|
836
|
+
if name not in added_pfam:
|
|
837
|
+
if near_pfam:
|
|
838
|
+
n += 1
|
|
839
|
+
if n == 1:
|
|
840
|
+
y = 0.28
|
|
841
|
+
elif n == 2:
|
|
842
|
+
y = 0
|
|
843
|
+
elif n == 3:
|
|
844
|
+
y = -0.295
|
|
845
|
+
n = 0
|
|
846
|
+
else:
|
|
847
|
+
y = -0.04
|
|
848
|
+
axes[ax].text(((start + end) / 2)+0.5, y, name, ha='center', va='center', fontsize=10, color="black")
|
|
849
|
+
added_pfam.append(name)
|
|
850
|
+
axes[ax].set_yticks([])
|
|
851
|
+
axes[ax].set_yticklabels([], fontsize=12)
|
|
852
|
+
axes[ax].set_ylabel('Pfam', fontsize=13.5, rotation=0, va='center')
|
|
853
|
+
axes[ax].set_ylim(-0.5, 0.5)
|
|
854
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
855
|
+
|
|
856
|
+
# Prosite
|
|
857
|
+
# -------
|
|
858
|
+
if "prosite" in annotations:
|
|
859
|
+
ax = annotations.index("prosite")
|
|
860
|
+
|
|
861
|
+
prosite_gene = uni_feat_gene[(uni_feat_gene["Type"] == "DOMAIN") & (uni_feat_gene["Evidence"] != "Pfam")]
|
|
862
|
+
|
|
863
|
+
prosite_gene = prosite_gene.sort_values("Begin").reset_index(drop=True)
|
|
864
|
+
prosite_color_dict = {}
|
|
865
|
+
|
|
866
|
+
for n, name in enumerate(prosite_gene["Description"].unique()):
|
|
867
|
+
prosite_color_dict[name] = f"C{n}"
|
|
868
|
+
|
|
869
|
+
n = 0
|
|
870
|
+
added_prosite = []
|
|
871
|
+
for i, row in prosite_gene.iterrows():
|
|
872
|
+
if pd.Series([row["Description"], row["Begin"], row["End"]]).isnull().any():
|
|
873
|
+
continue
|
|
874
|
+
|
|
875
|
+
name = row["Description"]
|
|
876
|
+
start = int(row["Begin"])
|
|
877
|
+
end = int(row["End"])
|
|
878
|
+
axes[ax].fill_between(range(start, end+1), -0.45, 0.45, alpha=0.5, color=prosite_color_dict[name])
|
|
879
|
+
if name not in added_prosite:
|
|
880
|
+
if near_prosite:
|
|
881
|
+
n += 1
|
|
882
|
+
if n == 1:
|
|
883
|
+
y = 0.28
|
|
884
|
+
elif n == 2:
|
|
885
|
+
y = 0
|
|
886
|
+
elif n == 3:
|
|
887
|
+
y = -0.295
|
|
888
|
+
n = 0
|
|
889
|
+
else:
|
|
890
|
+
y = -0.04
|
|
891
|
+
axes[ax].text(((start + end) / 2)+0.5, y, name, ha='center', va='center', fontsize=10, color="black")
|
|
892
|
+
added_prosite.append(name)
|
|
893
|
+
axes[ax].set_yticks([])
|
|
894
|
+
axes[ax].set_yticklabels([], fontsize=12)
|
|
895
|
+
axes[ax].set_ylabel('Prosite', fontsize=13.5, rotation=0, va='center')
|
|
896
|
+
axes[ax].set_ylim(-0.5, 0.5)
|
|
897
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
898
|
+
|
|
899
|
+
# Membrane
|
|
900
|
+
# --------
|
|
901
|
+
if "membrane" in annotations:
|
|
902
|
+
ax = annotations.index("membrane")
|
|
903
|
+
|
|
904
|
+
membrane_gene = uni_feat_gene[(uni_feat_gene["Type"] == "MEMBRANE")]
|
|
905
|
+
membrane_color_dict = {}
|
|
906
|
+
|
|
907
|
+
for n, name in enumerate(membrane_gene["Description"].unique()):
|
|
908
|
+
membrane_color_dict[name] = f"C{n}"
|
|
909
|
+
|
|
910
|
+
n = 0
|
|
911
|
+
added_membrane = []
|
|
912
|
+
for i, row in membrane_gene.iterrows():
|
|
913
|
+
if pd.Series([row["Description"], row["Begin"], row["End"]]).isnull().any():
|
|
914
|
+
continue
|
|
915
|
+
|
|
916
|
+
name = row["Description"]
|
|
917
|
+
start = int(row["Begin"])
|
|
918
|
+
end = int(row["End"])
|
|
919
|
+
axes[ax].fill_between(range(start, end+1), -0.45, 0.45, alpha=0.5, color=membrane_color_dict[name])
|
|
920
|
+
if name not in added_membrane:
|
|
921
|
+
y = -0.04
|
|
922
|
+
axes[ax].text(((start + end) / 2)+0.5, y, name, ha='center', va='center', fontsize=10, color="black")
|
|
923
|
+
added_membrane.append(name)
|
|
924
|
+
axes[ax].set_yticks([])
|
|
925
|
+
axes[ax].set_yticklabels([], fontsize=12)
|
|
926
|
+
axes[ax].set_ylabel('Membrane', fontsize=13.5, rotation=0, va='center')
|
|
927
|
+
axes[ax].set_ylim(-0.5, 0.5)
|
|
928
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
929
|
+
|
|
930
|
+
# Motifs
|
|
931
|
+
# ------
|
|
932
|
+
if "motif" in annotations:
|
|
933
|
+
ax = annotations.index("motif")
|
|
934
|
+
|
|
935
|
+
motif_gene = uni_feat_gene[(uni_feat_gene["Type"] == "MOTIF")]
|
|
936
|
+
|
|
937
|
+
motif_gene = motif_gene.sort_values("Begin").reset_index(drop=True)
|
|
938
|
+
motif_color_dict = {}
|
|
939
|
+
|
|
940
|
+
for n, name in enumerate(motif_gene["Full_description"].unique()):
|
|
941
|
+
motif_color_dict[name] = f"C{n}"
|
|
942
|
+
|
|
943
|
+
n = 0
|
|
944
|
+
added_motif = []
|
|
945
|
+
for i, row in motif_gene.iterrows():
|
|
946
|
+
if pd.Series([row["Full_description"], row["Begin"], row["End"]]).isnull().any():
|
|
947
|
+
continue
|
|
948
|
+
|
|
949
|
+
name = row["Full_description"]
|
|
950
|
+
start = int(row["Begin"])
|
|
951
|
+
end = int(row["End"])
|
|
952
|
+
axes[ax].fill_between(range(start, end+1), -0.45, 0.45, alpha=0.5, color=motif_color_dict[name])
|
|
953
|
+
if name not in added_motif:
|
|
954
|
+
if near_motif:
|
|
955
|
+
n += 1
|
|
956
|
+
if n == 1:
|
|
957
|
+
y = 0.28
|
|
958
|
+
elif n == 2:
|
|
959
|
+
y = 0
|
|
960
|
+
elif n == 3:
|
|
961
|
+
y = -0.295
|
|
962
|
+
n = 0
|
|
963
|
+
else:
|
|
964
|
+
y = -0.04
|
|
965
|
+
axes[ax].text(((start + end) / 2)+0.5, y, name, ha='center', va='center', fontsize=10, color="black")
|
|
966
|
+
added_motif.append(name)
|
|
967
|
+
axes[ax].set_yticks([])
|
|
968
|
+
axes[ax].set_yticklabels([], fontsize=12)
|
|
969
|
+
axes[ax].set_ylabel('Motif', fontsize=13.5, rotation=0, va='center')
|
|
970
|
+
axes[ax].set_ylim(-0.5, 0.5)
|
|
971
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
972
|
+
|
|
973
|
+
axes[len(axes)-1].set_xlabel(None)
|
|
974
|
+
|
|
975
|
+
# Save
|
|
976
|
+
# ====
|
|
977
|
+
if title:
|
|
978
|
+
fig.suptitle(f'{title}\n{gene} - {uni_id}', fontsize=16)
|
|
979
|
+
else:
|
|
980
|
+
fig.suptitle(f'{gene} - {uni_id}', fontsize=16)
|
|
981
|
+
filename = f"{cohort}.genes_plot_{j+1}.{gene}_{uni_id}.png"
|
|
982
|
+
output_path = os.path.join(output_dir, filename)
|
|
983
|
+
htop = 0.947
|
|
984
|
+
if title:
|
|
985
|
+
htop -= 0.018
|
|
986
|
+
plt.subplots_adjust(top=htop)
|
|
987
|
+
|
|
988
|
+
if save_plot:
|
|
989
|
+
plt.savefig(output_path, dpi=300, bbox_inches='tight')
|
|
990
|
+
logger.debug(f"Saved {output_path}")
|
|
991
|
+
if show_plot:
|
|
992
|
+
plt.show()
|
|
993
|
+
plt.close()
|
|
994
|
+
|
|
995
|
+
# Store annotated result
|
|
996
|
+
pos_result_gene = get_enriched_result(pos_result_gene,
|
|
997
|
+
disorder_gene,
|
|
998
|
+
pdb_tool_gene,
|
|
999
|
+
seq_df)
|
|
1000
|
+
annotated_result_lst.append(pos_result_gene)
|
|
1001
|
+
uni_feat_result_lst.append(uni_feat_gene)
|
|
1002
|
+
|
|
1003
|
+
pos_result_annotated = pd.concat(annotated_result_lst)
|
|
1004
|
+
feat_processed = pd.concat(uni_feat_result_lst)
|
|
1005
|
+
|
|
1006
|
+
return pos_result_annotated, feat_processed
|
|
1007
|
+
|
|
1008
|
+
|
|
1009
|
+
# Comparative plots
|
|
1010
|
+
# =================
|
|
1011
|
+
|
|
1012
|
+
def comparative_plots(shared_genes,
|
|
1013
|
+
pos_result_1,
|
|
1014
|
+
maf_1,
|
|
1015
|
+
maf_nonmiss_1,
|
|
1016
|
+
miss_prob_dict_1,
|
|
1017
|
+
cohort_1,
|
|
1018
|
+
pos_result_2,
|
|
1019
|
+
maf_2,
|
|
1020
|
+
maf_nonmiss_2,
|
|
1021
|
+
miss_prob_dict_2,
|
|
1022
|
+
cohort_2,
|
|
1023
|
+
seq_df,
|
|
1024
|
+
output_dir,
|
|
1025
|
+
annotations_dir,
|
|
1026
|
+
disorder,
|
|
1027
|
+
uniprot_feat,
|
|
1028
|
+
pdb_tool,
|
|
1029
|
+
plot_pars,
|
|
1030
|
+
save_plot=True,
|
|
1031
|
+
show_plot=False):
|
|
1032
|
+
"""
|
|
1033
|
+
Generate plot to compare each gene that are processed in both 3D-clustering analysis.
|
|
1034
|
+
"""
|
|
1035
|
+
|
|
1036
|
+
warnings.filterwarnings("ignore", category=UserWarning)
|
|
1037
|
+
|
|
1038
|
+
for j, gene in enumerate(shared_genes):
|
|
1039
|
+
|
|
1040
|
+
logger.debug(f"Generating comparative plots for {len(shared_genes)} genes..")
|
|
1041
|
+
|
|
1042
|
+
# Load and parse
|
|
1043
|
+
# ==============
|
|
1044
|
+
|
|
1045
|
+
uni_id = seq_df[seq_df["Gene"] == gene].Uniprot_ID.values[0]
|
|
1046
|
+
af_f = seq_df[seq_df["Gene"] == gene].F.values[0]
|
|
1047
|
+
gene_len = len(seq_df[seq_df["Gene"] == gene].Seq.values[0])
|
|
1048
|
+
maf_gene_1 = maf_1[maf_1["Gene"] == gene]
|
|
1049
|
+
maf_gene_2 = maf_2[maf_2["Gene"] == gene]
|
|
1050
|
+
|
|
1051
|
+
# Parse
|
|
1052
|
+
pos_result_gene_1 = pos_result_1[pos_result_1["Gene"] == gene].sort_values("Pos").reset_index(drop=True)
|
|
1053
|
+
pos_result_gene_2 = pos_result_2[pos_result_2["Gene"] == gene].sort_values("Pos").reset_index(drop=True)
|
|
1054
|
+
|
|
1055
|
+
if len(pos_result_gene_1) > 0 and len(pos_result_gene_2) > 0:
|
|
1056
|
+
pos_result_gene_1 = pos_result_gene_1[["Pos", "Mut_in_res", "Mut_in_vol",
|
|
1057
|
+
"Score_obs_sim", "C", "C_ext",
|
|
1058
|
+
"pval", "Clump", "PAE_vol"]]
|
|
1059
|
+
pos_result_gene_2 = pos_result_gene_2[["Pos", "Mut_in_res", "Mut_in_vol",
|
|
1060
|
+
"Score_obs_sim", "C", "C_ext",
|
|
1061
|
+
"pval", "Clump", "PAE_vol"]]
|
|
1062
|
+
pos_result_gene_1, max_mut_1 = parse_pos_result_for_genes_plot(pos_result_gene_1)
|
|
1063
|
+
pos_result_gene_2, max_mut_2 = parse_pos_result_for_genes_plot(pos_result_gene_2)
|
|
1064
|
+
|
|
1065
|
+
# Counts
|
|
1066
|
+
mut_count_1, mut_count_nonmiss_1 = get_count_for_genes_plot(maf_gene_1,
|
|
1067
|
+
maf_nonmiss_1,
|
|
1068
|
+
gene,
|
|
1069
|
+
non_missense_count="nonmiss_count" in plot_pars["h_ratios"])
|
|
1070
|
+
mut_count_2, mut_count_nonmiss_2 = get_count_for_genes_plot(maf_gene_2,
|
|
1071
|
+
maf_nonmiss_2,
|
|
1072
|
+
gene,
|
|
1073
|
+
non_missense_count="nonmiss_count" in plot_pars["h_ratios"])
|
|
1074
|
+
|
|
1075
|
+
# Get prob vec
|
|
1076
|
+
prob_vec_1 = np.array(miss_prob_dict_1[f"{uni_id}-F{af_f}"])
|
|
1077
|
+
prob_vec_2 = np.array(miss_prob_dict_2[f"{uni_id}-F{af_f}"])
|
|
1078
|
+
|
|
1079
|
+
# Get per-pos score and normalize score
|
|
1080
|
+
pos_result_gene_1, score_vec_1, score_norm_vec_1 = get_score_for_genes_plot(pos_result_gene_1,
|
|
1081
|
+
mut_count_1,
|
|
1082
|
+
prob_vec_1)
|
|
1083
|
+
pos_result_gene_2, score_vec_2, score_norm_vec_2 = get_score_for_genes_plot(pos_result_gene_2,
|
|
1084
|
+
mut_count_2,
|
|
1085
|
+
prob_vec_2)
|
|
1086
|
+
|
|
1087
|
+
# Get annotations
|
|
1088
|
+
pos_result_gene_1, disorder_gene, pdb_tool_gene, uni_feat_gene = get_id_annotations(uni_id,
|
|
1089
|
+
pos_result_gene_1,
|
|
1090
|
+
maf_gene_1,
|
|
1091
|
+
annotations_dir,
|
|
1092
|
+
disorder,
|
|
1093
|
+
pdb_tool,
|
|
1094
|
+
uniprot_feat)
|
|
1095
|
+
pos_result_gene_2, _, _, _ = get_id_annotations(uni_id,
|
|
1096
|
+
pos_result_gene_2,
|
|
1097
|
+
maf_gene_2,
|
|
1098
|
+
annotations_dir,
|
|
1099
|
+
disorder,
|
|
1100
|
+
pdb_tool,
|
|
1101
|
+
uniprot_feat)
|
|
1102
|
+
|
|
1103
|
+
# Pos result for background filling
|
|
1104
|
+
pos_result_gene_shared = pos_result_gene_1.copy()
|
|
1105
|
+
pos_result_gene_shared["C"] = np.nan
|
|
1106
|
+
pos_result_gene_shared["C_A"] = pos_result_gene_1["C"]
|
|
1107
|
+
pos_result_gene_shared["C_B"] = pos_result_gene_2["C"]
|
|
1108
|
+
pos_result_gene_shared["C"] = pos_result_gene_shared.apply(lambda x:
|
|
1109
|
+
"A" if x.C_A == 1 and x.C_B != 1 else
|
|
1110
|
+
"B" if x.C_A != 1 and x.C_B == 1 else
|
|
1111
|
+
"AB" if x.C_A == 1 and x.C_B == 1 else np.nan, axis=1)
|
|
1112
|
+
|
|
1113
|
+
# Generate plot
|
|
1114
|
+
# =============
|
|
1115
|
+
|
|
1116
|
+
if not maf_nonmiss_1 or not maf_nonmiss_2:
|
|
1117
|
+
maf_nonmiss = None
|
|
1118
|
+
else:
|
|
1119
|
+
maf_nonmiss = maf_nonmiss_1
|
|
1120
|
+
h_ratios, near_pfam, near_prosite, near_motif = get_gene_arg(pd.concat((pos_result_gene_1, pos_result_gene_2)),
|
|
1121
|
+
plot_pars,
|
|
1122
|
+
uni_feat_gene,
|
|
1123
|
+
maf_nonmiss)
|
|
1124
|
+
annotations = list(h_ratios.keys())
|
|
1125
|
+
|
|
1126
|
+
fig, axes = plt.subplots(len(h_ratios), 1,
|
|
1127
|
+
figsize=plot_pars["figsize"],
|
|
1128
|
+
sharex=True,
|
|
1129
|
+
gridspec_kw={'hspace': 0.1,
|
|
1130
|
+
'height_ratios': h_ratios.values()})
|
|
1131
|
+
|
|
1132
|
+
|
|
1133
|
+
# Plot for Non-missense mut track ## TO DO: Enable not mirror for non-missense
|
|
1134
|
+
# -------------------------------
|
|
1135
|
+
if "nonmiss_count" in annotations:
|
|
1136
|
+
ax = annotations.index("nonmiss_count")
|
|
1137
|
+
|
|
1138
|
+
if len(mut_count_nonmiss_1.Consequence.unique()) > 6:
|
|
1139
|
+
ncol = 3
|
|
1140
|
+
else:
|
|
1141
|
+
ncol = 2
|
|
1142
|
+
i = 0
|
|
1143
|
+
axes[ax].vlines(mut_count_nonmiss_1["Pos"], ymin=0, ymax=mut_count_nonmiss_1["Count"],
|
|
1144
|
+
color="gray", lw=0.7, zorder=0, alpha=0.5) # To cover the overlapping needle top part
|
|
1145
|
+
axes[ax].scatter(mut_count_nonmiss_1["Pos"], mut_count_nonmiss_1["Count"], color='white', zorder=4, lw=plot_pars["s_lw"])
|
|
1146
|
+
for cnsq in mut_count_nonmiss_1.Consequence.unique():
|
|
1147
|
+
count_cnsq = mut_count_nonmiss_1[mut_count_nonmiss_1["Consequence"] == cnsq]
|
|
1148
|
+
if cnsq == "synonymous_variant":
|
|
1149
|
+
order = 1
|
|
1150
|
+
else:
|
|
1151
|
+
order = 2
|
|
1152
|
+
if cnsq in plot_pars["color_cnsq"]:
|
|
1153
|
+
color = plot_pars["color_cnsq"][cnsq]
|
|
1154
|
+
else:
|
|
1155
|
+
color=sns.color_palette("tab10")[i]
|
|
1156
|
+
i+=1
|
|
1157
|
+
axes[ax].scatter(count_cnsq.Pos.values, count_cnsq.Count.values, label=capitalize(cnsq),
|
|
1158
|
+
color=color, zorder=order, alpha=0.7, lw=plot_pars["s_lw"], ec="black") # ec="black",
|
|
1159
|
+
axes[ax].legend(fontsize=11.5, ncol=ncol, framealpha=0.75)
|
|
1160
|
+
axes[ax].set_ylabel('Non\nmissense\nmutations', fontsize=13.5, rotation=0, va='center')
|
|
1161
|
+
ymargin = max(max(mut_count_nonmiss_1["Count"]), max(mut_count_nonmiss_2["Count"])) * 0.1
|
|
1162
|
+
axes[ax].set_ylim(-(max(mut_count_nonmiss_1["Count"])-ymargin), max(mut_count_nonmiss_1["Count"])+ymargin)
|
|
1163
|
+
|
|
1164
|
+
|
|
1165
|
+
# Plot for Missense mut track
|
|
1166
|
+
# ---------------------------
|
|
1167
|
+
mut_pos_1 = pos_result_gene_1[pos_result_gene_1["Mut_in_res"] > 0].Pos.values
|
|
1168
|
+
mut_res_pos_1 = pos_result_gene_1[pos_result_gene_1["Mut_in_res"] > 0].Mut_in_res.values
|
|
1169
|
+
mut_pos_2 = pos_result_gene_2[pos_result_gene_2["Mut_in_res"] > 0].Pos.values
|
|
1170
|
+
mut_res_pos_2 = pos_result_gene_2[pos_result_gene_2["Mut_in_res"] > 0].Mut_in_res.values
|
|
1171
|
+
|
|
1172
|
+
if plot_pars["count_mirror"]:
|
|
1173
|
+
if "miss_count" in annotations:
|
|
1174
|
+
ax = annotations.index("miss_count")
|
|
1175
|
+
|
|
1176
|
+
axes[ax].hlines(0, xmin=0, xmax=gene_len, color="gray", lw=0.6, zorder=1)
|
|
1177
|
+
axes[ax].vlines(mut_count_1["Pos"], ymin=0, ymax=mut_count_1["Count"], color="gray", lw=0.7, zorder=1, alpha=0.5) # A
|
|
1178
|
+
axes[ax].vlines(mut_count_2["Pos"], ymin=-mut_count_2["Count"], ymax=0, color="gray", lw=0.7, zorder=1, alpha=0.5) # B
|
|
1179
|
+
|
|
1180
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], 0, 0, where=(pos_result_gene_1['C'] == "NA"),
|
|
1181
|
+
color=sns.color_palette("pastel")[2], alpha=0.4, label='Position in cluster A', zorder=0, lw=2) # Just for the legend
|
|
1182
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], 0, 0, where=(pos_result_gene_1['C'] == "NA"),
|
|
1183
|
+
color=sns.color_palette("pastel")[3], alpha=0.4, label='Position in cluster B', zorder=0, lw=2) # Just for the legend
|
|
1184
|
+
axes[ax].fill_between(pos_result_gene_shared['Pos'], -max_mut_2, max_mut_1,
|
|
1185
|
+
where=(pos_result_gene_shared['C'] == "A") | (pos_result_gene_shared['C'] == "B") | (pos_result_gene_shared['C'] == "AB"),
|
|
1186
|
+
color='skyblue', alpha=0.4, label='Position in cluster A or B', zorder=0, lw=2)
|
|
1187
|
+
|
|
1188
|
+
axes[ax].scatter(mut_pos_1, mut_res_pos_1, color='white', zorder=3, lw=plot_pars["s_lw"], ec="white") # A
|
|
1189
|
+
axes[ax].scatter(mut_pos_2, -mut_res_pos_2, color='white', zorder=3, lw=plot_pars["s_lw"], ec="white") # B
|
|
1190
|
+
|
|
1191
|
+
axes[ax].scatter(mut_pos_1, mut_res_pos_1, color="C2", zorder=4, alpha=0.6, # A
|
|
1192
|
+
lw=plot_pars["s_lw"], ec="black", s=60, label='Cohort A')
|
|
1193
|
+
axes[ax].scatter(mut_pos_2, -mut_res_pos_2, color="tomato", zorder=4, alpha=0.6, # B
|
|
1194
|
+
lw=plot_pars["s_lw"], ec="black", s=60, label='Cohort B')
|
|
1195
|
+
|
|
1196
|
+
|
|
1197
|
+
legend = axes[ax].legend(fontsize=11.5, ncol=2, framealpha=0.75, bbox_to_anchor=(0.95, 2.3),
|
|
1198
|
+
borderaxespad=0., loc='upper right')
|
|
1199
|
+
legend.set_title("Global legend")
|
|
1200
|
+
legend.get_title().set_fontsize(12)
|
|
1201
|
+
|
|
1202
|
+
axes[ax].set_ylabel('Missense\nmutations', fontsize=13.5, rotation=0, va='center')
|
|
1203
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1204
|
+
ymargin = max(max(mut_res_pos_2), max(mut_res_pos_1)) * 0.1
|
|
1205
|
+
axes[ax].set_ylim(-max(mut_res_pos_2)-ymargin, max(mut_res_pos_1)+ymargin)
|
|
1206
|
+
|
|
1207
|
+
tick_labels = [f'{abs(label):.4g}' for label in axes[ax].get_yticks()]
|
|
1208
|
+
axes[ax].set_yticklabels(tick_labels)
|
|
1209
|
+
|
|
1210
|
+
else:
|
|
1211
|
+
if "miss_count" in annotations and "miss_count_2" in annotations:
|
|
1212
|
+
|
|
1213
|
+
# A
|
|
1214
|
+
ax = annotations.index("miss_count")
|
|
1215
|
+
axes[ax].vlines(mut_count_1["Pos"], ymin=0, ymax=mut_count_1["Count"], color="gray", lw=0.7, zorder=1, alpha=0.5)
|
|
1216
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], 0, max(mut_res_pos_1), where=(pos_result_gene_1['C'] == 1),
|
|
1217
|
+
color=sns.color_palette("pastel")[2], alpha=0.4, label='Position in cluster A', zorder=0, lw=2)
|
|
1218
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], 0, 0, where=(pos_result_gene_1['C'] == "NA"),
|
|
1219
|
+
color=sns.color_palette("pastel")[3], alpha=0.4, label='Position in cluster B', zorder=0, lw=2) # Just for the legend
|
|
1220
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], 0, 0, where=(pos_result_gene_1['C'] == "NA"),
|
|
1221
|
+
color="skyblue", alpha=0.4, label='Position in cluster A or B', zorder=0, lw=2) # Just for the legend
|
|
1222
|
+
|
|
1223
|
+
axes[ax].scatter(mut_pos_1, mut_res_pos_1, color='white', zorder=3, lw=plot_pars["s_lw"], ec="white")
|
|
1224
|
+
axes[ax].scatter(mut_pos_1, mut_res_pos_1, color="C2", zorder=4, alpha=0.6,
|
|
1225
|
+
lw=plot_pars["s_lw"], ec="black", s=60, label='Cohort A')
|
|
1226
|
+
axes[ax].scatter(-20, -20, color="tomato", zorder=4, alpha=0.6, # Just for the legend
|
|
1227
|
+
lw=plot_pars["s_lw"], ec="black", s=60, label='Cohort B')
|
|
1228
|
+
|
|
1229
|
+
legend = axes[ax].legend(fontsize=11.5, ncol=2, framealpha=0.75,
|
|
1230
|
+
bbox_to_anchor=(0.95, 2.45), borderaxespad=0., loc='upper right')
|
|
1231
|
+
legend.set_title("Global legend")
|
|
1232
|
+
legend.get_title().set_fontsize(12)
|
|
1233
|
+
|
|
1234
|
+
axes[ax].set_ylabel('Missense\nmutations A', fontsize=13.5, rotation=0, va='center')
|
|
1235
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1236
|
+
ymargin = max(mut_res_pos_1) * 0.1
|
|
1237
|
+
axes[ax].set_ylim(0-ymargin, max(mut_res_pos_1)+ymargin)
|
|
1238
|
+
|
|
1239
|
+
# B
|
|
1240
|
+
ax = annotations.index("miss_count_2")
|
|
1241
|
+
axes[ax].vlines(mut_count_2["Pos"], ymin=0, ymax=mut_count_2["Count"], color="gray", lw=0.7, zorder=1, alpha=0.5)
|
|
1242
|
+
axes[ax].fill_between(pos_result_gene_2['Pos'], 0, max(mut_res_pos_2), where=(pos_result_gene_2['C'] == 1),
|
|
1243
|
+
color=sns.color_palette("pastel")[3], alpha=0.4, label='Position in cluster B', zorder=0, lw=2)
|
|
1244
|
+
axes[ax].scatter(mut_pos_2, mut_res_pos_2, color='white', zorder=3, lw=plot_pars["s_lw"], ec="white")
|
|
1245
|
+
axes[ax].scatter(mut_pos_2, mut_res_pos_2, color="tomato", zorder=4, alpha=0.6,
|
|
1246
|
+
lw=plot_pars["s_lw"], ec="black", s=60, label='Cohort B')
|
|
1247
|
+
axes[ax].set_ylabel('Missense\nmutations B', fontsize=13.5, rotation=0, va='center')
|
|
1248
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1249
|
+
ymargin = max(mut_res_pos_2) * 0.1
|
|
1250
|
+
axes[ax].set_ylim(0-ymargin, max(mut_res_pos_2)+ymargin)
|
|
1251
|
+
|
|
1252
|
+
|
|
1253
|
+
# Plot for Miss prob track
|
|
1254
|
+
# ------------------------
|
|
1255
|
+
if "miss_prob" in annotations:
|
|
1256
|
+
ax = annotations.index("miss_prob")
|
|
1257
|
+
|
|
1258
|
+
if plot_pars["prob_mirror"]:
|
|
1259
|
+
max_value = max(prob_vec_1)
|
|
1260
|
+
min_value = -max(prob_vec_2)
|
|
1261
|
+
prob_vec_2 = -np.array(prob_vec_2)
|
|
1262
|
+
else:
|
|
1263
|
+
max_value = max(max(prob_vec_2), max(prob_vec_1))
|
|
1264
|
+
min_value = 0
|
|
1265
|
+
|
|
1266
|
+
axes[ax].fill_between(pos_result_gene_shared['Pos'], min_value, max_value,
|
|
1267
|
+
where=(pos_result_gene_shared['C'] == "A") | (pos_result_gene_shared['C'] == "B") | (pos_result_gene_shared['C'] == "AB"),
|
|
1268
|
+
color='skyblue', alpha=0.4, label='Position in cluster', zorder=0, lw=2)
|
|
1269
|
+
|
|
1270
|
+
axes[ax].hlines(0, xmin=0, xmax=gene_len, color="gray", lw=0.6, zorder=1)
|
|
1271
|
+
axes[ax].plot(range(1, len(prob_vec_1)+1), prob_vec_1, label="Cohort A", zorder=3, color="C2", lw=1)
|
|
1272
|
+
axes[ax].plot(range(1, len(prob_vec_2)+1), prob_vec_2, label="Cohort B", zorder=3,
|
|
1273
|
+
color="tomato", lw=1)
|
|
1274
|
+
|
|
1275
|
+
axes[ax].set_ylabel('Missense\nmut prob', fontsize=13.5, rotation=0, va='center')
|
|
1276
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1277
|
+
if plot_pars["prob_mirror"]:
|
|
1278
|
+
tick_labels = [f'{abs(label):.4g}' for label in axes[ax].get_yticks()]
|
|
1279
|
+
axes[ax].set_yticklabels(tick_labels)
|
|
1280
|
+
|
|
1281
|
+
|
|
1282
|
+
# Plot for Score track
|
|
1283
|
+
# --------------------
|
|
1284
|
+
if plot_pars["score_mirror"]:
|
|
1285
|
+
|
|
1286
|
+
if "score" in annotations:
|
|
1287
|
+
ax = annotations.index("score")
|
|
1288
|
+
|
|
1289
|
+
max_value = np.max(score_vec_1)
|
|
1290
|
+
min_value = -np.max(score_vec_2)
|
|
1291
|
+
axes[ax].fill_between(pos_result_gene_shared['Pos'], min_value, max_value,
|
|
1292
|
+
where=(pos_result_gene_shared['C'] == "A") | (pos_result_gene_shared['C'] == "B") | (pos_result_gene_shared['C'] == "AB"),
|
|
1293
|
+
color='skyblue', alpha=0.4, label='Position in cluster', zorder=0, lw=2)
|
|
1294
|
+
axes[ax].hlines(0, xmin=0, xmax=gene_len, color="gray", lw=0.7, zorder=1)
|
|
1295
|
+
axes[ax].plot(range(1, len(prob_vec_1)+1), score_vec_1, label="Cohort A", zorder=2, color="C2", lw=1)
|
|
1296
|
+
axes[ax].plot(range(1, len(prob_vec_2)+1), -np.array(score_vec_2), label="Cohort B", zorder=2, color="tomato", lw=1)
|
|
1297
|
+
|
|
1298
|
+
axes[ax].set_ylabel('Clustering\nscore\n(obs/sim)', fontsize=13.5, rotation=0, va='center')
|
|
1299
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1300
|
+
|
|
1301
|
+
tick_labels = [f'{abs(label):.4g}' for label in axes[ax].get_yticks()]
|
|
1302
|
+
axes[ax].set_yticklabels(tick_labels)
|
|
1303
|
+
|
|
1304
|
+
else:
|
|
1305
|
+
if "score" in annotations and "score_2" in annotations:
|
|
1306
|
+
|
|
1307
|
+
# A
|
|
1308
|
+
ax = annotations.index("score")
|
|
1309
|
+
|
|
1310
|
+
max_value = np.max(score_vec_1)
|
|
1311
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], 0, max_value, where=(pos_result_gene_1['C'] == 1),
|
|
1312
|
+
color=sns.color_palette("pastel")[2], alpha=0.4, label='Position in cluster A', zorder=0, lw=2)
|
|
1313
|
+
axes[ax].plot(range(1, len(prob_vec_1)+1), score_vec_1, label="Cohort A", zorder=2, color="C2", lw=1)
|
|
1314
|
+
axes[ax].set_ylabel('Clustering\nscore A\n(obs/sim)', fontsize=13.5, rotation=0, va='center')
|
|
1315
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1316
|
+
|
|
1317
|
+
# B
|
|
1318
|
+
ax = annotations.index("score_2")
|
|
1319
|
+
|
|
1320
|
+
max_value = np.max(score_vec_2)
|
|
1321
|
+
axes[ax].fill_between(pos_result_gene_2['Pos'], 0, max_value, where=(pos_result_gene_2['C'] == 1),
|
|
1322
|
+
color=sns.color_palette("pastel")[3], alpha=0.4, label='Position in cluster B', zorder=0, lw=2)
|
|
1323
|
+
axes[ax].plot(range(1, len(prob_vec_2)+1), np.array(score_vec_2), label="Cohort B", zorder=2, color="tomato", lw=1)
|
|
1324
|
+
axes[ax].set_ylabel('Clustering\nscore B\n(obs/sim)', fontsize=13.5, rotation=0, va='center')
|
|
1325
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1326
|
+
|
|
1327
|
+
|
|
1328
|
+
# Clusters label A
|
|
1329
|
+
# ----------------
|
|
1330
|
+
|
|
1331
|
+
# A
|
|
1332
|
+
if "clusters" in annotations:
|
|
1333
|
+
ax = annotations.index("clusters")
|
|
1334
|
+
|
|
1335
|
+
clusters_label = pos_result_gene_1.Clump.dropna().unique()
|
|
1336
|
+
clusters_label_2 = pos_result_gene_2.Clump.dropna().unique()
|
|
1337
|
+
n_colors = max(len(clusters_label), len(clusters_label_2))
|
|
1338
|
+
palette = sns.color_palette(cc.glasbey, n_colors=n_colors)
|
|
1339
|
+
for i, cluster in enumerate(clusters_label):
|
|
1340
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], -0.5, 0.46,
|
|
1341
|
+
where=((pos_result_gene_1['Clump'] == cluster) & (pos_result_gene_1['C'] == 1)),
|
|
1342
|
+
color=palette[i], lw=0.4) # alpha=0.6
|
|
1343
|
+
axes[ax].set_ylabel('Clusters A ', fontsize=13.5, rotation=0, va='center')
|
|
1344
|
+
axes[ax].set_yticks([])
|
|
1345
|
+
axes[ax].yaxis.set_label_coords(-0.034, 0.5)
|
|
1346
|
+
|
|
1347
|
+
# B
|
|
1348
|
+
if "clusters_2" in annotations:
|
|
1349
|
+
ax = annotations.index("clusters_2")
|
|
1350
|
+
|
|
1351
|
+
clusters_label_2 = pos_result_gene_2.Clump.dropna().unique()
|
|
1352
|
+
for i, cluster in enumerate(clusters_label_2):
|
|
1353
|
+
axes[ax].fill_between(pos_result_gene_2['Pos'], -0.5, 0.46,
|
|
1354
|
+
where=((pos_result_gene_2['Clump'] == cluster) & (pos_result_gene_2['C'] == 1)),
|
|
1355
|
+
color=palette[i], lw=0.4) # alpha=0.6
|
|
1356
|
+
axes[ax].set_ylabel('Clusters B ', fontsize=13.5, rotation=0, va='center')
|
|
1357
|
+
axes[ax].set_yticks([])
|
|
1358
|
+
axes[ax].yaxis.set_label_coords(-0.034, 0.5)
|
|
1359
|
+
|
|
1360
|
+
|
|
1361
|
+
# Plot annotations
|
|
1362
|
+
# ================
|
|
1363
|
+
|
|
1364
|
+
# Plot PAE
|
|
1365
|
+
# --------
|
|
1366
|
+
if "pae" in annotations:
|
|
1367
|
+
ax = annotations.index("pae")
|
|
1368
|
+
|
|
1369
|
+
max_value = np.max(pos_result_gene_1["PAE_vol"])
|
|
1370
|
+
axes[ax].fill_between(pos_result_gene_shared['Pos'], 0, max_value,
|
|
1371
|
+
where=(pos_result_gene_shared['C'] == "A") | (pos_result_gene_shared['C'] == "B") | (pos_result_gene_shared['C'] == "AB"),
|
|
1372
|
+
color='skyblue', alpha=0.4, label='Position in cluster', zorder=0, lw=2)
|
|
1373
|
+
axes[ax].fill_between(pos_result_gene_1["Pos"], 0, pos_result_gene_1["PAE_vol"].fillna(0),
|
|
1374
|
+
zorder=2, color="white")
|
|
1375
|
+
axes[ax].fill_between(pos_result_gene_1["Pos"], 0, pos_result_gene_1["PAE_vol"].fillna(0),
|
|
1376
|
+
zorder=2, color=sns.color_palette("pastel")[4], alpha=0.6)
|
|
1377
|
+
axes[ax].plot(pos_result_gene_1['Pos'], pos_result_gene_1["PAE_vol"].fillna(0),
|
|
1378
|
+
label="Confidence", zorder=3, color=sns.color_palette("tab10")[4], lw=0.5)
|
|
1379
|
+
axes[ax].set_ylabel('Predicted\naligned\nerror\n(Å)', fontsize=13.5, rotation=0, va='center')
|
|
1380
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1381
|
+
|
|
1382
|
+
|
|
1383
|
+
# Plot disorder
|
|
1384
|
+
# -------------
|
|
1385
|
+
if "disorder" in annotations:
|
|
1386
|
+
ax = annotations.index("disorder")
|
|
1387
|
+
|
|
1388
|
+
axes[ax].fill_between(pos_result_gene_shared['Pos'], 0, 100,
|
|
1389
|
+
where=(pos_result_gene_shared['C'] == "A") | (pos_result_gene_shared['C'] == "B") | (pos_result_gene_shared['C'] == "AB"),
|
|
1390
|
+
color='skyblue', alpha=0.4, label='Position in cluster', zorder=0, lw=2)
|
|
1391
|
+
|
|
1392
|
+
# ## Comment out to use AF color palette
|
|
1393
|
+
|
|
1394
|
+
# af_colors = ["#1F6AD7",
|
|
1395
|
+
# "#65CBF3",
|
|
1396
|
+
# "#FFDC48",
|
|
1397
|
+
# "#FB7C44"]
|
|
1398
|
+
|
|
1399
|
+
# disorder_x, disorder_y = interpolate_x_y(disorder_gene["Pos"], disorder_gene["Confidence"])
|
|
1400
|
+
# condition_1 = disorder_y > 90
|
|
1401
|
+
# condition_2 = disorder_y <= 90
|
|
1402
|
+
# condition_3 = disorder_y <= 70
|
|
1403
|
+
# condition_4 = disorder_y <= 50
|
|
1404
|
+
# conditions = [condition_1, condition_2, condition_3, condition_4]
|
|
1405
|
+
# for color, condition in zip(af_colors, conditions):
|
|
1406
|
+
# axes[ax].fill_between(disorder_x, 0, disorder_y, where=(condition),
|
|
1407
|
+
# zorder=2, color="white")
|
|
1408
|
+
# axes[ax].fill_between(disorder_x, 0, disorder_y, where=(condition),
|
|
1409
|
+
# zorder=3, facecolor=color, alpha=0.8)
|
|
1410
|
+
|
|
1411
|
+
axes[ax].fill_between(disorder_gene["Pos"], 0, disorder_gene["Confidence"].fillna(0),
|
|
1412
|
+
zorder=2, color="white")
|
|
1413
|
+
axes[ax].fill_between(disorder_gene["Pos"], 0, disorder_gene["Confidence"].fillna(0),
|
|
1414
|
+
zorder=2, color=sns.color_palette("pastel")[4], alpha=0.6)
|
|
1415
|
+
|
|
1416
|
+
|
|
1417
|
+
axes[ax].plot(disorder_gene["Pos"], disorder_gene["Confidence"],
|
|
1418
|
+
label="Confidence", zorder=3, color=sns.color_palette("tab10")[4], lw=0.5)
|
|
1419
|
+
axes[ax].set_ylabel('pLDDT\n(disorder)', fontsize=13.5, rotation=0, va='center')
|
|
1420
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1421
|
+
axes[ax].set_ylim(-10, 110)
|
|
1422
|
+
|
|
1423
|
+
|
|
1424
|
+
# Plot pACC
|
|
1425
|
+
# ---------
|
|
1426
|
+
if "pacc" in annotations:
|
|
1427
|
+
ax = annotations.index("pacc")
|
|
1428
|
+
|
|
1429
|
+
axes[ax].fill_between(pos_result_gene_shared['Pos'], 0, 100,
|
|
1430
|
+
where=(pos_result_gene_shared['C'] == "A") | (pos_result_gene_shared['C'] == "B") | (pos_result_gene_shared['C'] == "AB"),
|
|
1431
|
+
color='skyblue', alpha=0.4, label='Position in cluster', zorder=0, lw=2)
|
|
1432
|
+
axes[ax].fill_between(pdb_tool_gene["Pos"], 0, pdb_tool_gene["pACC"].fillna(0),
|
|
1433
|
+
zorder=2, color="white")
|
|
1434
|
+
axes[ax].fill_between(pdb_tool_gene["Pos"], 0, pdb_tool_gene["pACC"].fillna(0),
|
|
1435
|
+
zorder=2, color=sns.color_palette("pastel")[4], alpha=0.6)
|
|
1436
|
+
axes[ax].plot(pdb_tool_gene['Pos'], pdb_tool_gene["pACC"].fillna(0),
|
|
1437
|
+
label="pACC", zorder=3, color=sns.color_palette("tab10")[4], lw=0.5)
|
|
1438
|
+
axes[ax].set_ylabel('Solvent\naccessibility', fontsize=13.5, rotation=0, va='center')
|
|
1439
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1440
|
+
axes[ax].set_ylim(-10, 110)
|
|
1441
|
+
|
|
1442
|
+
|
|
1443
|
+
# Plot stability change A
|
|
1444
|
+
# -----------------------
|
|
1445
|
+
if "ddg" in annotations:
|
|
1446
|
+
ax = annotations.index("ddg")
|
|
1447
|
+
|
|
1448
|
+
max_value, min_value = pos_result_gene_1["DDG"].max(), pos_result_gene_1["DDG"].min()
|
|
1449
|
+
|
|
1450
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], min_value, max_value, where=(pos_result_gene_1['C'] == 1),
|
|
1451
|
+
color=sns.color_palette("pastel")[2], alpha=0.4, label='Position in cluster A', zorder=0, lw=2)
|
|
1452
|
+
|
|
1453
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], 0, pos_result_gene_1["DDG"], zorder=1,
|
|
1454
|
+
color="white")
|
|
1455
|
+
axes[ax].fill_between(pos_result_gene_1['Pos'], 0, pos_result_gene_1["DDG"], zorder=1,
|
|
1456
|
+
color=sns.color_palette("pastel")[4], alpha=0.6)
|
|
1457
|
+
axes[ax].plot(pos_result_gene_1['Pos'], pos_result_gene_1["DDG"],
|
|
1458
|
+
label="Stability change", zorder=2, color=sns.color_palette("tab10")[4], lw=0.5)
|
|
1459
|
+
axes[ax].set_ylabel('ΔΔG A\n(kcal/mol)', fontsize=13.5, rotation=0, va='center')
|
|
1460
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1461
|
+
|
|
1462
|
+
|
|
1463
|
+
# Plot stability change B
|
|
1464
|
+
# -----------------------
|
|
1465
|
+
if "ddg_2" in annotations:
|
|
1466
|
+
ax = annotations.index("ddg_2")
|
|
1467
|
+
|
|
1468
|
+
max_value, min_value = pos_result_gene_2["DDG"].max(), pos_result_gene_1["DDG"].min()
|
|
1469
|
+
|
|
1470
|
+
axes[ax].fill_between(pos_result_gene_2['Pos'], min_value, max_value, where=(pos_result_gene_2['C'] == 1),
|
|
1471
|
+
color=sns.color_palette("pastel")[3], alpha=0.4, label='Position in cluster B', zorder=0, lw=2)
|
|
1472
|
+
|
|
1473
|
+
axes[ax].fill_between(pos_result_gene_2['Pos'], 0, pos_result_gene_2["DDG"], zorder=1,
|
|
1474
|
+
color="white")
|
|
1475
|
+
axes[ax].fill_between(pos_result_gene_2['Pos'], 0, pos_result_gene_2["DDG"], zorder=1,
|
|
1476
|
+
color=sns.color_palette("pastel")[4], alpha=0.6)
|
|
1477
|
+
axes[ax].plot(pos_result_gene_2['Pos'], pos_result_gene_2["DDG"],
|
|
1478
|
+
label="Stability change", zorder=2, color=sns.color_palette("tab10")[4], lw=0.5)
|
|
1479
|
+
axes[ax].set_ylabel('ΔΔG B\n(kcal/mol)', fontsize=13.5, rotation=0, va='center')
|
|
1480
|
+
axes[ax].yaxis.set_label_coords(-0.06, 0.5)
|
|
1481
|
+
|
|
1482
|
+
|
|
1483
|
+
# PTM
|
|
1484
|
+
# ---
|
|
1485
|
+
if "ptm" in annotations:
|
|
1486
|
+
ax = annotations.index("ptm")
|
|
1487
|
+
|
|
1488
|
+
ptm_gene = uni_feat_gene[uni_feat_gene["Type"] == "PTM"]
|
|
1489
|
+
ptm_names = ptm_gene["Description"].unique()
|
|
1490
|
+
sb_width = 0.5
|
|
1491
|
+
max_value = (len(ptm_names) * sb_width) - 0.2
|
|
1492
|
+
min_value = - 0.3
|
|
1493
|
+
|
|
1494
|
+
axes[ax].fill_between(pos_result_gene_shared['Pos'], min_value, max_value,
|
|
1495
|
+
where=(pos_result_gene_shared['C'] == "A") | (pos_result_gene_shared['C'] == "B") | (pos_result_gene_shared['C'] == "AB"),
|
|
1496
|
+
color='skyblue', alpha=0.4, label='Position in cluster', zorder=0, lw=2)
|
|
1497
|
+
|
|
1498
|
+
for n, name in enumerate(ptm_names):
|
|
1499
|
+
c = sns.color_palette("tab10")[n]
|
|
1500
|
+
ptm = ptm_gene[ptm_gene["Description"] == name]
|
|
1501
|
+
ptm_pos = ptm.Begin.values
|
|
1502
|
+
axes[ax].scatter(ptm_pos, np.repeat(n*sb_width, len(ptm_pos)), label=name, alpha=0.7, color=c) #label=name
|
|
1503
|
+
axes[ax].hlines(y=n*sb_width, xmin=0, xmax=gene_len, linewidth=1, color='lightgray', alpha=0.7, zorder=0)
|
|
1504
|
+
|
|
1505
|
+
axes[ax].set_ylim(min_value, max_value)
|
|
1506
|
+
y_ticks_positions = sb_width * np.arange(len(ptm_names))
|
|
1507
|
+
axes[ax].set_yticks(y_ticks_positions)
|
|
1508
|
+
axes[ax].set_yticklabels(ptm_names)
|
|
1509
|
+
axes[ax].set_ylabel(' PTM ', fontsize=13.5, rotation=0, va='center')
|
|
1510
|
+
|
|
1511
|
+
|
|
1512
|
+
# SITES
|
|
1513
|
+
# --------------
|
|
1514
|
+
if "site" in annotations:
|
|
1515
|
+
ax = annotations.index("site")
|
|
1516
|
+
|
|
1517
|
+
site_gene = uni_feat_gene[uni_feat_gene["Type"] == "SITE"]
|
|
1518
|
+
site_names = site_gene["Description"].unique()
|
|
1519
|
+
sb_width = 0.5
|
|
1520
|
+
max_value = (len(site_names) * sb_width) - 0.2
|
|
1521
|
+
min_value = - 0.3
|
|
1522
|
+
|
|
1523
|
+
axes[ax].fill_between(pos_result_gene_shared['Pos'], min_value, max_value,
|
|
1524
|
+
where=(pos_result_gene_shared['C'] == "A") | (pos_result_gene_shared['C'] == "B") | (pos_result_gene_shared['C'] == "AB"),
|
|
1525
|
+
color='skyblue', alpha=0.4, label='Position in cluster', zorder=0, lw=2)
|
|
1526
|
+
|
|
1527
|
+
for n, name in enumerate(site_names):
|
|
1528
|
+
c = sns.color_palette("tab10")[n]
|
|
1529
|
+
site = site_gene[site_gene["Description"] == name]
|
|
1530
|
+
site_pos = site.Begin.values
|
|
1531
|
+
axes[ax].scatter(site_pos, np.repeat(n*sb_width, len(site_pos)), label=name, alpha=0.7, color=c) #label=name
|
|
1532
|
+
axes[ax].hlines(y=n*sb_width, xmin=0, xmax=gene_len, linewidth=1, color='lightgray', alpha=0.7, zorder=0)
|
|
1533
|
+
|
|
1534
|
+
axes[ax].set_ylim(min_value, max_value)
|
|
1535
|
+
y_ticks_positions = sb_width * np.arange(len(site_names))
|
|
1536
|
+
axes[ax].set_yticks(y_ticks_positions)
|
|
1537
|
+
axes[ax].set_yticklabels(site_names)
|
|
1538
|
+
axes[ax].set_ylabel('Site ', fontsize=13.5, rotation=0, va='center')
|
|
1539
|
+
|
|
1540
|
+
|
|
1541
|
+
# Secondary structure
|
|
1542
|
+
# -------------------
|
|
1543
|
+
if "sse" in annotations:
|
|
1544
|
+
ax = annotations.index("sse")
|
|
1545
|
+
|
|
1546
|
+
for i, sse in enumerate(['Helix', 'Ladder', 'Coil']):
|
|
1547
|
+
c = 0+i
|
|
1548
|
+
ya, yb = c-plot_pars["sse_fill_width"], c+plot_pars["sse_fill_width"]
|
|
1549
|
+
axes[ax].fill_between(pdb_tool_gene["Pos"].values, ya, yb, where=(pdb_tool_gene["SSE"] == sse),
|
|
1550
|
+
color=sns.color_palette("tab10")[7+i], label=sse)
|
|
1551
|
+
axes[ax].set_yticks([0, 1, 2])
|
|
1552
|
+
axes[ax].set_yticklabels(['Helix', 'Ladder', 'Coil'], fontsize=10)
|
|
1553
|
+
axes[ax].set_ylabel('SSE ', fontsize=13.5, rotation=0, va='center')
|
|
1554
|
+
axes[ax].yaxis.set_label_coords(-0.051, 0.5)
|
|
1555
|
+
|
|
1556
|
+
|
|
1557
|
+
# Pfam
|
|
1558
|
+
# ----
|
|
1559
|
+
if "pfam" in annotations:
|
|
1560
|
+
ax = annotations.index("pfam")
|
|
1561
|
+
|
|
1562
|
+
pfam_gene = uni_feat_gene[(uni_feat_gene["Type"] == "DOMAIN") & (uni_feat_gene["Evidence"] == "Pfam")]
|
|
1563
|
+
pfam_gene = pfam_gene.sort_values("Begin").reset_index(drop=True)
|
|
1564
|
+
pfam_color_dict = {}
|
|
1565
|
+
|
|
1566
|
+
for n, name in enumerate(pfam_gene["Description"].unique()):
|
|
1567
|
+
pfam_color_dict[name] = f"C{n}"
|
|
1568
|
+
|
|
1569
|
+
n = 0
|
|
1570
|
+
added_pfam = []
|
|
1571
|
+
for i, row in pfam_gene.iterrows():
|
|
1572
|
+
if pd.Series([row["Description"], row["Begin"], row["End"]]).isnull().any():
|
|
1573
|
+
continue
|
|
1574
|
+
|
|
1575
|
+
name = row["Description"]
|
|
1576
|
+
start = int(row["Begin"])
|
|
1577
|
+
end = int(row["End"])
|
|
1578
|
+
axes[ax].fill_between(range(start, end+1), -0.45, 0.45, alpha=0.5, color=pfam_color_dict[name])
|
|
1579
|
+
if name not in added_pfam:
|
|
1580
|
+
if near_pfam:
|
|
1581
|
+
n += 1
|
|
1582
|
+
if n == 1:
|
|
1583
|
+
y = 0.28
|
|
1584
|
+
elif n == 2:
|
|
1585
|
+
y = 0
|
|
1586
|
+
elif n == 3:
|
|
1587
|
+
y = -0.295
|
|
1588
|
+
n = 0
|
|
1589
|
+
else:
|
|
1590
|
+
y = -0.04
|
|
1591
|
+
axes[ax].text(((start + end) / 2)+0.5, y, name, ha='center', va='center', fontsize=10, color="black")
|
|
1592
|
+
added_pfam.append(name)
|
|
1593
|
+
axes[ax].set_yticks([])
|
|
1594
|
+
axes[ax].set_yticklabels([], fontsize=12)
|
|
1595
|
+
axes[ax].set_ylabel('Pfam ', fontsize=13.5, rotation=0, va='center')
|
|
1596
|
+
axes[ax].set_ylim(-0.5, 0.5)
|
|
1597
|
+
axes[ax].yaxis.set_label_coords(-0.051, 0.5)
|
|
1598
|
+
|
|
1599
|
+
|
|
1600
|
+
# Prosite
|
|
1601
|
+
# -------
|
|
1602
|
+
if "prosite" in annotations:
|
|
1603
|
+
ax = annotations.index("prosite")
|
|
1604
|
+
|
|
1605
|
+
prosite_gene = uni_feat_gene[(uni_feat_gene["Type"] == "DOMAIN") & (uni_feat_gene["Evidence"] != "Pfam")]
|
|
1606
|
+
prosite_gene = prosite_gene.sort_values("Begin").reset_index(drop=True)
|
|
1607
|
+
prosite_color_dict = {}
|
|
1608
|
+
|
|
1609
|
+
for n, name in enumerate(prosite_gene["Description"].unique()):
|
|
1610
|
+
prosite_color_dict[name] = f"C{n}"
|
|
1611
|
+
|
|
1612
|
+
n = 0
|
|
1613
|
+
added_prosite = []
|
|
1614
|
+
for i, row in prosite_gene.iterrows():
|
|
1615
|
+
if pd.Series([row["Description"], row["Begin"], row["End"]]).isnull().any():
|
|
1616
|
+
continue
|
|
1617
|
+
|
|
1618
|
+
name = row["Description"]
|
|
1619
|
+
start = int(row["Begin"])
|
|
1620
|
+
end = int(row["End"])
|
|
1621
|
+
axes[ax].fill_between(range(start, end+1), -0.45, 0.45, alpha=0.5, color=prosite_color_dict[name])
|
|
1622
|
+
if name not in added_prosite:
|
|
1623
|
+
if near_prosite:
|
|
1624
|
+
n += 1
|
|
1625
|
+
if n == 1:
|
|
1626
|
+
y = 0.28
|
|
1627
|
+
elif n == 2:
|
|
1628
|
+
y = 0
|
|
1629
|
+
elif n == 3:
|
|
1630
|
+
y = -0.295
|
|
1631
|
+
n = 0
|
|
1632
|
+
else:
|
|
1633
|
+
y = -0.04
|
|
1634
|
+
axes[ax].text(((start + end) / 2)+0.5, y, name, ha='center', va='center', fontsize=10, color="black")
|
|
1635
|
+
added_prosite.append(name)
|
|
1636
|
+
axes[ax].set_yticks([])
|
|
1637
|
+
axes[ax].set_yticklabels([], fontsize=12)
|
|
1638
|
+
axes[ax].set_ylabel('Prosite ', fontsize=13.5, rotation=0, va='center')
|
|
1639
|
+
axes[ax].set_ylim(-0.5, 0.5)
|
|
1640
|
+
axes[ax].yaxis.set_label_coords(-0.051, 0.5)
|
|
1641
|
+
|
|
1642
|
+
|
|
1643
|
+
# Membrane
|
|
1644
|
+
# --------
|
|
1645
|
+
if "membrane" in annotations:
|
|
1646
|
+
ax = annotations.index("membrane")
|
|
1647
|
+
|
|
1648
|
+
membrane_gene = uni_feat_gene[(uni_feat_gene["Type"] == "MEMBRANE")]
|
|
1649
|
+
membrane_gene = membrane_gene.sort_values("Begin").reset_index(drop=True)
|
|
1650
|
+
membrane_color_dict = {}
|
|
1651
|
+
|
|
1652
|
+
for n, name in enumerate(membrane_gene["Description"].unique()):
|
|
1653
|
+
membrane_color_dict[name] = f"C{n}"
|
|
1654
|
+
|
|
1655
|
+
n = 0
|
|
1656
|
+
added_membrane = []
|
|
1657
|
+
for i, row in membrane_gene.iterrows():
|
|
1658
|
+
if pd.Series([row["Description"], row["Begin"], row["End"]]).isnull().any():
|
|
1659
|
+
continue
|
|
1660
|
+
|
|
1661
|
+
name = row["Description"]
|
|
1662
|
+
start = int(row["Begin"])
|
|
1663
|
+
end = int(row["End"])
|
|
1664
|
+
axes[ax].fill_between(range(start, end+1), -0.45, 0.45, alpha=0.5, color=membrane_color_dict[name])
|
|
1665
|
+
if name not in added_membrane:
|
|
1666
|
+
y = -0.04
|
|
1667
|
+
axes[ax].text(((start + end) / 2)+0.5, y, name, ha='center', va='center', fontsize=10, color="black")
|
|
1668
|
+
added_membrane.append(name)
|
|
1669
|
+
axes[ax].set_yticks([])
|
|
1670
|
+
axes[ax].set_yticklabels([], fontsize=12)
|
|
1671
|
+
axes[ax].set_ylabel('Membrane ', fontsize=13.5, rotation=0, va='center')
|
|
1672
|
+
axes[ax].set_ylim(-0.5, 0.5)
|
|
1673
|
+
axes[ax].yaxis.set_label_coords(-0.051, 0.5)
|
|
1674
|
+
|
|
1675
|
+
|
|
1676
|
+
# Motifs
|
|
1677
|
+
# ------
|
|
1678
|
+
if "motif" in annotations:
|
|
1679
|
+
ax = annotations.index("motif")
|
|
1680
|
+
|
|
1681
|
+
motif_gene = uni_feat_gene[(uni_feat_gene["Type"] == "MOTIF")]
|
|
1682
|
+
motif_gene = motif_gene.sort_values("Begin").reset_index(drop=True)
|
|
1683
|
+
motif_color_dict = {}
|
|
1684
|
+
|
|
1685
|
+
for n, name in enumerate(motif_gene["Full_description"].unique()):
|
|
1686
|
+
motif_color_dict[name] = f"C{n}"
|
|
1687
|
+
|
|
1688
|
+
n = 0
|
|
1689
|
+
added_motif = []
|
|
1690
|
+
for i, row in motif_gene.iterrows():
|
|
1691
|
+
if pd.Series([row["Full_description"], row["Begin"], row["End"]]).isnull().any():
|
|
1692
|
+
continue
|
|
1693
|
+
|
|
1694
|
+
name = row["Full_description"]
|
|
1695
|
+
start = int(row["Begin"])
|
|
1696
|
+
end = int(row["End"])
|
|
1697
|
+
axes[ax].fill_between(range(start, end+1), -0.45, 0.45, alpha=0.5, color=motif_color_dict[name])
|
|
1698
|
+
if name not in added_motif:
|
|
1699
|
+
if near_motif:
|
|
1700
|
+
n += 1
|
|
1701
|
+
if n == 1:
|
|
1702
|
+
y = 0.28
|
|
1703
|
+
elif n == 2:
|
|
1704
|
+
y = 0
|
|
1705
|
+
elif n == 3:
|
|
1706
|
+
y = -0.295
|
|
1707
|
+
n = 0
|
|
1708
|
+
else:
|
|
1709
|
+
y = -0.04
|
|
1710
|
+
axes[ax].text(((start + end) / 2)+0.5, y, name, ha='center', va='center', fontsize=10, color="black")
|
|
1711
|
+
added_motif.append(name)
|
|
1712
|
+
axes[ax].set_yticks([])
|
|
1713
|
+
axes[ax].set_yticklabels([], fontsize=12)
|
|
1714
|
+
axes[ax].set_ylabel('Motif ', fontsize=13.5, rotation=0, va='center')
|
|
1715
|
+
axes[ax].set_ylim(-0.5, 0.5)
|
|
1716
|
+
axes[ax].yaxis.set_label_coords(-0.051, 0.5)
|
|
1717
|
+
|
|
1718
|
+
|
|
1719
|
+
# Save
|
|
1720
|
+
# ====
|
|
1721
|
+
|
|
1722
|
+
fig.suptitle(f'{cohort_1} (A) - {cohort_2} (B)\n\n{gene} ({uni_id})', fontsize=16)
|
|
1723
|
+
if save_plot:
|
|
1724
|
+
filename = f"{cohort_1}.{cohort_2}.comp_plot_{j+1}.{gene}_{uni_id}.png"
|
|
1725
|
+
output_path = os.path.join(output_dir, filename)
|
|
1726
|
+
plt.subplots_adjust(top=0.9)
|
|
1727
|
+
plt.savefig(output_path, dpi=300, bbox_inches='tight')
|
|
1728
|
+
logger.debug(f"Saved {output_path}")
|
|
1729
|
+
if show_plot:
|
|
1730
|
+
plt.show()
|
|
1731
|
+
plt.close()
|
|
1732
|
+
|
|
1733
|
+
else:
|
|
1734
|
+
logger.warning("Nothing to plot!")
|
|
1735
|
+
|
|
1736
|
+
|
|
1737
|
+
|
|
1738
|
+
# Associations plots
|
|
1739
|
+
# ==================
|
|
1740
|
+
|
|
1741
|
+
def expand_uniprot_feat_rows(df):
|
|
1742
|
+
"""
|
|
1743
|
+
Convert Uniprot features df from ranges of positions to individual positions.
|
|
1744
|
+
"""
|
|
1745
|
+
|
|
1746
|
+
expanded_list = []
|
|
1747
|
+
for _, row in df.iterrows():
|
|
1748
|
+
begin, end = int(row['Begin']), int(row['End'])
|
|
1749
|
+
expanded_data = [{'Uniprot_ID': row['Uniprot_ID'], 'Type': row['Type'], 'Pos': pos, 'Description': row['Description']}
|
|
1750
|
+
for pos in range(begin, end + 1)]
|
|
1751
|
+
expanded_list.extend(expanded_data)
|
|
1752
|
+
expanded_df = pd.DataFrame(expanded_list)
|
|
1753
|
+
|
|
1754
|
+
return expanded_df
|
|
1755
|
+
|
|
1756
|
+
|
|
1757
|
+
def get_dummy(df, pos, annot):
|
|
1758
|
+
|
|
1759
|
+
return int(annot in df[df["Pos"] == pos].Type.values)
|
|
1760
|
+
|
|
1761
|
+
|
|
1762
|
+
def get_dummies_annot(df, col):
|
|
1763
|
+
|
|
1764
|
+
pos = pd.Series(df.Pos.unique(), name="Pos")
|
|
1765
|
+
lst_results = [pos]
|
|
1766
|
+
for annot in df[col].unique():
|
|
1767
|
+
series = pd.Series(df.Pos.unique()).apply(lambda x: get_dummy(df, pos=x, annot=annot))
|
|
1768
|
+
series.name = annot.capitalize()
|
|
1769
|
+
lst_results.append(series)
|
|
1770
|
+
|
|
1771
|
+
return pd.concat(lst_results, axis=1)
|
|
1772
|
+
|
|
1773
|
+
|
|
1774
|
+
def get_uni_feat_for_odds(uni_id, uni_feat_df):
|
|
1775
|
+
"""
|
|
1776
|
+
Preprocess Uniprot features df for logistic regression.
|
|
1777
|
+
"""
|
|
1778
|
+
|
|
1779
|
+
uni_feat_df = uni_feat_df.copy()
|
|
1780
|
+
uni_feat_df = uni_feat_df[uni_feat_df["Uniprot_ID"] == uni_id]
|
|
1781
|
+
uni_feat_df = get_dummies_annot(uni_feat_df, col="Type")
|
|
1782
|
+
uni_feat_df.insert(0, "Uniprot_ID", uni_id)
|
|
1783
|
+
|
|
1784
|
+
return uni_feat_df
|
|
1785
|
+
|
|
1786
|
+
|
|
1787
|
+
def uni_log_reg(df, labels):
|
|
1788
|
+
"""
|
|
1789
|
+
Univariate logistic regression analysis.
|
|
1790
|
+
"""
|
|
1791
|
+
|
|
1792
|
+
df = df.copy()
|
|
1793
|
+
results = {}
|
|
1794
|
+
|
|
1795
|
+
df = df.drop(columns=[col for col in df.columns if df[col].nunique() == 1])
|
|
1796
|
+
columns = df.columns
|
|
1797
|
+
|
|
1798
|
+
# Keep tracks of NA in ddG before standardizing
|
|
1799
|
+
if "ΔΔG" in columns:
|
|
1800
|
+
ddg_ix = ~df["ΔΔG"].isna().values
|
|
1801
|
+
df = df.fillna(0)
|
|
1802
|
+
|
|
1803
|
+
scaler = StandardScaler()
|
|
1804
|
+
df = scaler.fit_transform(df)
|
|
1805
|
+
|
|
1806
|
+
for i, col in enumerate(columns):
|
|
1807
|
+
|
|
1808
|
+
# Drop NA only in since it is the only annotation that depends on mutations
|
|
1809
|
+
if col == "ΔΔG":
|
|
1810
|
+
X_col = df[ddg_ix, i]
|
|
1811
|
+
y_col = labels[ddg_ix]
|
|
1812
|
+
if y_col.nunique() < 2:
|
|
1813
|
+
results[col] = {'p_value': np.nan, 'log_odds': np.nan, 'std_err': np.nan}
|
|
1814
|
+
continue
|
|
1815
|
+
else:
|
|
1816
|
+
X_col = df[:, i]
|
|
1817
|
+
y_col = labels
|
|
1818
|
+
|
|
1819
|
+
with warnings.catch_warnings():
|
|
1820
|
+
warnings.simplefilter('ignore', ConvergenceWarning)
|
|
1821
|
+
X = sm.add_constant(X_col)
|
|
1822
|
+
model = sm.Logit(y_col, X)
|
|
1823
|
+
|
|
1824
|
+
try:
|
|
1825
|
+
result = model.fit(disp=0)
|
|
1826
|
+
p_value = result.pvalues[1]
|
|
1827
|
+
coeff = result.params[1]
|
|
1828
|
+
std_err = result.bse[1]
|
|
1829
|
+
|
|
1830
|
+
except np.linalg.LinAlgError as e:
|
|
1831
|
+
logger.debug("Logistic regression singular matrix: Skipping..")
|
|
1832
|
+
logger.debug(e)
|
|
1833
|
+
p_value = np.nan
|
|
1834
|
+
coeff = np.nan
|
|
1835
|
+
std_err = np.nan
|
|
1836
|
+
|
|
1837
|
+
except sm.tools.sm_exceptions.PerfectSeparationError as e:
|
|
1838
|
+
logger.debug("Logistic regression perfect separation: Skipping..")
|
|
1839
|
+
logger.debug(e)
|
|
1840
|
+
p_value = np.nan
|
|
1841
|
+
coeff = np.nan
|
|
1842
|
+
std_err = np.nan
|
|
1843
|
+
|
|
1844
|
+
results[col] = {'p_value': p_value, 'log_odds': coeff, 'std_err': std_err}
|
|
1845
|
+
|
|
1846
|
+
return pd.DataFrame(results)
|
|
1847
|
+
|
|
1848
|
+
|
|
1849
|
+
def uni_log_reg_all_genes(df_annotated, uni_feat_df):
|
|
1850
|
+
"""
|
|
1851
|
+
Univariate logistic regression analysis of all genes.
|
|
1852
|
+
"""
|
|
1853
|
+
|
|
1854
|
+
results_lst = []
|
|
1855
|
+
df_gene_lst = []
|
|
1856
|
+
|
|
1857
|
+
for uni_id in df_annotated.Uniprot_ID.unique():
|
|
1858
|
+
|
|
1859
|
+
# Process each gene individually
|
|
1860
|
+
uni_feat_df_gene = get_uni_feat_for_odds(uni_id=uni_id, uni_feat_df=uni_feat_df)
|
|
1861
|
+
|
|
1862
|
+
df_gene = df_annotated[df_annotated["Uniprot_ID"] == uni_id].reset_index(drop=True)
|
|
1863
|
+
gene = df_gene.Gene.unique()[0]
|
|
1864
|
+
|
|
1865
|
+
df_gene = df_gene.merge(uni_feat_df_gene, on=["Uniprot_ID", "Pos"], how="left")
|
|
1866
|
+
target_cols = df_gene.drop(columns=["Pos", "C", "Uniprot_ID", "Gene"]).columns.values
|
|
1867
|
+
|
|
1868
|
+
y_data = df_gene["C"]
|
|
1869
|
+
X_data = df_gene[target_cols]
|
|
1870
|
+
y_data = y_data.fillna(0)
|
|
1871
|
+
|
|
1872
|
+
if y_data.nunique() > 1:
|
|
1873
|
+
results_gene = uni_log_reg(X_data, y_data)
|
|
1874
|
+
results_gene["Gene"] = gene
|
|
1875
|
+
results_gene["Uniprot_ID"] = uni_id
|
|
1876
|
+
|
|
1877
|
+
else:
|
|
1878
|
+
results_gene = pd.DataFrame(np.nan, index=["p_value", "log_odds", "std_err"], columns=target_cols)
|
|
1879
|
+
results_gene["Gene"] = gene
|
|
1880
|
+
results_gene["Uniprot_ID"] = uni_id
|
|
1881
|
+
|
|
1882
|
+
df_gene_lst.append(df_gene)
|
|
1883
|
+
results_lst.append(results_gene)
|
|
1884
|
+
|
|
1885
|
+
uni_log_result = pd.concat(results_lst)
|
|
1886
|
+
df_genes = pd.concat(df_gene_lst)
|
|
1887
|
+
|
|
1888
|
+
return uni_log_result, df_genes
|
|
1889
|
+
|
|
1890
|
+
|
|
1891
|
+
def rename_columns(df):
|
|
1892
|
+
"""
|
|
1893
|
+
Simply rename columns after dummy transformation.
|
|
1894
|
+
"""
|
|
1895
|
+
|
|
1896
|
+
new_columns = {}
|
|
1897
|
+
for column in df.columns:
|
|
1898
|
+
for prefix in ["SSE", "TYPE"]:
|
|
1899
|
+
if column.startswith(f'{prefix}_'):
|
|
1900
|
+
new_column = column.replace(f'{prefix}_', '').capitalize()
|
|
1901
|
+
new_columns[column] = new_column
|
|
1902
|
+
|
|
1903
|
+
return df.rename(columns=new_columns)
|
|
1904
|
+
|
|
1905
|
+
|
|
1906
|
+
def volcano_plot(logreg_results,
|
|
1907
|
+
fsize=(10, 6),
|
|
1908
|
+
expand_text_xy=(3, 2),
|
|
1909
|
+
text_fontsize=10,
|
|
1910
|
+
top_n=15,
|
|
1911
|
+
top_by_gene=False,
|
|
1912
|
+
gene_text=False,
|
|
1913
|
+
save_plot=True,
|
|
1914
|
+
show_plot=False,
|
|
1915
|
+
output_dir=None,
|
|
1916
|
+
cohort="o3d_run"):
|
|
1917
|
+
"""
|
|
1918
|
+
Volcano plot all genes.
|
|
1919
|
+
"""
|
|
1920
|
+
|
|
1921
|
+
genes = logreg_results[~logreg_results.drop(columns=["Gene", "Uniprot_ID"]).isna().all(axis=1)].Gene.unique()
|
|
1922
|
+
with warnings.catch_warnings():
|
|
1923
|
+
warnings.simplefilter("ignore", category=DeprecationWarning)
|
|
1924
|
+
cmap = plt.cm.get_cmap('tab20', len(genes))
|
|
1925
|
+
lgray_rgb = 0.7803921568627451, 0.7803921568627451, 0.7803921568627451, 1.0
|
|
1926
|
+
used_colors = []
|
|
1927
|
+
|
|
1928
|
+
all_gene_results = []
|
|
1929
|
+
plt.figure(figsize=fsize)
|
|
1930
|
+
|
|
1931
|
+
for i, gene in enumerate(genes):
|
|
1932
|
+
gene_results = logreg_results[logreg_results["Gene"] == gene].drop(columns=["Gene", "Uniprot_ID"]).dropna(axis=1)
|
|
1933
|
+
gene_logodds = gene_results.loc["log_odds", :]
|
|
1934
|
+
gene_pvals = gene_results.loc["p_value", :]
|
|
1935
|
+
gene_logpvals = -np.log10(gene_pvals)
|
|
1936
|
+
|
|
1937
|
+
# Volcano plot
|
|
1938
|
+
significant_mask = gene_pvals < 0.01
|
|
1939
|
+
non_significant_mask = ~significant_mask
|
|
1940
|
+
marker = '*' if cmap(i) in used_colors else 'o'
|
|
1941
|
+
used_colors.append(cmap(i))
|
|
1942
|
+
plt.scatter(gene_logodds[non_significant_mask], gene_logpvals[non_significant_mask], zorder=1, color='lightgray', alpha=0.7, marker=marker)
|
|
1943
|
+
plt.scatter(gene_logodds[significant_mask], gene_logpvals[significant_mask], zorder=2, label=gene,
|
|
1944
|
+
color="black" if cmap(i) == lgray_rgb else cmap(i), alpha=0.7, marker=marker)
|
|
1945
|
+
|
|
1946
|
+
# Append results for annotation
|
|
1947
|
+
gene_data = pd.DataFrame({
|
|
1948
|
+
'Gene': gene,
|
|
1949
|
+
'Log_odds': gene_logodds.values,
|
|
1950
|
+
'Pval': gene_pvals.values,
|
|
1951
|
+
'Log_pval': gene_logpvals.values,
|
|
1952
|
+
'Feature': gene_logodds.index})
|
|
1953
|
+
all_gene_results.append(gene_data)
|
|
1954
|
+
|
|
1955
|
+
# Annotated top significant n points
|
|
1956
|
+
all_gene_results = pd.concat(all_gene_results)
|
|
1957
|
+
if top_by_gene:
|
|
1958
|
+
top_significant_points = all_gene_results[all_gene_results["Pval"] < 0.01].groupby("Gene").apply(lambda x: x.nsmallest(top_n, 'Pval')).reset_index(drop=True)
|
|
1959
|
+
else:
|
|
1960
|
+
top_significant_points = all_gene_results[all_gene_results["Pval"] < 0.01].nsmallest(top_n, 'Pval')
|
|
1961
|
+
|
|
1962
|
+
annotations = []
|
|
1963
|
+
for _, row in top_significant_points.iterrows():
|
|
1964
|
+
if gene_text:
|
|
1965
|
+
text = f"{row['Gene']}-{row['Feature']}"
|
|
1966
|
+
else:
|
|
1967
|
+
text = row['Feature']
|
|
1968
|
+
annotations.append(plt.text(row['Log_odds'], row['Log_pval'], text, ha='center', va='center', fontsize=text_fontsize, color='black'))
|
|
1969
|
+
adjust_text(annotations, expand=expand_text_xy, # expand text bounding boxes by 1.2 fold in x direction and 2 fold in y direction
|
|
1970
|
+
arrowprops=dict(arrowstyle='->', color='gray'), lw=0.5)
|
|
1971
|
+
|
|
1972
|
+
plt.xlabel('Log odds', fontsize=12)
|
|
1973
|
+
plt.ylabel('-log10(p-value)', fontsize=12)
|
|
1974
|
+
plt.axhline(y=-np.log10(0.01), color='lightgrey', linestyle='--', zorder=0)
|
|
1975
|
+
plt.axvline(x=0, color='lightgrey', linestyle='--', zorder=0)
|
|
1976
|
+
plt.legend(ncol=1 if len(genes) < 20 else 2)
|
|
1977
|
+
plt.suptitle(f"{cohort} - Residues' cluster status and annotations associations", y=0.93)
|
|
1978
|
+
|
|
1979
|
+
if save_plot and output_dir:
|
|
1980
|
+
filename = f"{cohort}.volcano_plot.png"
|
|
1981
|
+
output_path = os.path.join(output_dir, filename)
|
|
1982
|
+
plt.savefig(output_path, dpi=300, bbox_inches='tight')
|
|
1983
|
+
logger.debug(f"Saved {output_path}")
|
|
1984
|
+
if show_plot:
|
|
1985
|
+
plt.show()
|
|
1986
|
+
plt.close()
|
|
1987
|
+
|
|
1988
|
+
|
|
1989
|
+
def volcano_plot_each_gene(logreg_results,
|
|
1990
|
+
fsize=(3.2, 3),
|
|
1991
|
+
expand_text_xy=(3, 2),
|
|
1992
|
+
text_fontsize=10,
|
|
1993
|
+
top_n=5,
|
|
1994
|
+
ncols=5,
|
|
1995
|
+
all_significant=True,
|
|
1996
|
+
save_plot=True,
|
|
1997
|
+
show_plot=False,
|
|
1998
|
+
output_dir=None,
|
|
1999
|
+
cohort="o3d_run"):
|
|
2000
|
+
"""
|
|
2001
|
+
Volcano plot of individual genes.
|
|
2002
|
+
"""
|
|
2003
|
+
|
|
2004
|
+
genes = logreg_results[~logreg_results.drop(columns=["Gene", "Uniprot_ID"]).isna().all(axis=1)].Gene.unique()
|
|
2005
|
+
num_genes = len(genes)
|
|
2006
|
+
with warnings.catch_warnings():
|
|
2007
|
+
warnings.simplefilter("ignore", category=DeprecationWarning)
|
|
2008
|
+
cmap = plt.cm.get_cmap('tab20', num_genes)
|
|
2009
|
+
lgray_rgb = 0.7803921568627451, 0.7803921568627451, 0.7803921568627451, 1.0
|
|
2010
|
+
|
|
2011
|
+
all_gene_results = []
|
|
2012
|
+
|
|
2013
|
+
# Figsize
|
|
2014
|
+
if num_genes <= 5:
|
|
2015
|
+
ncols = num_genes
|
|
2016
|
+
elif num_genes <= 10:
|
|
2017
|
+
ncols = int(np.ceil(num_genes / 2))
|
|
2018
|
+
elif num_genes <= 20:
|
|
2019
|
+
ncols = 5
|
|
2020
|
+
else:
|
|
2021
|
+
ncols = 6
|
|
2022
|
+
nrows = int(np.ceil(num_genes / ncols))
|
|
2023
|
+
|
|
2024
|
+
fsize_x, fsize_y = fsize
|
|
2025
|
+
fsize_x = fsize_x * ncols
|
|
2026
|
+
fsize_y = fsize_y * nrows
|
|
2027
|
+
|
|
2028
|
+
fig, axes = plt.subplots(nrows=nrows, ncols=ncols, figsize=(fsize_x, fsize_y), constrained_layout=True)
|
|
2029
|
+
# Ensure that the axes is always a 1D subscriptable array
|
|
2030
|
+
if not isinstance(axes, Axes):
|
|
2031
|
+
axes = axes.flatten()
|
|
2032
|
+
axes = np.atleast_1d(axes)
|
|
2033
|
+
|
|
2034
|
+
for i, ax in enumerate(axes):
|
|
2035
|
+
|
|
2036
|
+
if i < len(genes):
|
|
2037
|
+
gene = genes[i]
|
|
2038
|
+
gene_results = logreg_results[logreg_results["Gene"] == gene].drop(columns=["Gene", "Uniprot_ID"]).dropna(axis=1)
|
|
2039
|
+
gene_logodds = gene_results.loc["log_odds", :]
|
|
2040
|
+
gene_pvals = gene_results.loc["p_value", :]
|
|
2041
|
+
gene_logpvals = -np.log10(gene_pvals)
|
|
2042
|
+
|
|
2043
|
+
# Volcano plot
|
|
2044
|
+
significant_mask = gene_pvals < 0.01
|
|
2045
|
+
non_significant_mask = ~significant_mask
|
|
2046
|
+
ax.scatter(gene_logodds[non_significant_mask], gene_logpvals[non_significant_mask], zorder=1, color='lightgray', alpha=0.7)
|
|
2047
|
+
ax.scatter(gene_logodds[significant_mask], gene_logpvals[significant_mask], zorder=2,
|
|
2048
|
+
color="black" if cmap(i) == lgray_rgb else cmap(i), alpha=0.7)
|
|
2049
|
+
|
|
2050
|
+
# Annotated top significant n points
|
|
2051
|
+
gene_data = pd.DataFrame({
|
|
2052
|
+
'Gene': gene,
|
|
2053
|
+
'Log_odds': gene_logodds.values,
|
|
2054
|
+
'Pval': gene_pvals.values,
|
|
2055
|
+
'Log_pval': gene_logpvals.values,
|
|
2056
|
+
'Feature': gene_logodds.index})
|
|
2057
|
+
all_gene_results.append(gene_data)
|
|
2058
|
+
|
|
2059
|
+
if all_significant:
|
|
2060
|
+
top_significant_points = gene_data[gene_data["Pval"] < 0.01]
|
|
2061
|
+
else:
|
|
2062
|
+
top_significant_points = gene_data.nsmallest(top_n, 'Pval')
|
|
2063
|
+
annotations = []
|
|
2064
|
+
for _, row in top_significant_points.iterrows():
|
|
2065
|
+
annotations.append(ax.text(row['Log_odds'], row['Log_pval'], row['Feature'], ha='center', va='center', fontsize=text_fontsize, color='black'))
|
|
2066
|
+
adjust_text(annotations, expand=expand_text_xy,
|
|
2067
|
+
arrowprops=dict(arrowstyle='->', color='gray'), lw=0.5, ax=ax)
|
|
2068
|
+
|
|
2069
|
+
ax.set_xlabel(None)
|
|
2070
|
+
ax.set_ylabel(None)
|
|
2071
|
+
ax.set_title(gene)
|
|
2072
|
+
ax.axhline(y=-np.log10(0.01), color='lightgrey', linestyle='--', zorder=0)
|
|
2073
|
+
ax.axvline(x=0, color='lightgrey', linestyle='--', zorder=0)
|
|
2074
|
+
else:
|
|
2075
|
+
ax.remove()
|
|
2076
|
+
|
|
2077
|
+
fig.supxlabel('Log odds')
|
|
2078
|
+
fig.supylabel('-log10(p-value)')
|
|
2079
|
+
plt.suptitle(f"{cohort} - Residues' cluster status and annotations associations")
|
|
2080
|
+
|
|
2081
|
+
if save_plot and output_dir:
|
|
2082
|
+
filename = f"{cohort}.volcano_plot_gene.png"
|
|
2083
|
+
output_path = os.path.join(output_dir, filename)
|
|
2084
|
+
plt.savefig(output_path, dpi=300, bbox_inches='tight')
|
|
2085
|
+
logger.debug(f"Saved {output_path}")
|
|
2086
|
+
if show_plot:
|
|
2087
|
+
plt.show()
|
|
2088
|
+
plt.close()
|
|
2089
|
+
|
|
2090
|
+
|
|
2091
|
+
def log_odds_plot(logreg_results,
|
|
2092
|
+
fsize=(1.7,3.6),
|
|
2093
|
+
save_plot=True,
|
|
2094
|
+
show_plot=False,
|
|
2095
|
+
output_dir=None,
|
|
2096
|
+
cohort="o3d_run"):
|
|
2097
|
+
"""
|
|
2098
|
+
Log odds plot.
|
|
2099
|
+
"""
|
|
2100
|
+
|
|
2101
|
+
genes = logreg_results[~logreg_results.drop(columns=["Gene", "Uniprot_ID"]).isna().all(axis=1)].Gene.unique()
|
|
2102
|
+
num_genes = len(genes)
|
|
2103
|
+
with warnings.catch_warnings():
|
|
2104
|
+
warnings.simplefilter("ignore", category=DeprecationWarning)
|
|
2105
|
+
cmap = plt.cm.get_cmap('tab20', num_genes)
|
|
2106
|
+
lgray_rgb = 0.7803921568627451, 0.7803921568627451, 0.7803921568627451, 1.0
|
|
2107
|
+
|
|
2108
|
+
# Figsize
|
|
2109
|
+
if num_genes > 10:
|
|
2110
|
+
nrows = 2
|
|
2111
|
+
else:
|
|
2112
|
+
nrows = 1
|
|
2113
|
+
|
|
2114
|
+
ncols = int(np.ceil(num_genes / nrows))
|
|
2115
|
+
fsize_x, fsize_y = fsize
|
|
2116
|
+
fsize_x = fsize_x * ncols
|
|
2117
|
+
fsize_y = fsize_y * nrows
|
|
2118
|
+
|
|
2119
|
+
fig, axes = plt.subplots(nrows, ncols,
|
|
2120
|
+
figsize=(fsize_x, fsize_y),
|
|
2121
|
+
sharey=True,
|
|
2122
|
+
gridspec_kw={'hspace': 0.1*nrows})
|
|
2123
|
+
|
|
2124
|
+
# Ensure that the axes is always a 1D subscriptable array
|
|
2125
|
+
if not isinstance(axes, Axes):
|
|
2126
|
+
axes = axes.flatten()
|
|
2127
|
+
axes = np.atleast_1d(axes)
|
|
2128
|
+
|
|
2129
|
+
for i, ax in enumerate(axes):
|
|
2130
|
+
|
|
2131
|
+
if i < len(genes):
|
|
2132
|
+
gene = genes[i]
|
|
2133
|
+
gene_results = logreg_results[logreg_results["Gene"] == gene].drop(columns=["Gene", "Uniprot_ID"])
|
|
2134
|
+
gene_logodds = gene_results.loc["log_odds", :]
|
|
2135
|
+
gene_pvals = gene_results.loc["p_value", :]
|
|
2136
|
+
gene_stderr = gene_results.loc["std_err", :]
|
|
2137
|
+
|
|
2138
|
+
# Get 95% confidence interval
|
|
2139
|
+
z = 1.96
|
|
2140
|
+
lower_ci = np.array(gene_logodds) - z * np.array(gene_stderr)
|
|
2141
|
+
upper_ci = np.array(gene_logodds) + z * np.array(gene_stderr)
|
|
2142
|
+
|
|
2143
|
+
# Calculate error bars
|
|
2144
|
+
lower_error = np.array(gene_logodds) - lower_ci
|
|
2145
|
+
upper_error = upper_ci - np.array(gene_logodds)
|
|
2146
|
+
error = [lower_error, upper_error]
|
|
2147
|
+
|
|
2148
|
+
# Plot
|
|
2149
|
+
significant_mask = gene_pvals < 0.01
|
|
2150
|
+
non_significant_mask = ~significant_mask
|
|
2151
|
+
|
|
2152
|
+
ax.errorbar(gene_logodds, gene_logodds.index.values, yerr=None, xerr=error, fmt='o', capsize=5, capthick=1, markersize=5)
|
|
2153
|
+
ax.errorbar(gene_logodds[non_significant_mask], gene_logodds.index.values[non_significant_mask], yerr=None,
|
|
2154
|
+
xerr=[err[non_significant_mask] for err in error], fmt='o', capsize=5, capthick=1, markersize=5, color='lightgray')
|
|
2155
|
+
ax.errorbar(gene_logodds[significant_mask], gene_logodds.index.values[significant_mask], yerr=None,
|
|
2156
|
+
xerr=[err[significant_mask] for err in error], fmt='o', capsize=5, capthick=1, markersize=5,
|
|
2157
|
+
color="black" if cmap(i) == lgray_rgb else cmap(i))
|
|
2158
|
+
ax.axvline(x=0, color='lightgrey', linestyle='--', zorder=0, lw=1)
|
|
2159
|
+
ax.set_xlim(gene_logodds.min()-1.5, gene_logodds.max()+1.5)
|
|
2160
|
+
ax.set_xlabel(f"\n\n{gene}", fontsize=12, rotation=0, va='center')
|
|
2161
|
+
ax.xaxis.set_label_coords(0.5, 1.11)
|
|
2162
|
+
else:
|
|
2163
|
+
ax.remove()
|
|
2164
|
+
|
|
2165
|
+
plt.suptitle(f"{cohort} - Residues' cluster status and annotations associations", y=1)
|
|
2166
|
+
if nrows == 1:
|
|
2167
|
+
fig.supxlabel('Log odds', y=-0.015)
|
|
2168
|
+
plt.subplots_adjust(top=0.868)
|
|
2169
|
+
else:
|
|
2170
|
+
fig.supxlabel('Log odds', y=0.037)
|
|
2171
|
+
plt.subplots_adjust(top=0.925)
|
|
2172
|
+
|
|
2173
|
+
|
|
2174
|
+
if save_plot and output_dir:
|
|
2175
|
+
filename = f"{cohort}.logodds_plot.png"
|
|
2176
|
+
output_path = os.path.join(output_dir, filename)
|
|
2177
|
+
plt.savefig(output_path, dpi=300, bbox_inches='tight')
|
|
2178
|
+
logger.debug(f"Saved {output_path}")
|
|
2179
|
+
if show_plot:
|
|
2180
|
+
plt.show()
|
|
2181
|
+
plt.close()
|
|
2182
|
+
|
|
2183
|
+
|
|
2184
|
+
def associations_plots(df_annotated,
|
|
2185
|
+
uni_feat_processed,
|
|
2186
|
+
output_dir,
|
|
2187
|
+
plot_pars,
|
|
2188
|
+
miss_prob_dict,
|
|
2189
|
+
cohort="o3d_run"):
|
|
2190
|
+
"""
|
|
2191
|
+
Generate volcano plots and log odds plot to look for associations
|
|
2192
|
+
between cluster status and annotated features.
|
|
2193
|
+
"""
|
|
2194
|
+
|
|
2195
|
+
# Prepare data
|
|
2196
|
+
df_annotated = df_annotated.copy()
|
|
2197
|
+
df_annotated["Miss_prob"] = df_annotated.apply(lambda x: (miss_prob_dict[f"{x.Uniprot_ID}-F{x.F}"][x.Pos-1]), axis=1)
|
|
2198
|
+
df_annotated = df_annotated[df_annotated["Miss_prob"] > 0]
|
|
2199
|
+
cols_drop = "Mut_in_res", "Mut_in_vol", "Score_obs_sim", "C_ext", "pval", "Clump", "Res", "F", "Ens_Gene_ID", "Ens_Transcr_ID", "PAE_vol", "Miss_prob"
|
|
2200
|
+
df_annotated = df_annotated.drop(columns=[col for col in cols_drop if col in df_annotated.columns])
|
|
2201
|
+
sse_dummies = pd.get_dummies(df_annotated['SSE'], prefix='SSE')
|
|
2202
|
+
df_annotated = pd.concat((df_annotated.drop(columns="SSE"), sse_dummies), axis=1)
|
|
2203
|
+
df_annotated = df_annotated.rename(columns={"pLDDT_res" : "pLDDT", "PAE_vol" : "PAE", "DDG" : "ΔΔG"})
|
|
2204
|
+
|
|
2205
|
+
# Add Uniprot features
|
|
2206
|
+
uni_feat_processed = uni_feat_processed[uni_feat_processed["Type"] != "REGION"].reset_index(drop=True)
|
|
2207
|
+
uni_feat_processed_expanded = expand_uniprot_feat_rows(uni_feat_processed)
|
|
2208
|
+
|
|
2209
|
+
# Perform univariate log reg
|
|
2210
|
+
logreg_results, df_annotated_uni_feat = uni_log_reg_all_genes(df_annotated, uni_feat_processed_expanded)
|
|
2211
|
+
logreg_results = rename_columns(logreg_results)
|
|
2212
|
+
|
|
2213
|
+
# Plots
|
|
2214
|
+
genes = logreg_results[~logreg_results.drop(columns=["Gene", "Uniprot_ID"]).isna().all(axis=1)].Gene.unique()
|
|
2215
|
+
if len(genes) > 0:
|
|
2216
|
+
output_dir_associations_plots = os.path.join(output_dir, f"{cohort}.associations_plots")
|
|
2217
|
+
logger.info(f"Generating associations plots in {output_dir_associations_plots}")
|
|
2218
|
+
os.makedirs(output_dir_associations_plots, exist_ok=True)
|
|
2219
|
+
log_odds_plot(logreg_results,
|
|
2220
|
+
output_dir=output_dir_associations_plots,
|
|
2221
|
+
cohort=cohort,
|
|
2222
|
+
fsize=(plot_pars["log_odds_fsize_x"], plot_pars["log_odds_fsize_y"]))
|
|
2223
|
+
volcano_plot(logreg_results,
|
|
2224
|
+
top_n=plot_pars["volcano_top_n"],
|
|
2225
|
+
output_dir=output_dir_associations_plots,
|
|
2226
|
+
cohort=cohort,
|
|
2227
|
+
fsize=(plot_pars["volcano_fsize_x"], plot_pars["volcano_fsize_y"]))
|
|
2228
|
+
volcano_plot_each_gene(logreg_results,
|
|
2229
|
+
output_dir=output_dir_associations_plots,
|
|
2230
|
+
cohort=cohort,
|
|
2231
|
+
fsize=(plot_pars["volcano_subplots_fsize_x"], plot_pars["volcano_subplots_fsize_y"]))
|
|
2232
|
+
else:
|
|
2233
|
+
logger.debug("There aren't any relationship to plot: Skipping associations plots..")
|
|
2234
|
+
|
|
2235
|
+
uni_feat_cols = ["Uniprot_ID", "Pos", "Domain", "Ptm", "Membrane", "Motif", "Site"]
|
|
2236
|
+
df_annotated_uni_feat = df_annotated_uni_feat[[col for col in uni_feat_cols if col in df_annotated_uni_feat.columns]]
|
|
2237
|
+
|
|
2238
|
+
return df_annotated_uni_feat
|
|
2239
|
+
|
|
2240
|
+
|
|
2241
|
+
# PLOT WRAPPER
|
|
2242
|
+
# ============
|
|
2243
|
+
|
|
2244
|
+
def generate_plots(gene_result_path,
|
|
2245
|
+
pos_result_path,
|
|
2246
|
+
maf_path,
|
|
2247
|
+
miss_prob_path,
|
|
2248
|
+
seq_df_path,
|
|
2249
|
+
cohort,
|
|
2250
|
+
datasets_dir,
|
|
2251
|
+
annotations_dir,
|
|
2252
|
+
output_dir,
|
|
2253
|
+
plot_pars,
|
|
2254
|
+
maf_path_for_nonmiss=None,
|
|
2255
|
+
c_genes_only=True,
|
|
2256
|
+
n_genes=30,
|
|
2257
|
+
lst_genes=None,
|
|
2258
|
+
save_plot=True,
|
|
2259
|
+
show_plot=False,
|
|
2260
|
+
save_csv=True,
|
|
2261
|
+
include_all_pos=False,
|
|
2262
|
+
c_ext=True,
|
|
2263
|
+
title=None,
|
|
2264
|
+
plot_associations=True):
|
|
2265
|
+
|
|
2266
|
+
# Load data tracks
|
|
2267
|
+
# ================
|
|
2268
|
+
|
|
2269
|
+
# Load data
|
|
2270
|
+
logger.debug("Loading data")
|
|
2271
|
+
|
|
2272
|
+
gene_result = pd.read_csv(gene_result_path)
|
|
2273
|
+
pos_result = pd.read_csv(pos_result_path)
|
|
2274
|
+
maf = pd.read_csv(maf_path, sep="\t")
|
|
2275
|
+
miss_prob_dict = json.load(open(miss_prob_path))
|
|
2276
|
+
seq_df = pd.read_csv(seq_df_path, sep="\t")
|
|
2277
|
+
uniprot_feat = pd.read_csv(os.path.join(annotations_dir, "uniprot_feat.tsv"), sep="\t")
|
|
2278
|
+
pdb_tool = pd.read_csv(os.path.join(annotations_dir, "pdb_tool_df.tsv"), sep="\t")
|
|
2279
|
+
disorder = pd.read_csv(os.path.join(datasets_dir, "confidence.tsv"), sep="\t", low_memory=False)
|
|
2280
|
+
|
|
2281
|
+
# Clean up MOTIF description TO DO: it should be moved in the build-annotations step
|
|
2282
|
+
uniprot_feat.loc[(uniprot_feat["Type"] == "MOTIF") & (
|
|
2283
|
+
uniprot_feat["Description"] == "Zinc finger"), "Full_description"] = "Zinc finger"
|
|
2284
|
+
uniprot_feat.loc[(uniprot_feat["Type"] == "MOTIF") & (uniprot_feat["Full_description"].str.contains('WIN', case=False)), "Full_description"] = "WIN"
|
|
2285
|
+
uniprot_feat.loc[uniprot_feat["Type"] == "MOTIF", "Full_description"] = uniprot_feat.loc[uniprot_feat["Type"] == "MOTIF", "Full_description"].apply(
|
|
2286
|
+
lambda x: x.split(";")[0] if len(x.split(";")) > 1 else x)
|
|
2287
|
+
|
|
2288
|
+
# Filter Oncodrive3D result
|
|
2289
|
+
logger.debug("Filtering result")
|
|
2290
|
+
maf = filter_non_processed_mut(maf, pos_result)
|
|
2291
|
+
gene_result, pos_result, genes, uni_ids = filter_o3d_result(gene_result,
|
|
2292
|
+
pos_result,
|
|
2293
|
+
n_genes,
|
|
2294
|
+
lst_genes)
|
|
2295
|
+
|
|
2296
|
+
if len(gene_result) > 0:
|
|
2297
|
+
|
|
2298
|
+
# Subset dfs by selected genes and IDs
|
|
2299
|
+
logger.debug("Subset genes")
|
|
2300
|
+
seq_df, disorder, pdb_tool, uniprot_feat = subset_genes_and_ids(genes,
|
|
2301
|
+
uni_ids,
|
|
2302
|
+
seq_df,
|
|
2303
|
+
disorder,
|
|
2304
|
+
pdb_tool,
|
|
2305
|
+
uniprot_feat)
|
|
2306
|
+
|
|
2307
|
+
# Summary plot
|
|
2308
|
+
os.makedirs(output_dir, exist_ok=True)
|
|
2309
|
+
logger.info(f"Generating summary plot in {output_dir}")
|
|
2310
|
+
count_mut_gene_df, count_pos_df, cluster_df = get_summary_counts(gene_result, pos_result, seq_df)
|
|
2311
|
+
summary_plot(gene_result,
|
|
2312
|
+
pos_result,
|
|
2313
|
+
count_mut_gene_df,
|
|
2314
|
+
count_pos_df,
|
|
2315
|
+
cluster_df,
|
|
2316
|
+
output_dir,
|
|
2317
|
+
cohort,
|
|
2318
|
+
plot_pars,
|
|
2319
|
+
save_plot=save_plot,
|
|
2320
|
+
show_plot=show_plot,
|
|
2321
|
+
title=title)
|
|
2322
|
+
|
|
2323
|
+
# Individual gene plots
|
|
2324
|
+
if "nonmiss_count" in plot_pars["h_ratios"]:
|
|
2325
|
+
maf_nonmiss = get_nonmiss_mut(maf_path_for_nonmiss)
|
|
2326
|
+
else:
|
|
2327
|
+
maf_nonmiss = None
|
|
2328
|
+
output_dir_genes_plots = os.path.join(output_dir, f"{cohort}.genes_plots")
|
|
2329
|
+
os.makedirs(output_dir_genes_plots, exist_ok=True)
|
|
2330
|
+
logger.info(f"Generating genes plots in {output_dir_genes_plots}")
|
|
2331
|
+
|
|
2332
|
+
if c_genes_only:
|
|
2333
|
+
n_genes = len(gene_result[gene_result["C_gene"] == 1])
|
|
2334
|
+
gene_result, pos_result, genes, uni_ids = filter_o3d_result(gene_result,
|
|
2335
|
+
pos_result,
|
|
2336
|
+
n_genes,
|
|
2337
|
+
lst_genes)
|
|
2338
|
+
|
|
2339
|
+
if c_genes_only == False or (c_genes_only and n_genes > 1):
|
|
2340
|
+
|
|
2341
|
+
pos_result_annotated, uni_feat_processed = genes_plots(gene_result,
|
|
2342
|
+
pos_result,
|
|
2343
|
+
seq_df,
|
|
2344
|
+
maf,
|
|
2345
|
+
maf_nonmiss,
|
|
2346
|
+
miss_prob_dict,
|
|
2347
|
+
output_dir_genes_plots,
|
|
2348
|
+
cohort,
|
|
2349
|
+
annotations_dir,
|
|
2350
|
+
disorder,
|
|
2351
|
+
uniprot_feat,
|
|
2352
|
+
pdb_tool,
|
|
2353
|
+
plot_pars,
|
|
2354
|
+
save_plot=save_plot,
|
|
2355
|
+
show_plot=show_plot,
|
|
2356
|
+
c_ext=c_ext,
|
|
2357
|
+
title=title)
|
|
2358
|
+
|
|
2359
|
+
# Associations plots
|
|
2360
|
+
if plot_associations and len(pos_result_annotated) > 0:
|
|
2361
|
+
pos_result_annotated_uni_feat = associations_plots(pos_result_annotated,
|
|
2362
|
+
uni_feat_processed,
|
|
2363
|
+
output_dir,
|
|
2364
|
+
plot_pars,
|
|
2365
|
+
miss_prob_dict,
|
|
2366
|
+
cohort)
|
|
2367
|
+
pos_result_annotated = pos_result_annotated.merge(
|
|
2368
|
+
pos_result_annotated_uni_feat.fillna(0), how="left", on=["Uniprot_ID", "Pos"])
|
|
2369
|
+
|
|
2370
|
+
|
|
2371
|
+
# Save annotations
|
|
2372
|
+
if save_csv and pos_result_annotated is not None:
|
|
2373
|
+
logger.info(f"Saving annotated Oncodrive3D result in {output_dir}")
|
|
2374
|
+
save_annotated_result(pos_result,
|
|
2375
|
+
pos_result_annotated,
|
|
2376
|
+
uni_feat_processed,
|
|
2377
|
+
output_dir,
|
|
2378
|
+
cohort,
|
|
2379
|
+
include_all_pos)
|
|
2380
|
+
|
|
2381
|
+
logger.info("Plotting completed!")
|
|
2382
|
+
else:
|
|
2383
|
+
logger.warning("There aren't any significant genes to plot!")
|
|
2384
|
+
else:
|
|
2385
|
+
logger.warning("There aren't any genes to plot!")
|
|
2386
|
+
|
|
2387
|
+
|
|
2388
|
+
def generate_comparative_plots(o3d_result_dir_1,
|
|
2389
|
+
cohort_1,
|
|
2390
|
+
o3d_result_dir_2,
|
|
2391
|
+
cohort_2,
|
|
2392
|
+
datasets_dir,
|
|
2393
|
+
annotations_dir,
|
|
2394
|
+
output_dir,
|
|
2395
|
+
plot_pars,
|
|
2396
|
+
maf_path_nonmiss_1=None,
|
|
2397
|
+
maf_path_nonmiss_2=None,
|
|
2398
|
+
n_genes=30,
|
|
2399
|
+
lst_genes=None):
|
|
2400
|
+
|
|
2401
|
+
# Load data tracks
|
|
2402
|
+
# ================
|
|
2403
|
+
|
|
2404
|
+
# Load data
|
|
2405
|
+
logger.debug("Loading data")
|
|
2406
|
+
gene_result_1, pos_result_1, maf_1, miss_prob_dict_1 = load_o3d_result(o3d_result_dir_1, cohort_1)
|
|
2407
|
+
gene_result_2, pos_result_2, maf_2, miss_prob_dict_2 = load_o3d_result(o3d_result_dir_2, cohort_2)
|
|
2408
|
+
|
|
2409
|
+
seq_df_path = os.path.join(datasets_dir, "seq_for_mut_prob.tsv")
|
|
2410
|
+
seq_df = pd.read_csv(seq_df_path, sep="\t")
|
|
2411
|
+
uniprot_feat = pd.read_csv(os.path.join(annotations_dir, "uniprot_feat.tsv"), sep="\t")
|
|
2412
|
+
pdb_tool = pd.read_csv(os.path.join(annotations_dir, "pdb_tool_df.tsv"), sep="\t")
|
|
2413
|
+
disorder = pd.read_csv(os.path.join(datasets_dir, "confidence.tsv"), sep="\t", low_memory=False)
|
|
2414
|
+
|
|
2415
|
+
# Clean up MOTIF description TO DO: it should be moved in the build-annotations step
|
|
2416
|
+
uniprot_feat.loc[(uniprot_feat["Type"] == "MOTIF") & (
|
|
2417
|
+
uniprot_feat["Description"] == "Zinc finger"), "Full_description"] = "Zinc finger"
|
|
2418
|
+
uniprot_feat.loc[(uniprot_feat["Type"] == "MOTIF") & (uniprot_feat["Full_description"].str.contains('WIN', case=False)), "Full_description"] = "WIN"
|
|
2419
|
+
uniprot_feat.loc[uniprot_feat["Type"] == "MOTIF", "Full_description"] = uniprot_feat.loc[uniprot_feat["Type"] == "MOTIF", "Full_description"].apply(
|
|
2420
|
+
lambda x: x.split(";")[0] if len(x.split(";")) > 1 else x)
|
|
2421
|
+
|
|
2422
|
+
# Filter Oncodrive3D result
|
|
2423
|
+
logger.debug("Filtering result")
|
|
2424
|
+
maf_1 = filter_non_processed_mut(maf_1, pos_result_1)
|
|
2425
|
+
maf_2 = filter_non_processed_mut(maf_2, pos_result_2)
|
|
2426
|
+
gene_result_1, pos_result_1, genes_1, uni_ids_1 = filter_o3d_result(gene_result_1,
|
|
2427
|
+
pos_result_1,
|
|
2428
|
+
n_genes,
|
|
2429
|
+
lst_genes)
|
|
2430
|
+
gene_result_2, pos_result_2, genes_2, uni_ids_2 = filter_o3d_result(gene_result_2,
|
|
2431
|
+
pos_result_2,
|
|
2432
|
+
n_genes,
|
|
2433
|
+
lst_genes)
|
|
2434
|
+
|
|
2435
|
+
# Get shared genes and Uniprot IDs
|
|
2436
|
+
shared_genes = [gene for gene in genes_1 if gene in genes_2]
|
|
2437
|
+
shared_uni_ids = [uid for uid in uni_ids_1 if uid in uni_ids_2]
|
|
2438
|
+
|
|
2439
|
+
if len(shared_genes) > 0:
|
|
2440
|
+
|
|
2441
|
+
# Subset dfs by selected genes and IDs
|
|
2442
|
+
logger.debug("Subset genes")
|
|
2443
|
+
seq_df, disorder, pdb_tool, uniprot_feat = subset_genes_and_ids(shared_genes,
|
|
2444
|
+
shared_uni_ids,
|
|
2445
|
+
seq_df,
|
|
2446
|
+
disorder,
|
|
2447
|
+
pdb_tool,
|
|
2448
|
+
uniprot_feat)
|
|
2449
|
+
|
|
2450
|
+
# Comparative plots
|
|
2451
|
+
if "nonmiss_count" in plot_pars["h_ratios"]:
|
|
2452
|
+
maf_nonmiss_1 = get_nonmiss_mut(maf_path_nonmiss_1)
|
|
2453
|
+
maf_nonmiss_2 = get_nonmiss_mut(maf_path_nonmiss_2)
|
|
2454
|
+
else:
|
|
2455
|
+
maf_nonmiss_1 = None
|
|
2456
|
+
maf_nonmiss_2 = None
|
|
2457
|
+
output_dir = os.path.join(output_dir, f"{cohort_1}.{cohort_2}.comparative_plots")
|
|
2458
|
+
os.makedirs(output_dir, exist_ok=True)
|
|
2459
|
+
|
|
2460
|
+
logger.info(f"Generating comparative plots in {output_dir}")
|
|
2461
|
+
comparative_plots(shared_genes,
|
|
2462
|
+
pos_result_1,
|
|
2463
|
+
maf_1,
|
|
2464
|
+
maf_nonmiss_1,
|
|
2465
|
+
miss_prob_dict_1,
|
|
2466
|
+
cohort_1,
|
|
2467
|
+
pos_result_2,
|
|
2468
|
+
maf_2,
|
|
2469
|
+
maf_nonmiss_2,
|
|
2470
|
+
miss_prob_dict_2,
|
|
2471
|
+
cohort_2,
|
|
2472
|
+
seq_df,
|
|
2473
|
+
output_dir,
|
|
2474
|
+
annotations_dir,
|
|
2475
|
+
disorder,
|
|
2476
|
+
uniprot_feat,
|
|
2477
|
+
pdb_tool,
|
|
2478
|
+
plot_pars,
|
|
2479
|
+
save_plot=True,
|
|
2480
|
+
show_plot=False)
|
|
2481
|
+
logger.info("Plotting completed!")
|
|
2482
|
+
|
|
2483
|
+
else:
|
|
2484
|
+
logger.warning("There aren't any genes to plot!")
|