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0000000..609480e --- /dev/null +++ b/pills/pyproject.toml @@ -0,0 +1,26 @@ +[tool.poetry] +name = "pills" +version = "0.0.0" +description = "Examples that show how to interact with JUMP data" +authors = ["Alan Munoz"] +readme = "README.md" + +[tool.poetry.dependencies] +python = "^3.9" +boto3 = ">=1.33.1" +matplotlib = "^3.8.2" +polars = "^0.19.19" +pyarrow = "^14.0.1" +s3fs = "^2023.12.1" +seaborn = "^0.13.2" + +[tool.poetry.group.dev.dependencies] +jupyter = "^1.0.0" +jupytext = "^1.15.0" +pytest = "^7.4.1" +ruff-lsp = "^0.0.48" +ruff = "<0.2.0" + +[tool.jupytext.formats] +"notebooks/" = ".qmd" +"scripts/" = "py:percent" diff --git a/pills/scripts/basic.py b/pills/scripts/basic.py new file mode 100644 index 0000000..69ecbd7 --- /dev/null +++ b/pills/scripts/basic.py @@ -0,0 +1,65 @@ +#!/usr/bin/env jupyter +# --- +# jupyter: +# jupytext: +# text_representation: +# extension: .py +# format_name: percent +# format_version: '1.3' +# jupytext_version: 1.16.1 +# kernelspec: +# display_name: Python 3 +# language: python +# name: python3 +# --- +# %% Overview [markdown] +# # Basic JUMP data access +# This is a tutorial on how to access +# We will use polars to fetch the data frame lazily, with the help of s3fs and pyarrow. +# We prefer lazy loading because the data can be too big to be handled in memory. +# %% Imports +import polars as pl +from pyarrow.dataset import dataset +from s3fs import S3FileSystem + +# %% [markdown] +# The shapes of the available datasets are: +# - crispr: Knock-out genetic perturbations. +# - orf: Overexpression genetic perturbations. +# - compounds: Chemical genetic perturbations. +# +# The aws paths of the dataframes are shown below: +# %% Paths +prefix = ( + "s3://cellpainting-gallery/cpg0016-jump-integrated/source_all/workspace/profiles" +) +filepaths = dict( + crispr=f"{prefix}/chandrasekaran_2024_0000000/crispr/wellpos_cellcount_mad_outlier_nan_featselect_harmony.parquet", + 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+adbc-driver-sqlite = "^0.8.0" + + +[tool.poetry.group.dev.dependencies] +jupytext = "^1.15.2" +ipdb = "^0.13.13" +pyflakes = "^3.1.0" +ruff-lsp = "^0.0.48" + +[build-system] +requires = ["poetry-core"] +build-backend = "poetry.core.masonry.api" diff --git a/workspace/analysis/CD44_HAS2/1_correlations.py b/workspace/analysis/CD44_HAS2/1_correlations.py new file mode 100644 index 0000000..f651b96 --- /dev/null +++ b/workspace/analysis/CD44_HAS2/1_correlations.py @@ -0,0 +1,88 @@ +#!/usr/bin/env jupyter +# --- +# jupyter: +# jupytext: +# text_representation: +# extension: .py +# format_name: percent +# format_version: '1.3' +# jupytext_version: 1.15.2 +# kernelspec: +# display_name: Python 3 +# language: python +# name: python3 +# --- +# %% [Markdown] +""" +Find correlations between CD44 and HAS2. Question inspired by Prof. Chonghui Chen from Baylor College of Medicine during ASCB2 2023. +""" + +from itertools import product +from pathlib import Path + +import matplotlib.pyplot as plt +import numpy as np +import pandas as pd +import seaborn as sns +from broad_babel.query import run_query +from copairs.compute import pairwise_cosine + +from utils import get_figs_dir, load_path + +figs_dir = get_figs_dir() +df = load_path("../../profiles/harmonized_no_sphering_profiles.parquet") + +genes_of_interest = ("CD44", "HAS2") +cd44_crispr = run_query(query="CD44", input_column="standard_key", output_column="*") + +gene_matches = {pert: dict() for pert in genes_of_interest} +for gene in genes_of_interest: + results = list( + map( + lambda x: x, + run_query(query=gene, input_column="standard_key", output_column="*"), + ) + ) + for pert_type in ("crispr", "orf"): + result_array = [x[1] for x in results if x[0] == pert_type] + if len(result_array): + gene_matches[gene][pert_type] = result_array[0] + +# %% Calculate the correlations between has2 and cd44 based on CRISPR data + + +feat_cols = [x for x in df.columns if not x.startswith("Metadata")] +translator_crispr_jump_gene = {v.get("crispr"): k for k, v in gene_matches.items()} +subset = df.loc[df["Metadata_JCP2022"].isin(translator_crispr_jump_gene)] +subset.set_index( + subset["Metadata_JCP2022"].map(translator_crispr_jump_gene), + inplace=True, +) + +data_subset_no_features = subset[feat_cols] +n_samples = len(subset) +all_pair_ixs = np.array(list(product(range(n_samples), range(n_samples)))) +cosine_distance = pairwise_cosine( + data_subset_no_features.values, all_pair_ixs, batch_size=min(200, n_samples) +).reshape((n_samples, n_samples)) +cosine_df = ( + pd.DataFrame( + data=cosine_distance, + index=subset.index, + columns=subset.index, + ) + .sort_index(axis=0) + .sort_index(axis=1) +) +sns.heatmap( + cosine_df, + robust=True, +) +plt.tight_layout() +plt.savefig( + figs_dir / f"heatmap_cosdist_harmony_{'_'.join(genes_of_interest).lower() }.png", + dpi=300, +) +plt.close() + +# %% TODO Once acquired, use ORF data to have a look at these profiles. diff --git a/workspace/analysis/CD44_HAS2/utils.py b/workspace/analysis/CD44_HAS2/utils.py new file mode 100644 index 0000000..e76d40d --- /dev/null +++ b/workspace/analysis/CD44_HAS2/utils.py @@ -0,0 +1,14 @@ +#!/usr/bin/env jupyter + +import pandas as pd +from pathlib import Path + + +def load_path(path: str or Path): + return pd.read_parquet(Path(path)) + + +def get_figs_dir(): + figs_dir = Path("../../figs") + figs_dir.mkdir(exist_ok=True) + return figs_dir diff --git a/workspace/analysis/MYT1_RNF41/1_correlations.py b/workspace/analysis/MYT1_RNF41/1_correlations.py new file mode 100644 index 0000000..8ca9742 --- /dev/null +++ b/workspace/analysis/MYT1_RNF41/1_correlations.py @@ -0,0 +1,86 @@ +#!/usr/bin/env jupyter +#!/usr/bin/env jupyter +# --- +# jupyter: +# jupytext: +# text_representation: +# extension: .py +# format_name: percent +# format_version: '1.3' +# jupytext_version: 1.15.2 +# kernelspec: +# display_name: Python 3 +# language: python +# name: python3 +# --- +from itertools import product +from pathlib import Path + +import matplotlib.pyplot as plt +import numpy as np +import pandas as pd +import seaborn as sns +from broad_babel.query import run_query +from copairs.compute import pairwise_cosine + +dataset_filepath = ( + Path("..") / ".." / "profiles" / "harmonized_no_sphering_profiles.parquet" +) +figs_dir = Path("../figs") +figs_dir.mkdir(exist_ok=True) + +df = pd.read_parquet(dataset_filepath) + +genes_of_interest = ("RNF41", "MYT1") +# cd44_crispr = run_query(query="CD44", input_column="standard_key", output_column="*") + +gene_matches = {pert: dict() for pert in genes_of_interest} +for gene in genes_of_interest: + results = list( + map( + lambda x: x, + run_query(query=gene, input_column="standard_key", output_column="*"), + ) + ) + for pert_type in ("crispr", "orf"): + result_array = [x[1] for x in results if x[0] == pert_type] + if len(result_array): + gene_matches[gene][pert_type] = result_array[0] + + +# %% Calculate the correlations of myt1 and rnf41 +# They were reported to interact by collaborators, and Ardigen found them to correlate + +feat_cols = [x for x in df.columns if not x.startswith("Metadata")] +translator_crispr_jump_gene = {v.get("crispr"): k for k, v in gene_matches.items()} +subset = df.loc[df["Metadata_JCP2022"].isin(translator_crispr_jump_gene)] +subset.set_index( + subset["Metadata_JCP2022"].map(translator_crispr_jump_gene), + inplace=True, +) + +data_subset_no_features = subset[feat_cols] +n_samples = len(subset) +all_pair_ixs = np.array(list(product(range(n_samples), range(n_samples)))) +cosine_distance = pairwise_cosine( + data_subset_no_features.values, all_pair_ixs, batch_size=min(200, n_samples) +).reshape((n_samples, n_samples)) +cosine_df = ( + pd.DataFrame( + data=cosine_distance, + index=subset.index, + columns=subset.index, + ) + .sort_index(axis=0) + .sort_index(axis=1) +) +sns.heatmap( + cosine_df, + robust=True, +) +plt.tight_layout() +plt.savefig( + figs_dir / f"heatmap_cosdist_harmony_{'_'.join(genes_of_interest).lower() }.png", + dpi=300, +) +plt.close() diff --git a/workspace/analysis/RAB40B/compare_features.py b/workspace/analysis/RAB40B/compare_features.py new file mode 100644 index 0000000..77d45a7 --- /dev/null +++ b/workspace/analysis/RAB40B/compare_features.py @@ -0,0 +1,72 @@ +#!/usr/bin/env jupyter + +# Linked issue: https://github.com/broadinstitute/2023_12_JUMP_data_only_vignettes/issues/4 apply_scaler, +# Compare the four genes of interest that have been shown as anticorrelated: +# - Cluster A: +# - RAB40B +# - RAB40C +# - Cluster B: +# - INSYN1 +# - PIK3R3 + +from pathlib import Path + +import pandas as pd # TODO stick to polars +import polars as pl +import scipy.stats as stats +from statsmodels.stats.multitest import multipletests + +fpath = Path( + "/dgx1nas1/storage/data/shared/morphmap_profiles/orf/full_profiles_cc_adj_mean_corr.parquet" +) +genes_of_interest = ("RAB40B", "RAB40C", "INSYN1", "PIK3R3") + + +df = pl.read_parquet(fpath) +sub_df = df.filter(pl.col("Metadata_Symbol").is_in(genes_of_interest)) +groups = dict( + (x, f"{'RAB40B/C' if x.startswith('RAB') else 'INS/PIK'}") + for x in genes_of_interest +) + +clusters = sub_df.with_columns( + pl.col("Metadata_Symbol").replace(groups).alias("Metadata_Cluster") +) + + +medians = clusters.group_by("Metadata_Cluster").median() +diff = medians.select(pl.all().exclude("^Metadata.*$").diff()) +feature_diff = diff.filter(~pl.all_horizontal(pl.all().is_null())).melt() +feature_diff.sort(by="value").write_csv("feature_diffs.csv") + + +cluster_a = clusters.filter(pl.col("Metadata_Cluster") == "RAB40B/C").select( + pl.all().exclude("^Metadata.*$") +) +cluster_b = clusters.filter(pl.col("Metadata_Cluster") == "INS/PIK").select( + pl.all().exclude("^Metadata.*$") +) +results = [] +for feature in cluster_a.columns: + cluster_A = cluster_a.get_column(feature) + cluster_B = cluster_b.get_column(feature) + + # Use t-test or Mann-Whitney U test based on data distribution + t_stat, p_val = stats.ttest_ind(cluster_A, cluster_B, equal_var=False) + + results.append({"Feature": feature, "T-Statistic": t_stat, "P-Value": p_val}) + + +results_df = pd.DataFrame(results) + +# drop rows with NaN +results_df = results_df.dropna() + +# Apply multiple testing correction + +corrected_pvals = multipletests(results_df["P-Value"], method="fdr_bh")[1] +results_df["Corrected P-Value"] = corrected_pvals + +# Filter significant features +significant_features = results_df[results_df["Corrected P-Value"] < 0.05] +significant_features.to_csv("significant_features.csv") diff --git a/workspace/analysis/RAB40B/feature_diffs.csv b/workspace/analysis/RAB40B/feature_diffs.csv new file mode 100644 index 0000000..f76c12c --- /dev/null +++ b/workspace/analysis/RAB40B/feature_diffs.csv @@ -0,0 +1,4764 @@ 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+1,225 @@ +#!/usr/bin/env jupyter + +# --- +# jupyter: +# jupytext: +# text_representation: +# extension: .py +# format_name: percent +# format_version: '1.3' +# jupytext_version: 1.15.2 +# kernelspec: +# display_name: Python 3 +# language: python +# name: python3 +# --- + +""" +Calculate cosine similarity of the CRISPR profiles using GPU, +then wrangle information and produce an explorable data frame. + +The GPU section is based off this function +https://github.com/UKPLab/sentence-transformers/blob/master/sentence_transformers/util.py#L31 +""" +from itertools import cycle +from pathlib import Path + +import numpy as np +import polars as pl +import torch +from broad_babel.query import run_query +from torch import Tensor, device + +from utils import batch_processing, parallel + +device = device("cuda" if torch.cuda.is_available() else "cpu") + +assert device.type == "cuda", "Not running on GPUs" + + +def get_first_last_n(tensor: Tensor, n: int): + return tensor[:, [range(n), range(-n - 1, -1)]].reshape(-1, 2 * n) + + +@batch_processing +def jcp_to_standard(x): + return run_query(query=x, input_column="JCP2022", output_column="standard_key")[0][ + 0 + ] + + +@batch_processing +def jcp_to_ncbi(x): + return run_query(query=x, input_column="JCP2022", output_column="NCBI_Gene_ID")[0][ + 0 + ] + + +def cos_sim(a: Tensor, b: Tensor) -> Tensor: + """ + Computes the cosine similarity cos_sim(a[i], b[j]) for all i and j. + + :return: Matrix with res[i][j] = cos_sim(a[i], b[j]) + """ + a_norm = torch.nn.functional.normalize(a, p=2, dim=1) + b_norm = torch.nn.functional.normalize(b, p=2, dim=1) + return torch.mm(a_norm, b_norm.transpose(0, 1)) + + +filename = "harmonized_no_sphering_profiles" +dir_path = Path("../../profiles/") +profiles_path = dir_path / f"{filename}.parquet" +checkpoint_path = Path("jcp_df.parquet") + +# %% Set names +jcp_col = "Metadata_JCP2022" # Name of columns in input data frames +url_col = "Metadata_image" # Must start with "Metadata" +match_jcp_col = "Match" +match_url_col = "Match Example" +std_outname = "Gene/Compound" +ext_links_col = "Match resources" +ncbi_formatter = '{{"href": "https://www.ncbi.nlm.nih.gov/gene/{}", "label":"NCBI"}}' +url_template = ( + '"https://phenaid.ardigen.com/static-jumpcpexplorer/' 'images/{}_{{}}.jpg"' +) +img_formatter = '{{"img_src": {}, "href": {}, "width": 200}}' +n_vals_used = 25 + +# %% Load Metadata +df = pl.read_parquet(profiles_path) + +# %% add build url from individual wells +df = df.with_columns( + pl.concat_str( + pl.col("Metadata_Source"), + pl.col("Metadata_Plate"), + pl.col("Metadata_Well"), + separator="/", + ) + .map_elements(lambda x: url_template.format(x)) + .alias(url_col) +) +grouped = df.group_by("Metadata_JCP2022") +med = grouped.median() +meta = grouped.agg(pl.col("^Metadata_.*$").map_elements(cycle)) + +urls = grouped.agg(pl.col(url_col).map_elements(cycle)) + +for srs in meta.iter_columns(): + med.replace_column(med.columns.index(srs.name), srs) + +vals = Tensor(med.select(pl.all().exclude("^Metadata.*$")).to_numpy()) + +# Calculate cosine similarty +cosine_sim = cos_sim(vals, vals) + +# Sort by correlation +_sorted = cosine_sim.sort(axis=1) + +indices, values = [ + get_first_last_n(x, n_vals_used) for x in (_sorted.indices, _sorted.values) +] +## Build a dataframe containing matches +# Minimise repetition +jcp_ids = urls.select(pl.col(jcp_col)).to_series().to_numpy().astype("" https://sandbox.zenodo.org/api/deposit/depositions/165/actions/newversion + +""" + +""" +Future plans: +- TODO Incorporate NCBI ids (already added on broad-babel) +- TODO add differentiating features when compared to their controls +- TODO add Average precision metrics +"""