예제 #1
0
def test_quick_pipeline_with_fragmented_compute():

	"""
	How can I used tcrdist3 to test for TCRs that may HLA restricted. 

	
	"""

	import os
	import pandas as pd
	import numpy as np
	from scipy import sparse
	from tcrdist.repertoire import TCRrep
	from tcrdist.rep_funcs import  compute_pw_sparse_out_of_memory
	
	f = 'mira_epitope_67_382_APHGVVFL_APHGVVFLHV_GVVFLHVTY_VVFLHVTYV.tcrdist3.csv'
	f = os.path.join('tcrdist','data','covid19',f)
	assert os.path.isfile(f)

	df = pd.read_csv(f)
	df = df[['subject', 'cell_type', 'v_b_gene', 'j_b_gene', 'cdr3_b_aa', 'cdr3_b_nucseq',  'cohort', 'hla-a', 'hla-a_1','hla-b', 'hla-b_1']]
	tr = TCRrep(cell_df = df,               
				organism = 'human',
				chains = ['beta'],
				db_file = 'alphabeta_gammadelta_db.tsv',
				compute_distances = False,
				store_all_cdr = False)

	from tcrdist.rep_funcs import  compute_pw_sparse_out_of_memory
	
	S, fragments = compute_pw_sparse_out_of_memory(	tr = tr,
													row_size      = 100,
													pm_processes  = 2,
													pm_pbar       = True,
													max_distance  = 1000,
													matrix_name   = 'rw_beta',
													reassemble    = True,
													cleanup       = False)

	tr.clone_df['B07'] = (tr.clone_df['hla-b'].str.startswith("B*07") | tr.clone_df['hla-b_1'].str.startswith("B*07"))
	tr.clone_df['B07'] = ["B*07" if (x) else "NOTB*07 " for x in tr.clone_df['B07']]

	#sparse.save_npz("S.npz", S)
	from tcrdist.rep_funcs import  compute_n_tally_out_of_memory
	nn_tally_df_cohort = compute_n_tally_out_of_memory(fragments,
												matrix_name = "rw_beta",
												pm_processes  = 6,
												to_file = False,
												to_memory = True, 
												knn_radius = 25, 
												x_cols = ['B07'])

	from hierdiff.association_testing import cluster_association_test
	nn_associations = cluster_association_test(res = nn_tally_df_cohort, y_col='cmember', method='fishers')
	nn_associations = nn_associations.sort_values('pvalue', ascending = True)
	import ast 
	nn_associations['neighbors_i'] = nn_associations.neighbors.apply(lambda x: ast.literal_eval(x))

	from tcrdist.summarize import test_for_almost_subsets, filter_is, filter_gt
	nn_associations['mostly_unique'] = test_for_almost_subsets(nn_associations['neighbors_i'], thr = 5)
	nr_nn_associations = filter_is(nn_associations, 'mostly_unique', 1).copy()

	#nr_nn_associations = filter_gt(nr_nn_associations, 'K_neighbors', 25).copy()
	nr_nn_associations


	# MOTIF GENERATION
	from tcrsampler.sampler import TCRsampler
	t = TCRsampler()
	if  'olga_human_beta_t.sampler.tsv' not in t.currently_available_backgrounds():
		t.download_background_file('olga_sampler.zip')
	#t.download_background_file('olga_sampler.zip') # ONLY IF NOT ALREADY DONE
	tcrsampler_beta = TCRsampler(default_background = 'olga_human_beta_t.sampler.tsv')
	tcrsampler_beta.build_background(max_rows = 1000)

	"""SEE PALMOTIF DOCS (https://github.com/agartland/palmotif)"""
	from palmotif import compute_pal_motif, svg_logo
	from tcrdist.summarize import _select
	
	"""GENERATE SVG GRAPHIC FOR EACH NODE OF THE TREE"""
	#pwmat_str = 'pw_beta'
	cdr3_name = 'cdr3_b_aa'
	gene_names = ['v_b_gene','j_b_gene']
	svgs_beta = list()
	svgs_beta_raw = list()
	info_list = list()

	from tcrdist.rep_diff import member_summ
	summary = member_summ(  res_df = nr_nn_associations,
							clone_df = tr.clone_df,
							addl_cols=['cohort','hla-a', 'hla-a_1', 'hla-b', 'hla-b_1', 'subject'])

	nr_nn_associations = pd.concat([nr_nn_associations, summary], axis = 1).reset_index()

	for i,r in nr_nn_associations.head(25).iterrows():
		dfnode  = tr.clone_df.iloc[r['neighbors_i'],:].copy()
		# <pwnode> Pairwise Matrix for node sequences
		pwnode = S[r['neighbors_i'],:] [:,r['neighbors_i']].todense()
		if dfnode.shape[0] > 2:
			iloc_idx = pwnode.sum(axis = 0).argmin()
			centroid = dfnode[cdr3_name].to_list()[iloc_idx]
		else:
			centroid = dfnode[cdr3_name].to_list()[0]

		print(f"CENTROID: {centroid}")

		gene_usage_beta = dfnode.groupby(gene_names).size()
		sampled_rep = tcrsampler_beta.sample( gene_usage_beta.reset_index().to_dict('split')['data'],
			flatten = True, depth = max(100, 1000 // dfnode.shape[0]))

		sampled_rep  = [x for x in sampled_rep if x is not None]

		motif, stat = compute_pal_motif(
						seqs = _select(df = tr.clone_df,
									   iloc_rows = r['neighbors_i'],
									   col = cdr3_name),
						refs = sampled_rep,
						centroid = centroid)

		svgs_beta.append(svg_logo(motif, return_str= True))

		sampled_rep = sampled_rep.append(centroid)
		motif_raw, _ = compute_pal_motif(
					 seqs =_select(df = tr.clone_df,
									iloc_rows = r['neighbors_i'],
									col = cdr3_name),
					 centroid = centroid)
		svgs_beta_raw.append(svg_logo(motif_raw, return_str= True))
		info_list.append(r)


	def row_to_string(r, vals = ['ct_columns', 'val_0', 'ct_0', 'val_1', 'ct_1', 'val_2', 'ct_2','val_3', 'ct_3', 'levels', 'K_neighbors', 'R_radius', 'RR', 'OR', 'pvalue', 'FWERp','FDRq']):
		#d = {v:r[v] for v in vals}
		return "<br></br>".join([f"\t{v} : {r[v]}" for v in vals])

	def to_html_table(r, vals = ['ct_columns', 'hla-a', 'hla-a_1', 'hla-b', 'hla-b_1', 'val_0', 'ct_0', 'val_2', 'ct_2', 'K_neighbors', 'R_radius', 'pvalue', 'FDRq','cdr3_b_aa','v_b_gene', 'j_b_gene', 'cohort','subject']):
		return pd.DataFrame(r[vals]).transpose().to_html()

	def shrink(html_str):
		return html_str.replace('height="100%"',  'height="10%"').\
			replace('width="100%"', 'width="10%"')

	with open('svgs_in_line.html', 'w') as fh:
		fh.write(f"<html><body>\n")
		

		for svg, svg_raw, details in zip(svgs_beta, svgs_beta_raw, info_list):
			fh.write(f"{shrink(svg_raw)}{shrink(svg)}")
			try:
				fh.write(to_html_table(details))
			except:
				print("F")
			fh.write("<div></div>")
		fh.write(f"</html></body>\n")
예제 #2
0
def _get_britanova_human_beta_chord_blood_subject_stratified_background(
        size=100000, random_state=24082020):
    """
    Produce a background, stratfied by 8 subjects up to 960,000 TCR clones. 

    Unique TCRs are returned without consideration of their clonal frequency.

    Parameters
    ----------
    size : int 
        Size of background
    random_state : int
        Seed for random. sample
    """
    """Check for background file. If not present, download"""
    if not 'britanova_human_beta_t_cb.tsv.sampler.tsv' in TCRsampler.currently_available_backgrounds(
    ):
        TCRsampler.download_background_file(
            'britanova_human_beta_t_cb.tsv.sampler.tsv.zip')
    else:
        pass
        # print("CONGRATS 'britanova_human_beta_t_cb.tsv.sampler.tsv' ALREADY INSTALLED")

    ts = TCRsampler(
        default_background='britanova_human_beta_t_cb.tsv.sampler.tsv')
    ts = get_stratified_gene_usage_frequency(ts=ts, replace=True)
    # In [10]: ts.ref_df.subject.value_counts()
    # Out[10]:
    # A5-S18.txt    1073416
    # A5-S17.txt     825507
    # A5-S13.txt     692050
    # A5-S12.txt     573373
    # A5-S16.txt     559980
    # A5-S11.txt     519582
    # A5-S14.txt     302288
    # A5-S15.txt     120302 (NOTE THIS IS THE SMALLED STAMPLE)

    total = size  #100K
    nsubject = 8
    import math
    per_sample = math.ceil(total / nsubject)
    if per_sample > 120000:
        raise ValueError(
            "Size: {size} exceed max size (960000) for valid stratification based on smallest sample"
        )

    samples = []
    for subject_name, subject_df in ts.ref_df.groupby('subject'):
        if subject_name == 'A5-S15.txt':
            samples.append(
                subject_df.sample(
                    per_sample, replace=False,
                    random_state=random_state).copy().reset_index(drop=True))
        else:
            samples.append(
                subject_df.sample(
                    per_sample, replace=False,
                    random_state=random_state).copy().reset_index(drop=True))

    bitanova_unique_clones_sampled = pd.concat(samples).reset_index(drop=True)
    bitanova_unique_clones_sampled = bitanova_unique_clones_sampled[[
        'v_reps', 'j_reps', 'cdr3'
    ]].rename(columns={
        'v_reps': 'v_b_gene',
        'j_reps': 'j_b_gene',
        'cdr3': 'cdr3_b_aa'
    })
    return bitanova_unique_clones_sampled