o Uݢg)@sdZddlmZddlmZddlZddlmZddl m Z ddl m ZddlmZddlmZmZmZmZmZmZmZdZdZdZd Zd Zd Zd d ZddZ GdddeZ!d"ddZ"d#ddZ#eeddd$d d!Z$dS)%z/Functions for calling cell-associated barcodes.) annotations) NamedTupleN)adjust_pvalue_bh)CHEMISTRY_DESCRIPTION_FIELDCHEMISTRY_SC3P_LTHT_CHEMISTRIESSC3P_V3_CHEMISTRIESSC3P_V4_CHEMISTRIESSC5P_CHEMISTRIESSC5P_V3_CHEMISTRIESgY@ii c Cs|dd|f}t||ddfjdd}t|dk}t|t|\}}t|}|dkr;||}d} n||} t| t|} || t|<t| dsXJ| S)atEstimate a gene expression profile by Simple Good Turing. Args: raw_mat (sparse matrix): Sparse matrix of all counts barcode_indices (np.array(int)): Barcode indices to use nz_feat (np.array(int)): Indices of features that are non-zero at least once Returns: profile (np.array(float)): Estimated probabilities of length len(nz_feat). Nr )axisrgg?) npravelsum flatnonzerocr_sgtZsgt_proportionslenrepeatisclose) matrixZbarcode_indicesZnz_featZprof_matprofileZ zero_featZ p_smoothedp0n0Zp0_iZ profile_prf/oak/stanford/groups/akundaje/marinovg/programs/cellranger-9.0.1/lib/python/cellranger/cell_calling.pyestimate_profile_sgt/s  rcCs*tt|d}t|||}||fS)aEstimate a gene expression profile on a given subset of barcodes. Use Good-Turing to smooth the estimated profile. Args: matrix (scipy.sparse.csc_matrix): Sparse matrix of all counts use_bcs (np.array(int)): Indices of barcodes to use (col indices into matrix) Returns: profile (use_features, np.array(float)): Estimated probabilities of length use_features. r )rrasarrayrr)rZuse_bcsZ use_featsZ bg_profile_prrrest_background_profile_sgtTs rc@s>eZdZUded<ded<ded<ded<ded<ded<d S) NonAmbientBarcodeResultz np.ndarrayeval_bcslog_likelihoodpvalues pvalues_adj is_nonambientintemptydrops_minimum_umisN)__name__ __module__ __qualname____annotations__rrrrr is  r chemistry_descriptionstrreturnfloatcCs.tttt}dd|D}||vrdSdS)zCGets the maximum adjusted p-value to call a barcode as non-ambient.cSg|]}|tqSrr.0Zchemrrr vsz'get_empty_drops_fdr..gMbP?g{Gz?)r rr r)r,Z chemistriesZ chem_namesrrrget_empty_drops_fdrrsr5 num_probe_bcs int | Nonetuple[int, int]cCsf|ttkr d}n$|ddtttDvr"|durd}nd|}n |dur+d|}nd}|d|fS) a#Gets the range of values to use for empty drops background given a chemistry description. Args: chemistry_description: A string describing the chemistry num_probe_bcs: The number of probe or OCM multiplexing barcodes Returns: (lower_range, upper_range) i(#cSr0rr1r2rrrr4sz)get_empty_drops_range..Niqi@i_)rrrr r )r,r6Z n_partitionsrrrget_empty_drops_rangezs     r: multinomial)r'num_simsmethodNonAmbientBarcodeResult | Nonec s|dvsJ|}t|}t||\} } t|} td| d| |ddd| | } | t|} | tj| | dd}t |dkr{zt |j |\}}|d kr_t |j ||}Wn'tjyz}z tt|WYd}~dSd}~wwtjdtjd }td}t|ttjfd d |jDt |jtd }|dkrdStjt|j}tj||<tj|| dd}t|d|}td|tj|||k<t ||j}ttj||jdd|}|t |dkrdSt t!||rJt t!|| rJtdt |td||"d||tdt | tdt ||j |ddfdd|f}t |dkrrt#tj$t |}t#dt |}t#tj$t |}dS|d krt %|||}t j&|||||d\}}nt '|t(|}t j)||||d\}}t *|||||}t+|}td| tdt"||| k}tdt|t,||||||dS)aCall barcodes as being sufficiently distinct from the ambient profile. Args: matrix (CountMatrix): Full expression matrix. orig_cell_bcs (iterable of str): Strings of initially-called cell barcodes. chemistry_description: Change ambient RNA estimation for LT chemistry num_probe_bcs: The number of probe or OCM multiplexing barcodes emptydrops_minimum_umis: Minimum UMI threshold num_sims: Number of simulations Returns: NonAmbientBarcodeResult ) dirichletr;zRange empty barcodes: z - NT) assume_uniquerr?)dtypec3s|]}|vVqdS)Nr)r3bcZorig_cell_bc_setrr sz+find_nonambient_barcodes..)countrB)initialr zMax background UMIs: )maskzNumber of candidate bcs: zRange candidate bc umis: z, zNumber of empty bcs: zNumber of original cell calls: )r<zMax adjusted P-value: zMin observed P-value: z+Non-ambient bcs identified by empty drops: )r!r"r#r$r%r')-get_counts_per_bcrargsortr:r5printsortr intersect1drrmcr_statsZ!estimate_dirichlet_overdispersionrZSimpleGoodTuringErrorr-zerosint64setfromiterbcsboolrmaarrayarangebcs_dimmaskedmaxrH masked_arrayanyisinminrnanZ)eval_dirichlet_multinomial_loglikelihoodsZ-simulate_dirichlet_multinomial_loglikelihoodsZeval_multinomial_loglikelihoodslogZ#simulate_multinomial_loglikelihoodsZcompute_ambient_pvaluesrr )r orig_cell_bcsr,r6r'r<r= umis_per_bcZbc_orderlowhighZmax_adj_pvalueZ empty_bcsZnz_bcsZ ambient_bcsZ eval_featuresZambient_profile_palphaeZ orig_cellsr!Zmax_background_umisZn_unmasked_bcsZeval_matZ obs_loglkr#Z sim_loglkZ distinct_nsr$r%rrDrfind_nonambient_barcodess         $     rh)r,r-r.r/)r,r-r6r7r.r8)r.r>)%__doc__ __future__rtypingrnumpyrnumpy.marVZcellranger.sgtZsgtrZcellranger.statsstatsrOZcellranger.analysis.diffexprcellranger.chemistryrrrrr r r MIN_GLOBAL_UMIS MAX_MITO_PCTMIN_UMISNUM_SIMS%TARGETED_CC_MIN_UMIS_ADDITIONAL_CELLS&TARGETED_CC_MIN_UMIS_FROM_TARGET_GENESrrr r5r:rhrrrrs0      $ % #