def plot_auprc(
truth,
preds,
title_prefix: str = "Precision recall curve",
fname: str = "",
):
"""Plot AUPRC"""
truth = utils.ensure_arr(truth).flatten()
preds = utils.ensure_arr(preds).flatten()
precision, recall, _thresholds = metrics.precision_recall_curve(
truth, preds)
average_precision = metrics.average_precision_score(truth, preds)
logging.info(f"Found AUPRC of {average_precision:.4f}")
fig, ax = plt.subplots(dpi=SAVEFIG_DPI, figsize=(7, 5))
ax.plot(recall, precision)
ax.set(
xlabel="Recall",
ylabel="Precision",
title=f"{title_prefix} (AUPRC={average_precision:.4f})",
)
if fname:
fig.savefig(fname, bbox_inches="tight")
return fig
def do_evaluation_atac_from_rna(
spliced_net,
sc_dual_full_dataset,
gene_names: str,
atac_names: str,
outdir: str,
ext: str,
marker_genes: List[str],
prefix: str = "",
):
### RNA > ATAC
logging.info("Inferring ATAC from RNA")
sc_rna_atac_full_preds = spliced_net.translate_1_to_2(sc_dual_full_dataset)
sc_rna_atac_full_preds_anndata = sc.AnnData(
scipy.sparse.csr_matrix(sc_rna_atac_full_preds),
obs=sc_dual_full_dataset.dataset_x.data_raw.obs,
)
sc_rna_atac_full_preds_anndata.var_names = atac_names
logging.info("Writing ATAC from RNA")
sc_rna_atac_full_preds_anndata.write(
os.path.join(outdir, f"{prefix}_rna_atac_adata.h5ad".strip("_"))
)
if hasattr(sc_dual_full_dataset.dataset_y, "data_raw") and ext is not None:
logging.info("Plotting ATAC from RNA")
plot_utils.plot_auroc(
utils.ensure_arr(sc_dual_full_dataset.dataset_y.data_raw.X).flatten(),
utils.ensure_arr(sc_rna_atac_full_preds).flatten(),
title_prefix=f"{DATASET_NAME} RNA > ATAC".strip(),
fname=os.path.join(outdir, f"{prefix}_rna_atac_auroc.{ext}".strip("_")),
)
def main():
"""Run script"""
parser = build_parser()
args = parser.parse_args()
truth = load_file_flex_format(args.truth)
truth.X = utils.ensure_arr(truth.X)
logging.info(f"Loaded truth {args.truth}: {truth.shape}")
preds = load_file_flex_format(args.preds)
preds.X = utils.ensure_arr(preds.X)
logging.info(f"Loaded preds {args.preds}: {preds.shape}")
common_genes = sorted(
list(set(truth.var_names).intersection(preds.var_names)))
logging.info(f"Shared genes: {len(common_genes)}")
common_obs = sorted(
list(set(truth.obs_names).intersection(preds.obs_names)))
# All obs naames should intersect between preds and truth
assert len(common_obs) == len(truth.obs_names) == len(preds.obs_names)
plot_utils.plot_var_vs_explained_var(
truth,
preds,
highlight_genes={k: REF_MARKER_GENES[k]
for k in args.highlight},
logscale=not args.linear,
constrain_y_axis=not args.unconstriained,
label_outliers=args.outliers,
fname=args.plotname,
fname_gene_list=args.genelist,
)
def plot_auroc(
truth,
preds,
title_prefix: str = "Receiver operating characteristic",
fname: str = "",
):
"""
Plot AUROC after flattening inputs
"""
truth = utils.ensure_arr(truth).flatten()
preds = utils.ensure_arr(preds).flatten()
fpr, tpr, _thresholds = metrics.roc_curve(truth, preds)
auc = metrics.auc(fpr, tpr)
logging.info(f"Found AUROC of {auc:.4f}")
fig, ax = plt.subplots(dpi=300, figsize=(7, 5))
ax.plot(fpr, tpr)
ax.set(
xlim=(0, 1.0),
ylim=(0.0, 1.05),
xlabel="False positive rate",
ylabel="True positive rate",
title=f"{title_prefix} (AUROC={auc:.2f})",
)
if fname:
fig.savefig(fname, dpi=SAVEFIG_DPI, bbox_inches="tight")
return fig
def plot_bulk_scatter(
x: AnnData,
y: AnnData,
x_subset: dict = None,
y_subset: dict = None,
logscale: bool = True,
corr_func: Callable = scipy.stats.pearsonr,
title: str = "",
xlabel: str = "Average measured counts",
ylabel: str = "Average inferred counts",
fname: str = "",
):
"""
Create bulk signature and plot
"""
if x_subset is not None:
orig_size = x.n_obs
x = adata_utils.filter_adata(x, filt_cells=x_subset)
logging.info(f"Subsetted x from {orig_size} to {x.n_obs}")
if y_subset is not None:
orig_size = y.n_obs
y = adata_utils.filter_adata(y, filt_cells=y_subset)
logging.info(f"Subsetted y from {orig_size} to {y.n_obs}")
# Make sure variables match
shared_var_names = sorted(list(set(x.var_names).intersection(y.var_names)))
logging.info(f"Found {len(shared_var_names)} shared variables")
x = x[:, shared_var_names]
y = y[:, shared_var_names]
x_vals = x.X
y_vals = y.X
if logscale:
x_vals = np.log1p(x_vals)
y_vals = np.log1p(y_vals)
# Ensure correct format
x_vals = utils.ensure_arr(x_vals).mean(axis=0)
y_vals = utils.ensure_arr(y_vals).mean(axis=0)
assert not np.any(np.isnan(x_vals))
assert not np.any(np.isnan(y_vals))
pearson_r, pearson_p = corr_func(x_vals, y_vals)
logging.info(f"Found pearson's correlation of {pearson_r:.4f}")
fig, ax = plt.subplots(dpi=SAVEFIG_DPI, figsize=(7, 5))
ax.scatter(x_vals, y_vals, alpha=0.4)
ax.set(
xlabel=xlabel + (" (log)" if logscale else ""),
ylabel=ylabel + (" (log)" if logscale else ""),
title=(title + f" ($r={pearson_r:.2f}$)").strip(),
)
if fname:
fig.savefig(fname, bbox_inches="tight")
return fig
def load_rna_files(rna_counts_fnames: List[str],
model_dir: str,
transpose: bool = True) -> ad.AnnData:
"""Load the RNA files in, filling in unmeasured genes as necessary"""
# Find the genes that the model understands
rna_genes_list_fname = os.path.join(model_dir, "rna_genes.txt")
assert os.path.isfile(
rna_genes_list_fname
), f"Cannot find RNA genes file: {rna_genes_list_fname}"
learned_rna_genes = utils.read_delimited_file(rna_genes_list_fname)
assert isinstance(learned_rna_genes, list)
assert utils.is_all_unique(
learned_rna_genes), "Learned genes list contains duplicates"
temp_ad = utils.sc_read_multi_files(
rna_counts_fnames,
feature_type="Gene Expression",
transpose=transpose,
join="outer",
)
logging.info(f"Read input RNA files for {temp_ad.shape}")
temp_ad.X = utils.ensure_arr(temp_ad.X)
# Filter for mouse genes and remove human/mouse prefix
temp_ad.var_names_make_unique()
kept_var_names = [
vname for vname in temp_ad.var_names if not vname.startswith("MOUSE_")
]
if len(kept_var_names) != temp_ad.n_vars:
temp_ad = temp_ad[:, kept_var_names]
temp_ad.var = pd.DataFrame(
index=[v.strip("HUMAN_") for v in kept_var_names])
# Expand adata to span all genes
# Initiating as a sparse matrix doesn't allow vectorized building
intersected_genes = set(temp_ad.var_names).intersection(learned_rna_genes)
assert intersected_genes, "No overlap between learned and input genes!"
expanded_mat = np.zeros((temp_ad.n_obs, len(learned_rna_genes)))
skip_count = 0
for gene in intersected_genes:
dest_idx = learned_rna_genes.index(gene)
src_idx = temp_ad.var_names.get_loc(gene)
if not isinstance(src_idx, int):
logging.warn(f"Got multiple source matches for {gene}, skipping")
skip_count += 1
continue
v = utils.ensure_arr(temp_ad.X[:, src_idx]).flatten()
expanded_mat[:, dest_idx] = v
if skip_count:
logging.warning(
f"Skipped {skip_count}/{len(intersected_genes)} genes due to multiple matches"
)
expanded_mat = sparse.csr_matrix(expanded_mat) # Compress
retval = ad.AnnData(expanded_mat,
obs=temp_ad.obs,
var=pd.DataFrame(index=learned_rna_genes))
return retval
def do_evaluation_atac_from_atac(
spliced_net,
sc_dual_full_dataset,
gene_names: str,
atac_names: str,
outdir: str,
ext: str,
marker_genes: List[str],
prefix: str = "",
):
### ATAC > ATAC
logging.info("Inferring ATAC from ATAC")
sc_atac_full_preds = spliced_net.translate_2_to_2(sc_dual_full_dataset)
sc_atac_full_preds_anndata = sc.AnnData(
sc_atac_full_preds,
obs=sc_dual_full_dataset.dataset_y.data_raw.obs.copy(deep=True),
)
sc_atac_full_preds_anndata.var_names = atac_names
logging.info("Writing ATAC from ATAC")
# Infer marker bins
# logging.info("Getting marker bins for ATAC from ATAC")
# plot_utils.preprocess_anndata(sc_atac_full_preds_anndata)
# adata_utils.find_marker_genes(sc_atac_full_preds_anndata)
# inferred_marker_bins = adata_utils.flatten_marker_genes(
# sc_atac_full_preds_anndata.uns["rank_genes_leiden"]
# )
# logging.info(f"Found {len(inferred_marker_bins)} marker bins for ATAC from ATAC")
# with open(
# os.path.join(outdir, f"{prefix}_atac_atac_marker_bins.txt".strip("_")), "w"
# ) as sink:
# sink.write("\n".join(inferred_marker_bins) + "\n")
sc_atac_full_preds_anndata.write(
os.path.join(outdir, f"{prefix}_atac_atac_adata.h5ad".strip("_"))
)
if hasattr(sc_dual_full_dataset.dataset_y, "data_raw") and ext is not None:
logging.info("Plotting ATAC from ATAC")
plot_utils.plot_auroc(
utils.ensure_arr(sc_dual_full_dataset.dataset_y.data_raw.X).flatten(),
utils.ensure_arr(sc_atac_full_preds).flatten(),
title_prefix=f"{DATASET_NAME} ATAC > ATAC".strip(),
fname=os.path.join(outdir, f"{prefix}_atac_atac_auroc.{ext}".strip("_")),
)
# plot_utils.plot_auprc(
# utils.ensure_arr(sc_dual_full_dataset.dataset_y.data_raw.X).flatten(),
# utils.ensure_arr(sc_atac_full_preds).flatten(),
# title_prefix=f"{DATASET_NAME} ATAC > ATAC".strip(),
# fname=os.path.join(outdir, f"{prefix}_atac_atac_auprc.{ext}".strip("_")),
# )
# Remove some objects to free memory
del sc_atac_full_preds
del sc_atac_full_preds_anndata
def main():
parser = build_parser()
args = parser.parse_args()
_, input_ext = os.path.splitext(args.input)
if input_ext == ".h5ad":
x = ad.read_h5ad(args.input)
elif input_ext == ".h5":
x = sc.read_10x_h5(args.input)
else:
raise ValueError(f"Unrecognized file extension: {args.input}")
logging.info(f"Read input: {x}")
logging.info("Reading gtf for gene name map")
gene_name_map = utils.read_gtf_gene_symbol_to_id()
# Tranpose because BIRD wants features x obs
x_df = pd.DataFrame(utils.ensure_arr(x.X),
index=x.obs_names,
columns=x.var_names).T
assert np.all(x_df.values >= 0.0)
x_df.index = [gene_name_map[g] for g in x_df.index]
# Write output (tab-separated table
logging.info(f"Writing output to {args.output_table_txt}")
x_df.to_csv(args.output_table_txt, sep="\t")
def reindex_adata_vars(adata: AnnData, target_vars: List[str]) -> AnnData:
"""Reindexes the adata to match the given var_list, verbatim"""
assert len(adata.var_names) == adata.n_vars
if not utils.is_all_unique(adata.var_names):
logging.warn("De-duping variable names before reindexing")
adata.var_names_make_unique()
assert utils.is_all_unique(target_vars), "Target vars are not all unique"
intersected = set(adata.var_names).intersection(target_vars)
logging.info(
f"Overlap of {len(intersected)}/{adata.n_vars}, 0 vector will be filled in for {len(target_vars) - len(intersected)} 'missing' features"
)
vars_to_cols = dict(zip(adata.var_names, utils.ensure_arr(adata.X).T))
assert (len(vars_to_cols) == adata.n_vars
), f"Size mismatch: {len(vars_to_cols)} {adata.n_vars}"
default_null = np.zeros(adata.n_obs)
mat = np.vstack([
vars_to_cols[v] if v in vars_to_cols else np.copy(default_null)
for v in target_vars
]).T
target_shape = (adata.n_obs, len(target_vars))
assert mat.shape == target_shape, f"Size mismatch: {mat.shape} {target_shape}"
retval = AnnData(mat)
retval.obs_names = adata.obs_names
retval.var_names = target_vars
return retval
def main():
"""Run script"""
parser = build_parser()
args = parser.parse_args()
adata = ad.read_h5ad(args.h5ad)
logging.info(f"Read {args.h5ad} for adata of {adata.shape}")
if args.discrete:
# Use the discrete algorithm from pyitlib
# https://pafoster.github.io/pyitlib/#discrete_random_variable.entropy_joint
# https://github.com/pafoster/pyitlib/blob/master/pyitlib/discrete_random_variable.py#L3535
# Successive realisations of a random variable are indexed by the last axis in the array; multiple random variables may be specified using preceding axes.
# In other words, different variables are axis 0, samples are axis 1
# This is contrary to the default ML format which is samples axis 0, variables axes 1
# Therefore we must transpose
input_arr = utils.ensure_arr(adata.X).T
h = drv.entropy_joint(input_arr, base=np.e)
logging.info(f"Found discrete joint entropy of {h:.6f}")
else:
raise NotImplementedError
def main():
parser = build_parser()
args = parser.parse_args()
if args.x_rna.endswith(".h5ad"):
x_rna = ad.read_h5ad(args.x_rna)
elif args.x_rna.endswith(".h5"):
x_rna = sc.read_10x_h5(args.x_rna, gex_only=False)
else:
raise ValueError(f"Unrecognized file extension: {args.x_rna}")
x_rna.X = utils.ensure_arr(x_rna.X)
x_rna.obs_names = sanitize_obs_names(x_rna.obs_names)
x_rna.obs_names_make_unique()
logging.info(f"Read in {args.x_rna} for {x_rna.shape}")
if args.y_rna.endswith(".h5ad"):
y_rna = ad.read_h5ad(args.y_rna)
elif args.y_rna.endswith(".h5"):
y_rna = sc.read_10x_h5(args.y_rna, gex_only=False)
else:
raise ValueError(f"Unrecognized file extension: {args.y_rna}")
y_rna.X = utils.ensure_arr(y_rna.X)
y_rna.obs_names = sanitize_obs_names(y_rna.obs_names)
y_rna.obs_names_make_unique()
logging.info(f"Read in {args.y_rna} for {y_rna.shape}")
if not (len(x_rna.obs_names) == len(y_rna.obs_names)
and np.all(x_rna.obs_names == y_rna.obs_names)):
logging.warning("Rematching obs axis")
shared_obs_names = sorted(
list(set(x_rna.obs_names).intersection(y_rna.obs_names)))
logging.info(f"Found {len(shared_obs_names)} shared obs")
assert shared_obs_names, ("Got empty list of shared obs" + "\n" +
str(x_rna.obs_names) + "\n" +
str(y_rna.obs_names))
x_rna = x_rna[shared_obs_names]
y_rna = y_rna[shared_obs_names]
assert np.all(x_rna.obs_names == y_rna.obs_names)
if not (len(x_rna.var_names) == len(y_rna.var_names)
and np.all(x_rna.var_names == y_rna.var_names)):
logging.warning("Rematching variable axis")
shared_var_names = sorted(
list(set(x_rna.var_names).intersection(y_rna.var_names)))
logging.info(f"Found {len(shared_var_names)} shared variables")
assert shared_var_names, ("Got empty list of shared vars" + "\n" +
str(x_rna.var_names) + "\n" +
str(y_rna.var_names))
x_rna = x_rna[:, shared_var_names]
y_rna = y_rna[:, shared_var_names]
assert np.all(x_rna.var_names == y_rna.var_names)
# Subset by gene list if given
if args.genelist:
gene_list = utils.read_delimited_file(args.genelist)
logging.info(f"Read {len(gene_list)} genes from {args.genelist}")
x_rna = x_rna[:, gene_list]
y_rna = y_rna[:, gene_list]
assert x_rna.shape == y_rna.shape, f"Mismatched shapes {x_rna.shape} {y_rna.shape}"
fig = plot_utils.plot_scatter_with_r(
x_rna.X,
y_rna.X,
subset=args.subset,
one_to_one=True,
logscale=not args.linear,
density_heatmap=args.density,
density_logstretch=args.densitylogstretch,
fname=args.outfname,
title=args.title,
xlabel=args.xlabel,
ylabel=args.ylabel,
figsize=args.figsize,
)
def plot_scatter_with_r(
x: Union[np.ndarray, scipy.sparse.csr_matrix],
y: Union[np.ndarray, scipy.sparse.csr_matrix],
color=None,
subset: int = 0,
logscale: bool = False,
density_heatmap: bool = False,
density_dpi: int = 150,
density_logstretch: int = 1000,
title: str = "",
xlabel: str = "Original norm counts",
ylabel: str = "Inferred norm counts",
xlim: Tuple[int, int] = None,
ylim: Tuple[int, int] = None,
one_to_one: bool = False,
corr_func: Callable = scipy.stats.pearsonr,
figsize: Tuple[float, float] = (7, 5),
fname: str = "",
ax=None,
):
"""
Plot the given x y coordinates, appending Pearsons r
Setting xlim/ylim will affect both plot and R2 calculation
In other words, plot view mirrors the range for which correlation is calculated
"""
assert x.shape == y.shape, f"Mismatched shapes: {x.shape} {y.shape}"
if color is not None:
assert color.size == x.size
if one_to_one and (xlim is not None or ylim is not None):
assert xlim == ylim
if xlim:
keep_idx = utils.ensure_arr((x >= xlim[0]).multiply(x <= xlim[1]))
x = utils.ensure_arr(x[keep_idx])
y = utils.ensure_arr(y[keep_idx])
if ylim:
keep_idx = utils.ensure_arr((y >= ylim[0]).multiply(x <= xlim[1]))
x = utils.ensure_arr(x[keep_idx])
y = utils.ensure_arr(y[keep_idx])
# x and y may or may not be sparse at this point
assert x.shape == y.shape
if subset > 0 and subset < x.size:
logging.info(f"Subsetting to {subset} points")
random.seed(1234)
# Converts flat index to coordinates
indices = np.unravel_index(np.array(
random.sample(range(np.product(x.shape)), k=subset)),
shape=x.shape)
x = utils.ensure_arr(x[indices])
y = utils.ensure_arr(y[indices])
if isinstance(color, (tuple, list, np.ndarray)):
color = np.array([color[i] for i in indices])
if logscale:
x = np.log1p(x)
y = np.log1p(y)
# Ensure correct format
x = utils.ensure_arr(x).flatten()
y = utils.ensure_arr(y).flatten()
assert not np.any(np.isnan(x))
assert not np.any(np.isnan(y))
pearson_r, pearson_p = scipy.stats.pearsonr(x, y)
logging.info(
f"Found pearson's correlation/p of {pearson_r:.4f}/{pearson_p:.4g}")
spearman_corr, spearman_p = scipy.stats.spearmanr(x, y)
logging.info(
f"Found spearman's collelation/p of {spearman_corr:.4f}/{spearman_p:.4g}"
)
if ax is None:
fig = plt.figure(dpi=300, figsize=figsize)
if density_heatmap:
# https://github.com/astrofrog/mpl-scatter-density
ax = fig.add_subplot(1, 1, 1, projection="scatter_density")
else:
ax = fig.add_subplot(1, 1, 1)
else:
fig = None
if density_heatmap:
norm = None
if density_logstretch:
norm = ImageNormalize(vmin=0,
vmax=100,
stretch=LogStretch(a=density_logstretch))
ax.scatter_density(x, y, dpi=density_dpi, norm=norm, color="tab:blue")
else:
ax.scatter(x, y, alpha=0.2, c=color)
if one_to_one:
unit = np.linspace(*ax.get_xlim())
ax.plot(unit,
unit,
linestyle="--",
alpha=0.5,
label="$y=x$",
color="grey")
ax.legend()
ax.set(
xlabel=xlabel + (" (log)" if logscale else ""),
ylabel=ylabel + (" (log)" if logscale else ""),
title=(title + f" ($r={pearson_r:.2f}$)").strip(),
)
if xlim:
ax.set(xlim=xlim)
if ylim:
ax.set(ylim=ylim)
if fig is not None and fname:
fig.savefig(fname, dpi=SAVEFIG_DPI, bbox_inches="tight")
return fig
def archr_gene_activity_matrix_from_adata(
adata: ad.AnnData,
annotation: str = sc_data_loaders.HG38_GTF,
gene_model: Callable = lambda x: np.exp(-np.abs(x) / 5000) + np.exp(-1),
extension: int = 100000,
gene_upstream: int = 5000,
use_gene_boundaries: bool = True,
use_TSS: bool = False,
gene_scale_factor: float = 5.0, # Numeric scaling factor to weight genes based on inverse of length
ceiling: float = 4.0,
scale_to: float = 10000.0,
) -> ad.AnnData:
"""
Use the more sophisiticated gene activity scoring method described here:
https://www.archrproject.com/bookdown/calculating-gene-scores-in-archr.html
https://github.com/GreenleafLab/ArchR/blob/ddcaae4a6093685875052219141e5ea41030fc55/R/MatrixGeneScores.R
Note this isn't a FULL reimplementation since we do slightly different handling of distances
and tiling and such, but this should be a very close approximation
Some other notes:
- By default, ArchR appears to be doing distance calculations based on the entire gene body, which we do
"""
gene_to_pos = utils.read_gtf_gene_to_pos(annotation, extend_upstream=gene_upstream)
genes = list(gene_to_pos.keys())
# Map each gene and bin to a corresponding index in axis
gene_to_idx = {g: i for i, g in enumerate(genes)}
bin_to_idx = {b: i for i, b in enumerate(adata.var_names)}
# Map of chrom without chr prefix to intervaltree
chrom_to_gene_intervals = utils.gene_pos_dict_to_range(gene_to_pos)
# Create a mapping of where atac bins are, so we can easily grep for overlap later
chrom_to_atac_intervals = collections.defaultdict(itree.IntervalTree)
for atac_bin in adata.var_names:
chrom, span = atac_bin.split(":")
if chrom.startswith("chr"):
chrom = chrom.strip("chr")
start, stop = map(int, span.split("-"))
chrom_to_atac_intervals[chrom][start:stop] = atac_bin
# Create a matrix that maps each feature to overlapping genes with weight
weights = scipy.sparse.lil_matrix((adata.shape[1], len(genes)), dtype=float)
# Create per-gene weights based on size of the gene
logging.info("Determining gene weights based on gene size")
gene_widths = np.array([gene_to_pos[g][2] - gene_to_pos[g][1] for g in genes])
assert np.all(gene_widths > 0)
inv_gene_widths = 1 / gene_widths
gene_weight = 1 + inv_gene_widths * (gene_scale_factor - 1) / (
np.max(inv_gene_widths) - np.min(inv_gene_widths)
)
assert np.all(gene_weight >= 1)
if not np.all(gene_weight <= gene_scale_factor):
logging.warning(
f"Found values exceeding gene scale factor {gene_scale_factor}: {gene_weight[np.where(gene_weight > gene_scale_factor)]}"
)
if not np.all(gene_weight >= 1.0):
logging.warning(
f"Found values below minimum expected value of 1: {gene_weight[np.where(gene_weight < 1.0)]}"
)
logging.info("Constructing bin to gene matrix")
for gene in genes: # Compute weight for each gene
gene_gi = genomic_interval.GenomicInterval(
gene_to_pos[gene], metadata_dict={"gene": gene}
)
chrom, start, stop = gene_to_pos[gene]
assert start < stop
# Get all ATAC bins
gene_overlap_atac_bins = chrom_to_atac_intervals[chrom][
start - extension : stop + extension
]
# Drop the ATAC bins that overlap a gene that isn't this current gene
filtered_gene_overlap_atac_bins = []
for o in gene_overlap_atac_bins:
atac_start, atac_end = o.begin, o.end
atac_bin_gene_overlaps = chrom_to_gene_intervals[chrom][atac_start:atac_end]
is_matched = [g.data != gene for g in atac_bin_gene_overlaps]
if any(is_matched):
continue
filtered_gene_overlap_atac_bins.append(o)
# Calculate the distance and the corresponding weight
for o in filtered_gene_overlap_atac_bins:
bin_gi = genomic_interval.GenomicInterval((chrom, o.begin, o.end))
d = gene_gi.difference(bin_gi)
assert d >= 0
w = gene_model(d)
assert weights[bin_to_idx[o.data], gene_to_idx[gene]] == 0
# Note, ArchR works on 500bp bins, so may count a little differently
# To adjust multiply by teh size of the bin divided by 500
# This approximates how many times each bin might be counted
# as fragments
v = w * gene_weight[gene_to_idx[gene]] * max(bin_gi.size / 500, 1)
weights[bin_to_idx[o.data], gene_to_idx[gene]] = v
weights = scipy.sparse.csc_matrix(weights)
if ceiling > 0:
logging.info(
f"Calculating maximum capped counts per bin at {ceiling} per 500bp"
)
bin_to_width = lambda x: genomic_interval.GenomicInterval(x).size
per_bin_cap = np.array(
[max(bin_to_width(b) / 500, 1) * ceiling for b in adata.var_names]
)
assert np.all(per_bin_cap >= ceiling)
adata.X = np.minimum(utils.ensure_arr(adata.X), per_bin_cap)
# Map the ATAC bins to features
# Converting to an array is necessary for correct broadcasting
logging.info("Calculating gene activity scores")
mat = utils.ensure_arr(adata.X @ weights)
# Normalize depths
if scale_to > 0:
logging.info(f"Depth normalizing gene activity scores to {scale_to}")
per_cell_depths = np.array(mat.sum(axis=1)).flatten()
per_cell_scaling = scale_to / per_cell_depths
per_cell_scaling[np.where(per_cell_depths == 0)] = 0.0
mat = scipy.sparse.csr_matrix(mat * per_cell_scaling[:, np.newaxis])
assert np.all(
np.logical_or(
np.isclose(scale_to, mat.sum(axis=1)), np.isclose(0, mat.sum(axis=1))
) # Either is the correct size, or is all 0
)
retval = ad.AnnData(mat)
if hasattr(adata, "obs_names"):
retval.obs_names = adata.obs_names
retval.var_names = genes
return retval