smftools 0.3.1__py3-none-any.whl → 0.3.2__py3-none-any.whl

smftools/cli/variant_adata.py

@@ -0,0 +1,423 @@
+from __future__ import annotations
+
+import logging
+from pathlib import Path
+from typing import Optional, Tuple
+
+import anndata as ad
+
+from smftools.constants import LOGGING_DIR, VARIANT_DIR
+from smftools.logging_utils import get_logger, setup_logging
+
+logger = get_logger(__name__)
+
+
+def variant_adata(
+    config_path: str,
+) -> Tuple[Optional[ad.AnnData], Optional[Path]]:
+    """
+    CLI-facing wrapper for variant analyses.
+
+    Called by: `smftools variant <config_path>`
+
+    Responsibilities:
+    - Ensure a usable AnnData exists.
+    - Determine which AnnData stages exist.
+    - Decide whether to skip (return existing) or run the core.
+    - Call `variant_adata_core(...)` when actual work is needed.
+    """
+    from ..readwrite import safe_read_h5ad
+    from .helpers import get_adata_paths, load_experiment_config
+
+    # 1) Ensure config + basic paths via load_adata
+    cfg = load_experiment_config(config_path)
+
+    paths = get_adata_paths(cfg)
+
+    pp_path = paths.pp
+    pp_dedup_path = paths.pp_dedup
+    spatial_path = paths.spatial
+    chimeric_path = paths.chimeric
+    variant_path = paths.variant
+    hmm_path = paths.hmm
+    latent_path = paths.latent
+
+    # Stage-skipping logic
+    if not getattr(cfg, "force_redo_variant_analyses", False):
+        if variant_path.exists():
+            logger.info(f"Variant AnnData found: {variant_path}\nSkipping smftools variant")
+            return None, spatial_path
+
+    # Helper to load from disk, reusing loaded_adata if it matches
+    def _load(path: Path):
+        adata, _ = safe_read_h5ad(path)
+        return adata
+
+    # 3) Decide which AnnData to use as the *starting point* for  analyses
+    if hmm_path.exists():
+        start_adata = _load(hmm_path)
+        source_path = hmm_path
+    elif latent_path.exists():
+        start_adata = _load(latent_path)
+        source_path = latent_path
+    elif spatial_path.exists():
+        start_adata = _load(spatial_path)
+        source_path = spatial_path
+    elif chimeric_path.exists():
+        start_adata = _load(chimeric_path)
+        source_path = chimeric_path
+    elif variant_path.exists():
+        start_adata = _load(variant_path)
+        source_path = variant_path
+    elif pp_dedup_path.exists():
+        start_adata = _load(pp_dedup_path)
+        source_path = pp_dedup_path
+    elif pp_path.exists():
+        start_adata = _load(pp_path)
+        source_path = pp_path
+    else:
+        logger.warning(
+            "No suitable AnnData found for variant analyses (need at least preprocessed)."
+        )
+        return None, None
+
+    # 4) Run the core
+    adata_variant, variant_path = variant_adata_core(
+        adata=start_adata,
+        cfg=cfg,
+        paths=paths,
+        source_adata_path=source_path,
+        config_path=config_path,
+    )
+
+    return adata_variant, variant_path
+
+
+def variant_adata_core(
+    adata: ad.AnnData,
+    cfg,
+    paths: AdataPaths,
+    source_adata_path: Optional[Path] = None,
+    config_path: Optional[str] = None,
+) -> Tuple[ad.AnnData, Path]:
+    """
+    Core variant analysis pipeline.
+
+    Assumes:
+    - `cfg` is the ExperimentConfig.
+
+    Does:
+    -
+    - Save AnnData
+    """
+    import os
+    import warnings
+    from datetime import datetime
+    from pathlib import Path
+
+    import numpy as np
+    import pandas as pd
+
+    from ..metadata import record_smftools_metadata
+    from ..plotting import (
+        plot_mismatch_base_frequency_by_position,
+        plot_sequence_integer_encoding_clustermaps,
+        plot_variant_segment_clustermaps,
+    )
+    from ..preprocessing import (
+        append_mismatch_frequency_sites,
+        append_sequence_mismatch_annotations,
+        append_variant_call_layer,
+        append_variant_segment_layer,
+        load_sample_sheet,
+    )
+    from ..readwrite import make_dirs
+    from .helpers import write_gz_h5ad
+
+    # -----------------------------
+    # General setup
+    # -----------------------------
+    date_str = datetime.today().strftime("%y%m%d")
+    now = datetime.now()
+    time_str = now.strftime("%H%M%S")
+    log_level = getattr(logging, cfg.log_level.upper(), logging.INFO)
+
+    output_directory = Path(cfg.output_directory)
+    variant_directory = output_directory / VARIANT_DIR
+    logging_directory = variant_directory / LOGGING_DIR
+
+    make_dirs([output_directory, variant_directory])
+
+    if cfg.emit_log_file:
+        log_file = logging_directory / f"{date_str}_{time_str}_log.log"
+        make_dirs([logging_directory])
+    else:
+        log_file = None
+
+    setup_logging(level=log_level, log_file=log_file, reconfigure=log_file is not None)
+
+    smf_modality = cfg.smf_modality
+    if smf_modality == "conversion":
+        deaminase = False
+    else:
+        deaminase = True
+
+    # -----------------------------
+    # Optional sample sheet metadata
+    # -----------------------------
+    if getattr(cfg, "sample_sheet_path", None):
+        load_sample_sheet(
+            adata,
+            cfg.sample_sheet_path,
+            mapping_key_column=cfg.sample_sheet_mapping_column,
+            as_category=True,
+            force_reload=cfg.force_reload_sample_sheet,
+        )
+
+    # ============================================================
+    # 1) Reference variant position annotation
+    # ============================================================
+    seq1_col, seq2_col = getattr(cfg, "references_to_align_for_variant_annotation", [None, None])
+    if seq1_col and seq2_col:
+        append_sequence_mismatch_annotations(adata, seq1_col, seq2_col)
+
+    ############################################### Append mismatch frequency per position ###############################################
+    append_mismatch_frequency_sites(
+        adata,
+        ref_column=cfg.reference_column,
+        mismatch_layer=cfg.mismatch_frequency_layer,
+        read_span_layer=cfg.mismatch_frequency_read_span_layer,
+        mismatch_frequency_range=cfg.mismatch_frequency_range,
+        bypass=cfg.bypass_append_mismatch_frequency_sites,
+        force_redo=cfg.force_redo_append_mismatch_frequency_sites,
+    )
+
+    # ============================================================
+    # 2) Per-read variant call layer at reference mismatch sites
+    # ============================================================
+    if seq1_col and seq2_col:
+        # For conversion SMF, derive converted column names so variant calling
+        # compares read bases against the converted reference (which reads are mapped to).
+        # Unconverted: "{chrom}_{strand}_strand_FASTA_base"
+        # Converted:   "{chrom}_{conversion}_{strand}_{strand}_strand_FASTA_base"
+        # e.g. "6B6_top_strand_FASTA_base" -> "6B6_5mC_top_top_strand_FASTA_base"
+        def _find_converted_column(unconverted_col: str, var_columns) -> str | None:
+            """Find the converted FASTA column corresponding to an unconverted one.
+
+            Unconverted columns follow the pattern ``{chromosome}_{strand}_strand_FASTA_base``.
+            Converted columns follow ``{chromosome}_{conversion}_{strand}_{strand}_strand_FASTA_base``
+            (e.g. ``6B6_5mC_top_top_strand_FASTA_base`` for unconverted ``6B6_top_strand_FASTA_base``).
+            """
+            suffix = "_strand_FASTA_base"
+            if not unconverted_col.endswith(suffix):
+                return None
+            stem = unconverted_col[: -len(suffix)]  # e.g. "6B6_top"
+            # Parse strand from end of stem: "6B6_top" -> strand="top", chrom="6B6"
+            for strand in ("top", "bottom"):
+                if stem.endswith(f"_{strand}"):
+                    chrom = stem[: -len(f"_{strand}")]
+                    # Converted column: {chrom}_{conversion}_{strand}_{strand}_strand_FASTA_base
+                    # The strand appears twice: once in the record name, once in the suffix.
+                    prefix = f"{chrom}_"
+                    end = f"_{strand}_{strand}{suffix}"
+                    candidates = [
+                        c
+                        for c in var_columns
+                        if c.startswith(prefix) and c.endswith(end) and c != unconverted_col
+                    ]
+                    if len(candidates) == 1:
+                        return candidates[0]
+                    if len(candidates) > 1:
+                        logger.info(
+                            "Multiple converted column candidates for '%s': %s",
+                            unconverted_col,
+                            candidates,
+                        )
+                        return candidates[0]
+                    break
+            return None
+
+        seq1_conv = _find_converted_column(seq1_col, adata.var.columns)
+        seq2_conv = _find_converted_column(seq2_col, adata.var.columns)
+        if seq1_conv and seq2_conv:
+            logger.info("Using converted columns: '%s', '%s'", seq1_conv, seq2_conv)
+
+        append_variant_call_layer(
+            adata,
+            seq1_column=seq1_col,
+            seq2_column=seq2_col,
+            seq1_converted_column=seq1_conv,
+            seq2_converted_column=seq2_conv,
+            read_span_layer=cfg.mismatch_frequency_read_span_layer,
+            reference_col=cfg.reference_column,
+        )
+
+        append_variant_segment_layer(
+            adata,
+            seq1_column=seq1_col,
+            seq2_column=seq2_col,
+            read_span_layer=cfg.mismatch_frequency_read_span_layer,
+            reference_col=cfg.reference_column,
+        )
+
+    ############################################### Plot mismatch base frequencies ###############################################
+    if cfg.mismatch_frequency_layer not in adata.layers:
+        logger.debug(
+            "Mismatch layer '%s' not found; skipping mismatch base frequency plots.",
+            cfg.mismatch_frequency_layer,
+        )
+    elif not adata.uns.get("mismatch_integer_encoding_map"):
+        logger.debug("Mismatch encoding map not found; skipping mismatch base frequency plots.")
+    else:
+        mismatch_base_freq_dir = (
+            variant_directory / "deduplicated" / "01_mismatch_base_frequency_plots"
+        )
+        if mismatch_base_freq_dir.is_dir() and not cfg.force_redo_preprocessing:
+            logger.debug(
+                f"{mismatch_base_freq_dir} already exists. Skipping mismatch base frequency plots."
+            )
+        else:
+            make_dirs([mismatch_base_freq_dir])
+            plot_mismatch_base_frequency_by_position(
+                adata,
+                sample_col=cfg.sample_name_col_for_plotting,
+                reference_col=cfg.reference_column,
+                mismatch_layer=cfg.mismatch_frequency_layer,
+                read_span_layer=cfg.mismatch_frequency_read_span_layer,
+                exclude_mod_sites=True,  # cfg.mismatch_base_frequency_exclude_mod_sites,
+                mod_site_bases=cfg.mod_target_bases,
+                save_path=mismatch_base_freq_dir,
+                plot_zscores=True,
+            )
+
+    ############################################### Plot integer sequence encoding clustermaps ###############################################
+    if "sequence_integer_encoding" not in adata.layers:
+        logger.debug(
+            "sequence_integer_encoding layer not found; skipping integer encoding clustermaps."
+        )
+    else:
+        seq_clustermap_dir = (
+            variant_directory / "deduplicated" / "02_sequence_integer_encoding_clustermaps"
+        )
+        if seq_clustermap_dir.is_dir() and not cfg.force_redo_preprocessing:
+            logger.debug(
+                f"{seq_clustermap_dir} already exists. Skipping sequence integer encoding clustermaps."
+            )
+        else:
+            make_dirs([seq_clustermap_dir])
+            plot_sequence_integer_encoding_clustermaps(
+                adata,
+                sample_col=cfg.sample_name_col_for_plotting,
+                reference_col=cfg.reference_column,
+                demux_types=cfg.clustermap_demux_types_to_plot,
+                min_quality=None,
+                min_length=None,
+                min_mapped_length_to_reference_length_ratio=None,
+                sort_by="none",
+                max_unknown_fraction=0.5,
+                save_path=seq_clustermap_dir,
+                show_position_axis=True,
+            )
+
+        if "mismatch_integer_encoding" in adata.layers:
+            mismatch_clustermap_dir = (
+                variant_directory
+                / "deduplicated"
+                / "03_mismatch_integer_encoding_clustermaps_no_mod_sites"
+            )
+            if mismatch_clustermap_dir.is_dir():
+                logger.debug(
+                    f"{mismatch_clustermap_dir} already exists. "
+                    "Skipping mismatch clustermaps without mod sites."
+                )
+            else:
+                make_dirs([mismatch_clustermap_dir])
+                plot_sequence_integer_encoding_clustermaps(
+                    adata,
+                    sample_col=cfg.sample_name_col_for_plotting,
+                    reference_col=cfg.reference_column,
+                    demux_types=cfg.clustermap_demux_types_to_plot,
+                    min_quality=None,
+                    min_length=None,
+                    min_mapped_length_to_reference_length_ratio=None,
+                    sort_by="none",
+                    max_unknown_fraction=0.5,
+                    save_path=mismatch_clustermap_dir,
+                    show_position_axis=True,
+                    exclude_mod_sites=True,
+                    mod_site_bases=cfg.mod_target_bases,
+                )
+
+    # ============================================================
+    # 4) Variant segment clustermaps
+    # ============================================================
+    if seq1_col and seq2_col:
+        segment_layer_name = f"{seq1_col}__{seq2_col}_variant_segments"
+        if segment_layer_name in adata.layers:
+            segment_dir = variant_directory / "deduplicated" / "04_variant_segment_clustermaps"
+            if segment_dir.exists():
+                logger.info(
+                    "Variant segment clustermaps already exist at %s; skipping.",
+                    segment_dir,
+                )
+            else:
+                make_dirs([segment_dir])
+                plot_variant_segment_clustermaps(
+                    adata,
+                    seq1_column=seq1_col,
+                    seq2_column=seq2_col,
+                    sample_col=cfg.sample_name_col_for_plotting,
+                    reference_col=cfg.reference_column,
+                    variant_segment_layer=segment_layer_name,
+                    read_span_layer=cfg.mismatch_frequency_read_span_layer,
+                    save_path=segment_dir,
+                    ref1_marker_color=getattr(cfg, "variant_overlay_seq1_color", "white"),
+                    ref2_marker_color=getattr(cfg, "variant_overlay_seq2_color", "black"),
+                    marker_size=getattr(cfg, "variant_overlay_marker_size", 4.0),
+                    show_position_axis=True,
+                )
+
+            segment_type_dir = (
+                variant_directory
+                / "deduplicated"
+                / "05_variant_segment_clustermaps_with_mismatch_type"
+            )
+            if segment_type_dir.exists():
+                logger.info(
+                    "Variant segment mismatch-type clustermaps already exist at %s; skipping.",
+                    segment_type_dir,
+                )
+            else:
+                make_dirs([segment_type_dir])
+                plot_variant_segment_clustermaps(
+                    adata,
+                    seq1_column=seq1_col,
+                    seq2_column=seq2_col,
+                    sample_col=cfg.sample_name_col_for_plotting,
+                    reference_col=cfg.reference_column,
+                    variant_segment_layer=segment_layer_name,
+                    read_span_layer=cfg.mismatch_frequency_read_span_layer,
+                    save_path=segment_type_dir,
+                    ref1_marker_color=getattr(cfg, "variant_overlay_seq1_color", "white"),
+                    ref2_marker_color=getattr(cfg, "variant_overlay_seq2_color", "black"),
+                    marker_size=getattr(cfg, "variant_overlay_marker_size", 4.0),
+                    show_position_axis=True,
+                    mismatch_type_obs_col="chimeric_variant_sites_type",
+                )
+
+    # ============================================================
+    # 5) Save AnnData
+    # ============================================================
+    if not paths.variant.exists():
+        logger.info("Saving variant AnnData")
+        record_smftools_metadata(
+            adata,
+            step_name="variant",
+            cfg=cfg,
+            config_path=config_path,
+            input_paths=[source_adata_path] if source_adata_path else None,
+            output_path=paths.variant,
+        )
+        write_gz_h5ad(adata, paths.variant)
+
+    return adata, paths.variant

smftools/cli_entry.py

@@ -7,11 +7,14 @@ from typing import Sequence
 import click
 import pandas as pd
 
+from .cli.chimeric_adata import chimeric_adata
 from .cli.hmm_adata import hmm_adata
 from .cli.latent_adata import latent_adata
 from .cli.load_adata import load_adata
 from .cli.preprocess_adata import preprocess_adata
+from .cli.recipes import full_flow
 from .cli.spatial_adata import spatial_adata
+from .cli.variant_adata import variant_adata
 from .informatics.pod5_functions import subsample_pod5
 from .logging_utils import get_logger, setup_logging
 from .readwrite import concatenate_h5ads
@@ -64,7 +67,7 @@ def cli(log_file: Path | None, log_level: str):
 @cli.command()
 @click.argument("config_path", type=click.Path(exists=True))
 def load(config_path):
-    """Load and process data from CONFIG_PATH."""
+    """Load raw data into AnnData."""
     load_adata(config_path)
 
 
@@ -75,7 +78,7 @@ def load(config_path):
 @cli.command()
 @click.argument("config_path", type=click.Path(exists=True))
 def preprocess(config_path):
-    """Preprocess data from CONFIG_PATH."""
+    """Preprocessing."""
     preprocess_adata(config_path)
 
 
@@ -86,7 +89,7 @@ def preprocess(config_path):
 @cli.command()
 @click.argument("config_path", type=click.Path(exists=True))
 def spatial(config_path):
-    """Process data from CONFIG_PATH."""
+    """Spatial signal analysis"""
     spatial_adata(config_path)
 
 
@@ -97,7 +100,7 @@ def spatial(config_path):
 @cli.command()
 @click.argument("config_path", type=click.Path(exists=True))
 def hmm(config_path):
-    """Process data from CONFIG_PATH."""
+    """HMM feature annotations and plotting"""
     hmm_adata(config_path)
 
 
@@ -108,13 +111,46 @@ def hmm(config_path):
 @cli.command()
 @click.argument("config_path", type=click.Path(exists=True))
 def latent(config_path):
-    """Process data from CONFIG_PATH."""
+    """Latent representations of signal"""
     latent_adata(config_path)
 
 
 ##########################################
 
 
+####### Variant ###########
+@cli.command()
+@click.argument("config_path", type=click.Path(exists=True))
+def variant(config_path):
+    """Sequence variation analyses"""
+    variant_adata(config_path)
+
+
+##########################################
+
+
+####### Chimeric ###########
+@cli.command()
+@click.argument("config_path", type=click.Path(exists=True))
+def chimeric(config_path):
+    """Finding putative PCR chimeras"""
+    chimeric_adata(config_path)
+
+
+##########################################
+
+
+####### Recipes ###########
+@cli.command()
+@click.argument("config_path", type=click.Path(exists=True))
+def full(config_path):
+    """Workflow: load preprocess spatial variant chimeric hmm latent"""
+    full_flow(config_path)
+
+
+##########################################
+
+
 ####### batch command ###########
 @cli.command()
 @click.argument(

smftools/config/conversion.yaml

@@ -15,16 +15,6 @@ autocorr_site_types:
 
 # Spatial Analysis - Clustermap params
 layer_for_clustermap_plotting: 'nan0_0minus1'
-rolling_nn_layer: "nan0_0minus1"
-rolling_nn_plot_layer: "nan0_0minus1"
-rolling_nn_window: 30
-rolling_nn_step: 2
-rolling_nn_min_overlap: 20
-rolling_nn_return_fraction: true
-rolling_nn_obsm_key: "rolling_nn_dist"
-rolling_nn_site_types: 
-  - "GpC"
-  - "CpG"
 clustermap_cmap_c: "coolwarm"
 clustermap_cmap_gpc: "coolwarm"
 clustermap_cmap_cpg: "viridis"

smftools/config/deaminase.yaml

@@ -39,6 +39,9 @@ autocorr_site_types:
 correlation_matrix_site_types:
   - "C_site"
 
+rolling_nn_site_types: 
+- "C"
+
 # ######## smftools hmm params #########
 cpg: False # whether to use the default HMM endogenous CpG patch params
 hmm_methbases:

smftools/config/default.yaml

@@ -110,7 +110,7 @@ read_len_to_ref_ratio_filter_thresholds:
   - null
   - null
 read_quality_filter_thresholds:
-  - 15
+  - 10
   - null
 read_mapping_quality_filter_thresholds:
   - null
@@ -130,7 +130,7 @@ read_mod_filtering_a_thresholds:
   - 0.025
   - 0.975
 read_mod_filtering_use_other_c_as_background: False
-min_valid_fraction_positions_in_read_vs_ref: 0.5
+min_valid_fraction_positions_in_read_vs_ref: 0.2
 
 # Plotting params for read length histograms
 obs_to_plot_pp_qc:
@@ -162,12 +162,13 @@ duplicate_detection_hierarchical_linkage: "average" # Method for hierarchical cl
 duplicate_detection_do_pca: False # Whether to do PCA before hierarchical linkage based duplicate detection.
 
 # Position QC params
-position_max_nan_threshold: 0.1 # The maximum amount of nans to tolerate in a column
+position_max_nan_threshold: 0.8 # The maximum amount of nans to tolerate in a column
 mismatch_frequency_range:
   - 0.01
   - 0.99
 mismatch_frequency_layer: "mismatch_integer_encoding"
 mismatch_frequency_read_span_layer: "read_span_mask"
+mismatch_base_frequency_exclude_mod_sites: True
 
 ######## smftools spatial params #########
 invert_adata: False # Whether to invert the AnnData along the positions axis.
@@ -186,13 +187,56 @@ clustermap_cmap_gpc: "coolwarm"
 clustermap_cmap_cpg: "coolwarm"
 clustermap_cmap_a: "coolwarm"
 spatial_clustermap_sortby: "gpc"
+
+# Clustermap variant params
+overlay_variant_calls: false
+variant_overlay_seq1_color: "black"
+variant_overlay_seq2_color: "white"
+variant_overlay_marker_size: 4.0
+
+# Spatial analysis - Rolling NN Hamming
+rolling_nn_layer: "nan0_0minus1"
+rolling_nn_plot_layer: "nan0_0minus1"
+rolling_nn_plot_layers:
+  - "nan0_0minus1"
+  - "zero_hamming_distance_spans"
+rolling_nn_window: 10
+rolling_nn_step: 1
+rolling_nn_min_overlap: 8
+rolling_nn_return_fraction: true
+rolling_nn_obsm_key: "rolling_nn_dist"
 rolling_nn_site_types: 
   - "GpC"
   - "CpG"
-
-# Spatial Analysis - UMAP/Leiden params
+rolling_nn_write_zero_pairs_csvs: true
+rolling_nn_zero_pairs_uns_key: null
+rolling_nn_zero_pairs_segments_key: null
+rolling_nn_zero_pairs_layer_key: null
+rolling_nn_zero_pairs_refine: true
+rolling_nn_zero_pairs_max_nan_run: 2
+rolling_nn_zero_pairs_merge_gap: 1
+rolling_nn_zero_pairs_max_segments_per_read: 2
+rolling_nn_zero_pairs_max_overlap: 5
+rolling_nn_zero_pairs_layer_overlap_mode: "sum"
+rolling_nn_zero_pairs_layer_overlap_value: null
+rolling_nn_zero_pairs_keep_uns: true
+rolling_nn_zero_pairs_segments_keep_uns: true
+rolling_nn_zero_pairs_top_segments_per_read: 3
+rolling_nn_zero_pairs_top_segments_max_overlap: 5
+rolling_nn_zero_pairs_top_segments_min_span: 300
+rolling_nn_zero_pairs_top_segments_write_csvs: true
+rolling_nn_zero_pairs_segment_histogram_bins: 30
+
+# Cross-sample rolling NN analysis
+cross_sample_analysis: true
+cross_sample_grouping_col: null
+cross_sample_random_seed: 42
+delta_hamming_chimeric_span_threshold: 200
+
+# Latent Analysis - UMAP/Leiden params
 layer_for_umap_plotting: 'nan_half'
 umap_layers_to_plot:
+  - "leiden"
   - "mapped_length"
   - "Raw_modification_signal"
 
@@ -279,21 +323,13 @@ hmm_merge_layer_features:
   - ["all_accessible_features", 60]
 clustermap_cmap_hmm: "coolwarm"
 hmm_clustermap_feature_layers:
-  - all_accessible_features
   - all_accessible_features_merged
-  - small_accessible_patch
-  - mid_accessible_patch
-  - large_accessible_patch
-  - large_accessible_patch_merged
-  - nucleosome_depleted_region
   - nucleosome_depleted_region_merged
   - small_bound_stretch
   - medium_bound_stretch
   - putative_nucleosome
-  - large_bound_stretch
   - all_footprint_features
 hmm_clustermap_length_layers:
-  - all_accessible_features
   - all_accessible_features_merged
   - all_footprint_features
 hmm_clustermap_sortby: "hmm"