consenrich 0.7.4b2__cp312-cp312-macosx_10_13_x86_64.whl

consenrich/core.py

@@ -0,0 +1,1428 @@
+# -*- coding: utf-8 -*-
+r"""
+Consenrich core functions and classes.
+
+"""
+
+import logging
+import os
+from tempfile import NamedTemporaryFile
+from typing import (
+    Callable,
+    List,
+    Optional,
+    Tuple,
+    DefaultDict,
+    Any,
+    NamedTuple,
+)
+
+import numpy as np
+import numpy.typing as npt
+import pybedtools as bed
+from scipy import signal, ndimage
+
+from . import cconsenrich
+
+logging.basicConfig(
+    level=logging.INFO,
+    format="%(asctime)s - %(module)s.%(funcName)s -  %(levelname)s - %(message)s",
+)
+
+logger = logging.getLogger(__name__)
+
+
+def resolveExtendBP(extendBP, bamFiles: List[str]) -> List[int]:
+    numFiles = len(bamFiles)
+
+    if isinstance(extendBP, str):
+        stringValue = extendBP.replace(" ", "")
+        try:
+            extendBP = (
+                [int(x) for x in stringValue.split(",")]
+                if stringValue
+                else []
+            )
+        except ValueError:
+            raise ValueError(
+                "`extendBP` string must be comma-separated values (castable to integers)"
+            )
+    if extendBP is None:
+        return [0] * numFiles
+    elif isinstance(extendBP, list):
+        valuesList = [int(x) for x in extendBP]
+        valuesLen = len(valuesList)
+        if valuesLen == 0:
+            return [0] * numFiles
+        if valuesLen == 1:
+            return [valuesList[0]] * numFiles
+        if valuesLen == numFiles:
+            return valuesList
+        raise ValueError(
+            f"extendBP length {valuesLen} does not match number of bamFiles {numFiles}; "
+            f"provide 0, 1, or {numFiles} values."
+        )
+    elif isinstance(extendBP, int) or isinstance(extendBP, float):
+        return [int(extendBP)] * numFiles
+    raise TypeError(
+        f"Invalid extendBP type: {type(extendBP).__name__}. "
+        "Expecting a single number (broadcast), a list of numbers matching `bamFiles`."
+    )
+
+
+class processParams(NamedTuple):
+    r"""Parameters related to the process model of Consenrich.
+
+    The process model governs the signal and variance propagation
+    through the state transition :math:`\mathbf{F} \in \mathbb{R}^{2 \times 2}`
+    and process noise covariance :math:`\mathbf{Q}_{[i]} \in \mathbb{R}^{2 \times 2}`
+    matrices.
+
+    :param deltaF: Scales the signal and variance propagation between adjacent genomic intervals.
+    :param minQ: Minimum process noise level (diagonal in :math:`\mathbf{Q}_{[i]}`)
+        for each state variable. Adjust relative to data quality (more reliable data --> lower minQ).
+    :type minQ: float
+    :param dStatAlpha: Threshold on the deviation between the data and estimated signal -- used to determine whether the process noise is scaled up.
+    :type dStatAlpha: float
+    :param dStatd: Constant :math:`d` in the scaling expression :math:`\sqrt{d|D_{[i]} - \alpha_D| + c}`
+        that is used to up/down-scale the process noise covariance in the event of a model mismatch.
+    :type dStatd: float
+    :param dStatPC: Constant :math:`c` in the scaling expression :math:`\sqrt{d|D_{[i]} - \alpha_D| + c}`
+        that is used to up/down-scale the process noise covariance in the event of a model mismatch.
+    :type dStatPC: float
+    :param scaleResidualsByP11: If `True`, the primary state variances :math:`\widetilde{P}_{[i], (11)}, i=1\ldots n` are included in the inverse-variance (precision) weighting of residuals :math:`\widetilde{\mathbf{y}}_{[i]}, i=1\ldots n`.
+        If `False`, only the per-sample observation noise levels are used to reduce computational overhead.
+    :type scaleResidualsByP11: Optional[bool]
+
+    """
+
+    deltaF: float
+    minQ: float
+    maxQ: float
+    offDiagQ: float
+    dStatAlpha: float
+    dStatd: float
+    dStatPC: float
+    scaleResidualsByP11: Optional[bool] = False
+
+
+class observationParams(NamedTuple):
+    r"""Parameters related to the observation model of Consenrich.
+    The observation model is used to integrate sequence alignment count
+    data from the multiple input samples and account for region-and-sample-specific
+    noise processes corrupting data. The observation model matrix
+    :math:`\mathbf{H} \in \mathbb{R}^{m \times 2}` maps from the state dimension (2)
+    to the dimension of measurements/data (:math:`m`).
+
+    :param minR: The minimum observation noise level for each sample
+        :math:`j=1\ldots m` in the observation noise covariance
+        matrix :math:`\mathbf{R}_{[i, (11:mm)]}`.
+    :type minR: float
+    :param numNearest: The number of nearest nearby sparse features to use for local
+        variance calculation. Ignored if `useALV` is True.
+    :type numNearest: int
+    :param localWeight: The coefficient for the local noise level (based on the local surrounding window / `numNearest` features) used in the weighted sum measuring sample-specific noise level at the current interval.
+    :type localWeight: float
+    :param globalWeight: The coefficient for the global noise level (based on all genomic intervals :math:`i=1\ldots n`) used in the weighted sum measuring sample-specific noise level at the current interval.
+    :type globalWeight: float
+    :param approximationWindowLengthBP: The length of the local approximation window in base pairs (BP)
+        for the local variance calculation.
+    :type approximationWindowLengthBP: int
+    :param sparseBedFile: The path to a BED file of 'sparse' regions for the local variance calculation. For genomes with default resources in `src/consenrich/data`, this may be left as `None`,
+      and a default annotation devoid of active regulatory elements will be used. Users can instead supply a custom BED file or set `observationParams.useALV` to `True` to avoid predefined annotations.
+    :type sparseBedFile: str, optional
+    :param noGlobal: If True, only the 'local' variances are used to approximate observation noise
+        covariance :math:`\mathbf{R}_{[:, (11:mm)]}`.
+    :type noGlobal: bool
+    :param useALV: Whether to use average local variance (ALV) heuristic exclusively to approximate observation noise
+        covariances per-sample, per-interval. Note that unrestricted ALV (i.e., without masking previously annotated high-signal regions) is comparatively vulnerable to inflated noise estimates in large enriched genomic domains.
+    :type useALV: bool
+    :param lowPassFilterType: The type of low-pass filter to use (e.g., 'median', 'mean') in the ALV calculation (:func:`consenrich.core.getAverageLocalVarianceTrack`).
+    :type lowPassFilterType: Optional[str]
+    """
+
+    minR: float
+    maxR: float
+    useALV: bool
+    useConstantNoiseLevel: bool
+    noGlobal: bool
+    numNearest: int
+    localWeight: float
+    globalWeight: float
+    approximationWindowLengthBP: int
+    lowPassWindowLengthBP: int
+    lowPassFilterType: Optional[str]
+    returnCenter: bool
+
+
+class stateParams(NamedTuple):
+    r"""Parameters related to state and uncertainty bounds and initialization.
+
+    :param stateInit: Initial value of the 'primary' state/signal at the first genomic interval: :math:`x_{[1]}`
+    :type stateInit: float
+    :param stateCovarInit: Initial state covariance (covariance) scale. Note, the *initial* state uncertainty :math:`\mathbf{P}_{[1]}` is a multiple of the identity matrix :math:`\mathbf{I}`. Final results are typically insensitive to this parameter, since the filter effectively 'forgets' its initialization after processing a moderate number of intervals and backward smoothing.
+    :type stateCovarInit: float
+    :param boundState: If True, the primary state estimate for :math:`x_{[i]}` is reported within `stateLowerBound` and `stateUpperBound`. Note that the internal filtering is unaffected by this setting and the bounds are only applied to the final state estimates for convenience.
+    :type boundState: bool
+    :param stateLowerBound: Lower bound for the state estimate.
+    :type stateLowerBound: float
+    :param stateUpperBound: Upper bound for the state estimate.
+    :type stateUpperBound: float
+    """
+
+    stateInit: float
+    stateCovarInit: float
+    boundState: bool
+    stateLowerBound: float
+    stateUpperBound: float
+
+
+class samParams(NamedTuple):
+    r"""Parameters related to reading BAM files
+
+    :param samThreads: The number of threads to use for reading BAM files.
+    :type samThreads: int
+    :param samFlagExclude: The SAM flag to exclude certain reads.
+    :type samFlagExclude: int
+    :param oneReadPerBin: If 1, only the interval with the greatest read overlap is incremented.
+    :type oneReadPerBin: int
+    :param chunkSize: maximum number of intervals' data to hold in memory before flushing to disk.
+    :type chunkSize: int
+    :param offsetStr: A string of two comma-separated integers -- first for the 5' shift on forward strand, second for the 5' shift on reverse strand.
+    :type offsetStr: str
+    :param extendBP: A list of integers specifying the number of base pairs to extend reads for each BAM file after shifting per `offsetStr`.
+        If all BAM files share the same expected frag. length, can supply a single numeric value to be broadcasted. Ignored for PE reads.
+    :type extendBP: List[int]
+    :param maxInsertSize: Maximum frag length/insert for paired-end reads.
+    :type maxInsertSize: int
+    :param pairedEndMode: If > 0, only proper pairs are counted subject to `maxInsertSize`.
+    :type pairedEndMode: int
+    :param inferFragmentLength: Intended for single-end data: if > 0, the maximum correlation lag
+       (avg.) between *strand-specific* read tracks is taken as the fragment length estimate and used to
+       extend reads from 5'. Ignored if `pairedEndMode > 0` or `extendBP` set. This parameter is particularly
+       important when targeting broader marks (e.g., ChIP-seq H3K27me3).
+    :type inferFragmentLength: int
+    :param countEndsOnly: If True, only the 5' ends of reads are counted. Overrides `inferFragmentLength` and `pairedEndMode`.
+    :type countEndsOnly: Optional[bool]
+
+    .. tip::
+
+        For an overview of SAM flags, see https://broadinstitute.github.io/picard/explain-flags.html
+
+    """
+
+    samThreads: int
+    samFlagExclude: int
+    oneReadPerBin: int
+    chunkSize: int
+    offsetStr: Optional[str] = "0,0"
+    extendBP: Optional[List[int]] = []
+    maxInsertSize: Optional[int] = 1000
+    pairedEndMode: Optional[int] = 0
+    inferFragmentLength: Optional[int] = 0
+    countEndsOnly: Optional[bool] = False
+
+
+class detrendParams(NamedTuple):
+    r"""Parameters related detrending and background-removal
+
+    :param useOrderStatFilter: Whether to use a local/moving order statistic (percentile filter) to model and remove trends in the read density data.
+    :type useOrderStatFilter: bool
+    :param usePolyFilter: Whether to use a low-degree polynomial fit to model and remove trends in the read density data.
+    :type usePolyFilter: bool
+    :param detrendSavitzkyGolayDegree: The polynomial degree of the Savitzky-Golay filter to use for detrending
+    :type detrendSavitzkyGolayDegree: int
+    :param detrendTrackPercentile: The percentile to use for the local/moving order-statistic filter.
+      Decrease for broad marks + sparse data if `useOrderStatFilter` is True.
+    :type detrendTrackPercentile: float
+    :param detrendWindowLengthBP: The length of the window in base pairs for detrending.
+      Increase for broader marks + sparse data.
+    :type detrendWindowLengthBP: int
+    """
+
+    useOrderStatFilter: bool
+    usePolyFilter: bool
+    detrendTrackPercentile: float
+    detrendSavitzkyGolayDegree: int
+    detrendWindowLengthBP: int
+
+
+class inputParams(NamedTuple):
+    r"""Parameters related to the input data for Consenrich.
+
+    :param bamFiles: A list of paths to distinct coordinate-sorted and indexed BAM files.
+    :type bamFiles: List[str]
+
+    :param bamFilesControl: A list of paths to distinct coordinate-sorted and
+        indexed control BAM files. e.g., IgG control inputs for ChIP-seq.
+
+    :type bamFilesControl: List[str], optional
+
+    """
+
+    bamFiles: List[str]
+    bamFilesControl: Optional[List[str]]
+    pairedEnd: Optional[bool]
+
+
+class genomeParams(NamedTuple):
+    r"""Specify assembly-specific resources, parameters.
+
+    :param genomeName: If supplied, default resources for the assembly (sizes file, blacklist, and 'sparse' regions) in `src/consenrich/data` are used.
+      ``ce10, ce11, dm6, hg19, hg38, mm10, mm39`` have default resources available.
+    :type genomeName: str
+    :param chromSizesFile: A two-column TSV-like file with chromosome names and sizes (in base pairs).
+    :type chromSizesFile: str
+    :param blacklistFile: A BED file with regions to exclude.
+    :type blacklistFile: str, optional
+    :param sparseBedFile: A BED file with 'sparse regions' used to estimate noise levels -- ignored if `observationParams.useALV` is True. 'Sparse regions' broadly refers to genomic intervals devoid of the targeted signal, based on prior annotations.
+      Users may supply a custom BED file and/or set `observationParams.useALV` to `True` to avoid relying on predefined annotations.
+    :type sparseBedFile: str, optional
+    :param chromosomes: A list of chromosome names to analyze. If None, all chromosomes in `chromSizesFile` are used.
+    :type chromosomes: List[str]
+    """
+
+    genomeName: str
+    chromSizesFile: str
+    blacklistFile: Optional[str]
+    sparseBedFile: Optional[str]
+    chromosomes: List[str]
+    excludeChroms: List[str]
+    excludeForNorm: List[str]
+
+
+class countingParams(NamedTuple):
+    r"""Parameters related to counting reads in genomic intervals.
+
+    :param stepSize: Step size (bp) for the genomic intervals (AKA bin size, interval length, width, etc.)
+    :type stepSize: int
+    :param scaleDown: If using paired treatment and control BAM files, whether to
+        scale down the larger of the two before computing the difference/ratio
+    :type scaleDown: bool, optional
+    :param scaleFactors: Scale factors for the read counts.
+    :type scaleFactors: List[float], optional
+    :param scaleFactorsControl: Scale factors for the control read counts.
+    :type scaleFactorsControl: List[float], optional
+    :param numReads: Number of reads to sample.
+    :type numReads: int
+    :param applyAsinh: If true, :math:`\textsf{arsinh}(x)` applied to counts :math:`x` (log-like for large values and linear near the origin)
+    :type applyAsinh: bool, optional
+    :param applyLog: If true, :math:`\textsf{log}(x + 1)` applied to counts :math:`x`
+    :type applyLog: bool, optional
+    """
+
+    stepSize: int
+    scaleDown: Optional[bool]
+    scaleFactors: Optional[List[float]]
+    scaleFactorsControl: Optional[List[float]]
+    numReads: int
+    applyAsinh: Optional[bool]
+    applyLog: Optional[bool]
+    rescaleToTreatmentCoverage: Optional[bool] = False
+
+
+class matchingParams(NamedTuple):
+    r"""Parameters related to the matching algorithm.
+
+    See :ref:`matching` for an overview of the approach.
+
+    :param templateNames: A list of str values -- each entry references a mother wavelet (or its corresponding scaling function). e.g., `[haar, db2]`
+    :type templateNames: List[str]
+    :param cascadeLevels: Number of cascade iterations used to approximate each template (wavelet or scaling function).
+        Must have the same length as `templateNames`, with each entry aligned to the
+        corresponding template. e.g., given templateNames `[haar, db2]`, then `[2,2]` would use 2 cascade levels for both templates.
+    :type cascadeLevels: List[int]
+    :param iters: Number of random blocks to sample in the response sequence while building
+        an empirical null to test significance. See :func:`cconsenrich.csampleBlockStats`.
+    :type iters: int
+    :param alpha: Primary significance threshold on detected matches. Specifically, the
+        minimum corr. empirical p-value approximated from randomly sampled blocks in the
+        response sequence.
+    :type alpha: float
+    :param minMatchLengthBP: Within a window of `minMatchLengthBP` length (bp), relative maxima in
+        the signal-template convolution must be greater in value than others to qualify as matches.
+        If set to a value less than 1, the minimum length is determined via :func:`consenrich.matching.autoMinLengthIntervals`.
+        If set to `None`, defaults to 250 bp.
+    :param minSignalAtMaxima: Secondary significance threshold coupled with `alpha`. Requires the *signal value*
+        at relative maxima in the response sequence to be greater than this threshold. Comparisons are made in log-scale
+        to temper genome-wide dynamic range. If a `float` value is provided, the minimum signal value must be greater
+        than this (absolute) value. *Set to a negative value to disable the threshold*.
+        If a `str` value is provided, looks for 'q:quantileValue', e.g., 'q:0.90'. The
+        threshold is then set to the corresponding quantile of the non-zero signal estimates.
+    :type minSignalAtMaxima: Optional[str | float]
+    :param useScalingFunction: If True, use (only) the scaling function to build the matching template.
+        If False, use (only) the wavelet function.
+    :type useScalingFunction: bool
+    :param excludeRegionsBedFile: A BED file with regions to exclude from matching
+    :type excludeRegionsBedFile: Optional[str]
+    :param penalizeBy: Specify a positional metric to scale/weight signal values by when matching.
+      For example, 'absResiduals' divides signal values by :math:`|\widetilde{y}_i|` at each
+      position :math:`i`, thereby down-weighting positions where the signal estimate deviates from
+      the data after accounting for observation noise. 'stateUncertainty' divides signal values by
+      the square root of the primary state variance :math:`\sqrt{\widetilde{P}_{i,(11)}}` at each position :math:`i`,
+      thereby down-weighting positions where the posterior state uncertainty is high. 'muncTrace' divides signal values by
+      the square root of the average observation noise trace :math:`\sqrt{\frac{\textsf{Trace}\left(\mathbf{R}_{[i]}\right)}{m}}` at each position :math:`i`,
+    :type penalizeBy: Optional[str]
+    :param eps: Tolerance parameter for relative maxima detection in the response sequence. Set to zero to enforce strict
+        inequalities when identifying discrete relative maxima.
+    :type eps: float
+    :seealso: :func:`cconsenrich.csampleBlockStats`, :ref:`matching`, :class:`outputParams`.
+    """
+
+    templateNames: List[str]
+    cascadeLevels: List[int]
+    iters: int
+    alpha: float
+    useScalingFunction: Optional[bool]
+    minMatchLengthBP: Optional[int]
+    maxNumMatches: Optional[int]
+    minSignalAtMaxima: Optional[str | float]
+    merge: Optional[bool]
+    mergeGapBP: Optional[int]
+    excludeRegionsBedFile: Optional[str]
+    penalizeBy: Optional[str]
+    randSeed: Optional[int] = 42
+    eps: Optional[float] = 1.0e-2
+
+
+class outputParams(NamedTuple):
+    r"""Parameters related to output files.
+
+    :param convertToBigWig: If True, output bedGraph files are converted to bigWig format.
+    :type convertToBigWig: bool
+    :param roundDigits: Number of decimal places to round output values (bedGraph)
+    :type roundDigits: int
+    :param writeResiduals: If True, write to a separate bedGraph the mean of precision-weighted residuals at each interval. These may be interpreted as
+        a measure of model mismatch. Where these quantities are large (+-) the estimated signal and uncertainty do not explain the observed deviation from the data.
+    :type writeResiduals: bool
+    :param writeMuncTrace: If True, write to a separate bedGraph :math:`\sqrt{\frac{\textsf{Trace}\left(\mathbf{R}_{[i]}\right)}{m}}` -- that is, square root of the 'average' observation noise level at each interval :math:`i=1\ldots n`, where :math:`m` is the number of samples/tracks.
+    :type writeMuncTrace: bool
+    :param writeStateStd: If True, write to a separate bedGraph estimated standard deviation of the primary state, :math:`\sqrt{\widetilde{P}_{i,(11)}}`, at each interval. Note that an absolute Gaussian interpretation of this metric depends on sample size, arguments in :class:`processParams` and :class:`observationParams`, etc.
+        In any case, this metric may be interpreted as a relative measure of uncertainty in the state estimate at each interval.
+    :type writeStateStd: bool
+    """
+
+    convertToBigWig: bool
+    roundDigits: int
+    writeResiduals: bool
+    writeMuncTrace: bool
+    writeStateStd: bool
+
+
+def _numIntervals(start: int, end: int, step: int) -> int:
+    # helper for consistency
+    length = max(0, end - start)
+    return (length + step) // step
+
+
+def getChromRanges(
+    bamFile: str,
+    chromosome: str,
+    chromLength: int,
+    samThreads: int,
+    samFlagExclude: int,
+) -> Tuple[int, int]:
+    r"""Get the start and end positions of reads in a chromosome from a BAM file.
+
+    :param bamFile: See :class:`inputParams`.
+    :type bamFile: str
+    :param chromosome: the chromosome to read in `bamFile`.
+    :type chromosome: str
+    :param chromLength: Base pair length of the chromosome.
+    :type chromLength: int
+    :param samThreads: See :class:`samParams`.
+    :type samThreads: int
+    :param samFlagExclude: See :class:`samParams`.
+    :type samFlagExclude: int
+    :return: Tuple of start and end positions (nucleotide coordinates) in the chromosome.
+    :rtype: Tuple[int, int]
+
+    :seealso: :func:`getChromRangesJoint`, :func:`cconsenrich.cgetFirstChromRead`, :func:`cconsenrich.cgetLastChromRead`
+    """
+    start: int = cconsenrich.cgetFirstChromRead(
+        bamFile, chromosome, chromLength, samThreads, samFlagExclude
+    )
+    end: int = cconsenrich.cgetLastChromRead(
+        bamFile, chromosome, chromLength, samThreads, samFlagExclude
+    )
+    return start, end
+
+
+def getChromRangesJoint(
+    bamFiles: List[str],
+    chromosome: str,
+    chromSize: int,
+    samThreads: int,
+    samFlagExclude: int,
+) -> Tuple[int, int]:
+    r"""For multiple BAM files, reconcile a single start and end position over which to count reads,
+    where the start and end positions are defined by the first and last reads across all BAM files.
+
+    :param bamFiles: List of BAM files to read.
+    :type bamFiles: List[str]
+    :param chromosome: Chromosome to read.
+    :type chromosome: str
+    :param chromSize: Size of the chromosome.
+    :type chromSize: int
+    :param samThreads: Number of threads to use for reading the BAM files.
+    :type samThreads: int
+    :param samFlagExclude: SAM flag to exclude certain reads.
+    :type samFlagExclude: int
+    :return: Tuple of start and end positions.
+    :rtype: Tuple[int, int]
+
+    :seealso: :func:`getChromRanges`, :func:`cconsenrich.cgetFirstChromRead`, :func:`cconsenrich.cgetLastChromRead`
+    """
+    starts = []
+    ends = []
+    for bam_ in bamFiles:
+        start, end = getChromRanges(
+            bam_,
+            chromosome,
+            chromLength=chromSize,
+            samThreads=samThreads,
+            samFlagExclude=samFlagExclude,
+        )
+        starts.append(start)
+        ends.append(end)
+    return min(starts), max(ends)
+
+
+def getReadLength(
+    bamFile: str,
+    numReads: int,
+    maxIterations: int,
+    samThreads: int,
+    samFlagExclude: int,
+) -> int:
+    r"""Infer read length from mapped reads in a BAM file.
+
+    Samples at least `numReads` reads passing criteria given by `samFlagExclude`
+    and returns the median read length.
+
+    :param bamFile: See :class:`inputParams`.
+    :type bamFile: str
+    :param numReads: Number of reads to sample.
+    :type numReads: int
+    :param maxIterations: Maximum number of iterations to perform.
+    :type maxIterations: int
+    :param samThreads: See :class:`samParams`.
+    :type samThreads: int
+    :param samFlagExclude: See :class:`samParams`.
+    :type samFlagExclude: int
+    :return: The median read length.
+    :rtype: int
+
+    :raises ValueError: If the read length cannot be determined after scanning `maxIterations` reads.
+
+    :seealso: :func:`cconsenrich.cgetReadLength`
+    """
+    init_rlen = cconsenrich.cgetReadLength(
+        bamFile, numReads, samThreads, maxIterations, samFlagExclude
+    )
+    if init_rlen == 0:
+        raise ValueError(
+            f"Failed to determine read length in {bamFile}. Revise `numReads`, and/or `samFlagExclude` parameters?"
+        )
+    return init_rlen
+
+
+def getReadLengths(
+    bamFiles: List[str],
+    numReads: int,
+    maxIterations: int,
+    samThreads: int,
+    samFlagExclude: int,
+) -> List[int]:
+    r"""Get read lengths for a list of BAM files.
+
+    :seealso: :func:`getReadLength`
+    """
+    return [
+        getReadLength(
+            bamFile,
+            numReads=numReads,
+            maxIterations=maxIterations,
+            samThreads=samThreads,
+            samFlagExclude=samFlagExclude,
+        )
+        for bamFile in bamFiles
+    ]
+
+
+def readBamSegments(
+    bamFiles: List[str],
+    chromosome: str,
+    start: int,
+    end: int,
+    stepSize: int,
+    readLengths: List[int],
+    scaleFactors: List[float],
+    oneReadPerBin: int,
+    samThreads: int,
+    samFlagExclude: int,
+    offsetStr: Optional[str] = "0,0",
+    applyAsinh: Optional[bool] = False,
+    applyLog: Optional[bool] = False,
+    extendBP: List[int] = [],
+    maxInsertSize: Optional[int] = 1000,
+    pairedEndMode: Optional[int] = 0,
+    inferFragmentLength: Optional[int] = 0,
+    countEndsOnly: Optional[bool] = False,
+) -> npt.NDArray[np.float32]:
+    r"""Calculate tracks of read counts (or a function thereof) for each BAM file.
+
+    See :func:`cconsenrich.creadBamSegment` for the underlying implementation in Cython.
+
+    :param bamFiles: See :class:`inputParams`.
+    :type bamFiles: List[str]
+    :param chromosome: Chromosome to read.
+    :type chromosome: str
+    :param start: Start position of the genomic segment.
+    :type start: int
+    :param end: End position of the genomic segment.
+    :type end: int
+    :param readLengths: List of read lengths for each BAM file.
+    :type readLengths: List[int]
+    :param scaleFactors: List of scale factors for each BAM file.
+    :type scaleFactors: List[float]
+    :param stepSize: See :class:`countingParams`.
+    :type stepSize: int
+    :param oneReadPerBin: See :class:`samParams`.
+    :type oneReadPerBin: int
+    :param samThreads: See :class:`samParams`.
+    :type samThreads: int
+    :param samFlagExclude: See :class:`samParams`.
+    :type samFlagExclude: int
+    :param offsetStr: See :class:`samParams`.
+    :type offsetStr: str
+    :param extendBP: See :class:`samParams`.
+    :type extendBP: int
+    :param maxInsertSize: See :class:`samParams`.
+    :type maxInsertSize: int
+    :param pairedEndMode: See :class:`samParams`.
+    :type pairedEndMode: int
+    :param inferFragmentLength: See :class:`samParams`.
+    :type inferFragmentLength: int
+    :param countEndsOnly: If True, only the 5' ends of reads are counted. This overrides `inferFragmentLength` and `pairedEndMode`.
+    :type countEndsOnly: Optional[bool]
+
+    """
+
+    if len(bamFiles) == 0:
+        raise ValueError("bamFiles list is empty")
+
+    if len(readLengths) != len(bamFiles) or len(scaleFactors) != len(
+        bamFiles
+    ):
+        raise ValueError(
+            "readLengths and scaleFactors must match bamFiles length"
+        )
+
+    extendBP = resolveExtendBP(extendBP, bamFiles)
+    offsetStr = ((str(offsetStr) or "0,0").replace(" ", "")).split(
+        ","
+    )
+    numIntervals = ((end - start) + stepSize - 1) // stepSize
+    counts = np.empty((len(bamFiles), numIntervals), dtype=np.float32)
+
+    if isinstance(countEndsOnly, bool) and countEndsOnly:
+        # note: setting this option ignores inferFragmentLength, pairedEndMode
+        inferFragmentLength = 0
+        pairedEndMode = 0
+
+    for j, bam in enumerate(bamFiles):
+        logger.info(f"Reading {chromosome}: {bam}")
+        arr = cconsenrich.creadBamSegment(
+            bam,
+            chromosome,
+            start,
+            end,
+            stepSize,
+            readLengths[j],
+            oneReadPerBin,
+            samThreads,
+            samFlagExclude,
+            int(offsetStr[0]),
+            int(offsetStr[1]),
+            extendBP[j],
+            maxInsertSize,
+            pairedEndMode,
+            inferFragmentLength,
+        )
+        # FFR: use ufuncs?
+        counts[j, :] = arr
+        counts[j, :] *= np.float32(scaleFactors[j])
+        if applyAsinh:
+            counts[j, :] = np.arcsinh(counts[j, :])
+        elif applyLog:
+            counts[j, :] = np.log1p(counts[j, :])
+    return counts
+
+
+def getAverageLocalVarianceTrack(
+    values: np.ndarray,
+    stepSize: int,
+    approximationWindowLengthBP: int,
+    lowPassWindowLengthBP: int,
+    minR: float,
+    maxR: float,
+    lowPassFilterType: Optional[str] = "median",
+) -> npt.NDArray[np.float32]:
+    r"""Generate positional noise-level tracks with first and second moments approximated from local windows
+
+    First, computes a moving average of ``values`` using a bp-length window
+    ``approximationWindowLengthBP`` and a moving average of ``values**2`` over the
+    same window. Their difference is used to approximate the local variance. A low-pass filter
+    (median or mean) with window ``lowPassWindowLengthBP`` then smooths the variance track.
+    Finally, the track is clipped to ``[minR, maxR]`` to yield the local noise level track.
+
+    :param values: 1D array of read-density-based values for a single sample.
+    :type values: np.ndarray
+    :param stepSize: Bin size (bp).
+    :type stepSize: int
+    :param approximationWindowLengthBP: Window (bp) for local mean and second-moment. See :class:`observationParams`.
+    :type approximationWindowLengthBP: int
+    :param lowPassWindowLengthBP: Window (bp) for the low-pass filter on the variance track. See :class:`observationParams`.
+    :type lowPassWindowLengthBP: int
+    :param minR: Lower clip for the returned noise level. See :class:`observationParams`.
+    :type minR: float
+    :param maxR: Upper clip for the returned noise level. See :class:`observationParams`.
+    :type maxR: float
+    :param lowPassFilterType: ``"median"`` (default) or ``"mean"``. Type of low-pass filter to use for smoothing the local variance track. See :class:`observationParams`.
+    :type lowPassFilterType: Optional[str]
+    :return: Local noise level per interval.
+    :rtype: npt.NDArray[np.float32]
+
+    :seealso: :class:`observationParams`
+    """
+    values = np.asarray(values, dtype=np.float32)
+    windowLength = int(approximationWindowLengthBP / stepSize)
+    if windowLength % 2 == 0:
+        windowLength += 1
+    if len(values) < 3:
+        constVar = np.var(values)
+        if constVar < minR:
+            return np.full_like(values, minR, dtype=np.float32)
+        return np.full_like(values, constVar, dtype=np.float32)
+
+    # first get a simple moving average of the values
+    localMeanTrack: npt.NDArray[np.float32] = ndimage.uniform_filter(
+        values, size=windowLength, mode="nearest"
+    )
+
+    #  ~ E[X_i^2] - E[X_i]^2 ~
+    localVarTrack: npt.NDArray[np.float32] = (
+        ndimage.uniform_filter(
+            values**2, size=windowLength, mode="nearest"
+        )
+        - localMeanTrack**2
+    )
+
+    # safe-guard: difference of convolutions returns negative values.
+    # shouldn't actually happen, but just in case there are some
+    # ...potential artifacts i'm unaware of edge effects, etc.
+    localVarTrack = np.maximum(localVarTrack, 0.0)
+
+    # low-pass filter on the local variance track: positional 'noise level' track
+    lpassWindowLength = int(lowPassWindowLengthBP / stepSize)
+    if lpassWindowLength % 2 == 0:
+        lpassWindowLength += 1
+
+    noiseLevel: npt.NDArray[np.float32] = np.zeros_like(
+        localVarTrack, dtype=np.float32
+    )
+    if lowPassFilterType is None or (
+        isinstance(lowPassFilterType, str)
+        and lowPassFilterType.lower() == "median"
+    ):
+        noiseLevel = ndimage.median_filter(
+            localVarTrack, size=lpassWindowLength
+        )
+    elif (
+        isinstance(lowPassFilterType, str)
+        and lowPassFilterType.lower() == "mean"
+    ):
+        noiseLevel = ndimage.uniform_filter(
+            localVarTrack, size=lpassWindowLength
+        )
+
+    return np.clip(noiseLevel, minR, maxR).astype(np.float32)
+
+
+def constructMatrixF(deltaF: float) -> npt.NDArray[np.float32]:
+    r"""Build the state transition matrix for the process model
+
+    :param deltaF: See :class:`processParams`.
+    :type deltaF: float
+    :return: The state transition matrix :math:`\mathbf{F}`
+    :rtype: npt.NDArray[np.float32]
+
+    :seealso: :class:`processParams`
+    """
+    initMatrixF: npt.NDArray[np.float32] = np.eye(2, dtype=np.float32)
+    initMatrixF[0, 1] = np.float32(deltaF)
+    return initMatrixF
+
+
+def constructMatrixQ(
+    minDiagQ: float, offDiagQ: float = 0.0
+) -> npt.NDArray[np.float32]:
+    r"""Build the initial process noise covariance matrix :math:`\mathbf{Q}_{[1]}`.
+
+    :param minDiagQ: See :class:`processParams`.
+    :type minDiagQ: float
+    :param offDiagQ: See :class:`processParams`.
+    :type offDiagQ: float
+    :return: The initial process noise covariance matrix :math:`\mathbf{Q}_{[1]}`.
+    :rtype: npt.NDArray[np.float32]
+
+    :seealso: :class:`processParams`
+    """
+    minDiagQ = np.float32(minDiagQ)
+    offDiagQ = np.float32(offDiagQ)
+    initMatrixQ: npt.NDArray[np.float32] = np.zeros(
+        (2, 2), dtype=np.float32
+    )
+    initMatrixQ[0, 0] = minDiagQ
+    initMatrixQ[1, 1] = minDiagQ
+    initMatrixQ[0, 1] = offDiagQ
+    initMatrixQ[1, 0] = offDiagQ
+    return initMatrixQ
+
+
+def constructMatrixH(
+    m: int, coefficients: Optional[np.ndarray] = None
+) -> npt.NDArray[np.float32]:
+    r"""Build the observation model matrix :math:`\mathbf{H}`.
+
+    :param m: Number of observations.
+    :type m: int
+    :param coefficients: Optional coefficients for the observation model,
+        which can be used to weight the observations manually.
+    :type coefficients: Optional[np.ndarray]
+    :return: The observation model matrix :math:`\mathbf{H}`.
+    :rtype: npt.NDArray[np.float32]
+
+    :seealso: :class:`observationParams`, class:`inputParams`
+    """
+    if coefficients is None:
+        coefficients = np.ones(m, dtype=np.float32)
+    elif isinstance(coefficients, list):
+        coefficients = np.array(coefficients, dtype=np.float32)
+    initMatrixH = np.empty((m, 2), dtype=np.float32)
+    initMatrixH[:, 0] = coefficients.astype(np.float32)
+    initMatrixH[:, 1] = np.zeros(m, dtype=np.float32)
+    return initMatrixH
+
+
+def runConsenrich(
+    matrixData: np.ndarray,
+    matrixMunc: np.ndarray,
+    deltaF: float,
+    minQ: float,
+    maxQ: float,
+    offDiagQ: float,
+    dStatAlpha: float,
+    dStatd: float,
+    dStatPC: float,
+    stateInit: float,
+    stateCovarInit: float,
+    boundState: bool,
+    stateLowerBound: float,
+    stateUpperBound: float,
+    chunkSize: int,
+    progressIter: int,
+    coefficientsH: Optional[np.ndarray] = None,
+    residualCovarInversionFunc: Optional[Callable] = None,
+    adjustProcessNoiseFunc: Optional[Callable] = None,
+) -> Tuple[
+    npt.NDArray[np.float32],
+    npt.NDArray[np.float32],
+    npt.NDArray[np.float32],
+]:
+    r"""Run consenrich on a contiguous segment (e.g. a chromosome) of read-density-based data.
+    Completes the forward and backward passes given data and approximated observation noise
+    covariance matrices :math:`\mathbf{R}_{[1:n, (11:mm)]}`.
+
+    This is the primary function implementing the core Consenrich algorithm. Users requiring specialized
+    preprocessing may prefer to call this function programmatically on their own preprocessed data rather
+    than using the command-line interface.
+
+
+    :param matrixData: Read density data for a single chromosome or general contiguous segment,
+      possibly preprocessed. Two-dimensional array of shape :math:`m \times n` where :math:`m`
+      is the number of samples/tracks and :math:`n` the number of genomic intervals.
+    :type matrixData: np.ndarray
+    :param matrixMunc: Uncertainty estimates for the read coverage data.
+        Two-dimensional array of shape :math:`m \times n` where :math:`m` is the number of samples/tracks
+        and :math:`n` the number of genomic intervals. See :func:`getMuncTrack`.
+    :type matrixMunc: np.ndarray
+    :param deltaF: See :class:`processParams`.
+    :type deltaF: float
+    :param minQ: See :class:`processParams`.
+    :type minQ: float
+    :param maxQ: See :class:`processParams`.
+    :type maxQ: float
+    :param offDiagQ: See :class:`processParams`.
+    :type offDiagQ: float
+    :param dStatAlpha: See :class:`processParams`.
+    :type dStatAlpha: float
+    :param dStatd: See :class:`processParams`.
+    :type dStatd: float
+    :param dStatPC: See :class:`processParams`.
+    :type dStatPC: float
+    :param stateInit: See :class:`stateParams`.
+    :type stateInit: float
+    :param stateCovarInit: See :class:`stateParams`.
+    :type stateCovarInit: float
+    :param chunkSize: Number of genomic intervals' data to keep in memory before flushing to disk.
+    :type chunkSize: int
+    :param progressIter: The number of iterations after which to log progress.
+    :type progressIter: int
+    :param coefficientsH: Optional coefficients for the observation model matrix :math:`\mathbf{H}`.
+        If None, the coefficients are set to 1.0 for all samples.
+    :type coefficientsH: Optional[np.ndarray]
+    :param residualCovarInversionFunc: Callable function to invert the observation covariance matrix :math:`\mathbf{E}_{[i]}`.
+        If None, defaults to :func:`cconsenrich.cinvertMatrixE`.
+    :type residualCovarInversionFunc: Optional[Callable]
+    :param adjustProcessNoiseFunc: Function to adjust the process noise covariance matrix :math:`\mathbf{Q}_{[i]}`.
+        If None, defaults to :func:`cconsenrich.updateProcessNoiseCovariance`.
+    :type adjustProcessNoiseFunc: Optional[Callable]
+    :return: Tuple of three numpy arrays:
+        - state estimates :math:`\widetilde{\mathbf{x}}_{[i]}` of shape :math:`n \times 2`
+        - state covariance estimates :math:`\widetilde{\mathbf{P}}_{[i]}` of shape :math:`n \times 2 \times 2`
+        - post-fit residuals :math:`\widetilde{\mathbf{y}}_{[i]}` of shape :math:`n \times m`
+    :rtype: Tuple[np.ndarray, np.ndarray, np.ndarray]
+
+    :raises ValueError: If the number of samples in `matrixData` is not equal to the number of samples in `matrixMunc`.
+    :seealso: :class:`observationParams`, :class:`processParams`, :class:`stateParams`
+    """
+    matrixData = np.ascontiguousarray(matrixData, dtype=np.float32)
+    matrixMunc = np.ascontiguousarray(matrixMunc, dtype=np.float32)
+    m: int = 1 if matrixData.ndim == 1 else matrixData.shape[0]
+    n: int = 1 if matrixData.ndim == 1 else matrixData.shape[1]
+    inflatedQ: bool = False
+    dStat: float = np.float32(0.0)
+    IKH: np.ndarray = np.zeros(shape=(2, 2), dtype=np.float32)
+    matrixEInverse: np.ndarray = np.zeros(
+        shape=(m, m), dtype=np.float32
+    )
+
+    matrixF: np.ndarray = constructMatrixF(deltaF)
+    matrixQ: np.ndarray = constructMatrixQ(minQ, offDiagQ=offDiagQ)
+    matrixQCopy: np.ndarray = matrixQ.copy()
+    matrixP: np.ndarray = np.eye(2, dtype=np.float32) * np.float32(
+        stateCovarInit
+    )
+    matrixH: np.ndarray = constructMatrixH(
+        m, coefficients=coefficientsH
+    )
+    matrixK: np.ndarray = np.zeros((2, m), dtype=np.float32)
+    vectorX: np.ndarray = np.array([stateInit, 0.0], dtype=np.float32)
+    vectorY: np.ndarray = np.zeros(m, dtype=np.float32)
+    matrixI2: np.ndarray = np.eye(2, dtype=np.float32)
+
+    if residualCovarInversionFunc is None:
+        residualCovarInversionFunc = cconsenrich.cinvertMatrixE
+    if adjustProcessNoiseFunc is None:
+        adjustProcessNoiseFunc = (
+            cconsenrich.updateProcessNoiseCovariance
+        )
+
+    # ==========================
+    # forward: 0,1,2,...,n-1
+    # ==========================
+    stateForward = np.memmap(
+        NamedTemporaryFile(delete=True),
+        dtype=np.float32,
+        mode="w+",
+        shape=(n, 2),
+    )
+    stateCovarForward = np.memmap(
+        NamedTemporaryFile(delete=True),
+        dtype=np.float32,
+        mode="w+",
+        shape=(n, 2, 2),
+    )
+    pNoiseForward = np.memmap(
+        NamedTemporaryFile(delete=True),
+        dtype=np.float32,
+        mode="w+",
+        shape=(n, 2, 2),
+    )
+    progressIter = max(1, progressIter)
+    for i in range(n):
+        if i % progressIter == 0:
+            logger.info(f"Forward pass interval: {i + 1}/{n}")
+        vectorZ = matrixData[:, i]
+        vectorX = matrixF @ vectorX
+        matrixP = matrixF @ matrixP @ matrixF.T + matrixQ
+        vectorY = vectorZ - (matrixH @ vectorX)
+
+        matrixEInverse = residualCovarInversionFunc(
+            matrixMunc[:, i], np.float32(matrixP[0, 0])
+        )
+        Einv_diag = np.diag(matrixEInverse)
+        dStat = np.median((vectorY**2) * Einv_diag)
+        matrixQ, inflatedQ = adjustProcessNoiseFunc(
+            matrixQ,
+            matrixQCopy,
+            dStat,
+            dStatAlpha,
+            dStatd,
+            dStatPC,
+            inflatedQ,
+            maxQ,
+            minQ,
+        )
+        matrixK = (matrixP @ matrixH.T) @ matrixEInverse
+        IKH = matrixI2 - (matrixK @ matrixH)
+
+        vectorX = vectorX + (matrixK @ vectorY)
+        matrixP = (IKH) @ matrixP @ (IKH).T + (
+            matrixK * matrixMunc[:, i]
+        ) @ matrixK.T
+        stateForward[i] = vectorX.astype(np.float32)
+        stateCovarForward[i] = matrixP.astype(np.float32)
+        pNoiseForward[i] = matrixQ.astype(np.float32)
+
+        if i % chunkSize == 0 and i > 0:
+            stateForward.flush()
+            stateCovarForward.flush()
+            pNoiseForward.flush()
+
+    stateForward.flush()
+    stateCovarForward.flush()
+    pNoiseForward.flush()
+    stateForwardArr = stateForward
+    stateCovarForwardArr = stateCovarForward
+    pNoiseForwardArr = pNoiseForward
+
+    # ==========================
+    # backward: n,n-1,n-2,...,0
+    # ==========================
+    stateSmoothed = np.memmap(
+        NamedTemporaryFile(delete=True),
+        dtype=np.float32,
+        mode="w+",
+        shape=(n, 2),
+    )
+    stateCovarSmoothed = np.memmap(
+        NamedTemporaryFile(delete=True),
+        dtype=np.float32,
+        mode="w+",
+        shape=(n, 2, 2),
+    )
+    postFitResiduals = np.memmap(
+        NamedTemporaryFile(delete=True),
+        dtype=np.float32,
+        mode="w+",
+        shape=(n, m),
+    )
+
+    stateSmoothed[-1] = np.float32(stateForwardArr[-1])
+    stateCovarSmoothed[-1] = np.float32(stateCovarForwardArr[-1])
+    postFitResiduals[-1] = np.float32(
+        matrixData[:, -1] - (matrixH @ stateSmoothed[-1])
+    )
+
+    for k in range(n - 2, -1, -1):
+        if k % progressIter == 0:
+            logger.info(f"Backward pass interval: {k + 1}/{n}")
+        forwardStatePosterior = stateForwardArr[k]
+        forwardCovariancePosterior = stateCovarForwardArr[k]
+        backwardInitialState = matrixF @ forwardStatePosterior
+        backwardInitialCovariance = (
+            matrixF @ forwardCovariancePosterior @ matrixF.T
+            + pNoiseForwardArr[k + 1]
+        )
+
+        smootherGain = np.linalg.solve(
+            backwardInitialCovariance.T,
+            (forwardCovariancePosterior @ matrixF.T).T,
+        ).T
+        stateSmoothed[k] = (
+            forwardStatePosterior
+            + smootherGain
+            @ (stateSmoothed[k + 1] - backwardInitialState)
+        ).astype(np.float32)
+
+        stateCovarSmoothed[k] = (
+            forwardCovariancePosterior
+            + smootherGain
+            @ (stateCovarSmoothed[k + 1] - backwardInitialCovariance)
+            @ smootherGain.T
+        ).astype(np.float32)
+        postFitResiduals[k] = np.float32(
+            matrixData[:, k] - matrixH @ stateSmoothed[k]
+        )
+
+        if k % chunkSize == 0 and k > 0:
+            stateSmoothed.flush()
+            stateCovarSmoothed.flush()
+            postFitResiduals.flush()
+
+    stateSmoothed.flush()
+    stateCovarSmoothed.flush()
+    postFitResiduals.flush()
+    if boundState:
+        stateSmoothed[:, 0] = np.clip(
+            stateSmoothed[:, 0], stateLowerBound, stateUpperBound
+        ).astype(np.float32)
+
+    return (
+        stateSmoothed[:],
+        stateCovarSmoothed[:],
+        postFitResiduals[:],
+    )
+
+
+def getPrimaryState(
+    stateVectors: np.ndarray, roundPrecision: int = 3
+) -> npt.NDArray[np.float32]:
+    r"""Get the primary state estimate from each vector after running Consenrich.
+
+    :param stateVectors: State vectors from :func:`runConsenrich`.
+    :type stateVectors: npt.NDArray[np.float32]
+    :return: A one-dimensional numpy array of the primary state estimates.
+    :rtype: npt.NDArray[np.float32]
+    """
+    out_ = np.ascontiguousarray(stateVectors[:, 0], dtype=np.float32)
+    np.round(out_, decimals=roundPrecision, out=out_)
+    return out_
+
+
+def getStateCovarTrace(
+    stateCovarMatrices: np.ndarray, roundPrecision: int = 3
+) -> npt.NDArray[np.float32]:
+    r"""Get a one-dimensional array of state covariance traces after running Consenrich
+
+    :param stateCovarMatrices: Estimated state covariance matrices :math:`\widetilde{\mathbf{P}}_{[i]}`
+    :type stateCovarMatrices: np.ndarray
+    :return: A one-dimensional numpy array of the traces of the state covariance matrices.
+    :rtype: npt.NDArray[np.float32]
+    """
+    stateCovarMatrices = np.ascontiguousarray(
+        stateCovarMatrices, dtype=np.float32
+    )
+    out_ = cconsenrich.cgetStateCovarTrace(stateCovarMatrices)
+    np.round(out_, decimals=roundPrecision, out=out_)
+    return out_
+
+
+def getPrecisionWeightedResidual(
+    postFitResiduals: np.ndarray,
+    matrixMunc: np.ndarray,
+    roundPrecision: int = 3,
+    stateCovarSmoothed: Optional[np.ndarray] = None,
+) -> npt.NDArray[np.float32]:
+    r"""Get a one-dimensional precision-weighted array residuals after running Consenrich.
+
+    Applies an inverse-variance weighting  of the post-fit residuals :math:`\widetilde{\mathbf{y}}_{[i]}` and
+    returns a one-dimensional array of "precision-weighted residuals". The state-level uncertainty can also be
+    incorporated given `stateCovarSmoothed`.
+
+    :param postFitResiduals: Post-fit residuals :math:`\widetilde{\mathbf{y}}_{[i]}` from :func:`runConsenrich`.
+    :type postFitResiduals: np.ndarray
+    :param matrixMunc: An :math:`m \times n` sample-by-interval matrix -- At genomic intervals :math:`i = 1,2,\ldots,n`, the respective length-:math:`m` column is :math:`\mathbf{R}_{[i,11:mm]}`.
+        That is, the observation noise levels for each sample :math:`j=1,2,\ldots,m` at interval :math:`i`. To keep memory usage minimal `matrixMunc` is not returned in full or computed in
+        in :func:`runConsenrich`. If using Consenrich programmatically, run :func:`consenrich.core.getMuncTrack` for each sample's count data (rows in the matrix output of :func:`readBamSegments`).
+    :type matrixMunc: np.ndarray
+    :param stateCovarSmoothed: Smoothed state covariance matrices :math:`\widetilde{\mathbf{P}}_{[i]}` from :func:`runConsenrich`.
+    :type stateCovarSmoothed: Optional[np.ndarray]
+    :return: A one-dimensional array of "precision-weighted residuals"
+    :rtype: npt.NDArray[np.float32]
+    """
+
+    n, m = postFitResiduals.shape
+    if matrixMunc.shape != (m, n):
+        raise ValueError(
+            f"matrixMunc should be (m,n)=({m}, {n}): observed {matrixMunc.shape}"
+        )
+    if stateCovarSmoothed is not None and (
+        stateCovarSmoothed.ndim < 3 or len(stateCovarSmoothed) != n
+    ):
+        raise ValueError(
+            "stateCovarSmoothed must be shape (n) x (2,2) (if provided)"
+        )
+
+    postFitResiduals_CContig = np.ascontiguousarray(
+        postFitResiduals, dtype=np.float32
+    )
+
+    needsCopy = (
+        (stateCovarSmoothed is not None)
+        and len(stateCovarSmoothed) == n
+    ) or (not matrixMunc.flags.writeable)
+
+    matrixMunc_CContig = np.array(
+        matrixMunc, dtype=np.float32, order="C", copy=needsCopy
+    )
+
+    if needsCopy:
+        # adds the 'primary' state uncertainty to observation noise covariance :math:`\mathbf{R}_{[i,:]}`
+        # primary state uncertainty (0,0) :math:`\mathbf{P}_{[i]} \in \mathbb{R}^{2 \times 2}`
+        stateCovarArr00 = np.asarray(
+            stateCovarSmoothed[:, 0, 0], dtype=np.float32
+        )
+        matrixMunc_CContig += stateCovarArr00
+
+    np.maximum(
+        matrixMunc_CContig, np.float32(1e-8), out=matrixMunc_CContig
+    )
+    out = cconsenrich.cgetPrecisionWeightedResidual(
+        postFitResiduals_CContig, matrixMunc_CContig
+    )
+    np.round(out, decimals=roundPrecision, out=out)
+    return out
+
+
+def getMuncTrack(
+    chromosome: str,
+    intervals: np.ndarray,
+    stepSize: int,
+    rowValues: np.ndarray,
+    minR: float,
+    maxR: float,
+    useALV: bool,
+    useConstantNoiseLevel: bool,
+    noGlobal: bool,
+    localWeight: float,
+    globalWeight: float,
+    approximationWindowLengthBP: int,
+    lowPassWindowLengthBP: int,
+    returnCenter: bool,
+    sparseMap: Optional[dict[int, int]] = None,
+    lowPassFilterType: Optional[str] = "median",
+) -> npt.NDArray[np.float32]:
+    r"""Get observation noise variance :math:`R_{[:,jj]}` for the sample :math:`j`.
+
+    Combines a local ALV estimate (see :func:`getAverageLocalVarianceTrack`) with an
+    optional global component. If ``useALV`` is True, *only* the ALV is used. If
+    ``useConstantNoiseLevel`` is True, a constant track set to the global mean is used.
+    When a ``sparseMap`` is provided, local values are aggregated over nearby 'sparse'
+    regions before mixing with the global component.
+
+    For heterochromatic or repressive marks (H3K9me3, H3K27me3, MNase-seq, etc.), consider setting
+    `useALV=True` to prevent inflated sample-level noise estimates.
+
+    :param chromosome: Tracks are approximated for this chromosome.
+    :type chromosome: str
+    :param intervals: Genomic intervals for which to compute the noise track.
+    :param stepSize: See :class:`countingParams`.
+    :type stepSize: int
+    :param rowValues: Read-density-based values for the sample :math:`j` at the genomic intervals :math:`i=1,2,\ldots,n`.
+    :type rowValues: np.ndarray
+    :param minR: See :class:`observationParams`.
+    :type minR: float
+    :param maxR: See :class:`observationParams`.
+    :type maxR: float
+    :param useALV: See :class:`observationParams`.
+    :type useALV: bool
+    :param useConstantNoiseLevel: See :class:`observationParams`.
+    :type useConstantNoiseLevel: bool
+    :param noGlobal: See :class:`observationParams`.
+    :type noGlobal: bool
+    :param localWeight: See :class:`observationParams`.
+    :type localWeight: float
+    :param globalWeight: See :class:`observationParams`.
+    :type globalWeight: float
+    :param approximationWindowLengthBP: See :class:`observationParams` and/or :func:`getAverageLocalVarianceTrack`.
+    :type approximationWindowLengthBP: int
+    :param lowPassWindowLengthBP: See :class:`observationParams` and/or :func:`getAverageLocalVarianceTrack`.
+    :type lowPassWindowLengthBP: int
+    :param sparseMap: Optional mapping (dictionary) of interval indices to the nearest sparse regions. See :func:`getSparseMap`.
+    :type sparseMap: Optional[dict[int, int]]
+    :param lowPassFilterType: The type of low-pass filter to use in average local variance track (e.g., 'median', 'mean').
+    :type lowPassFilterType: Optional[str]
+    :return: A one-dimensional numpy array of the observation noise track for the sample :math:`j`.
+    :rtype: npt.NDArray[np.float32]
+
+    """
+    trackALV = getAverageLocalVarianceTrack(
+        rowValues,
+        stepSize,
+        approximationWindowLengthBP,
+        lowPassWindowLengthBP,
+        minR,
+        maxR,
+        lowPassFilterType,
+    ).astype(np.float32)
+
+    globalNoise: float = np.float32(np.mean(trackALV))
+    if noGlobal or globalWeight == 0 or useALV:
+        return np.clip(trackALV, minR, maxR).astype(np.float32)
+
+    if (
+        useConstantNoiseLevel
+        or localWeight == 0
+        and sparseMap is None
+    ):
+        return np.clip(
+            globalNoise * np.ones_like(rowValues), minR, maxR
+        ).astype(np.float32)
+
+    if sparseMap is not None:
+        trackALV = cconsenrich.cSparseAvg(trackALV, sparseMap)
+
+    return np.clip(
+        trackALV * localWeight + np.mean(trackALV) * globalWeight,
+        minR,
+        maxR,
+    ).astype(np.float32)
+
+
+def sparseIntersection(
+    chromosome: str, intervals: np.ndarray, sparseBedFile: str
+) -> npt.NDArray[np.int64]:
+    r"""Returns intervals in the chromosome that overlap with the sparse features.
+
+    Not relevant if `observationParams.useALV` is True.
+
+    :param chromosome: The chromosome name.
+    :type chromosome: str
+    :param intervals: The genomic intervals to consider.
+    :type intervals: np.ndarray
+    :param sparseBedFile: Path to the sparse BED file.
+    :type sparseBedFile: str
+    :return: A numpy array of start positions of the sparse features that overlap with the intervals
+    :rtype: np.ndarray[Tuple[Any], np.dtype[Any]]
+    """
+
+    stepSize: int = intervals[1] - intervals[0]
+    chromFeatures: bed.BedTool = (
+        bed.BedTool(sparseBedFile)
+        .sort()
+        .merge()
+        .filter(
+            lambda b: (
+                b.chrom == chromosome
+                and b.start > intervals[0]
+                and b.end < intervals[-1]
+                and (b.end - b.start) >= stepSize
+            )
+        )
+    )
+    centeredFeatures: bed.BedTool = chromFeatures.each(
+        adjustFeatureBounds, stepSize=stepSize
+    )
+
+    start0: int = int(intervals[0])
+    last: int = int(intervals[-1])
+    chromFeatures: bed.BedTool = (
+        bed.BedTool(sparseBedFile)
+        .sort()
+        .merge()
+        .filter(
+            lambda b: (
+                b.chrom == chromosome
+                and b.start > start0
+                and b.end < last
+                and (b.end - b.start) >= stepSize
+            )
+        )
+    )
+    centeredFeatures: bed.BedTool = chromFeatures.each(
+        adjustFeatureBounds, stepSize=stepSize
+    )
+    centeredStarts = []
+    for f in centeredFeatures:
+        s = int(f.start)
+        if start0 <= s <= last and (s - start0) % stepSize == 0:
+            centeredStarts.append(s)
+    return np.asarray(centeredStarts, dtype=np.int64)
+
+
+def adjustFeatureBounds(
+    feature: bed.Interval, stepSize: int
+) -> bed.Interval:
+    r"""Adjust the start and end positions of a BED feature to be centered around a step."""
+    feature.start = cconsenrich.stepAdjustment(
+        (feature.start + feature.end) // 2, stepSize
+    )
+    feature.end = feature.start + stepSize
+    return feature
+
+
+def getSparseMap(
+    chromosome: str,
+    intervals: np.ndarray,
+    numNearest: int,
+    sparseBedFile: str,
+) -> dict:
+    r"""Build a map between each genomic interval and numNearest sparse features
+
+    :param chromosome: The chromosome name. Note, this function only needs to be run once per chromosome.
+    :type chromosome: str
+    :param intervals: The genomic intervals to map.
+    :type intervals: np.ndarray
+    :param numNearest: The number of nearest sparse features to consider
+    :type numNearest: int
+    :param sparseBedFile: path to the sparse BED file.
+    :type sparseBedFile: str
+    :return: A dictionary mapping each interval index to the indices of the nearest sparse regions.
+    :rtype: dict[int, np.ndarray]
+
+    """
+    numNearest = numNearest
+    sparseStarts = sparseIntersection(
+        chromosome, intervals, sparseBedFile
+    )
+    idxSparseInIntervals = np.searchsorted(
+        intervals, sparseStarts, side="left"
+    )
+    centers = np.searchsorted(sparseStarts, intervals, side="left")
+    sparseMap: dict = {}
+    for i, (interval, center) in enumerate(zip(intervals, centers)):
+        left = max(0, center - numNearest)
+        right = min(len(sparseStarts), center + numNearest)
+        candidates = np.arange(left, right)
+        dists = np.abs(sparseStarts[candidates] - interval)
+        take = np.argsort(dists)[:numNearest]
+        sparseMap[i] = idxSparseInIntervals[candidates[take]]
+    return sparseMap
+
+
+def getBedMask(
+    chromosome: str,
+    bedFile: str,
+    intervals: np.ndarray,
+) -> np.ndarray:
+    r"""Return a 1/0 mask for intervals overlapping a sorted and merged BED file.
+
+    This function is a wrapper for :func:`cconsenrich.cbedMask`.
+
+    :param chromosome: The chromosome name.
+    :type chromosome: str
+    :param intervals: chromosome-specific, sorted, non-overlapping start positions of genomic intervals.
+      Each interval is assumed `stepSize`.
+    :type intervals: np.ndarray
+    :param bedFile: Path to a sorted and merged BED file
+    :type bedFile: str
+    :return: An `intervals`-length mask s.t. True indicates the interval overlaps a feature in the BED file.
+    :rtype: np.ndarray
+    """
+    if not os.path.exists(bedFile):
+        raise ValueError(f"Could not find {bedFile}")
+    if len(intervals) < 2:
+        raise ValueError(
+            "intervals must contain at least two positions"
+        )
+    bedFile_ = str(bedFile)
+
+    # (possibly redundant) creation of uint32 version
+    # + quick check for constant steps
+    intervals_ = np.asarray(intervals, dtype=np.uint32)
+    if (intervals_[1] - intervals_[0]) != (
+        intervals_[-1] - intervals_[-2]
+    ):
+        raise ValueError("Intervals are not fixed in size")
+
+    stepSize_: int = intervals[1] - intervals[0]
+    return cconsenrich.cbedMask(
+        chromosome,
+        bedFile_,
+        intervals_,
+        stepSize_,
+    ).astype(np.bool_)