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ROCCO: [R]obust [O]pen [C]hromatin Detection via [C]onvex [O]ptimization

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What

ROCCO is an efficient algorithm for detection of "consensus peaks" in large datasets with multiple HTS data samples, where an enrichment in read counts/densities is observed in a nontrivial subset of samples.

Input/Output

  • Input: Samples' .bam alignments (-i) and a reference genome assembly (-g) for chromosome sizes
  • Output: BED file of consensus peak regions (Default format is BED3: chrom,start,end). narrowPeak and gappedPeak outputs are supported for BAM inputs. Use --peak_mode both.

How

ROCCO models consensus peak calling as an optimization problem: select the most enriched genomic regions as peaks while controlling total genomic coverage and discouraging fragmented calls.

  • Enrichment is measured by a read density score in the selected genomic regions
  • Budget proportions calibrate selection penalties that control total genomic coverage
  • Fragmentation is controlled via a total variation penalty, multiplied by a penalty parameter $\gamma$ ($\gamma \sum_i |x_{i+1} - x_i|$).

Why

  1. Consideration of enrichment magnitude and spatial characteristics of open chromatin signals
  2. Scaling to large sample sizes (100+)
  3. Unsupervised Does not require training data or a heuristically determined set of initial candidate peak regions
  4. Less rigid thresholds with respect to the minimum number/width of supporting samples/replicates.
  5. Mathematically tractable model permitting worst-case analysis of runtime and performance

Basic Usage

Run rocco --help for the complete command-line reference.

ROCCO accepts either one or more BAM files, separated by spaces.

rocco -i <BAM> [<BAM> ...] \
  -g <GENOME> \
  -o <OUTPUT.bed>

Genome assemblies hg38, hg19, mm10, mm39, and dm6 can be used with -g, to supply a built-in chromosome sizes file (canonical chromosomes only) and effective genome size.

If using ROCCO with another assembly, just provide the chromosome sizes file and effective genome size as described explicitly:

  • -s, --chrom_sizes_file <FILE>: chromosome names and sizes.
  • --effective_genome_size <BASES>: effective genome size, only required if using RPGC normalization.

For example:

rocco \
  -i sample1.bam sample2.bam sample3.bam \
  -s assemblyName.chrom.sizes \
  --effective_genome_size <BASES> \
  -o consensus_peaks.bed

When troubleshooting, consider processing a subset of the genome for faster evaluation:

rocco \
  -i sample1.bam sample2.bam sample3.bam \
  -g hg38 \
  -o consensus_peaks.bed \
  --chroms chr11 chr20 chr21 chr22 # at least four chroms

Example

Call consensus peaks from three BAM files and generate both narrowPeak and gappedPeak outputs:

rocco \
  -i sample1.bam sample2.bam sample3.bam \
  -g hg38 \
  -o consensus_peaks.bed \
  --peak_mode both

Paper/Citation

If using ROCCO in your research, please cite the original paper in Bioinformatics (DOI: btad725)

 Nolan H Hamilton, Terrence S Furey, ROCCO: a robust method for detection of open chromatin via convex optimization,
 Bioinformatics, Volume 39, Issue 12, December 2023

Installation

PyPI (pip)

python -m pip install rocco --upgrade

If lacking administrative control, you may need to append --user to the above.

Build from Source

If preferred, ROCCO can easily be built from source:

  • Clone or download this repository

    git clone https://github.com/nolan-h-hamilton/ROCCO.git
    cd ROCCO
    python setup.py sdist bdist_wheel
    python -m pip install -e .
    

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This release

1.14.0 This release

31 files

1.13.0

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1.12.0

31 files

1.11.0

31 files

1.10

31 files

1.7.0

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1.6.3

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1.6.0.post1

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0.2.0

2 files

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