PoolParty

PoolParty is a Python package for designing complex oligonucleotide sequence libraries. It provides a declarative, composable interface for generating DNA libraries used in MPRA (massively parallel reporter assays), deep mutational scanning, in silico analysis of genomic DNNs, and other high-throughput experiments.

Why PoolParty?

Designing DNA libraries often involves combining multiple types of sequence modifications — mutations, insertions, deletions, shuffles — across multiple regions with mixed coverage requirements. PoolParty lets you:

• Compose operations: Chain operations like .mutagenize(), .deletion_scan(), and .insertion_scan() to build complex libraries
• Tag regions: Use XML-like syntax to mark and manipulate specific regions of sequences
• Use lazy evaluation: Sequences are generated on-demand, enabling libraries with billions of potential variants
• Track provenance: Each sequence comes with a structured record of how it was built — ready for filtering, grouping, and modeling
• Style output: Visual annotations highlight sequence modifications and regions for quick auditing

Installation

pip install poolparty

For development:

git clone https://github.com/jbkinney/poolparty-statetracker.git
cd poolparty-statetracker/poolparty
pip install -e ".[dev]"

Quick Start

import poolparty as pp

# Initialize poolparty
pp.init()

# Create a template sequence with tagged regions
template = pp.from_seq("ACGT<cre>GGAAAGCGGGCAGTGAGC</cre>TTTT<bc/>GGGG")

# Generate single-nucleotide mutations in the CRE region
mutant_library = template.mutagenize(
    region="cre",
    num_mutations=1,
    mode="sequential"  # Generate all possible single mutants
)

# Generate the library as a DataFrame
df = mutant_library.generate_library()
print(df)

Key Features

Region Tagging

Mark regions of interest with XML-like tags:

# Self-closing tag for insertion points
seq = pp.from_seq("ACGT<barcode/>TTTT")

# Paired tags for regions
seq = pp.from_seq("ACGT<promoter>GGAAAGCGGG</promoter>TTTT")

Scanning Operations

Apply systematic mutations across a region:

# Tiled deletions
deletions = template.deletion_scan(
    region="cre",
    deletion_length=5,
    positions=slice(None, None, 3)  # Every 3rd position
)

# Tiled insertions
inserts = pp.from_seqs(["AAAAAA", "TTTTTT"])
insertions = template.insertion_scan(
    region="cre",
    ins_pool=inserts,
    positions=slice(0, 10, 2)
)

# Replacement scanning
replacements = template.replacement_scan(
    region="cre",
    ins_pool=pp.get_kmers(length=5),
)

Combining Libraries

Stack different variant types into a single library:

# Create different variant pools
mutations = template.mutagenize(region="cre", num_mutations=1)
deletions = template.deletion_scan(region="cre", deletion_length=5)

# Combine into one library
combined = pp.stack([mutations, deletions])

# Add barcodes to all variants
barcoded = combined.insert_kmers(region="bc", length=10)

# Generate final library
df = barcoded.generate_library()

Random vs Sequential Mode

Control how variants are generated:

# Sequential: enumerate all possible variants
all_mutants = template.mutagenize(
    num_mutations=1,
    mode="sequential"
)

# Random: sample from variant space
random_mutants = template.mutagenize(
    num_mutations=2,
    mode="random",
    num_states=100  # Generate 100 random double mutants
)

Codon-Aware Mutagenesis

Preserve reading frames during mutagenesis:

# Define a template with a coding region
orf_template = pp.from_seq("ACGT<gfp>ATGGTGAGCAAGGGCGAG</gfp>TTTT")

# Synonymous mutations preserve the amino acid sequence
orf_mutants = orf_template.mutagenize_orf(
    region="gfp",
    num_mutations=1,
    mutation_type="synonymous"  # or "missense", "nonsense"
)

Operations

PoolParty provides 50+ composable operations for DNA library design. See the full API reference for details.

Documentation

Full documentation is available at poolparty.readthedocs.io.

See Also

PoolParty is built on StateTracker, a library for composable state management that enables efficient random access to combinatorial spaces.

License

MIT License - see LICENSE for details.