Compressed Sequence Files (gzip / bzip2 / BGZF)

Hard rules

1. No fabricated citations. Every cited work must resolve to a verifiable
2. No claim without provenance. Every quantitative or factual claim
3. No silent failure. Every script invocation, API call, or tool use must declare its exit status and what to do on non-zero. A skill that silently swallows errors is a violation.

When to use

• Reading or writing .fasta.gz, .fastq.gz, .fasta.bz2 in Python.
• Producing or consuming indexable compressed FASTA (BGZF).
• Building pipelines that need random access into compressed records.

When NOT to use

"

• Plain uncompressed FASTA — open with SeqIO.parse(path, "fasta") directly.
• BAM/CRAM/VCF BGZF: use pysam (see ors-bioinformatics-sequence-pysam-genomics).
• Whole-genome-scale index needs → use samtools faidx + bgzip, not Biopython.

Prerequisites

• biopython>=1.83 (ships Bio.bgzf).
• For production BGZF: htslib ≥ 1.19 (bgzip + tabix).
• For bzip2: Python's stdlib bz2.

Core workflow

1. Open in text mode ('rt' / 'wt'). The parser expects text. 'rb' will trip on a bytes-vs-str TypeError.
2. Pick the format by use case:
   • .gz → archive only, not indexable.
   • .bz2 → smaller but slower; archive only.
   • .bgz → indexable via SeqIO.index(); native for BAM/VCF/tabix.
3. For new pipelines, prefer BGZF unless you have a hard reason to use plain gzip.
4. For BAM/VCF, always use htslib bgzip — its blocks are HTSlib-compatible; Biopython's BGZF works but is slower on huge files.

Code patterns

Read gzipped FASTA

import gzip
from Bio import SeqIO

with gzip.open("sequences.fasta.gz", "rt") as fh:
    for rec in SeqIO.parse(fh, "fasta"):
        print(rec.id, len(rec.seq))

Read bzip2

import bz2
from Bio import SeqIO

with bz2.open("reads.fastq.bz2", "rt") as fh:
    recs = list(SeqIO.parse(fh, "fastq"))

Write gzipped output

import gzip
from Bio import SeqIO

with gzip.open("clean.fasta.gz", "wt") as out:
    SeqIO.write(records, out, "fasta")

Read BGZF (text path) and via bgzf.open

from Bio import SeqIO, bgzf

# Either works
for rec in SeqIO.parse("seqs.fasta.bgz", "fasta"):
    ...

with bgzf.open("seqs.fasta.bgz", "rt") as fh:
    for rec in SeqIO.parse(fh, "fasta"):
        ...

Write BGZF for downstream indexing

from Bio import SeqIO, bgzf

with bgzf.open("indexable.fasta.bgz", "wt") as out:
    SeqIO.write(SeqIO.parse("raw.fasta", "fasta"), out, "fasta")

Index a BGZF file (random access by record ID)

from Bio import SeqIO

db = SeqIO.index("seqs.fasta.bgz", "fasta")
print(db["target_id"].seq)
db.close()

# Or persistent on-disk index for huge files
db = SeqIO.index_db("seqs.idx", "seqs.fasta.bgz", "fasta")

Auto-detect by extension (single entry point)

from pathlib import Path
import gzip, bz2
from Bio import SeqIO, bgzf

def open_seq(path: str, fmt: str):
    p = Path(path)
    sfx = "".join(p.suffixes).lower()
    if sfx.endswith(".bgz") or sfx.endswith(".bgzf"):
        fh = bgzf.open(p, "rt")
    elif sfx.endswith(".gz") or sfx.endswith(".bgzf"):
        fh = gzip.open(p, "rt")
    elif sfx.endswith(".bz2"):
        fh = bz2.open(p, "rt")
    else:
        fh = open(p, "r")
    return SeqIO.parse(fh, fmt)

Convert plain gzip to indexable BGZF

import gzip
from Bio import SeqIO, bgzf

with gzip.open("input.fasta.gz", "rt") as src, \
     bgzf.open("indexable.fasta.bgz", "wt") as dst:
    SeqIO.write(SeqIO.parse(src, "fasta"), dst, "fasta")

Low-memory record count (FASTA)

import gzip
from Bio.SeqIO.FastaIO import SimpleFastaParser

with gzip.open("sequences.fasta.gz", "rt") as fh:
    n = sum(1 for _ in SimpleFastaParser(fh))
print(f"{n} sequences")

Common pitfalls

• Using 'rb' instead of 'rt'. You'll get TypeError: a bytes-like object is required, not 'str'.
• Expecting SeqIO.index() to work on plain .gz. It does not — convert to BGZF first.
• Mixing Biopython BGZF with htslib bgzip blocks. They are wire-compatible for FASTA, but for .vcf.gz/.bcf use htslib bgzip end-to-end to avoid rare edge cases.
• Decompressing to disk then re-reading. Wastes 3-4x disk. Stream from the compressed handle.
• .bz2 is slow. For long-term archives, yes; for active work, prefer BGZF.

Validation

• File ends with the correct magic: gzip → 1f 8b, bzip2 → 42 5a, BGZF → 1f 8b 08 04 (with extra fields).
• After BGZF write, SeqIO.index("out.bgz", "fasta")["known_id"] returns the same record.
• Round-trip: bgzf open → gzip open byte counts differ only by BGZF block overhead.

Open alternatives

References

• BGZF spec: https://samtools.github.io/hts-specs/SAMv1.pdf (section 4)
• HTSlib bgzip: http://www.htslib.org/doc/bgzip.html
• Biopython bgzf: https://biopython.org/docs/latest/api/Bio.bgzf.html
• Companion: ors-bioinformatics-sequence-pysam-genomics, ors-bioinformatics-sequence-samtools-bam-processing.

Changelog

• 1.0.0 (2026-06-10): Initial adaptation by Pradyumna Jayaram from bio-compressed-files (bioSkills-main/sequence-io/compressed-files).

Cross-references

Other skills in this category:

• batch-processing
• bowtie2-alignment
• bwa-alignment
• bwa-mem2-alignment
• codon-usage
• fastq-quality-scores
• filter-sequences
• format-conversion
• hisat2-alignment
• motif-search
• paired-end-fastq
• pysam-genomics
• read-write-sequences
• reverse-complement
• sam-bam-basics
• samtools-bam-processing
• seq-objects
• sequence-properties
• sequence-slicing
• sequence-statistics
• star-alignment
• transcription-translation