Metagenomics · Software
SCiMS
Infers host chromosomal sex from sparse host reads in metagenomic sequencing data for XY and ZW species.
What SCiMS is
Metagenomic sequencing data contains a mixture of microbial and host genetic material. While host-derived reads are often filtered out, they retain biological information about the host organism. SCiMS (Sex Calling in Metagenomic Sequences) is a tool developed by the Davenport lab that infers the chromosomal sex of a host directly from the fraction of reads mapping to the host genome.
By evaluating alignment statistics across sex chromosomes and modelling read counts directly, SCiMS provides chromosomal sex assignments even when host DNA constitutes only a tiny proportion of the sequenced sample. This enables researchers to verify sample provenance, recover unrecorded demographic variables, and incorporate host sex into downstream metagenomic analyses.
How it works
SCiMS reads alignment metrics from sorted, indexed BAM files or pre-computed SAMtools idxstats files, accepting alignments generated by any aligner or sequencing platform against a chosen host reference genome. Users supply a list of target scaffolds alongside the specific identifiers for the homogametic (X or Z) and heterogametic (Y or W) sex chromosomes.
The software models observed read counts on the sex chromosomes relative to autosomes under a likelihood ratio framework, applying an expected mismapping rate for chromosomes with zero ploidy. It evaluates whether the mapping patterns best fit homogametic or heterogametic configurations under an XY or ZW model, outputting inferred sex, likelihood ratio statistics, and posterior probabilities.
Key facts
- Software version
- 2.0.0
- Input formats
- BAM files, SAMtools .idxstats files
- Output
- Inferred sex, posterior probability, likelihood ratio test statistics
- Supported systems
- XY (default) and ZW chromosomal sex determination systems
- Dependencies
- Python 3 (NumPy, pandas, SciPy); SAMtools for BAM input
What you can use it for
- Demographic recovery in metagenomic cohorts
- Determines the chromosomal sex of human or animal hosts when sample metadata is missing, incomplete, or unrecorded.
- Metagenomic sample identity and quality control
- Flags sample swaps and mislabelled sex metadata by checking inferred chromosomal sex against study records.
- Sex determination in non-human hosts
- Infers chromosomal sex for organisms utilising either XY (such as mammals) or ZW (such as birds) systems from raw whole metagenomic reads.
Run it here
The research agent sets SCiMS up on its machine the first time a task needs it, then runs it and reads the output back to you. Nothing to install on your side.
Try asking
“Call the host sex of these gut metagenomes with SCiMS from their BAMs against GRCh38.”
Strengths and limits
Good at
- Accurately determines sex even at very low host sequencing depth within predominantly microbial samples.
- Compatible with alignments from any sequencing platform, read aligner, or reference assembly.
- Includes batch processing modes that directly annotate existing study metadata files with sex predictions.
Watch out for
- Must be applied to raw sequencing alignments prior to host read removal, as filtering procedures distort chromosome ratios.
- Designed exclusively for binary XY and ZW chromosomal systems and cannot evaluate non-chromosomal or polygenic sex determination.
- May yield unreliable calls for individuals with sex chromosome aneuploidies such as XXY, XYY, or monosomy X.
- Can produce inconclusive results if host read counts mapping to sex chromosomes are excessively low, as found in some stool metagenomes.
Questions
Can I run SCiMS online without installing it?
The research agent sets SCiMS up on its machine the first time a task needs it, then runs it and reads the output back to you. Nothing to install on your side.
What licence is SCiMS under?
MIT. The terms are published at https://github.com/davenport-lab/SCiMS/blob/main/LICENSE.
Can SCiMS be run on publicly available, host-depleted metagenomes?
No. Host-filtering workflows alter the relative representation of chromosomes and bias inference. SCiMS requires raw sequencing reads aligned to the host reference before host depletion occurs.
Which sex determination systems are supported?
The software natively supports XY systems by default and ZW systems via the dedicated command-line flag. It is not validated for environmental, polygenic, or other non-chromosomal sex determination mechanisms.
What reference files are required to execute a run?
The SCiMS command line takes a file listing the scaffolds to use and the identifiers of the two sex chromosomes. Here the agent reads them from the BAM header when the reference uses RefSeq accessions or chromosome names, and asks for them otherwise.
Can the tool infer gender identity?
No. SCiMS infers biological chromosomal sex complements from read alignments and cannot infer gender identity.
How to cite it
Tran, Kirven & Davenport, Microbiome 2026, doi:10.1186/s40168-026-02547-x.
Written from SCiMS's own README and project page. Statements citing a figure that does not appear there are removed before publication. Licence and running details come from our registry.