A tool for diagnosing spinal muscular atrophy (SMA) using exome or genome sequencing data
Project description
SMA Finder
A tool for diagnosing spinal muscular atrophy (SMA) using exome or genome sequencing data. It takes 1 or more alignment files (CRAM or BAM) as input and reports whether the sample(s) have complete loss of functional SMN1.
Testing on 13 positive controls and 10,434 negative controls showed 100% sensitivity and specificity (details below).
Limitations: SMA Finder doesn't report SMA carrier status or SMN2 copy number. Also, it does not detect the ~5% of cases caused by unusual SMN1 loss-of-function mutations that do not involve the c.840 position. Finally, although SMA Finder may also work for RNA-seq, targeted sequencing, or long-read alignment files, we currently lack the positive controls needed to evaluate this. If you have such samples, or would like to collaborate in other ways, please contact weisburd at broadinstitute dot org.
Install
python3 -m pip install sma-finder
Example
Example command:
sma_finder --verbose --genome-version 38 --reference-fasta /ref/hg38.fa sample1.cram
Command output:
Input args:
--reference-fasta: /ref/hg38.fa
--genome-version: 38
--output-tsv: sample1.sma_finder_results.tsv
CRAMS or BAMS: sample1.cram
----
Output row #1:
filename_prefix sample1
file_type cram
sample_id s1
sma_status has SMA
confidence_score 168
c840_reads_with_smn1_base_C 0
c840_total_reads 174
Wrote 1 rows to sample1.sma_finder_results.tsv
Usage
Usage help text:
sma_finder --help
usage: sma_finder [-h] -R REFERENCE_FASTA -g {37,38,T2T} [-o OUTPUT_TSV]
[-v]
cram_or_bam_path [cram_or_bam_path ...]
positional arguments:
cram_or_bam_path One or more CRAM or BAM file paths
optional arguments:
-h, --help show this help message and exit
-R REFERENCE_FASTA, --reference-fasta REFERENCE_FASTA
Reference genome FASTA file path
-g {37,38,T2T}, --genome-version {37,38,T2T}
Reference genome version
-o OUTPUT_TSV, --output-tsv OUTPUT_TSV
Optional output tsv file path
-v, --verbose Whether to print extra details during the run
Output
The output .tsv contains one row per input CRAM or BAM file and has the following columns:
filename_prefix | CRAM or BAM filename prefix. If the input file is /path/sample1.cram this would be "sample1". |
file_type | "cram" or "bam" |
sample_id | sample id from the CRAM or BAM file header (parsed from the read group metadata) |
sma_status | possible values are: "has SMA" "does not have SMA" "not enough coverage at SMN c.840 position" |
confidence_score | PHRED-scaled integer score measuring the level of confidence that the sma_status is correct. The bigger the score, the higher the confidence. It is calculated in a similar way to the PL field in GATK HaplotypeCaller genotypes. |
c840_reads_with_smn1_base_C | number of reads that have a 'C' nucleotide at the c.840 position in SMN1 plus SMN2 |
c840_total_reads | total number of reads overlapping the c.840 position in SMN1 plus SMN2 |
Details
This poster on SMA Finder was presented at the SVAR22 conference:
Project details
Release history Release notifications | RSS feed
Download files
Download the file for your platform. If you're not sure which to choose, learn more about installing packages.