Bramble converts genomic BAM alignments to transcriptomic coordinates, enabling accurate transcript quantification while preserving the discovery power of genome alignments.

Traditional RNA-seq quantification involves a fundamental trade-off: lightweight pseudoalignment and alignment-based methods may efficiently estimate transcript abundance, but they are limited by dependence on existing annotations. They miss novel isoforms and splice junctions, divergent sequences (SNPs, mutations, strain variants), unannotated transcripts, and transcriptional noise. Genome-based methods capture all of these features through spliced alignment, but quantification tools expect transcriptomic coordinates, creating a compatibility barrier.

Bramble bridges this gap by projecting spliced genomic alignments into transcriptomic space, giving you the best of both worlds: discover novel isoforms, variants, and unannotated features through genome alignment, and also run standard quantification tools that expect transcriptomic coordinates. Some benefits of using Bramble include:

Improved quantification accuracy:

• More accurate downstream expression estimates compared to direct alignment-based transcriptome quantification
• Better handling of multimapped reads in transcript context
• Annotation-guided filtering removes noise and spurious alignments

Flexible workflow:

• Works with your existing genome aligner (HISAT2, STAR, minimap2, etc.)
• Compatible with downstream tools expecting transcriptomic BAMs (Salmon, Oarfish, TranSigner, etc.)
• Supports both short and long-read data

For the meson build system: currently, system dependencies are required for zlib, bz2, and lzma, though these could be built as dependencies later if wanted (an attempt will be made using wrapdb to build zlib and bz2 if not found on the system).

Also, to build you will need to have meson, ninja, and autotools installed.

To build you can either run build.sh directly, or do the following:

> meson setup build

then change to the build directory and build it

> cd build
> ninja

This should create the bramble executable!

This has been tested with meson 1.7 and 1.8, but likely also works with older versions.

Basic command:

bramble input.bam -G annotation.gtf -o output.bam

bramble <in.bam ...> [-G <guide_gff>] [-o <out.bam>] [-p <cpus>] [options]

Required:

<in.bam>: One or more input BAM files with genomic alignments
-G <file>: Reference annotation (GTF/GFF) to guide coordinate conversion
-o <file>: Output BAM file path

Options:

-p <int>: Number of threads to use (default: 1)
--long: Optimize for long-read alignments
--verbose: Print detailed processing information
--help: Show help message
--version: Print version and exit

Run bramble --help to see all available options. For issues or questions, please open an issue!

You may also contact us for questions or suggestions at zrudnic1@jh.edu.

Bramble is free, open source software released under an MIT License.