BWA-MEME: BWA-MEM emulated with a machine learning approach
- BWA-MEME produces identical results as BWA-MEM2 and achieves 1.4x higher alignment throughput.
- Seeding throughput of BWA-MEME is up to 3.32x higher than BWA-MEM2.
- BWA-MEME builds upon BWA-MEM2 and includes performance improvements to the seeding.
- BWA-MEME leverages learned index in suffix array search.
- BWA-MEME also provides feature to accomodate various memory size in servers.
Contents
- When to use BWA-MEME
- Performance of BWA-MEME
- Getting Started
- Changing memory requirement for index in BWA-MEME
- Notes
- Citation
When to use BWA-MEME
- Anyone who use BWA-MEM or BWA-MEM2 in CPU-only machine (BWA-MEME requires 38GB of memory for index at minimal mode)
- Building high-throughput NGS alignment cluster with low cost/throughput. CPU-only alignment can be cheaper than using hardware acceleration (GPU, FPGA).
- Just add single option "-7" to deploy BWA-MEME instead of BWA-MEM2 (BWA-MEME does not change anything, except the speed).
Performance of BWA-MEME
The seeding module of BWA-MEME uses Learned-index. This, in turn, results in 3.32x higher seeding throughput compared to FM-index of BWA-MEM2.
End-to-end alignment throughput is up to 1.4x higher than BWA-MEM2.
Getting Started
Install Option 1. Bioconda
# Install with conda, bwa-meme and the learned-index train script "build_rmis_dna.sh" will be installed
conda install -c conda-forge -c bioconda bwa-meme
# Print version and Mode of compiled binary executable
# bwa-meme binary automatically choose the binary based on the SIMD instruction supported (SSE, AVX2, AVX512 ...)
# Other modes of bwa-meme is available as bwa-meme_mode1 or bwa-meme_mode2
bwa-meme version
Build index of the reference DNA sequence
# Build index (Takes ~1hr for human genome)
# we recommend using at least 8 threads
bwa-meme index -a meme <input.fasta> -t <thread number>Training P-RMI
# Run code below to train P-RMI, suffix array is required which is generated in index build code
# takes about 15 minute for human genome with single thread
build_rmis_dna.sh <input.fasta>Run alignment and compare SAM output with BWA-MEM2
# Perform alignment with BWA-MEME, add -7 option
bwa-meme mem -7 -Y -K 100000000 -t <num_threads> <input.fasta> <input_1.fastq> -o <output_meme.sam>
# Below runs alignment with BWA-MEM2, without -7 option
bwa-meme mem -Y -K 100000000 -t <num_threads> <input.fasta> <input_1.fastq> -o <output_mem2.sam>
# Compare output SAM files
diff <output_mem2.sam> <output_meme.sam>
# To diff large SAM files use https://github.com/unhammer/diff-large-filesInstall Option 2. Build locally
Compile the code
# Compile from source
git clone https://github.com/kaist-ina/BWA-MEME.git BWA-MEME
cd BWA-MEME
# To compile all binary executables run below command.
# Put the highest number of available vCPU cores
# You should also have cmake installed. Download by sudo apt-get install cmake
make -j<num_threads>
# Print version and Mode of compiled binary executable
# bwa-meme binary automatically choose the binary based on the SIMD instruction supported (SSE, AVX2, AVX512 ...)
# Other modes of bwa-meme is available as bwa-meme_mode1 or bwa-meme_mode2
./bwa-meme version
# For bwa-meme with mode 1 or 2 see belowBuild index of the reference DNA sequence
# Build index (Takes ~1hr for human genome)
# we recommend using 32 threads
./bwa-meme index -a meme <input.fasta> -t <thread number>Training P-RMI
Prerequisites for building locally: To use the train code, please install Rust.
# Run code below to train P-RMI, suffix array is required which is generated in index build code
# takes about 15 minute for human genome with single thread
./build_rmis_dna.sh <input.fasta>Run alignment and compare SAM output with BWA-MEM2
# Perform alignment with BWA-MEME, add -7 option
./bwa-meme mem -7 -Y -K 100000000 -t <num_threads> <input.fasta> <input_1.fastq> -o <output_meme.sam>
# Below runs alignment with BWA-MEM2, without -7 option
./bwa-meme mem -Y -K 100000000 -t <num_threads> <input.fasta> <input_1.fastq> -o <output_mem2.sam>
# Compare output SAM files
diff <output_mem2.sam> <output_meme.sam>
# To diff large SAM files use https://github.com/unhammer/diff-large-filesTest scripts and executables are available in the BWA-MEME/test folder
Changing memory requirement for index in BWA-MEME
# You can check the MODE value by running version command
# mode 1: 38GB in index size
./bwa-meme_mode1 version
# mode 2: 88GB in index size
./bwa-meme_mode2 version
# mode 3: 118GB in index size, fastest mode
./bwa-meme version
# If binary executable does not exist, run below command to compile
make clean
make -j<number of threads>
Notes
-
BWA-MEME requires at least 64 GB RAM (with minimal acceleration BWA-MEME requires 38GB of memory). For WGS runs on human genome (>32 threads) with full acceleration of BWA-MEME, it is recommended to have 140-192 GB RAM.
-
When deploying BWA-MEME with many threads, mimalloc library is recommended for a better performance (Enabled at default).
Building pipeline with Samtools
Credits to @keiranmraine, see issue #10
- Due to increased alignment throughput, given enough threads the bottleneck moves from
alignmenttoSamtools sorting. As a result BWA-MEME might require additional pipeline modification (not a simple drop-in replacement) - While existing pipeline might be still faster (reported in issue #10), CPU can be wasted.
- To reduce the CPU waste, you might want to use
mbufferin the pipeline or write alignment outputs to a file with fast compression. - We will investigate a faster way to incorporate BWA-MEME and
Samtools sorting
Reference file download
You can download the reference using the command below.
# Download human_g1k_v37.fasta human genome and decompress it
wget -c ftp://ftp-trace.ncbi.nih.gov/1000genomes/ftp/technical/reference/human_g1k_v37.fasta.gz
gunzip human_g1k_v37.fasta.gz
# hg38 human reference
wget -c https://storage.googleapis.com/genomics-public-data/references/hg38/v0/Homo_sapiens_assembly38.fastaDownload MEME indices and pretrained P-RMI model
# We provide the pretrained models and all indices required alignment (for hg37 and hg38 human reference)
# you can download in the link below.
https://web.inalab.net/~bwa-meme/
# Indices of MEME and models should be in the same folder, we follow the prefix-based loading in bwa-memCitation
If you use BWA-MEME, please cite the following paper
Youngmok Jung, Dongsu Han, BWA-MEME: BWA-MEM emulated with a machine learning approach, Bioinformatics, Volume 38, Issue 9, 1 May 2022, Pages 2404–2413, https://doi.org/10.1093/bioinformatics/btac137
@article{10.1093/bioinformatics/btac137,
author = {Jung, Youngmok and Han, Dongsu},
title = "{BWA-MEME: BWA-MEM emulated with a machine learning approach}",
journal = {Bioinformatics},
volume = {38},
number = {9},
pages = {2404-2413},
year = {2022},
month = {03},
issn = {1367-4803},
doi = {10.1093/bioinformatics/btac137},
url = {https://doi.org/10.1093/bioinformatics/btac137},
eprint = {https://academic.oup.com/bioinformatics/article-pdf/38/9/2404/43480985/btac137.pdf},
}