bwa - Burrows-Wheeler Alignment Tool
bwa index ref.fa
bwa mem ref.fa reads.fq > aln-se.sam
bwa mem ref.fa read1.fq read2.fq > aln-pe.sam
bwa aln ref.fa short_read.fq > aln_sa.sai
bwa samse ref.fa aln_sa.sai short_read.fq > aln-se.sam
bwa sampe ref.fa aln_sa1.sai aln_sa2.sai read1.fq read2.fq > aln-pe.sam
bwa bwasw ref.fa long_read.fq > aln.sam
BWA is a software package for mapping low-divergent sequences against a large
reference genome, such as the human genome. It consists of three algorithms:
BWA-backtrack, BWA-SW and BWA-MEM. The first algorithm is designed for
Illumina sequence reads up to 100bp, while the rest two for longer sequences
ranged from 70bp to 1Mbp. BWA-MEM and BWA-SW share similar features such as
long-read support and split alignment, but BWA-MEM, which is the latest, is
generally recommended for high-quality queries as it is faster and more
accurate. BWA-MEM also has better performance than BWA-backtrack for 70-100bp
Illumina reads.
For all the algorithms, BWA first needs to construct the FM-index for the
reference genome (the
index command). Alignment algorithms are invoked
with different sub-commands:
aln/
samse/
sampe for
BWA-backtrack,
bwasw for BWA-SW and
mem for the BWA-MEM
algorithm.
- index
-
bwa index [-p prefix] [-a
algoType] db.fa
Index database sequences in the FASTA format.
OPTIONS:
-
-p STR
- Prefix of the output database [same as db filename]
-
-a STR
- Algorithm for constructing BWT index. BWA implements three
algorithms for BWT construction: is, bwtsw and rb2.
The first algorithm is a little faster for small database but requires
large RAM and does not work for databases with total length longer than
2GB. The second algorithm is adapted from the BWT-SW source code. It in
theory works with database with trillions of bases. When this option is
not specified, the appropriate algorithm will be chosen
automatically.
- mem
-
bwa mem [-aCHjMpP] [-t
nThreads] [-k minSeedLen] [-w
bandWidth] [-d zDropoff] [-r
seedSplitRatio] [-c maxOcc] [-D
chainShadow] [-m maxMateSW] [-W
minSeedMatch] [-A matchScore] [-B
mmPenalty] [-O gapOpenPen] [-E
gapExtPen] [-L clipPen] [-U unpairPen]
[-x readType] [-R RGline] [-H
HDlines] [-v verboseLevel] db.prefix
reads.fq [mates.fq]
Align 70bp-1Mbp query sequences with the BWA-MEM algorithm. Briefly, the
algorithm works by seeding alignments with maximal exact matches (MEMs)
and then extending seeds with the affine-gap Smith-Waterman algorithm
(SW).
If mates.fq file is absent and option -p is not set, this
command regards input reads are single-end. If mates.fq is present,
this command assumes the i-th read in reads.fq and the
i-th read in mates.fq constitute a read pair. If -p
is used, the command assumes the 2i-th and the (2i+1)-th
read in reads.fq constitute a read pair (such input file is said to
be interleaved). In this case, mates.fq is ignored. In the
paired-end mode, the mem command will infer the read orientation
and the insert size distribution from a batch of reads.
The BWA-MEM algorithm performs local alignment. It may produce multiple
primary alignments for different part of a query sequence. This is a
crucial feature for long sequences. However, some tools such as Picard's
markDuplicates does not work with split alignments. One may consider to
use option -M to flag shorter split hits as secondary.
- ALGORITHM OPTIONS:
-
-t INT
- Number of threads [1]
-
-k INT
- Minimum seed length. Matches shorter than INT will
be missed. The alignment speed is usually insensitive to this value unless
it significantly deviates from 20. [19]
-
-w INT
- Band width. Essentially, gaps longer than INT will
not be found. Note that the maximum gap length is also affected by the
scoring matrix and the hit length, not solely determined by this option.
[100]
-
-d INT
- Off-diagonal X-dropoff (Z-dropoff). Stop extension when the
difference between the best and the current extension score is above
|i-j|*A+INT, where i and j are
the current positions of the query and reference, respectively, and
A is the matching score. Z-dropoff is similar to BLAST's X-dropoff
except that it doesn't penalize gaps in one of the sequences in the
alignment. Z-dropoff not only avoids unnecessary extension, but also
reduces poor alignments inside a long good alignment. [100]
-
-r FLOAT
- Trigger re-seeding for a MEM longer than
minSeedLen*FLOAT. This is a key heuristic parameter for
tuning the performance. Larger value yields fewer seeds, which leads to
faster alignment speed but lower accuracy. [1.5]
-
-c INT
- Discard a MEM if it has more than INT occurrence in
the genome. This is an insensitive parameter. [500]
-
-D FLOAT
- Drop chains shorter than FLOAT fraction of the
longest overlapping chain [0.5]
-
-m INT
- Perform at most INT rounds of mate-SW [50]
-
-W INT
- Drop a chain if the number of bases in seeds is smaller
than INT. This option is primarily used for longer contigs/reads.
When positive, it also affects seed filtering. [0]
- -P
- In the paired-end mode, perform SW to rescue missing hits
only but do not try to find hits that fit a proper pair.
- SCORING OPTIONS:
-
-A INT
- Matching score. [1]
-
-B INT
- Mismatch penalty. The sequence error rate is approximately:
{.75 * exp[-log(4) * B/A]}. [4]
-
-O INT[,INT]
- Gap open penalty. If two numbers are specified, the first
is the penalty of opening a deletion and the second for opening an
insertion. [6]
-
-E INT[,INT]
- Gap extension penalty. If two numbers are specified, the
first is the penalty of extending a deletion and second for extending an
insertion. A gap of length k costs O + k*E (i.e. -O is for opening
a zero-length gap). [1]
-
-L INT[,INT]
- Clipping penalty. When performing SW extension, BWA-MEM
keeps track of the best score reaching the end of query. If this score is
larger than the best SW score minus the clipping penalty, clipping will
not be applied. Note that in this case, the SAM AS tag reports the best SW
score; clipping penalty is not deduced. If two numbers are provided, the
first is for 5'-end clipping and second for 3'-end clipping. [5]
-
-U INT
- Penalty for an unpaired read pair. BWA-MEM scores an
unpaired read pair as scoreRead1+scoreRead2-INT and scores a paired
as scoreRead1+scoreRead2-insertPenalty. It compares these two scores to
determine whether we should force pairing. A larger value leads to more
aggressive read pair. [17]
-
-x STR
- Read type. Changes multiple parameters unless overridden
[null]
-
pacbio:
-
-k17 -W40 -r10 -A1 -B1 -O1 -E1 -L0 (PacBio reads to
ref)
-
ont2d:
-
-k14 -W20 -r10 -A1 -B1 -O1 -E1 -L0 (Oxford Nanopore
2D-reads to ref)
-
intractg:
-
-B9 -O16 -L5 (intra-species contigs to ref)
- INPUT/OUTPUT OPTIONS:
- -p
- Smart pairing. If two adjacent reads have the same name,
they are considered to form a read pair. This way, paired-end and
single-end reads can be mixed in a single FASTA/Q stream.
-
-R STR
- Complete read group header line. '\t' can be used in
STR and will be converted to a TAB in the output SAM. The read
group ID will be attached to every read in the output. An example is
'@RG\tID:foo\tSM:bar'. [null]
-
-H ARG
- If ARG starts with @, it is interpreted as a string and
gets inserted into the output SAM header; otherwise, ARG is interpreted as
a file with all lines starting with @ in the file inserted into the SAM
header. [null]
-
-o FILE
- Write the output SAM file to FILE. For compatibility
with other BWA commands, this option may also be given as -f
FILE. [standard output]
- -q
-
Don't reduce the mapping quality of split alignment of lower alignment
score.
- -5
- For split alignment, mark the segment with the smallest
coordinate as the primary. It automatically applies option -q as
well. This option may help some Hi-C pipelines. By default, BWA-MEM marks
highest scoring segment as primary.
- -K INT
- Process INT input bases in each batch regardless of
the number of threads in use [10000000*nThreads]. By default, the
batch size is proportional to the number of threads in use. Because the
inferred insert size distribution slightly depends on the batch size,
using different number of threads may produce different output. Specifying
this option helps reproducibility.
-
-T INT
- Don't output alignment with score lower than INT.
This option affects output and occasionally SAM flag 2. [30]
- -j
- Treat ALT contigs as part of the primary assembly (i.e.
ignore the db.prefix.alt file).
-
-h INT[,INT2]
- If a query has not more than INT hits with score
higher than 80% of the best hit, output them all in the XA tag. If
INT2 is specified, BWA-MEM outputs up to INT2 hits if the
list contains a hit to an ALT contig. [5,200]
- -a
- Output all found alignments for single-end or unpaired
paired-end reads. These alignments will be flagged as secondary
alignments.
- -C
- Append FASTA/Q comment to SAM output. This option can be
used to transfer read meta information (e.g. barcode) to the SAM output.
Note that the FASTA/Q comment (the string after a space in the header
line) must conform the SAM spec (e.g. BC:Z:CGTAC). Malformated comments
lead to incorrect SAM output.
- -Y
- Use soft clipping CIGAR operation for supplementary
alignments. By default, BWA-MEM uses soft clipping for the primary
alignment and hard clipping for supplementary alignments.
- -M
- Mark shorter split hits as secondary (for Picard
compatibility).
-
-v INT
- Control the verbosity level of the output. This option has
not been fully supported throughout BWA. Ideally, a value 0 for disabling
all the output to stderr; 1 for outputting errors only; 2 for warnings and
errors; 3 for all normal messages; 4 or higher for debugging. When this
option takes value 4, the output is not SAM. [3]
-
-I FLOAT[,FLOAT[,INT[,INT]]]
- Specify the mean, standard deviation (10% of the mean if
absent), max (4 sigma from the mean if absent) and min (4 sigma if absent)
of the insert size distribution. Only applicable to the FR orientation. By
default, BWA-MEM infers these numbers and the pair orientations given
enough reads. [inferred]
- aln
- bwa aln [-n maxDiff] [-o maxGapO] [-e maxGapE] [-d
nDelTail] [-i nIndelEnd] [-k maxSeedDiff] [-l seedLen] [-t nThrds] [-cRN]
[-M misMsc] [-O gapOsc] [-E gapEsc] [-q trimQual] <in.db.fasta>
<in.query.fq> > <out.sai>
Find the SA coordinates of the input reads. Maximum maxSeedDiff
differences are allowed in the first seedLen subsequence and
maximum maxDiff differences are allowed in the whole sequence.
OPTIONS:
-
-n NUM
- Maximum edit distance if the value is INT, or the fraction
of missing alignments given 2% uniform base error rate if FLOAT. In the
latter case, the maximum edit distance is automatically chosen for
different read lengths. [0.04]
-
-o INT
- Maximum number of gap opens [1]
-
-e INT
- Maximum number of gap extensions, -1 for k-difference mode
(disallowing long gaps) [-1]
-
-d INT
- Disallow a long deletion within INT bp towards the 3'-end
[16]
-
-i INT
- Disallow an indel within INT bp towards the ends [5]
-
-l INT
- Take the first INT subsequence as seed. If INT is larger
than the query sequence, seeding will be disabled. For long reads, this
option is typically ranged from 25 to 35 for `-k 2'. [inf]
-
-k INT
- Maximum edit distance in the seed [2]
-
-t INT
- Number of threads (multi-threading mode) [1]
-
-M INT
- Mismatch penalty. BWA will not search for suboptimal hits
with a score lower than (bestScore-misMsc). [3]
-
-O INT
- Gap open penalty [11]
-
-E INT
- Gap extension penalty [4]
-
-R INT
- Proceed with suboptimal alignments if there are no more
than INT equally best hits. This option only affects paired-end mapping.
Increasing this threshold helps to improve the pairing accuracy at the
cost of speed, especially for short reads (~32bp).
- -c
- Reverse query but not complement it, which is required for
alignment in the color space. (Disabled since 0.6.x)
- -N
- Disable iterative search. All hits with no more than
maxDiff differences will be found. This mode is much slower than
the default.
-
-q INT
- Parameter for read trimming. BWA trims a read down to
argmax_x{\sum_{i=x+1}^l(INT-q_i)} if q_l<INT where l is the original
read length. [0]
- -I
- The input is in the Illumina 1.3+ read format (quality
equals ASCII-64).
-
-B INT
- Length of barcode starting from the 5'-end. When INT
is positive, the barcode of each read will be trimmed before mapping and
will be written at the BC SAM tag. For paired-end reads, the
barcode from both ends are concatenated. [0]
- -b
- Specify the input read sequence file is the BAM format. For
paired-end data, two ends in a pair must be grouped together and options
-1 or -2 are usually applied to specify which end should be
mapped. Typical command lines for mapping pair-end data in the BAM format
are:
bwa aln ref.fa -b1 reads.bam > 1.sai
bwa aln ref.fa -b2 reads.bam > 2.sai
bwa sampe ref.fa 1.sai 2.sai reads.bam reads.bam > aln.sam
- -0
- When -b is specified, only use single-end reads in
mapping.
- -1
- When -b is specified, only use the first read in a
read pair in mapping (skip single-end reads and the second reads).
- -2
- When -b is specified, only use the second read in a
read pair in mapping.
- samse
- bwa samse [-n maxOcc] <in.db.fasta> <in.sai>
<in.fq> > <out.sam>
Generate alignments in the SAM format given single-end reads. Repetitive
hits will be randomly chosen.
OPTIONS:
-
-n INT
- Maximum number of alignments to output in the XA tag for
reads paired properly. If a read has more than INT hits, the XA tag will
not be written. [3]
-
-r STR
- Specify the read group in a format like
`@RG\tID:foo\tSM:bar'. [null]
- sampe
- bwa sampe [-a maxInsSize] [-o maxOcc] [-n maxHitPaired] [-N
maxHitDis] [-P] <in.db.fasta> <in1.sai> <in2.sai>
<in1.fq> <in2.fq> > <out.sam>
Generate alignments in the SAM format given paired-end reads. Repetitive
read pairs will be placed randomly.
OPTIONS:
-
-a INT
- Maximum insert size for a read pair to be considered being
mapped properly. Since 0.4.5, this option is only used when there are not
enough good alignment to infer the distribution of insert sizes.
[500]
-
-o INT
- Maximum occurrences of a read for pairing. A read with more
occurrneces will be treated as a single-end read. Reducing this parameter
helps faster pairing. [100000]
- -P
- Load the entire FM-index into memory to reduce disk
operations (base-space reads only). With this option, at least 1.25N bytes
of memory are required, where N is the length of the genome.
-
-n INT
- Maximum number of alignments to output in the XA tag for
reads paired properly. If a read has more than INT hits, the XA tag will
not be written. [3]
-
-N INT
- Maximum number of alignments to output in the XA tag for
disconcordant read pairs (excluding singletons). If a read has more than
INT hits, the XA tag will not be written. [10]
-
-r STR
- Specify the read group in a format like
`@RG\tID:foo\tSM:bar'. [null]
- bwasw
- bwa bwasw [-a matchScore] [-b mmPen] [-q gapOpenPen] [-r
gapExtPen] [-t nThreads] [-w bandWidth] [-T thres] [-s hspIntv] [-z zBest]
[-N nHspRev] [-c thresCoef] <in.db.fasta> <in.fq> [mate.fq]
Align query sequences in the in.fq file. When mate.fq is
present, perform paired-end alignment. The paired-end mode only works for
reads Illumina short-insert libraries. In the paired-end mode, BWA-SW may
still output split alignments but they are all marked as not properly
paired; the mate positions will not be written if the mate has multiple
local hits.
OPTIONS:
-
-a INT
- Score of a match [1]
-
-b INT
- Mismatch penalty [3]
-
-q INT
- Gap open penalty [5]
-
-r INT
- Gap extension penalty. The penalty for a contiguous gap of
size k is q+k*r. [2]
-
-t INT
- Number of threads in the multi-threading mode [1]
-
-w INT
- Band width in the banded alignment [33]
-
-T INT
- Minimum score threshold divided by a [37]
-
-c FLOAT
- Coefficient for threshold adjustment according to query
length. Given an l-long query, the threshold for a hit to be retained is
a*max{T,c*log(l)}. [5.5]
-
-z INT
- Z-best heuristics. Higher -z increases accuracy at the cost
of speed. [1]
-
-s INT
- Maximum SA interval size for initiating a seed. Higher -s
increases accuracy at the cost of speed. [3]
-
-N INT
- Minimum number of seeds supporting the resultant alignment
to skip reverse alignment. [5]
The output of the
`aln' command is binary and designed for BWA use only.
BWA outputs the final alignment in the SAM (Sequence Alignment/Map) format.
Each line consists of:
| Col |
Field |
Description |
|
| 1 |
QNAME |
Query (pair) NAME |
| 2 |
FLAG |
bitwise FLAG |
| 3 |
RNAME |
Reference sequence NAME |
| 4 |
POS |
1-based leftmost POSition/coordinate of clipped sequence |
| 5 |
MAPQ |
MAPping Quality (Phred-scaled) |
| 6 |
CIAGR |
extended CIGAR string |
| 7 |
MRNM |
Mate Reference sequence NaMe (`=' if same as RNAME) |
| 8 |
MPOS |
1-based Mate POSistion |
| 9 |
ISIZE |
Inferred insert SIZE |
| 10 |
SEQ |
query SEQuence on the same strand as the reference |
| 11 |
QUAL |
query QUALity (ASCII-33 gives the Phred base quality) |
| 12 |
OPT |
variable OPTional fields in the format TAG:VTYPE:VALUE |
Each bit in the FLAG field is defined as:
| Chr |
Flag |
Description |
|
| p |
0x0001 |
the read is paired in sequencing |
| P |
0x0002 |
the read is mapped in a proper pair |
| u |
0x0004 |
the query sequence itself is unmapped |
| U |
0x0008 |
the mate is unmapped |
| r |
0x0010 |
strand of the query (1 for reverse) |
| R |
0x0020 |
strand of the mate |
| 1 |
0x0040 |
the read is the first read in a pair |
| 2 |
0x0080 |
the read is the second read in a pair |
| s |
0x0100 |
the alignment is not primary |
| f |
0x0200 |
QC failure |
| d |
0x0400 |
optical or PCR duplicate |
| S |
0x0800 |
supplementary alignment |
The Please check <
http://samtools.sourceforge.net> for the format
specification and the tools for post-processing the alignment.
BWA generates the following optional fields. Tags starting with `X' are specific
to BWA.
| Tag |
Meaning |
|
| NM |
Edit distance |
| MD |
Mismatching positions/bases |
| AS |
Alignment score |
| BC |
Barcode sequence |
| SA |
Supplementary alignments |
|
| X0 |
Number of best hits |
| X1 |
Number of suboptimal hits found by BWA |
| XN |
Number of ambiguous bases in the referenece |
| XM |
Number of mismatches in the alignment |
| XO |
Number of gap opens |
| XG |
Number of gap extensions |
| XT |
Type: Unique/Repeat/N/Mate-sw |
| XA |
Alternative hits; format: /(chr,pos,CIGAR,NM;)*/ |
|
| XS |
Suboptimal alignment score |
| XF |
Support from forward/reverse alignment |
| XE |
Number of supporting seeds |
Note that XO and XG are generated by BWT search while the CIGAR string by
Smith-Waterman alignment. These two tags may be inconsistent with the CIGAR
string. This is not a bug.
When seeding is disabled, BWA guarantees to find an alignment containing maximum
maxDiff differences including
maxGapO gap opens which do not
occur within
nIndelEnd bp towards either end of the query. Longer gaps
may be found if
maxGapE is positive, but it is not guaranteed to find
all hits. When seeding is enabled, BWA further requires that the first
seedLen subsequence contains no more than
maxSeedDiff
differences.
When gapped alignment is disabled, BWA is expected to generate the same
alignment as Eland version 1, the Illumina alignment program. However, as BWA
change `N' in the database sequence to random nucleotides, hits to these
random sequences will also be counted. As a consequence, BWA may mark a unique
hit as a repeat, if the random sequences happen to be identical to the
sequences which should be unqiue in the database.
By default, if the best hit is not highly repetitive (controlled by -R), BWA
also finds all hits contains one more mismatch; otherwise, BWA finds all
equally best hits only. Base quality is NOT considered in evaluating hits. In
the paired-end mode, BWA pairs all hits it found. It further performs
Smith-Waterman alignment for unmapped reads to rescue reads with a high erro
rate, and for high-quality anomalous pairs to fix potential alignment errors.
BWA estimates the insert size distribution per 256*1024 read pairs. It first
collects pairs of reads with both ends mapped with a single-end quality 20 or
higher and then calculates median (Q2), lower and higher quartile (Q1 and Q3).
It estimates the mean and the variance of the insert size distribution from
pairs whose insert sizes are within interval [Q1-2(Q3-Q1), Q3+2(Q3-Q1)]. The
maximum distance x for a pair considered to be properly paired (SAM flag 0x2)
is calculated by solving equation Phi((x-mu)/sigma)=x/L*p0, where mu is the
mean, sigma is the standard error of the insert size distribution, L is the
length of the genome, p0 is prior of anomalous pair and Phi() is the standard
cumulative distribution function. For mapping Illumina short-insert reads to
the human genome, x is about 6-7 sigma away from the mean. Quartiles, mean,
variance and x will be printed to the standard error output.
With bwtsw algorithm, 5GB memory is required for indexing the complete human
genome sequences. For short reads, the
aln command uses ~3.2GB memory
and the
sampe command uses ~5.4GB.
Indexing the human genome sequences takes 3 hours with bwtsw algorithm. Indexing
smaller genomes with IS algorithms is faster, but requires more memory.
The speed of alignment is largely determined by the error rate of the query
sequences (r). Firstly, BWA runs much faster for near perfect hits than for
hits with many differences, and it stops searching for a hit with l+2
differences if a l-difference hit is found. This means BWA will be very slow
if r is high because in this case BWA has to visit hits with many differences
and looking for these hits is expensive. Secondly, the alignment algorithm
behind makes the speed sensitive to [k log(N)/m], where k is the maximum
allowed differences, N the size of database and m the length of a query. In
practice, we choose k w.r.t. r and therefore r is the leading factor. I would
not recommend to use BWA on data with r>0.02.
Pairing is slower for shorter reads. This is mainly because shorter reads have
more spurious hits and converting SA coordinates to chromosomal coordinates
are very costly.
Since version 0.6, BWA has been able to work with a reference genome longer than
4GB. This feature makes it possible to integrate the forward and reverse
complemented genome in one FM-index, which speeds up both BWA-short and
BWA-SW. As a tradeoff, BWA uses more memory because it has to keep all
positions and ranks in 64-bit integers, twice larger than 32-bit integers used
in the previous versions.
The latest BWA-SW also works for paired-end reads longer than 100bp. In
comparison to BWA-short, BWA-SW tends to be more accurate for highly unique
reads and more robust to relative long INDELs and structural variants.
Nonetheless, BWA-short usually has higher power to distinguish the optimal hit
from many suboptimal hits. The choice of the mapping algorithm may depend on
the application.
BWA website <
http://bio-bwa.sourceforge.net>, Samtools website
<
http://samtools.sourceforge.net>
Heng Li at the Sanger Institute wrote the key source codes and integrated the
following codes for BWT construction: bwtsw
<
http://i.cs.hku.hk/~ckwong3/bwtsw/>, implemented by Chi-Kwong Wong at
the University of Hong Kong and IS
<
http://yuta.256.googlepages.com/sais> originally proposed by Nong Ge
<
http://www.cs.sysu.edu.cn/nong/> at the Sun Yat-Sen University and
implemented by Yuta Mori.
The full BWA package is distributed under GPLv3 as it uses source codes from
BWT-SW which is covered by GPL. Sorting, hash table, BWT and IS libraries are
distributed under the MIT license.
If you use the BWA-backtrack algorithm, please cite the following paper:
Li H. and Durbin R. (2009) Fast and accurate short read alignment with
Burrows-Wheeler transform. Bioinformatics, 25, 1754-1760. [PMID: 19451168]
If you use the BWA-SW algorithm, please cite:
Li H. and Durbin R. (2010) Fast and accurate long-read alignment with
Burrows-Wheeler transform. Bioinformatics, 26, 589-595. [PMID: 20080505]
If you use BWA-MEM or the fastmap component of BWA, please cite:
Li H. (2013) Aligning sequence reads, clone sequences and assembly contigs with
BWA-MEM. arXiv:1303.3997v1 [q-bio.GN].
It is likely that the BWA-MEM manuscript will not appear in a peer-reviewed
journal.
BWA is largely influenced by BWT-SW. It uses source codes from BWT-SW and mimics
its binary file formats; BWA-SW resembles BWT-SW in several ways. The initial
idea about BWT-based alignment also came from the group who developed BWT-SW.
At the same time, BWA is different enough from BWT-SW. The short-read
alignment algorithm bears no similarity to Smith-Waterman algorithm any more.
While BWA-SW learns from BWT-SW, it introduces heuristics that can hardly be
applied to the original algorithm. In all, BWA does not guarantee to find all
local hits as what BWT-SW is designed to do, but it is much faster than BWT-SW
on both short and long query sequences.
I started to write the first piece of codes on 24 May 2008 and got the initial
stable version on 02 June 2008. During this period, I was acquainted that
Professor Tak-Wah Lam, the first author of BWT-SW paper, was collaborating
with Beijing Genomics Institute on SOAP2, the successor to SOAP (Short
Oligonucleotide Analysis Package). SOAP2 has come out in November 2008.
According to the SourceForge download page, the third BWT-based short read
aligner, bowtie, was first released in August 2008. At the time of writing
this manual, at least three more BWT-based short-read aligners are being
implemented.
The BWA-SW algorithm is a new component of BWA. It was conceived in November
2008 and implemented ten months later.
The BWA-MEM algorithm is based on an algorithm finding super-maximal exact
matches (SMEMs), which was first published with the fermi assembler paper in
2012. I first implemented the basic SMEM algorithm in the
fastmap
command for an experiment and then extended the basic algorithm and added the
extension part in Feburary 2013 to make BWA-MEM a fully featured mapper.