Provided by: bwa_0.7.12-5_amd64 bug

NAME

       bwa - Burrows-Wheeler Alignment Tool

SYNOPSIS

       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

DESCRIPTION

       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.

COMMANDS AND OPTIONS

       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  two   algorithms   for   BWT
                        construction:  is  and bwtsw.  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] [-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 occurence in the genome. This  is  an  insensitive
                        parameter. [500]

              -D INT    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 openning a
                        deletion and the second for openning 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]

              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]

              -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  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  verbose  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]

SAM ALIGNMENT FORMAT

       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:

                       ┌────┬───────┬──────────────────────────────────────────────────────────┐
                       │ColFieldDescription                        │
                       ├────┼───────┼──────────────────────────────────────────────────────────┤
                       │ 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:

                                ┌────┬────────┬───────────────────────────────────────┐
                                │ChrFlagDescription              │
                                ├────┼────────┼───────────────────────────────────────┤
                                │ 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.

                               ┌────┬──────────────────────────────────────────────────┐
                               │TagMeaning                      │
                               ├────┼──────────────────────────────────────────────────┤
                               │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 extentions                         │
                               │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.

NOTES ON SHORT-READ ALIGNMENT

   Alignment Accuracy
       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.

   Estimating Insert Size Distribution
       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.

   Memory Requirement
       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.

   Speed
       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.

CHANGES IN BWA-0.6

       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.

SEE ALSO

       BWA website <http://bio-bwa.sourceforge.net>, Samtools website <http://samtools.sourceforge.net>

AUTHOR

       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.

LICENSE AND CITATION

       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.

HISTORY

       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.