swarm — find clusters of nearly-identical nucleotide
amplicons
swarm [ options ] filename
Environmental or clinical molecular studies generate large volumes
of amplicons (e.g., 16S or 18S SSU-rRNA sequences) that need to be clustered
into molecular operational taxonomic units (OTUs). Common clustering methods
are based on greedy, input-order dependent algorithms, with arbitrary
selection of global cluster size and cluster centroids. To address that
problem, we developed swarm, a fast and robust method that
recursively groups amplicons with d or less differences (i.e.
substitutions, insertions or deletions). swarm produces natural and
stable clusters centered on local peaks of abundance, mostly free from
input-order dependency induced by centroid selection.
Exact clustering is impractical on large data sets when using a
naïve all-vs-all approach (more precisely a 2-combination without
repetitions), as it implies unrealistic numbers of pairwise comparisons.
swarm is based on a maximum number of differences d between
two amplicons, and focuses only on very close local relationships. For
d = 1, the default value, swarm uses an algorithm of linear
complexity that generates all possible single mutations and performs
exact-string matching by comparing hash-values. For d = 2 or greater,
swarm uses an algorithm of quadratic complexity that performs
pairwise string comparisons. An efficient k-mer-based filtering and
an astute use of comparisons results obtained during the clustering process
allows swarm to avoid most of the amplicon comparisons needed in a
naïve approach. To speed up the remaining amplicon comparisons,
swarm implements an extremely fast Needleman-Wunsch algorithm making
use of the Streaming SIMD Extensions (SSE2) of modern x86-64 CPUs. If SSE2
instructions are not available, swarm exits with an error
message.
swarm can read nucleotide amplicons in fasta format from a
normal file or from the standard input (using a pipe or a redirection). The
amplicon identifier is defined as the string comprised between the '>'
symbol and the first space or the end of the line, whichever comes first. As
swarm outputs lists of amplicon identifiers, amplicon identifiers
must be unique to avoid ambiguity; swarm exits with an error message if
identifiers are not unique. Amplicon identifiers must end with a '_'
followed by a positive integer representing the amplicon copy number (or
abundance annotation; usearch/vsearch users can use the option -z to use the
';size=' annotation). Abundance annotations play a crucial role in the
clustering process, and swarm exits with an error message if that
information is not available. The amplicon sequence is defined as a string
of [ACGT] or [ACGU] symbols (case insensitive, 'U' is replaced with 'T'
internally), starting after the end of the identifier line and ending before
the next identifier line or the file end; swarm silently removes
newline symbols ('\n' or '\r') and exits with an error message if any other
symbol is present.
- -h, --help
- display this help and exit successfully.
- -t, --threads positive
integer
- number of computation threads to use. Values between 1 and 256 are
accepted, but we recommend to use a number of threads lesser or equal to
the number of available CPU cores. Default number of threads is 1.
- -v, --version
- output version information and exit successfully.
- --
- delimit the option list. Later arguments, if any, are treated as operands
even if they begin with '-'. For example, 'swarm -- -file.fasta' reads
from the file '-file.fasta'.
- -d, --differences zero
or positive integer
- maximum number of differences allowed between two amplicons, meaning that
two amplicons will be grouped if they have integer (or less)
differences. This is swarm's most important parameter. The number
of differences is calculated as the number of mismatches (substitutions,
insertions or deletions) between the two amplicons once the optimal
pairwise global alignment has been found (see 'pairwise alignment advanced
options' to influence that step). Any integer from 0 to 255 can be
used, but high d values will decrease the taxonomical resolution of
swarm results. Commonly used d values are 1, 2 or 3, rarely
higher. When using d = 0, swarm will output results
corresponding to a strict dereplication of the dataset, i.e. merging
identical amplicons. Warning, whatever the d value, swarm
requires fasta entries to present abundance values. Default number of
differences d is 1.
- -n, --no-otu-breaking
- deactivate the built-in OTU refinement (not recommended). Amplicon
abundance values are used to identify transitions among in-contact OTUs
and to separate them, yielding higher-resolution clustering results. That
option prevents that separation, and in practice, allows the creation of a
link between amplicons A and B, even if the abundance of B is higher than
the abundance of A.
- -b, --boundary positive
integer
- when using the option --fastidious (-f), define the minimum mass of a
large OTU. By default, an OTU with a mass of 3 or more is
considered large. Conversely, an OTU is small if it has a mass of less
than 3, meaning that it is composed of either one amplicon of abundance 2,
or two amplicons of abundance 1. Any positive value greater than 1 can be
specified. Using higher boundary values will speed up the second pass, but
also reduce the taxonomical resolution of swarm results. Default
mass of a large OTU is 3.
- -c, --ceiling positive
integer
- when using the option --fastidious (-f), define swarm's maximum
memory footprint (in megabytes). swarm will adjust the --bloom-bits
(-y) value of the Bloom filter to fit within the specified amount of
memory. The value must be at least 3.
- -f, --fastidious
- when working with d = 1, perform a second clustering pass to reduce
the number of small OTUs (recommended option). During the first clustering
pass, an intermediate amplicon can be missing for purely stochastic
reasons, interrupting the aggregation process. The fastidious option will
create virtual amplicons, allowing to graft small OTUs upon bigger ones.
By default, an OTU is small if it has a mass of 2 or less (see the
--boundary option to modify that value). To speed things up, swarm
uses a Bloom filter to store intermediate results. Warning, the second
clustering pass can be 2 to 3 times slower than the first pass and
requires much more memory to store the virtual amplicons in Bloom filters.
See the options --bloom-bits (-y) or --ceiling (-c) to control the memory
footprint of the Bloom filter. The fastidious option modifies clustering
results: the output files produced by the options --log (-l),
--output-file (-o), --mothur (-r), --uclust-file, and --seeds (-w) are
updated to reflect these modifications; the file --statistics-file (-s) is
partially updated (columns 6 and 7 are not updated); the output file
--internal-structure (-i) is partially updated (column 5 is not updated
for amplicons that belonged to the small OTU).
- -y, --bloom-bits positive
integer
- when using the option --fastidious (-f), define the size (in bits) of each
entry in the Bloom filter. That option allows to balance the efficiency
(i.e. speed) and the memory footprint of the Bloom filter. Large values
will make the Bloom filter more efficient but will require more memory.
Any value between 2 and 64 can be used. Default value is 16. See the
--ceiling (-c) option for an alternative way to control the memory
footprint.
- -a, --append-abundance positive
integer
- set abundance value to use when some or all amplicons in the input file
lack abundance values (_integer, or ;size=integer; when
using -z). Warning, it is not recommended to use swarm on datasets
where abundance values are all identical. We provide that option as a
courtesy to advanced users, please use it carefully. swarm exits
with an error message if abundance values are missing and if this option
is not used.
- -i, --internal-structure filename
- output all pairs of nearly-identical amplicons to filename using a
five-columns tab-delimited format:
- 1.
- amplicon A label.
- 2.
- amplicon B label.
- 3.
- number of differences between amplicons A and B (positive
integer).
- 4.
- OTU number (positive integer). OTUs are numbered in their order of
delineation, starting from 1. All pairs of amplicons belonging to the same
OTU will receive the same number.
- 5.
- cummulated number of steps from the OTU seed to amplicon B (positive
integer). When using the option --fastidious (-f), the actual number
of steps between grafted amplicons and the OTU seed cannot be re-computed
efficiently and is always set to 2 for the amplicon pair linking the small
OTU to the big OTU. Cummulated number of steps in the small OTU (if any)
are left unchanged.
- -l, --log filename
- output all messages to filename instead of standard error,
with the exception of error messages of course. That option is useful in
situations where writing to standard error is problematic (for
example, with certain job schedulers).
- -o, --output-file filename
- output clustering results to filename. Results consist of a list of
OTUs, one OTU per line. An OTU is a list of amplicon identifiers separated
by spaces. That output format can be modified by the option --mothur (-r).
Default is to write to standard output.
- -r, --mothur
- output clustering results in a format compatible with Mothur. That option
modifies swarm's default output format.
- -s, --statistics-file filename
- output statistics to filename. The file is a tab-separated table
with one OTU per row and seven columns of information:
- 1.
- number of unique amplicons in the OTU,
- 2.
- total abundance of amplicons in the OTU,
- 3.
- identifier of the initial seed,
- 4.
- initial seed abundance,
- 5.
- number of amplicons with an abundance of 1 in the OTU,
- 6.
- maximum number of iterations before the OTU reached its natural
limit,
- 7.
- cummulated number of steps along the path joining the seed and the
furthermost amplicon in the OTU. Please note that the actual number of
differences between the seed and the furthermost amplicon is usually much
smaller. When using the option --fastidious (-f), grafted amplicons are
not taken into account.
- -u, --uclust-file filename
- output clustering results in filename using a tab-separated
uclust-like format with 10 columns and 3 different type of entries (S, H
or C). That option does not modify swarm's default output format.
Each fasta sequence in the input file can be either a cluster centroid (S)
or a hit (H) assigned to a cluster. Cluster records (C) summarize
information (size, centroid label) for each cluster. Column content varies
with the type of entry (S, H or C):
- 1.
- Record type: S, H, or C.
- 2.
- Cluster number (zero-based).
- 3.
- Centroid length (S), query length (H), or cluster size (C).
- 4.
- Percentage of similarity with the centroid sequence (H), or set to '*' (S,
C).
- 5.
- Match orientation + or - (H), or set to '*' (S, C).
- 6.
- Not used, always set to '*' (S, C) or to zero (H).
- 7.
- Not used, always set to '*' (S, C) or to zero (H).
- 8.
- set to '*' (S, C) or, for H, compact representation of the pairwise
alignment using the CIGAR format (Compact Idiosyncratic Gapped Alignment
Report): M (match), D (deletion) and I (insertion). The equal sign '='
indicates that the query is identical to the centroid sequence.
- 9.
- Label of the query sequence (H), or of the centroid sequence (S, C).
- 10.
- Label of the centroid sequence (H), or set to '*' (S, C).
- -w, --seeds filename
- output OTU representatives to filename in fasta format. The
abundance value of each OTU representative is the sum of the abundances of
all the amplicons in the OTU.
- -z, --usearch-abundance
- accept amplicon abundance values in usearch/vsearch's style
(>label;size=integer[;]). That option influences the abundance
annotation style used in output files.
when using d > 1, swarm recognizes advanced
command-line options modifying the pairwise global alignment scoring
parameters:
As swarm focuses on close relationships (e.g., d = 2
or 3), clustering results are resilient to pairwise alignment model
parameters modifications. When clustering using a higher d value,
modifying model parameters has a stronger impact.
Clusterize the data set myfile.fasta into OTUs with the
finest resolution possible (1 difference, built-in breaking, fastidious
option) using 4 computation threads. OTUs are written to the file
myfile.swarms, and OTU representatives are written to
myfile.representatives.fasta.
swarm -t 4 -f -w myfile.representatives.fasta
< myfile.fasta > myfile.swarms
Concept by Frédéric Mahé, implementation by
Torbjørn Rognes.
Mahé F, Rognes T, Quince C, de Vargas C, Dunthorn M. (2014)
Swarm: robust and fast clustering method for amplicon-based studies.
PeerJ 2:e593 <https://doi.org/10.7717/peerj.593>
Mahé F, Rognes T, Quince C, de Vargas C, Dunthorn M. (2015)
Swarm v2: highly-scalable and high-resolution amplicon clustering.
PeerJ 3:e1420 <https://doi.org/10.7717/peerj.1420>
Submit suggestions and bug-reports at
<https://github.com/torognes/swarm/issues>, send a pull request on
<https://github.com/torognes/swarm>, or compose a friendly or
curmudgeonly e-mail to Frédéric Mahé
<mahe@rhrk.uni-kl.de> and Torbjørn Rognes
<torognes@ifi.uio.no>.
Source code and binaries are available at
<https://github.com/torognes/swarm>
Copyright (C) 2012-2017 Frédéric Mahé &
Torbjørn Rognes
This program is free software: you can redistribute it and/or
modify it under the terms of the GNU Affero General Public License as
published by the Free Software Foundation, either version 3 of the License,
or any later version.
This program is distributed in the hope that it will be useful,
but WITHOUT ANY WARRANTY; without even the implied warranty of
MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU Affero
General Public License for more details.
You should have received a copy of the GNU Affero General Public
License along with this program. If not, see
<http://www.gnu.org/licenses/>.
swipe, an extremely fast Smith-Waterman database search
tool by Torbjørn Rognes (available from
<https://github.com/torognes/swipe>).
vsearch, an open-source re-implementation of the classic
uclust clustering method (by Robert C. Edgar), along with other amplicon
filtering and searching tools. vsearch is implemented by
Torbjørn Rognes and documented by Frédéric Mahé,
and is available at <https://github.com/torognes/vsearch>.
New features and important modifications of swarm (short
lived or minor bug releases are not mentioned):
- v2.2.2 released
December 12, 2017
- Version 2.2.2 fixes a bug that would cause Swarm to wait forever in very
rare cases when multiple threads were used.
- v2.2.1 released
October 27, 2017
- Version 2.2.1 fixes a memory allocation bug for d = 1 and
duplicated sequences.
- v2.2.0 released
October 17, 2017
- Version 2.2.0 fixes several problems and improves usability. Corrected
output to structure and uclust files when using fastidious mode. Corrected
abundance output in some cases. Added check for duplicated sequences and
fixed check for duplicated sequence IDs. Checks for empty sequences. Sorts
sequences by additional fields to improve stability. Improves
compatibility with compilers and operating systems. Outputs sequences in
upper case. Allows 64-bit abundances. Shows message when waiting for input
from stdin. Improves error messages and warnings. Improves checking of
command line options. Fixes remaining errors reported by test suite.
Updates documentation.
- v2.1.13 released
March 8, 2017
- Version 2.1.13 removes a bug with the progress bar when writing
seeds.
- v2.1.12 released
January 16, 2017
- Version 2.1.12 removes a debugging message.
- v2.1.11 released
January 16, 2017
- Version 2.1.11 fixes two bugs related to the SIMD implementation of
alignment that might result in incorrect alignments and scores. The bug
only applies when d > 1.
- v2.1.10 released
December 22, 2016
- Version 2.1.10 fixes two bugs related to gap penalties of alignments. The
first bug may lead to wrong aligments and similarity percentages reported
in UCLUST (.uc) files. The second bug makes Swarm use a slightly higher
gap extension penalty than specified. The default gap extension penalty
used have actually been 4.5 instead of 4.
- v2.1.9 released
July 6, 2016
- Version 2.1.9 fixes errors when compiling with GCC version 6.
- v2.1.8 released
March 11, 2016
- Version 2.1.8 fixes a rare bug triggered when clustering extremely short
undereplicated sequences. Also, alignment parameters are not shown when
d = 1.
- v2.1.7 released
February 24, 2016
- Version 2.1.7 fixes a bug in the output of seeds with the -w option when
d > 1 that was not properly fixed in version 2.1.6. It also
handles ascii character #13 (CR) in FASTA files better. Swarm will now
exit with status 0 if the -h or the -v option is specified. The help text
and some error messages have been improved.
- v2.1.6 released
December 14, 2015
- Version 2.1.6 fixes problems with older compilers that do not have the
x86intrin.h header file. It also fixes a bug in the output of seeds with
the -w option when d > 1.
- v2.1.5 released
September 8, 2015
- Version 2.1.5 fixes minor bugs.
- v2.1.4 released
September 4, 2015
- Version 2.1.4 fixes minor bugs in the swarm algorithm used for d =
1.
- v2.1.3 released
August 28, 2015
- Version 2.1.3 adds checks of numeric option arguments.
- v2.1.1 released
March 31, 2015
- Version 2.1.1 fixes a bug with the fastidious option that caused it to
ignore some connections between large and small OTUs.
- v2.1.0 released
March 24, 2015
- Version 2.1.0 marks the first official release of swarm v2.
- v2.0.7 released
March 18, 2015
- Version 2.0.7 writes abundance information in usearch style when using
options -w (--seeds) in combination with -z (--usearch-abundance).
- v2.0.6 released
March 13, 2015
- Version 2.0.6 fixes a minor bug.
- v2.0.5 released
March 13, 2015
- Version 2.0.5 improves the implementation of the fastidious option and
adds options to control memory usage of the Bloom filter (-y and -c). In
addition, an option (-w) allows to output OTU representatives sequences
with updated abundances (sum of all abundances inside each OTU). This
version also enables swarm to run with d = 0.
- v2.0.4 released
March 6, 2015
- Version 2.0.4 includes a fully parallelised implementation of the
fastidious option.
- v2.0.3 released
March 4, 2015
- Version 2.0.3 includes a working implementation of the fastidious option,
but only the initial clustering is parallelized.
- v2.0.2 released
February 26, 2015
- Version 2.0.2 fixes SSSE3 problems.
- v2.0.1 released
February 26, 2015
- Version 2.0.1 is a development version that contains a partial
implementation of the fastidious option, but it is not usable yet.
- v2.0.0 released
December 3, 2014
- Version 2.0.0 is faster and easier to use, providing new output options
(--internal-structure and --log), new control options (--boundary,
--fastidious, --no-otu-breaking), and built-in OTU refinement (no need to
use the python script anymore). When using default parameters, a novel and
considerably faster algorithmic approach is used, guaranteeing
swarm's scalability.
- v1.2.21 released
February 26, 2015
- Version 1.2.21 is supposed to fix some problems related to the use of the
SSSE3 CPU instructions which are not always available.
- v1.2.20 released
November 6, 2014
- Version 1.2.20 presents a production-ready version of the alternative
algorithm (option -a), with optional built-in OTU breaking (option -n).
That alternative algorithmic approach (usable only with d = 1) is
considerably faster than currently used clustering algorithms, and can
deal with datasets of 100 million unique amplicons or more in a few hours.
Of course, results are rigourously identical to the results previously
produced with swarm. That release also introduces new options to control
swarm output (options -i and -l).
- v1.2.19 released
October 3, 2014
- Version 1.2.19 fixes a problem related to abundance information when the
sequence identifier includes multiple underscore characters.
- v1.2.18 released
September 29, 2014
- Version 1.2.18 reenables the possibility of reading sequences from
stdin if no file name is specified on the command line. It also
fixes a bug related to CPU features detection.
- v1.2.17 released
September 28, 2014
- Version 1.2.17 fixes a memory allocation bug introduced in version
1.2.15.
- v1.2.16 released
September 27, 2014
- Version 1.2.16 fixes a bug in the abundance sort introduced in version
1.2.15.
- v1.2.15 released
September 27, 2014
- Version 1.2.15 sorts the input sequences in order of decreasing abundance
unless they are detected to be sorted already. When using the alternative
algorithm for d = 1 it also sorts all subseeds in order of
decreasing abundance.
- v1.2.14 released
September 27, 2014
- Version 1.2.14 fixes a bug in the output with the --swarm_breaker option
(-b) when using the alternative algorithm (-a).
- v1.2.12 released
August 18, 2014
- Version 1.2.12 introduces an option --alternative-algorithm to use an
extremely fast, experimental clustering algorithm for the special case
d = 1. Multithreading scalability of the default algorithm has been
noticeably improved.
- v1.2.10 released
August 8, 2014
- Version 1.2.10 allows amplicon abundances to be specified using the
usearch style in the sequence header (e.g. '>id;size=1') when the -z
option is chosen.
- v1.2.8 released
August 5, 2014
- Version 1.2.8 fixes an error with the gap extension penalty. Previous
versions used a gap penalty twice as large as intended. That bug
correction induces small changes in clustering results.
- v1.2.6 released
May 23, 2014
- Version 1.2.6 introduces an option --mothur to output clustering results
in a format compatible with the microbial ecology community analysis
software suite Mothur (<http://www.mothur.org/>).
- v1.2.5 released
April 11, 2014
- Version 1.2.5 removes the need for a POPCNT hardware instruction to be
present. swarm now automatically checks whether POPCNT is available
and uses a slightly slower software implementation if not. Only basic SSE2
instructions are now required to run swarm.
- v1.2.4 released
January 30, 2014
- Version 1.2.4 introduces an option --break-swarms to output all pairs of
amplicons with d differences to standard error. That option is used
by the companion script `swarm_breaker.py` to refine swarm results.
The syntax of the inline assembly code is changed for compatibility with
more compilers.
- v1.2 released
May 16, 2013
- Version 1.2 greatly improves speed by using alignment-free comparisons of
amplicons based on k-mer word content. For each amplicon, the
presence-absence of all possible 5-mers is computed and recorded in a
1024-bits vector. Vector comparisons are extremely fast and drastically
reduce the number of costly pairwise alignments performed by swarm.
While remaining exact, swarm 1.2 can be more than 100-times faster
than swarm 1.1, when using a single thread with a large set of
sequences. The minor version 1.1.1, published just before, adds
compatibility with Apple computers, and corrects an issue in the pairwise
global alignment step that could lead to sub-optimal alignments.
- v1.1 released
February 26, 2013
- Version 1.1 introduces two new important options: the possibility to
output clustering results using the uclust output format, and the
possibility to output detailed statistics on each OTU. swarm 1.1 is
also faster: new filterings based on pairwise amplicon sequence lengths
and composition comparisons reduce the number of pairwise alignments
needed and speed up the clustering.
- v1.0 released
November 10, 2012
- First public release.