NAME¶
hmmsim - collect score distributions on random sequences
SYNOPSIS¶
hmmsim [options] hmmfile
DESCRIPTION¶
The
hmmsim program generates random sequences, scores them with the
model(s) in
hmmfile, and outputs various sorts of histograms, plots,
and fitted distributions for the resulting scores.
hmmsim is not a mainstream part of the HMMER package. Most users would
have no reason to use it. It is used to develop and test the statistical
methods used to determine P-values and E-values in HMMER3. For example, it was
used to generate most of the results in a 2008 paper on H3's local alignment
statistics (PLoS Comp Bio 4:e1000069, 2008;
http://www.ploscompbiol.org/doi/pcbi.1000069).
Because it is a research testbed, you should not expect it to be as robust as
other programs in the package. For example, options may interact in weird
ways; we haven't tested nor tried to anticipate all different possible
combinations.
The main task is to fit a maximum likelihood Gumbel distribution to Viterbi
scores or an maximum likelihood exponential tail to high-scoring Forward
scores, and to test that these fitted distributions obey the conjecture that
lambda ~ log_2 for both the Viterbi Gumbel and the Forward exponential tail.
The output is a table of numbers, one row for each model. Four different
parametric fits to the score data are tested: (1) maximum likelihood fits to
both location (mu/tau) and slope (lambda) parameters; (2) assuming
lambda=log_2, maximum likelihood fit to the location parameter only; (3) same
but assuming an edge-corrected lambda, using current procedures in H3 [Eddy,
2008]; and (4) using both parameters determined by H3's current procedures.
The standard simple, quick and dirty statistic for goodness-of-fit is 'E@10',
the calculated E-value of the 10th ranked top hit, which we expect to be about
10.
In detail, the columns of the output are:
- name
- Name of the model.
- tailp
- Fraction of the highest scores used to fit the
distribution. For Viterbi, MSV, and Hybrid scores, this defaults to 1.0 (a
Gumbel distribution is fitted to all the data). For Forward scores, this
defaults to 0.02 (an exponential tail is fitted to the highest 2% scores).
- mu/tau
- Location parameter for the maximum likelihood fit to the
data.
- lambda
- Slope parameter for the maximum likelihood fit to the data.
- E@10
- The E-value calculated for the 10th ranked high score
('E@10') using the ML mu/tau and lambda. By definition, this expected to
be about 10, if E-value estimation were accurate.
- mufix
- Location parameter, for a maximum likelihood fit with a
known (fixed) slope parameter lambda of log_2 (0.693).
- E@10fix
- The E-value calculated for the 10th ranked score using
mufix and the expected lambda = log_2 = 0.693.
- mufix2
- Location parameter, for a maximum likelihood fit with an
edge-effect-corrected lambda.
- E@10fix2
- The E-value calculated for the 10th ranked score using
mufix2 and the edge-effect-corrected lambda.
- pmu
- Location parameter as determined by H3's estimation
procedures.
- plambda
- Slope parameter as determined by H3's estimation
procedures.
- pE@10
- The E-value calculated for the 10th ranked score using pmu,
plambda.
At the end of this table, one more line is printed, starting with # and
summarizing the overall CPU time used by the simulations.
Some of the optional output files are in xmgrace xy format. xmgrace is powerful
and freely available graph-plotting software.
MISCELLANEOUS OPTIONS¶
- -h
- Help; print a brief reminder of command line usage and all
available options.
- -a
- Collect expected Viterbi alignment length statistics from
each simulated sequence. This only works with Viterbi scores (the default;
see --vit). Two additional fields are printed in the output table
for each model: the mean length of Viterbi alignments, and the standard
deviation.
- -v
- (Verbose). Print the scores too, one score per line.
- -L <n>
- Set the length of the randomly sampled (nonhomologous)
sequences to <n>. The default is 100.
- -N <n>
- Set the number of randomly sampled sequences to
<n>. The default is 1000.
- --mpi
- Run in MPI parallel mode, under mpirun. It is
parallelized at the level of sending one profile at a time to an MPI
worker process, so parallelization only helps if you have more than one
profile in the <hmmfile>, and you want to have at least as
many profiles as MPI worker processes. (Only available if optional MPI
support was enabled at compile-time.)
OPTIONS CONTROLLING OUTPUT¶
- -o <f>
- Save the main output table to a file <f>
rather than sending it to stdout.
- --afile <f>
- When collecting Viterbi alignment statistics (the -a
option), for each sampled sequence, output two fields per line to a file
<f>: the length of the optimal alignment, and the Viterbi bit
score. Requires that the -a option is also used.
- --efile <f>
- Output a rank vs. E-value plot in XMGRACE xy format to file
<f>. The x-axis is the rank of this sequence, from highest
score to lowest; the y-axis is the E-value calculated for this sequence.
E-values are calculated using H3's default procedures (i.e. the pmu,
plambda parameters in the output table). You expect a rough match between
rank and E-value if E-values are accurately estimated.
- --ffile <f>
- Output a "filter power" file to <f>:
for each model, a line with three fields: model name, number of sequences
passing the P-value threshold, and fraction of sequences passing the
P-value threshold. See --pthresh for setting the P-value threshold,
which defaults to 0.02 (the default MSV filter threshold in H3). The
P-values are as determined by H3's default procedures (the pmu,plambda
parameters in the output table). If all is well, you expect to see filter
power equal to the predicted P-value setting of the threshold.
- --pfile <f>
- Output cumulative survival plots (P(S>x)) to file
<f> in XMGRACE xy format. There are three plots: (1) the
observed score distribution; (2) the maximum likelihood fitted
distribution; (3) a maximum likelihood fit to the location parameter
(mu/tau) while
assuming lambda=log_2.
- --xfile <f>
- Output the bit scores as a binary array of double-precision
floats (8 bytes per score) to file <f>. Programs like Easel's
esl-histplot can read such binary files. This is useful when
generating extremely large sample sizes.
OPTIONS CONTROLLING MODEL CONFIGURATION (MODE)¶
H3 only uses multihit local alignment (
--fs mode), and this is where we
believe the statistical fits. Unihit local alignment scores (Smith/Waterman;
--sw mode) also obey our statistical conjectures. Glocal alignment
statistics (either multihit or unihit) are still not adequately understood nor
adequately fitted.
- --fs
- Collect multihit local alignment scores. This is the
default. alignment as 'fragment search mode'.
- --sw
- Collect unihit local alignment scores. The H3 J state is
disabled. alignment as 'Smith/Waterman search mode'.
- --ls
- Collect multihit glocal alignment scores. In glocal
(global/local) alignment, the entire model must align, to a subsequence of
the target. The H3 local entry/exit transition probabilities are disabled.
'ls' comes from HMMER2's historical terminology for multihit local
alignment as 'local search mode'.
- --s
- Collect unihit glocal alignment scores. Both the H3 J state
and local entry/exit transition probabilities are disabled. 's' comes from
HMMER2's historical terminology for unihit glocal alignment.
OPTIONS CONTROLLING SCORING ALGORITHM¶
- --vit
- Collect Viterbi maximum likelihood alignment scores. This
is the default.
- --fwd
- Collect Forward log-odds likelihood scores, summed over
alignment ensemble.
- --hyb
- Collect 'Hybrid' scores, as described in papers by Yu and
Hwa (for instance, Bioinformatics 18:864, 2002). These involve calculating
a Forward matrix and taking the maximum cell value. The number itself is
statistically somewhat unmotivated, but the distribution is expected be a
well-behaved extreme value distribution (Gumbel).
- --msv
- Collect MSV (multiple ungapped segment Viterbi) scores,
using H3's main acceleration heuristic.
- --fast
- For any of the above options, use H3's optimized production
implementation (using SIMD vectorization). The default is to use the
implementations sacrifice a small amount of numerical precision. This can
introduce confounding noise into statistical simulations and fits, so when
one gets super-concerned about exact details, it's better to be able to
factor that source of noise out.
OPTIONS CONTROLLING FITTED TAIL MASSES FOR FORWARD¶
In some experiments, it was useful to fit Forward scores to a range of different
tail masses, rather than just one. These options provide a mechanism for
fitting an evenly-spaced range of different tail masses. For each different
tail mass, a line is generated in the output.
- --tmin <x>
- Set the lower bound on the tail mass distribution. (The
default is 0.02 for the default single tail mass.)
- --tmax <x>
- Set the upper bound on the tail mass distribution. (The
default is 0.02 for the default single tail mass.)
- --tpoints <n>
- Set the number of tail masses to sample, starting from
--tmin and ending at --tmax. (The default is 1, for the
default 0.02 single tail mass.)
- --tlinear
- Sample a range of tail masses with uniform linear spacing.
The default is to use uniform logarithmic spacing.
OPTIONS CONTROLLING H3 PARAMETER ESTIMATION METHODS¶
H3 uses three short random sequence simulations to estimating the location
parameters for the expected score distributions for MSV scores, Viterbi
scores, and Forward scores. These options allow these simulations to be
modified.
- --EmL <n>
- Sets the sequence length in simulation that estimates the
location parameter mu for MSV E-values. Default is 200.
- --EmN <n>
- Sets the number of sequences in simulation that estimates
the location parameter mu for MSV E-values. Default is 200.
- --EvL <n>
- Sets the sequence length in simulation that estimates the
location parameter mu for Viterbi E-values. Default is 200.
- --EvN <n>
- Sets the number of sequences in simulation that estimates
the location parameter mu for Viterbi E-values. Default is 200.
- --EfL <n>
- Sets the sequence length in simulation that estimates the
location parameter tau for Forward E-values. Default is 100.
- --EfN <n>
- Sets the number of sequences in simulation that estimates
the location parameter tau for Forward E-values. Default is 200.
- --Eft <x>
- Sets the tail mass fraction to fit in the simulation that
estimates the location parameter tau for Forward evalues. Default is 0.04.
DEBUGGING OPTIONS¶
- --stall
- For debugging the MPI master/worker version: pause after
start, to enable the developer to attach debuggers to the running master
and worker(s) processes. Send SIGCONT signal to release the pause. (Under
gdb: (gdb) signal SIGCONT) (Only available if optional MPI support
was enabled at compile-time.)
- --seed <n>
- Set the random number seed to <n>. The default
is 0, which makes the random number generator use an arbitrary seed, so
that different runs of hmmsim will almost certainly generate a
different statistical sample. For debugging, it is useful to force
reproducible results, by fixing a random number seed.
EXPERIMENTAL OPTIONS¶
These options were used in a small variety of different exploratory experiments.
- --bgflat
- Set the background residue distribution to a uniform
distribution, both for purposes of the null model used in calculating
scores, and for generating the random sequences. The default is to use a
standard amino acid background frequency distribution.
- --bgcomp
- Set the background residue distribution to the mean
composition of the profile. This was used in exploring some of the effects
of biased composition.
- --x-no-lengthmodel
- Turn the H3 target sequence length model off. Set the
self-transitions for N,C,J and the null model to 350/351 instead; this
emulates HMMER2. Not a good idea in general. This was used to demonstrate
one of the main H2 vs. H3 differences.
- --nu <x>
- Set the nu parameter for the MSV algorithm -- the expected
number of ungapped local alignments per target sequence. The default is
2.0, corresponding to a E->J transition probability of 0.5. This was
used to test whether varying nu has significant effect on result (it
doesn't seem to, within reason). This option only works if --msv is
selected (it only affects MSV), and it will not work with --fast
(because the optimized implementations are hardwired to assume nu=2.0).
- --pthresh <x>
- Set the filter P-value threshold to use in generating
filter power files with --ffile. The default is 0.02 (which would
be appropriate for testing MSV scores, since this is the default MSV
filter threshold in H3's acceleration pipeline.) Other appropriate choices
(matching defaults in the acceleration pipeline) would be 0.001 for
Viterbi, and 1e-5 for Forward.
SEE ALSO¶
See
hmmer(1) for a master man page with a list of all the individual man
pages for programs in the HMMER package.
For complete documentation, see the user guide that came with your HMMER
distribution (Userguide.pdf); or see the HMMER web page (@HMMER_URL@).
COPYRIGHT¶
@HMMER_COPYRIGHT@
@HMMER_LICENSE@
For additional information on copyright and licensing, see the file called
COPYRIGHT in your HMMER source distribution, or see the HMMER web page
(@HMMER_URL@).
AUTHOR¶
Eddy/Rivas Laboratory
Janelia Farm Research Campus
19700 Helix Drive
Ashburn VA 20147 USA
http://eddylab.org