NAME

RNAmultifold - manual page for RNAmultifold 2.5.1

SYNOPSIS

RNAmultifold [ OPTION]... [FILE]...

DESCRIPTION

RNAmultifold 2.5.1
Compute secondary structures of multiple interacting RNAs
The program works much like RNAfold, but allows one to specify multiple RNA sequences which are then allowed to form conncected components. RNA sequences are read from stdin in the usual format, i.e. each line of input corresponds to one sequence, except for lines starting with ">" which contain the name of the next sequence(s). Multiple strands must be concatenated using the \'&\' character as separator. RNAmultifold can compute MFE, partition function, corresponding ensemble free energy and base pairing probabilities. These properties are either computed for a particular arrangement (concatenation) of sequences, for the full ensemble of the complex of input RNAs, or all complexes formed by the input sequences up to a specified number of interacting sequences. Output consists of a PostScript "dot plot" file containing the pair probabilities, see the RNAfold man page for details. The program will continue to read new sequences until a line consisting of the single character @ or an end of file condition is encountered.
-h, --help
Print help and exit
--detailed-help
Print help, including all details and hidden options, and exit
--full-help
Print help, including hidden options, and exit
-V, --version
Print version and exit

General Options:

Command line options which alter the general behavior of this program
-v, --verbose
Be verbose.
(default=off)
-j, --jobs[=number]
Split batch input into jobs and start processing in parallel using multiple threads. A value of 0 indicates to use as many parallel threads as computation cores are available.
(default=`0')
Default processing of input data is performed in a serial fashion, i.e. one sequence pair at a time. Using this switch, a user can instead start the computation for many sequence pairs in the input in parallel. RNAmultifold will create as many parallel computation slots as specified and assigns input sequences of the input file(s) to the available slots. Note, that this increases memory consumption since input alignments have to be kept in memory until an empty compute slot is available and each running job requires its own dynamic programming matrices.
--unordered
Do not try to keep output in order with input while parallel processing is in place.
(default=off)
When parallel input processing (--jobs flag) is enabled, the order in which input is processed depends on the host machines job scheduler. Therefore, any output to stdout or files generated by this program will most likely not follow the order of the corresponding input data set. The default of RNAmultifold is to use a specialized data structure to still keep the results output in order with the input data. However, this comes with a trade-off in terms of memory consumption, since all output must be kept in memory for as long as no chunks of consecutive, ordered output are available. By setting this flag, RNAmultifold will not buffer individual results but print them as soon as they have been computated.
--noconv
Do not automatically substitute nucleotide "T" with "U"
(default=off)
--auto-id
Automatically generate an ID for each sequence. (default=off)
The default mode of RNAmultifold is to automatically determine an ID from the input sequence data if the input file format allows to do that. Sequence IDs are usually given in the FASTA header of input sequences. If this flag is active, RNAmultifold ignores any IDs retrieved from the input and automatically generates an ID for each sequence. This ID consists of a prefix and an increasing number. This flag can also be used to add a FASTA header to the output even if the input has none.
--id-prefix=prefix
Prefix for automatically generated IDs (as used in output file names)
(default=`sequence')
If this parameter is set, each sequence will be prefixed with the provided string. Hence, the output files will obey the following naming scheme: "prefix_xxxx_ss.ps" (secondary structure plot), "prefix_xxxx_dp.ps" (dot-plot), "prefix_xxxx_dp2.ps" (stack probabilities), etc. where xxxx is the sequence number. Note: Setting this parameter implies --auto-id.
--id-delim=delimiter
Change the delimiter between prefix and increasing number for automatically generated IDs (as used in output file names)
(default=`_')
This parameter can be used to change the default delimiter "_" between
the prefix string and the increasing number for automatically generated ID.
--id-digits=INT
Specify the number of digits of the counter in automatically generated alignment IDs.
(default=`4')
When alignments IDs are automatically generated, they receive an increasing number, starting with 1. This number will always be left-padded by leading zeros, such that the number takes up a certain width. Using this parameter, the width can be specified to the users need. We allow numbers in the range [1:18]. This option implies --auto-id.
--id-start=LONG
Specify the first number in automatically generated alignment IDs.
(default=`1')
When sequence IDs are automatically generated, they receive an increasing number, usually starting with 1. Using this parameter, the first number can be specified to the users requirements. Note: negative numbers are not allowed. Note: Setting this parameter implies to ignore any IDs retrieved from the input data, i.e. it activates the --auto-id flag.
--filename-delim=delimiter
Change the delimiting character that is used
for sanitized filenames
(default=`ID-delimiter')
This parameter can be used to change the delimiting character used while sanitizing filenames, i.e. replacing invalid characters. Note, that the default delimiter ALWAYS is the first character of the "ID delimiter" as supplied through the --id-delim option. If the delimiter is a whitespace character or empty, invalid characters will be simply removed rather than substituted. Currently, we regard the following characters as illegal for use in filenames: backslash '\', slash '/', question mark '?', percent sign '%', asterisk '*', colon ':', pipe symbol '|', double quote '"', triangular brackets '<' and '>'.
--filename-full
Use full FASTA header to create filenames
(default=off)
This parameter can be used to deactivate the default behavior of limiting output filenames to the first word of the sequence ID. Consider the following example: An input with FASTA header ">NM_0001 Homo Sapiens some gene" usually produces output files with the prefix "NM_0001" without the additional data available in the FASTA header, e.g. "NM_0001_ss.ps" for secondary structure plots. With this flag set, no truncation of the output filenames is done, i.e. output filenames receive the full FASTA header data as prefixes. Note, however, that invalid characters (such as whitespace) will be substituted by a delimiting character or simply removed, (see also the parameter option --filename-delim).

Structure Constraints:

Command line options to interact with the structure constraints feature of this program
--maxBPspan=INT
Set the maximum base pair span
(default=`-1')
--commands=<filename>
Read additional commands from file
Commands include hard and soft constraints, but also structure motifs in hairpin and interior loops that need to be treeted differently. Furthermore, commands can be set for unstructured and structured domains.

Algorithms:

Select additional algorithms which should be included in the calculations. The Minimum free energy (MFE) and a structure representative are calculated in any case.
-p, --partfunc[=INT]
Calculate the partition function and base pairing probability matrix in addition to the MFE structure. Default is calculation of mfe structure only.
(default=`1')
In addition to the MFE structure we print a coarse representation of the pair probabilities in form of a pseudo bracket notation, followed by the ensemble free energy. Note that unless you also specify -d2 or -d0, the partition function and mfe calculations will use a slightly different energy model. See the discussion of dangling end options below.
An additionally passed value to this option changes the behavior of partition function calculation:
In order to calculate the partition function but not the pair probabilities
use the -p0 option and save about
50% in runtime. This prints the ensemble free energy -kT ln(Z).
-a, --all_pf[=INT]
Compute the partition function and free energies not only for the complex formed by the input sequences (the "ABC... mutimer"), but also of all complexes formed by the input sequences up to the number of input sequences, e.g. AAA, AAB, ABB, BBB, etc.
(default=`1')
The output will contain the free energies for each of these species. Using -a automatically switches on the -p option.
-c, --concentrations
In addition to everything listed under the -a option, read in initial monomer concentrations and compute the expected equilibrium concentrations of all possible species (A, B, AA, BB, AB, etc).
(default=off)
Start concentrations are read from stdin (unless the -f option is used) in [mol/l], equilibrium concentrations are given realtive to the sum of the inputs. An arbitrary number of initial concentrations can be specified (one tuple of concentrations per line).
-f, --concfile=filename
Specify a file with initial concentrations for the input sequences.
The table consits of arbitrary many lines with multiple numbers separated by whitespace (the concentration of the input sequences A, B, C, etc.). This option will automatically toggle the -c (and thus -a and -p) options (see above).
--absolute-concentrations Report absolute instead of relative
concentrations
(default=off)
-S, --pfScale=scaling factor
In the calculation of the pf use scale*mfe as an estimate for the ensemble free energy (used to avoid overflows).
The default is 1.07, useful values are 1.0 to 1.2. Occasionally needed for long sequences. You can also recompile the program to use double precision (see the README file).
--bppmThreshold=<value>
Set the threshold for base pair probabilities included in the postscript output
(default=`1e-5')
By setting the threshold the base pair probabilities that are included in the output can be varied. By default only those exceeding 1e-5 in probability will be shown as squares in the dot plot. Changing the threshold to any other value allows for increase or decrease of data.
-g, --gquad
Incoorporate G-Quadruplex formation into the structure prediction algorithm.
(default=off)
Note, only intramolecular G-quadruplexes are considered.

Model Details:

-T, --temp=DOUBLE
Rescale energy parameters to a temperature of temp C. Default is 37C.
-4, --noTetra
Do not include special tabulated stabilizing energies for tri-, tetra- and hexaloop hairpins.
(default=off)
Mostly for testing.
-d, --dangles=INT
How to treat "dangling end" energies for bases adjacent to helices in free ends and multi-loops
(default=`2')
With -d1 only unpaired bases can participate in at most one dangling end. With -d2 this check is ignored, dangling energies will be added for the bases adjacent to a helix on both sides in any case; this is the default for mfe and partition function folding ( -p). The option -d0 ignores dangling ends altogether (mostly for debugging). With -d3 mfe folding will allow coaxial stacking of adjacent helices in multi-loops. At the moment the implementation will not allow coaxial stacking of the two interior pairs in a loop of degree 3 and works only for mfe folding.
Note that with -d1 and -d3 only the MFE computations will be using this setting while partition function uses -d2 setting, i.e. dangling ends will be treated differently.
--noLP
Produce structures without lonely pairs (helices of length 1).
(default=off)
For partition function folding this only disallows pairs that can only occur isolated. Other pairs may still occasionally occur as helices of length 1.
--noGU
Do not allow GU pairs
(default=off)
--noClosingGU
Do not allow GU pairs at the end of helices
(default=off)
-P, --paramFile=paramfile
Read energy parameters from paramfile, instead of using the default parameter set.
Different sets of energy parameters for RNA and DNA should accompany your distribution. See the RNAlib documentation for details on the file format. When passing the placeholder file name "DNA", DNA parameters are loaded without the need to actually specify any input file.
--nsp=STRING
Allow other pairs in addition to the usual AU,GC,and GU pairs.
Its argument is a comma separated list of additionally allowed pairs. If the first character is a "-" then AB will imply that AB and BA are allowed pairs. e.g. RNAmultifold -nsp -GA will allow GA and AG pairs. Nonstandard pairs are given 0 stacking energy.
-e, --energyModel=INT
Rarely used option to fold sequences from the artificial ABCD... alphabet, where A pairs B, C-D etc. Use the energy parameters for GC ( -e 1) or AU (-e 2) pairs.
--betaScale=DOUBLE
Set the scaling of the Boltzmann factors (default=`1.')
The argument provided with this option enables to scale the thermodynamic temperature used in the Boltzmann factors independently from the temperature used to scale the individual energy contributions of the loop types. The Boltzmann factors then become exp( -dG/(kT*betaScale)) where k is the Boltzmann constant, dG the free energy contribution of the state and T the absolute temperature.

REFERENCES

If you use this program in your work you might want to cite:
 
R. Lorenz, S.H. Bernhart, C. Hoener zu Siederdissen, H. Tafer, C. Flamm, P.F. Stadler and I.L. Hofacker (2011), "ViennaRNA Package 2.0", Algorithms for Molecular Biology: 6:26
 
I.L. Hofacker, W. Fontana, P.F. Stadler, S. Bonhoeffer, M. Tacker, P. Schuster (1994), "Fast Folding and Comparison of RNA Secondary Structures", Monatshefte f. Chemie: 125, pp 167-188
 
R. Lorenz, I.L. Hofacker, P.F. Stadler (2016), "RNA folding with hard and soft constraints", Algorithms for Molecular Biology 11:1 pp 1-13
 
The energy parameters are taken from:
 
D.H. Mathews, M.D. Disney, D. Matthew, J.L. Childs, S.J. Schroeder, J. Susan, M. Zuker, D.H. Turner (2004), "Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure", Proc. Natl. Acad. Sci. USA: 101, pp 7287-7292
 
D.H Turner, D.H. Mathews (2009), "NNDB: The nearest neighbor parameter database for predicting stability of nucleic acid secondary structure", Nucleic Acids Research: 38, pp 280-282

REPORTING BUGS

If in doubt our program is right, nature is at fault. Comments should be sent to [email protected].