# Name of your program
package "RNAplfold" # don't use package if you're using automake
purpose "calculate locally stable secondary structure - pair probabilities"
#usage "RNAplfold [options]\n"

# Version of your program
#version "2.0"   # don't use version if you're using automake


# command line options passed to gengetopt
args "--file-name=RNAplfold_cmdl --include-getopt --default-optional --func-name=RNAplfold_cmdline_parser --arg-struct-name=RNAplfold_args_info"


description "Computes local pair probabilities for base pairs with a maximal span\
 of L. The probabilities are averaged over all windows of size L that contain the\
 base pair. For a sequence of length n and a window size of L the algorithm uses\
 only O(n+L*L) memory and O(n*L*L) CPU time. Thus it is practical to \"scan\" very\
 large genomes for short stable RNA structures.\n"

# Options

option  "verbose" v
"Be verbose.\n\n"
flag
off


section "I/O Options"
sectiondesc="Command line options for input and output (pre-)processing\n\n"

option  "cutoff"  c
"Report only base pairs with an average probability larger than 'cutoff' in the dot plot.\n\n"
float
default="0.01"
optional

option  "print_onthefly"  o
"Save memory by printing out everything during computation.\n"
details="NOTE: activated per default for sequences over 1M bp.\n\n"
flag
off

option  "opening_energies"  O
"Switch output from probabilities to their logarithms.\n"
details="This is NOT exactly the mean energies needed to unfold the respective stretch\
 of bases! (implies --ulength option).\n\n"
flag
off

option  "plex_output" -
"Create additional output files for RNAplex.\n\n"
flag
off
hidden

option  "binaries"  b
"Output accessibility profiles in binary format.\n"
details=" The binary files produced by RNAplfold do not need to be parsed\
 by RNAplex, so that they are directly loaded into memory. This is useful when large\
 sequences have to be searched for putative hybridization sites. Another advantage of\
 the binary format is the 50% file size decrease.\n\n" 
flag
off
hidden

option  "noconv"  -
"Do not automatically substitute nucleotide \"T\" with \"U\".\n\n"
flag
off

option  "auto-id"  -
"Automatically generate an ID for each sequence.\n"
details="The default mode of RNAplfold 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, RNAplfold 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.\n\n"
flag
off

option  "id-prefix" -
"Prefix for automatically generated IDs (as used in output file names).\n"
details="If this parameter is set, each sequences' FASTA id will be prefixed\
 with the provided string. FASTA ids then take the form \">prefix_xxxx\" where\
 xxxx is the sequence number. Hence, the output files will obey the following naming\
 scheme: \"prefix_xxxx_dp.ps\" (dot-plot), \"prefix_xxxx_lunp\" (unpaired probabilities),\
 etc. Note: Setting this parameter implies --auto-id.\n\n"
string
typestr="STRING"
default="sequence"
optional

option  "id-delim" -
"Change the delimiter between prefix and increasing number for automatically generated IDs (as used in output file names).\n"
details="This parameter can be used to change the default delimiter \"_\" between\
 the prefix string and the increasing number for automatically generated ID.\n\n"
string
typestr="CHAR"
default="_"
optional
hidden

option  "id-digits"  -
"Specify the number of digits of the counter in automatically generated alignment IDs.\n"
details="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.\n\n"
int
default="4"
optional
hidden

option  "id-start"  -
"Specify the first number in automatically generated IDs.\n"
details="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.\nNote: Setting this parameter implies\
 to ignore any IDs retrieved from the input data, i.e. it activates the --auto-id flag.\n\n"
long
default="1"
optional
hidden

option  "filename-delim" -
"Change the delimiting character used in sanitized filenames.\n"
details="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 '>'.\n\n"
string
typestr="CHAR"
default="ID-delimiter"
optional
hidden

option  "filename-full" -
"Use full FASTA header to create filenames.\n"
details="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).\n\n"
flag
off
hidden


section "Algorithms"
sectiondesc="Select and change parameters of (additional) algorithms which should be included in the calculations.\n\n"

option  "winsize" W
"Average the pair probabilities over windows of given size.\n\n"
int
default="70"
typestr="size"
optional

option  "span"  L
"Set the maximum allowed separation of a base pair to span.\n"
details="By setting the maximum base pair span no pairs (i,j) with\
 j-i > span will be allowed. Defaults to winsize if parameter is omitted.\n\n"
int
typestr="size"
optional

option  "ulength" u
"Compute the mean probability that regions of length 1 to a given length are unpaired.\n"
details="Output is saved in a '_lunp' file.\n\n"
int
typestr="length"
default="31"
optional

option  "betaScale" -
"Set the scaling of the Boltzmann factors.\n"
details="The argument provided with this option is used to scale the thermodynamic temperature\
 in the Boltzmann factors independently from the temperature of the individual loop energy contributions.\
 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.\n\n"
double
default="1."
optional
hidden

option  "pfScale" S
"In the calculation of the pf use scale*mfe as an estimate for the ensemble free energy (used to avoid\
 overflows).\n"
details="The default is 1.07, useful values are 1.0 to 1.2. Occasionally needed for long sequences.\n\n"
double
default="1.07"
optional
hidden


section "Structure Constraints"
sectiondesc="Command line options to interact with the structure constraints feature of this program\n\n"

option  "shape" -
"Use SHAPE reactivity data to guide structure predictions.\n\n"
string
typestr="filename"
optional

option  "shapeMethod" -
"Select SHAPE reactivity data incorporation strategy.\n\n"
details="The following methods can be used to convert SHAPE reactivities into pseudo energy contributions.\n\n\
 'D': Convert by using the linear equation according to Deigan et al 2009. Derived pseudo energy terms\
 will be applied for every nucleotide involved in a stacked pair. This method is recognized by a capital\
 'D' in the provided parameter, i.e.: --shapeMethod=\"D\" is the default setting. The slope 'm' and the\
 intercept 'b' can be set to a non-default value if necessary, otherwise m=1.8 and b=-0.6. To alter these\
 parameters, e.g. m=1.9 and b=-0.7, use a parameter string like this: --shapeMethod=\"Dm1.9b-0.7\". You\
 may also provide only one of the two parameters like: --shapeMethod=\"Dm1.9\" or --shapeMethod=\"Db-0.7\".\n\n\
 'Z': Convert SHAPE reactivities to pseudo energies according to Zarringhalam et al 2012.\
 SHAPE reactivities will be converted to pairing probabilities by using linear mapping.\
 Aberration from the observed pairing probabilities will be penalized during the folding recursion.\
 The magnitude of the penalties can affected by adjusting the factor beta\
 (e.g. --shapeMethod=\"Zb0.8\").\n\n\
 'W': Apply a given vector of perturbation energies to unpaired nucleotides according to Washietl et al 2012.\
 Perturbation vectors can be calculated by using RNApvmin.\n\n"
string
typestr="method"
dependon="shape"
default="D"
optional
hidden

option  "shapeConversion" -
"Select method for SHAPE reactivity conversion.\n\n"
details="This parameter is useful when dealing with the SHAPE incorporation according to Zarringhalam et al. \
The following methods can be used to convert SHAPE reactivities into the probability for a certain nucleotide to be unpaired.\n
'M': Use linear mapping according to Zarringhalam et al.
'C': Use a cutoff-approach to divide into paired and unpaired nucleotides (e.g. \"C0.25\")
'S': Skip the normalizing step since the input data already represents probabilities for being unpaired rather than raw reactivity values
'L': Use a linear model to convert the reactivity into a probability for being unpaired (e.g. \"Ls0.68i0.2\" to use a slope of 0.68 and an intercept of 0.2)
'O': Use a linear model to convert the log of the reactivity into a probability for being unpaired (e.g. \"Os1.6i-2.29\" to use a slope of 1.6 and an intercept of -2.29)\n\n"
string
typestr="method"
default="O"
optional
hidden

option  "commands"   -
"Read additional commands from file\n"
details="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.\n\n"
string
typestr="filename"
optional
hidden


section "Energy Parameters"
sectiondesc="Energy parameter sets can be adapted or loaded from user-provided input files\n\n"

option  "temp"  T
"Rescale energy parameters to a temperature of temp C. Default is 37C.\n\n"
double
default="37.0"
optional

option  "paramFile" P
"Read energy parameters from paramfile, instead of using the default parameter set.\n"
details="Different sets of energy parameters for RNA and DNA should accompany your distribution.\nSee the\
 RNAlib documentation for details on the file format. The placeholder file name 'DNA' can be used\
 to load DNA parameters without the need to actually specify any input file.\n\n"
string
typestr="paramfile"
optional

option  "noTetra" 4
"Do not include special tabulated stabilizing energies for tri-, tetra- and hexaloop hairpins.\n"
details="Mostly for testing.\n\n"
flag
off
hidden

option  "salt" -
"Set salt concentration in molar (M). Default is 1.021M.\n\n"
double
optional

option  "modifications" m
"Allow for modified bases within the RNA sequence string.\n"
details="Treat modified bases within the RNA sequence differently, i.e. use corresponding\
 energy corrections and/or pairing partner rules if available. For that, the modified bases\
 in the input sequence must be marked by their corresponding one-letter code. If no additional\
 arguments are supplied, all available corrections are performed. Otherwise, the user may\
 limit the modifications to a particular subset of modifications, resp. one-letter codes,\
 e.g. -mP6 will only correct for pseudouridine and m6A bases.\n\
 Currently supported one-letter codes and energy corrections are:\n\n\
 '7': 7-deaza-adenonsine (7DA)\n\n\
 'I': Inosine\n\n\
 '6': N6-methyladenosine (m6A)\n\n\
 'P': Pseudouridine\n\n\
 '9': Purine (a.k.a. nebularine)\n\n\
 'D': Dihydrouridine\n\n"
string
argoptional
default="7I6P9D"

option  "mod-file"  -
"Use additional modified base data from JSON file.\n\n"
string
multiple
optional


section "Model Details"
sectiondesc="Tweak the energy model and pairing rules additionally using the following parameters\n\n"

option  "dangles" d
"Specify \"dangling end\" model for bases adjacent to helices in free ends and multi-loops.\n"
details="With -d2 dangling energies will be added for the bases adjacent to a helix on both sides in\
 any case while -d0 ignores dangling ends altogether (mostly for debugging).\n\n"
int
default="2"
optional

option  "noLP"  -
"Produce structures without lonely pairs (helices of length 1).\n"
details="For partition function folding this only disallows pairs that can only occur isolated. Other\
 pairs may still occasionally occur as helices of length 1.\n\n"
flag
off

option  "noGU"  -
"Do not allow GU pairs.\n\n"
flag
off
hidden

option  "noClosingGU" -
"Do not allow GU pairs at the end of helices.\n\n"
flag
off
hidden

option  "nsp" -
"Allow other pairs in addition to the usual AU,GC,and GU pairs.\n"
details="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.\
 --nsp=\"-GA\"  will allow GA and AG pairs. Nonstandard pairs are given 0 stacking\
 energy.\n\n"
string
optional
hidden

option  "energyModel" e
"Set energy model.\n"
details="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.\n\n"
int
optional
hidden

option  "helical-rise"  -
"Set the helical rise of the helix in units of Angstrom.\n"
details="Use with caution! This value will be re-set automatically to 3.4 in case DNA\
 parameters are loaded via -P DNA and no further value is provided.\n\n"
float
optional
default="2.8"
hidden

option  "backbone-length"  -
"Set the average backbone length for looped regions in units of Angstrom.\n"
details="Use with caution! This value will be re-set automatically to 6.76 in case DNA\
 parameters are loaded via -P DNA and no further value is provided.\n\n"
float
optional
default="6.0"
hidden


text    "\nIf in doubt our program is right, nature is at fault.\nComments should be sent to\
 rna@tbi.univie.ac.at.\n\n"
