RNAdesign (empty) → 0.0.2.1
raw patch · 11 files changed
+1422/−0 lines, 11 filesdep +BiobaseTurnerdep +BiobaseViennadep +BiobaseXNAsetup-changed
Dependencies added: BiobaseTurner, BiobaseVienna, BiobaseXNA, ParsecTools, PrimitiveArray, RNAFold, ViennaRNA-bindings, array, base, cmdargs, containers, fgl, fgl-extras-decompositions, lens, monad-primitive, mwc-random-monad, parallel, parsec, primitive, random, transformers, tuple, vector
Files
- BioInf/RNAdesign.hs +255/−0
- BioInf/RNAdesign/Assignment.hs +71/−0
- BioInf/RNAdesign/Graph.hs +61/−0
- BioInf/RNAdesign/LogMultinomial.hs +15/−0
- BioInf/RNAdesign/OptParser.hs +89/−0
- LICENSE +675/−0
- README.md +1/−0
- RNAdesign.cabal +104/−0
- RNAdesign.hs +146/−0
- Setup.hs +2/−0
- changelog +3/−0
+ BioInf/RNAdesign.hs view
@@ -0,0 +1,255 @@+{-# LANGUAGE RankNTypes #-}+{-# LANGUAGE NoMonomorphismRestriction #-}+{-# LANGUAGE RecordWildCards #-}++module BioInf.RNAdesign where++import qualified Data.Array.IArray as A+import System.IO.Unsafe+import Control.Monad.IO.Class+import Control.Monad.Primitive.Class+import Control.Monad.Primitive+import System.Random.MWC.Monad+import Control.Monad+import qualified Data.Vector.Unboxed as VU+import qualified Data.Vector as V+import Data.List (sort,group)+import qualified Data.Map as M+import qualified Data.Vector.Fusion.Stream.Monadic as SM+import Control.Arrow+import System.IO.Unsafe -- TODO remove+import Data.List+import Data.Tuple.Select++import Biobase.Primary+import Biobase.Secondary.Diagrams+import Biobase.Secondary+import Biobase.Vienna+import qualified BioInf.ViennaRNA.Bindings as RNA -- NOTE removes the ability to call into ghci!+import BioInf.ViennaRNA.Eval++import BioInf.RNAdesign.Graph+import BioInf.RNAdesign.OptParser+import BioInf.RNAdesign.Assignment+import BioInf.RNAdesign.LogMultinomial++import Debug.Trace++++-- A single candidate, with its sequence and the score, this sequence receives.+-- Candidates are ordered by their scores.++data Candidate = Candidate+ { candidate :: Primary+ , score :: Score+ } deriving (Eq,Show)++instance Ord Candidate where+ (Candidate _ a) <= (Candidate _ b) = ropt a <= ropt b++-- | Create an initial, legal, candidate. Give it a really bad score.++mkInitial :: (MonadPrim m, PrimMonad m) => Int -> DesignProblem -> Rand m Candidate+mkInitial l dp = do+ let z = VU.replicate l nA+ c <- foldM mutateOneAssignment z $ assignments dp+ return $ Candidate c (Score [] 999999)++{-+-- | Sum probabilities over base pairs in the structural constraints++sumProbStructures :: Primary -> [D1Secondary] -> Double+sumProbStructures inp ss = s where+ s = sum $ map ((bp A.!) . first (+1) . second (+1)) ps+ ps = concatMap snd (map fromD1S ss :: [(Int,[PairIdx])])+ bp = let (_,_,bp') = unsafePerformIO (RNA.part $ concatMap show $ VU.toList inp) in bp'++sumProbNotStructures :: Primary -> [D1Secondary] -> Double+sumProbNotStructures inp ss = undefined++probabilityDefect inp str = s where+ s = sum (map (bp A.!) ps) - sum (map (bp A.!) ups)+ ups = [ (i,j) | i<-[1..l], j<-[i..l] ] \\ ps+ (l,ps) = second (map (first (+1) . second (+1))) $ fromD1S str :: (Int,[PairIdx])+ bp = let (_,_,bp') = unsafePerformIO (RNA.part $ concatMap show $ VU.toList inp) in bp'+-}++probabilityDefectAll inp ss = s where+ ca :: A.Array (Int,Int) Double+ ca = A.amap (\c -> c / n) . A.accumArray (+) 0 ((1,1),(l,l)) $ zip ps (repeat 1)+ n = genericLength ss+-- s = sum (map (abs . (n-) . (bp A.!)) ps) + sum (map (bp A.!) ups)+ s = sum (map (\ix -> abs $ ca A.! ix - bp A.! ix) ps) + sum (map (bp A.!) ups)+ l = VU.length inp+ ups = [ (i,j) | i<-[1..l], j<-[i..l] ] \\ ps+ ps = map (first (+1) . second (+1)) $ concatMap snd (map fromD1S ss :: [(Int,[PairIdx])])+ bp = let (_,_,bp') = unsafePerformIO (RNA.part $ concatMap show $ VU.toList inp) in bp'++ensembleDefect inp str = s where+ s = n - 2 * sps - sus+ n = fromIntegral $ VU.length inp+ sps = sum $ map (bp A.!) ps+ sus = sum $ [bp A.! (i,j) | i <- us, j <- [i..n]]+ ps = map (first (+1) . second (+1)) $ snd $ (fromD1S str :: (Int,[PairIdx]))+ us = [1..n] \\ (map fst ps ++ map snd ps)+ (_,_,bp) = unsafePerformIO (RNA.part $ concatMap show $ VU.toList inp)++-- | Resolve the optimization task. Each possible optimization function is+-- given here. Try to keep the functions defined here in sync with some+-- (non-existent ;-) documentation.++resolveOpt :: String -> t -> Primary -> [D1Secondary] -> Double+resolveOpt optfun ener inp secs = parseOptString l sops mops gops props optfun where+ l = length secs+ sops =+ [ ("eos" , \k -> unsafePerformIO $ RNA.eos (concatMap show (VU.toList inp)) (fromD1S $ secs !! (k-1)))+ , ("ed" , \k -> ensembleDefect inp (secs !! (k-1))) -- ensemble defect+-- , ("pdef" , \k -> probabilityDefect inp (secs !! (k-1)))+-- [ ("EOS",\k -> let (Deka e) = fst $ rnaEval ener inp $ secs !! (k-1) in fromIntegral e / 100)+-- , ("PF" ...+ ]+ mops =+ [ ("sum",sum)+ , ("max",maximum)+ , ("min",minimum)+ ]+ gops =+ [ ("Ged" , probabilityDefectAll inp secs) -- global ensemble defect a la ``me''+ , ("gibbs" , sel1 . unsafePerformIO $ RNA.part (concatMap show (VU.toList inp)))+ , ("mfe" , fst . unsafePerformIO $ RNA.mfe (concatMap show (VU.toList inp)))+-- , ("Pin" , sumProbStructures inp secs)+ ]+ props =+ [ ("logMN", \ps -> lmn ps inp)+ ]++lmn ps inp = logMultinomial l p c where+ l = VU.length inp+ p = VU.fromList ps+ cM = M.fromList . map (\z -> (head z, length z)) . group . sort $ VU.toList inp+ c = VU.fromList $ map (\z -> M.findWithDefault 0 z cM) acgu++data Score = Score+ { eoss :: [Deka]+ , ropt :: Double+ } deriving (Eq,Show,Read)++instance Ord Score where+ (Score _ a) <= (Score _ b) = a<=b++scoreSequence :: String -> Vienna2004 -> DesignProblem -> Primary -> Score+scoreSequence optfun ener DesignProblem{..} s = score where+ score = Score+ { eoss = error "don't call this" -- map (fst . rnaEval ener s) structures+ , ropt = resolveOpt optfun ener s structures+ }++-- | This structure defines a "design problem"++data DesignProblem = DesignProblem+ { structures :: [D1Secondary]+ , assignments :: [Assignment]+ } deriving (Eq,Read,Show)++-- | Given a set of structures, create the set of independent graphs and+-- assignment possibilities.++mkDesignProblem :: Int -> [String] -> [String] -> DesignProblem+mkDesignProblem asnLimit xs scs = dp where+ dp = DesignProblem+ { structures = map mkD1S xs+ , assignments = as+ }+ gs = independentGraphs xs+ as = map (allCandidates asnLimit sv) gs+ ss = M.map fixup . M.unionsWith (++) $ map (M.fromList . zip [0..] . (map ((:[]). mkNuc))) scs+ sv = V.fromList $ map (\k -> M.findWithDefault acgu k ss) [0 .. length (head xs) - 1]+ fixup zs = filter (/=nN) $ if (all (==nN) zs) then acgu else zs++unfoldStreamNew+ :: forall m . (MonadPrim m, PrimMonad m)+ => Int -> Int -> Int -> (Primary -> Score) -> (Candidate -> Candidate -> Rand m Bool) -> DesignProblem -> Candidate -> SM.Stream (Rand m) Candidate+unfoldStreamNew burnin number thin score f dp = go where+ go s = SM.map snd -- remove remaining indices from stream+ . SM.take number -- take the number of sequences we want+ . SM.filter ((==0) . flip mod thin . fst) -- keep only every thin'th sequence+ . SM.indexed -- add index+ . SM.drop burnin -- drop the burnin sequences+ . SM.drop 1 -- drop original input+ . SM.scanlM' (mutateOneAssignmentCandidateWith score f) s -- starting with 's', mutate s further and further using cycled assignments+ $ SM.unfoldr (Just . first head . splitAt 1) (cycle $ assignments dp) -- create inifinite cycled assignments++unfoldStream+ :: forall m . (MonadPrim m, PrimMonad m)+ => Int -> Int -> Int -> (Primary -> Primary -> Rand m Bool) -> DesignProblem -> Primary -> SM.Stream (Rand m) Primary+unfoldStream burnin number thin f dp = go where+ go s = SM.map snd -- remove remaining indices from stream+ . SM.take number -- take the number of sequences we want+ . SM.filter ((==0) . flip mod thin . fst) -- keep only every thin'th sequence+ . SM.indexed -- add index+ . SM.drop burnin -- drop the burnin sequences+ . SM.drop 1 -- drop original input+ . SM.scanlM' (mutateOneAssignmentWith f) s -- starting with 's', mutate s further and further using cycled assignments+ $ SM.unfoldr (Just . first head . splitAt 1) (cycle $ assignments dp) -- create inifinite cycled assignments++-- | Mutate the sequence in a candidate++mutateOneAssignmentCandidateWith+ :: (MonadPrim m, PrimMonad m)+ => (Primary -> Score) -> (Candidate -> Candidate -> Rand m Bool) -> Candidate -> Assignment -> Rand m Candidate+mutateOneAssignmentCandidateWith score f old Assignment{..} = do+ i <- uniformR (0,V.length assignment -1) -- inclusive range for Int+ let cs = VU.zip columns (assignment V.! i)+ let nw = VU.update (candidate old) cs+ let new = Candidate nw (score nw)+ b <- f old new+ return $ if b then new else old++-- | Mutate the sequence using one assignment with evaluation function.++mutateOneAssignmentWith+ :: (MonadPrim m, PrimMonad m)+ => (Primary -> Primary -> Rand m Bool) -> Primary -> Assignment -> Rand m Primary+mutateOneAssignmentWith f old Assignment{..} = do+ i <- uniformR (0,V.length assignment -1) -- inclusive range for Int+ let cs = VU.zip columns (assignment V.! i)+ let new = VU.update old cs+ b <- f old new+ return $ if b then new else old++-- | Create a number of sequences, thinning the list of candidates to yield+-- more independent candidates. The optimization function is used to make the+-- choice between emitting the current candidate again and selecting a new one.++generateSequences+ :: (MonadPrim m, PrimMonad m)+ => Int -> Int -> (Primary -> Primary -> Rand m Bool) -> DesignProblem -> Primary -> Rand m [Primary]+generateSequences number thin f dp s = go number thin s where+ go n t s+ | n < 1 = return []+ | t == 0 = do s' <- mutateSequence f dp s+ ss <- go (n-1) thin s'+ return $ s' : ss+ | otherwise = mutateSequence f dp s >>= go n (t-1)++-- | Mutate a sequence using the possible assignments.++mutateSequence+ :: (MonadPrim m, PrimMonad m)+ => (Primary -> Primary -> Rand m Bool) -> DesignProblem -> Primary -> Rand m Primary+mutateSequence f dp old = do+ new <- foldM mutateOneAssignment old $ assignments dp+ b <- f old new+ return $ if b then new else old++-- | Mutate the sequence using one assignment.++mutateOneAssignment+ :: (MonadPrim m, PrimMonad m)+ => Primary -> Assignment -> Rand m Primary+mutateOneAssignment s Assignment{..} = do+ i <- uniformR (0,V.length assignment -1) -- inclusive range for Int+ let cs = VU.zip columns (assignment V.! i)+ return $ VU.update s cs+
+ BioInf/RNAdesign/Assignment.hs view
@@ -0,0 +1,71 @@+{-# LANGUAGE PatternGuards #-}+{-# LANGUAGE ScopedTypeVariables #-}++module BioInf.RNAdesign.Assignment where++import Control.Arrow+import Data.Graph.Inductive.Graph+import Data.List (nub,sortBy,sort,genericLength)+import Data.Ord+import qualified Data.Vector as V+import qualified Data.Vector.Unboxed as VU+import Control.Lens.Tuple+import Control.Lens+import Data.Function++import Biobase.Primary+import Biobase.Secondary.Vienna+import Data.Graph.Inductive.Query.Ear++import BioInf.RNAdesign.Graph++import Data.Graph.Inductive.Query+import Debug.Trace++++data Assignment = Assignment+ { columns :: VU.Vector Int+ , assignment :: V.Vector (VU.Vector Nuc)+ , isExhaustive :: Bool+ , numAssignments :: Integer+ } deriving (Eq,Read,Show)++-- | Given a graph with base pairing constraints, return a 'Assignments' data+-- structure that provides all legal assignments.++allCandidates :: (DynGraph gr) => Int -> V.Vector [Nuc] -> gr () () -> Assignment+allCandidates maxC sv g+ | noNodes g == 1 = let [n] = nodes g+ svn = sv V.! n+ in Assignment (VU.singleton n) (V.fromList $ map VU.singleton svn) True (genericLength svn)+ | noNodes g == 2 = let [n,m] = nodes g+ svnm = [[a,b] | a <- sv V.! n, b <- sv V.! m, isViennaPair a b]+ in Assignment (VU.fromList [n,m]) (V.fromList $ map VU.fromList $ svnm) True (genericLength svnm)+ | noNodes g > 2 = let es :: [(Int,Int)] = nub . filter (uncurry (<)) . map (\(a,b,_) -> (a,b)) . sortBy (compare `on` sel3) . labEdges $ g' -- $ ears g+ g' = case bcc g of+ [_] -> ears g+ xs -> emap (const 0) g+ o = sort $ mkEL es+ (as,num) = second genericLength . splitAt maxC . map VU.fromList $ mkAssignments sv es+ in Assignment (VU.fromList o) (V.fromList $ take maxC as) (num==1) (genericLength as + num)++mkEL = nub . concatMap (\(a,b) -> [a,b])++mkAssignments sv es = map (map snd . sortBy (comparing fst)) $ mkA [] es where+ mkA :: [(Int,Nuc)] -> [(Int,Int)] -> [[(Int,Nuc)]]+ mkA dones [] = [[]]+ mkA dones ((a,b):ds)+ | Nothing <- a', Nothing <- b'+ = [ (a,n):(b,m):ns | n <- sv V.! a, m <- sv V.! b, isViennaPair n m, ns <- mkA ((a,n):(b,m):dones) ds ]+ | Nothing <- a', Just m <- b'+ = [ (a,n):ns | n <- sv V.! a, isViennaPair n m, ns <- mkA ((a,n):dones) ds ]+ | Just n <- a', Nothing <- b'+ = [ (b,m):ns | m <- sv V.! b, isViennaPair n m, ns <- mkA ((b,m):dones) ds ]+ | Just n <- a', Just m <- b'+ = if isViennaPair n m then mkA dones ds else []+ where+ a' = lookup a dones+ b' = lookup b dones++vps = filter (uncurry isViennaPair) [(a,b) | a<-cgau, b<-cgau]
+ BioInf/RNAdesign/Graph.hs view
@@ -0,0 +1,61 @@++module BioInf.RNAdesign.Graph where++import Data.Graph.Inductive.Graph+import Data.Graph.Inductive.Basic+import Data.Graph.Inductive.PatriciaTree+import Data.Graph.Inductive.Query+import Data.List (nub,partition)+import Control.Arrow (first,second)++import Biobase.Secondary.Diagrams++++-- | Given the one to many structures, create the independent graphs, where+-- each graph describes a set of dependent edges in the basepairing.++independentGraphs xs+ | null xs = error "You should give at least one structure. If you did, you have found a bug, yeah!"+ | any ((/=lx).length) xs = error $ "At least one structure with different length was found" ++ show xs+ | otherwise = independentComponents g+ where+ lx = length $ head xs+ g = mkUnionGraph xs++-- | Union of several graphs, created from secondary structure.++mkUnionGraph = unions . map (pairlistToGraph . (mkD1S :: String -> D1Secondary))++-- | Given k graphs, each with nodes [1..n], provide the union of all edges.++unions :: Eq b => [Gr a b] -> Gr a b+unions [] = empty+unions xs@(x:_) = mkGraph (labNodes x) (nub $ concatMap labEdges xs) where++-- | Given a pairlist, generate the secondary structure graph.++pairlistToGraph :: D1Secondary -> Gr () ()+pairlistToGraph d =+ let (len, ps) = fromD1S d+ in undir $ mkUGraph [0..len -1] ps++-- | Split the graph into (simple, complex) components. The simple components+-- can trivially be filled with any pair. The complex components require an Ear+-- or Woffle decomposition. Simple components are acyclic.++independentComponents :: DynGraph gr => gr () () -> [gr () ()]+independentComponents g = map f $ components g where+ f ns = mkUGraph ns (edges g)++-- | Tests if the given graph is bipartite, which is true if the even/odd BST+-- trees contain no edges++isBipartite :: DynGraph gr => gr a b -> Bool+isBipartite g = e && o where+ -- True, if there are no edges+ (e,o) = both (null . edges) $ f g+ -- generate the (even,odd) distance graphs+ f g = both (flip delNodes g . map fst) . partition (even . snd) $ level (fst $ head $ labNodes g) g+ both f = second f . first f+
+ BioInf/RNAdesign/LogMultinomial.hs view
@@ -0,0 +1,15 @@++module BioInf.RNAdesign.LogMultinomial where++import qualified Data.Vector.Unboxed as VU+++logMultinomial :: Int -> VU.Vector Double -> VU.Vector Int -> Double+logMultinomial n' ps xs'+ | VU.length ps /= VU.length xs' = error "logMultinomial: P-vector and count-vector of unequal length"+ | otherwise = n - x + p where+ n = logSum1k n'+ x = VU.sum $ VU.map logSum1k xs'+ p = VU.sum $ VU.zipWith (*) (VU.map log ps) (VU.map fromIntegral xs')+ logSum1k k = VU.sum . VU.map (log . fromIntegral) $ VU.enumFromTo 1 k+
+ BioInf/RNAdesign/OptParser.hs view
@@ -0,0 +1,89 @@++-- | A simple parser designed to read the optimization string from an argument+-- and together with the input computes the result of the the optimization+-- query. Without 'mkSingleOp' and 'mkMultiOp' this just a trivial parser for+-- simple arithmetic. The addional operations provide access to user-defined+-- functions that can, for example, be used to calculate the energy of a+-- sequence-structure pair. Those functions are not defined here but in the+-- application that uses the parser.++module BioInf.RNAdesign.OptParser+ ( parseOptString+ ) where++import Text.Parsec.Expr+import Text.Parsec hiding ((<|>))+import Text.Parsec.Language+import Text.Parsec.Token+import Control.Applicative+import Text.Parsec.String++import Text.Parsec.Numbers++++type SingleOp = (String,Int -> Double)+type MultiOp = (String,[Double] -> Double)+type GlobalOp = (String,Double)+type PropOp = (String,[Double] -> Double)+type NumSecStructs = Int++parseOptString :: NumSecStructs -> [SingleOp] -> [MultiOp] -> [GlobalOp] -> [PropOp] -> String -> Double+parseOptString nss sops mops gops props s = case parse expr "" $ prepString s of+ Right res -> res+ Left err -> error $ show err+ where+ prepString = filter (/= ' ')+ expr :: GenParser Char st Double+ expr+ = buildExpressionParser optable term+ <?> "expression"+ term :: GenParser Char st Double+ term+ = between (char '(') (char ')') expr+ <|> parseSingleOp sops+ <|> parseMultiOp nss sops mops+ <|> parseGlobalOp gops+ <|> parsePropOp props+ <|> parseFloat+ <?> "term"++parsePropOp xs = choice $ map mkPropOp xs++mkPropOp :: PropOp -> GenParser Char st Double+mkPropOp (s,f) = try $ f <$ string s <* string "(" <*> parseFloat `sepBy` string "," <* string ")" where++mkSingleOp :: SingleOp -> GenParser Char st Double+mkSingleOp (s,f) = try $ g <$ string s <* string "(" <*> many1 digit <* string ")" where+ g x = f (read x)++mkMultiOp :: NumSecStructs -> (SingleOp,MultiOp) -> GenParser Char st Double+mkMultiOp nss ((s,sf),(m,mf)) = {- (\xs -> error $ show (xs, map sf xs, mf $ map sf xs)) <$ -} (\xs -> mf $ map sf xs) <$+ string m <* string "(" <* string s <* string "," <*> secs <* string ")" where+ secs = try ([1..nss] <$ string "all")+ <|> map read <$> many1 digit `sepBy1` string ","++mkGlobalOp :: GlobalOp -> GenParser Char st Double+mkGlobalOp (s,f) = try $ f <$ string s++parseSingleOp xs = choice $ map mkSingleOp xs++parseMultiOp nss sops mops = choice $ map (try . mkMultiOp nss) [(s,m) | s<-sops, m<-mops]++parseGlobalOp gops = choice $ map (try . mkGlobalOp) gops++optable = [ [prefix "-" negate, prefix "+" id]+ , [binary "^" (**) AssocLeft] --, binary "**" (**) AssocLeft]+ , [binary "*" (*) AssocLeft, binary "/" (/) AssocLeft]+ , [binary "+" (+) AssocLeft, binary "-" (-) AssocLeft]+ ]++pow b e+ | (fromIntegral $ round e) /= e+ = error $ "exponent " ++ show e ++ " needs to be integral, sorry"+ | otherwise+ = b ^ (round e)++prefix name fun = Prefix (fun <$ string name)+binary name fun assoc = Infix (fun <$ string name) assoc+
+ LICENSE view
@@ -0,0 +1,675 @@+ GNU GENERAL PUBLIC LICENSE+ Version 3, 29 June 2007++ Copyright (C) 2007 Free Software Foundation, Inc. <http://fsf.org/>+ Everyone is permitted to copy and distribute verbatim copies+ of this license document, but changing it is not allowed.++ Preamble++ The GNU General Public License is a free, copyleft license for+software and other kinds of works.++ The licenses for most software and other practical works are designed+to take away your freedom to share and change the works. By contrast,+the GNU General Public License is intended to guarantee your freedom to+share and change all versions of a program--to make sure it remains free+software for all its users. We, the Free Software Foundation, use the+GNU General Public License for most of our software; it applies also to+any other work released this way by its authors. You can apply it to+your programs, too.++ When we speak of free software, we are referring to freedom, not+price. 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+ README.md view
@@ -0,0 +1,1 @@+
+ RNAdesign.cabal view
@@ -0,0 +1,104 @@+name: RNAdesign+version: 0.0.2.1+author: Christian Hoener zu Siederdissen+maintainer: choener@tbi.univie.ac.at+category: Bioinformatics+synopsis: Multi-target RNA sequence design+license: GPL-3+license-file: LICENSE+build-type: Simple+stability: experimental+cabal-version: >= 1.6.0+description:+ The RNA sequence design problem asks for a single sequence that+ readily folds into the one or more structural targets that are+ given as input.+ .+ This program expects on standard input a file with one or more+ structures and, possibly, additional sequence constraints. It+ will then run a Markov chain to find a sequence that is optimal+ with regard to the structural targets and the user-defineable+ optimization function.+ .+ The user can give different optimization criteria on the+ command line, akin to a simple calculator.+ .+ .+ .+ If you find this program useful, please cite:+ .+ Christian Hoener zu Siederdissen, Stefan Hammer, Ingrid Abfalter, Ivo L. Hofacker, Christoph Flamm, Peter F. Stadler+ .+ @A Graph Coloring Approach to Designing Multi-Stable Nucleic Acid Sequences@+ .+ Biopolymers, 99, 12, 1124-1136, 2013, Wiley++++extra-source-files:+ changelog+ README.md++library+ build-depends:+ base >= 4 && < 5 ,+ array >= 0.4 ,+ containers ,+ fgl >= 5.4 ,+ lens >= 3.9 ,+ monad-primitive >= 0.1 ,+ mwc-random-monad >= 0.6 ,+ parallel >= 3.2 ,+ parsec >= 3 ,+ primitive >= 0.5 ,+ random >= 1.0 ,+ transformers >= 0.3 ,+ tuple >= 0.2 ,+ vector >= 0.10 ,+ fgl-extras-decompositions >= 0.1.0.0 ,+ BiobaseTurner >= 0.3.1.1 ,+ BiobaseVienna >= 0.3 ,+ BiobaseXNA >= 0.7.0.1 ,+ ParsecTools >= 0.0.2 && < 0.0.3 ,+ PrimitiveArray >= 0.5 ,+ RNAFold >= 1.99.3.3 ,+ ViennaRNA-bindings >= 0.0.2.3+ exposed-modules:+ BioInf.RNAdesign+ BioInf.RNAdesign.Assignment+ BioInf.RNAdesign.Graph+ BioInf.RNAdesign.LogMultinomial+ BioInf.RNAdesign.OptParser+ ghc-options:+ -O2++executable RNAdesign+ build-depends:+ base >= 4 && < 5 ,+ array >= 0.4 ,+ cmdargs == 0.10.* ,+ containers ,+ fgl >= 5.4 ,+ lens >= 3.9 ,+ monad-primitive >= 0.1 ,+ mwc-random-monad >= 0.6 ,+ parallel >= 3.2 ,+ parsec >= 3 ,+ primitive >= 0.5 ,+ random >= 1.0 ,+ transformers >= 0.3 ,+ tuple >= 0.2 ,+ vector >= 0.10 ,+ fgl-extras-decompositions >= 0.1.0.0 ,+ BiobaseTurner >= 0.3.1.1 ,+ BiobaseVienna >= 0.3 ,+ BiobaseXNA >= 0.7.0.1 ,+ ParsecTools >= 0.0.2 && < 0.0.3 ,+ PrimitiveArray >= 0.5 ,+ RNAFold >= 1.99.3.3 ,+ ViennaRNA-bindings >= 0.0.2.3+ main-is:+ RNAdesign.hs+ ghc-options:+ -O2 -rtsopts+
+ RNAdesign.hs view
@@ -0,0 +1,146 @@+{-# LANGUAGE QuasiQuotes #-}+{-# LANGUAGE BangPatterns #-}+{-# LANGUAGE ScopedTypeVariables #-}+{-# LANGUAGE DeriveDataTypeable #-}+{-# LANGUAGE NoMonomorphismRestriction #-}+{-# LANGUAGE RecordWildCards #-}++-- |++module Main where++import System.Console.CmdArgs+import Data.List+import Data.Char (isAlpha)+import Control.Monad+import System.Random.MWC.Monad+import System.Random.MWC.Distributions.Monad+import qualified Data.Vector.Unboxed as VU+import Text.Printf+import Data.Ord+import qualified Data.Vector.Fusion.Stream.Monadic as SM+import Control.Arrow+import Data.Function+import System.IO++import Biobase.Primary+import Biobase.Vienna+import qualified Biobase.Turner.Import as TI++import BioInf.RNAdesign+import BioInf.RNAdesign.Assignment++import Debug.Trace++++-- * configuration++data Config = Config+ { number :: Int+ , thin :: Int+ , burnin :: Int+ , scale :: Double+ , optfun :: String+ , veclen :: Int+ , turner :: String+-- , exhaustive :: Bool -- TODO want to think about this for number of structures > 3, IF the total sequence space size is less than say 100.000+ , initial :: String+ , sequenceConstraints :: Bool+ , explore :: Bool+ } deriving (Show,Data,Typeable)++config = Config+ { number = 50 &= help "Number of candidate sequences to generate (50)"+ , thin = 50 &= help "keep only every n'th sequence (50)"+ , burnin = 100 &= help "remove the first burnin sequences (100)"+ , scale = 1 &= help "acceptance scale parameter (1); exponentially distributed with mean 'scale^(-1)' (smaller scale means longer jumps)"+ , optfun = "sum(eos,all)" &= help "optimization function, \"sum(eos,all)\" tries to minimize the sum of the energies"+ , veclen = 1000000 &= help "multiple structure constraints lead to large connected components, veclen restricts the number of component solutions to store."+ , turner = "./params" &= help "directory containing the Turner 2004 RNA energy tables (with a default of \"./params/\""+-- , exhaustive = False &= help "exhaustively search the nucleotide space"+ , initial = "" &= help "start from this initial sequence"+ , explore = def &= help "explore sequences, do not sort of nub list"+ , sequenceConstraints = def &= help "activate sequence constraints"+ } &= help shortHelp &= details longHelp &= summary "RNAdesign v0.0.2, (C) Christian Hoener zu Siederdissen 2013, choener@tb.univie.ac.at" &= program "RNAdesign"++shortHelp = "The defaults work acceptably well and produce a results extremely fast. "++longHelp =+ [ "RNAdesign designs RNA sequences given one or more structural targets. The"+ , "program offers a variety of optimization functions that each can be used to"+ , "optimize candidate sequence towards a certain goal, say, minimal ensemble"+ , "defect or small energetic distance to another target structure. By giving a"+ , "complex \"--optun\", many different design goals can be tried. The following"+ , "functions are available:"+ , "binary, combining:"+ , "+ - * / :: the four basic operations"+ , "^ :: (^) generalized power function"+ , ""+ , "binary, apply function to many targets:"+ , "sum max min :: run function over set of targets: sum(eos,1,2) or sum(eos,all)"+ , ""+ , "unary, apply to single target:"+ , "eos :: energy of a structure: eos(1)"+ , "ed :: ensemble defect of a structure: ed(3)"+ , "nullary, constant for the current sequence:"+ , "Ged :: global, weighted ensemble defect: Ged"+ , "gibbs :: gibbs free energy of sequence"+ , "mfe :: minimum free energy of sequence"+ , ""+ , "special:"+ , "logMN :: requires four parameters logMN(0.2,0.3,0.3,0.2) penalizes according to given mono-nucleotide distribution"+ , ""+ , "A good optimization goal is (as an example for three targets):"+ , "--optfun \"eos(1)+eos(2)+eos(3) - 3*gibbs +"+ , " 1 * ((eos(1)-eos(2))^2 + (eos(1)-eos(3))^2 + (eos(2)-eos(3))^2)\""+ , "This way, the sequence produces close-to-mfe foldings with the targets (left) and the targets are close together in terms of energy. (1 *) scales the two terms according to user choice."+ , "\n\n\n"+ , "If you find this tool useful, please cite:"+ , ""+ , "Christian Hoener zu Siederdissen, Stefan Hammer, Ingrid Abfalter, Ivo L. Hofacker, Christoph Flamm, Peter F. Stadler."+ , "A Graph Coloring Approach to Designing Multi-Stable Nucleic Acid Sequences."+ , "submitted, 2013."+ , ""+ , "Contact: choener@tbi.univie.ac.at"+ , "Given one or more structures in dot-bracket format of the same length, returns a compatible assignment of nucleotides."+ , "Compatible nucleotides are those that allow folding of the sequence into all given structures."+ ]++main = do+ hSetBuffering stdout NoBuffering+ hSetBuffering stderr NoBuffering+ cmds@Config{..} <- cmdArgs config+ turner <- fmap turnerToVienna $ TI.fromDir turner "" ".dat" + strs' <- fmap lines $ getContents+ let (scs,strs) = first (filter ((">"/=) . take 1)) . partition (any isAlpha) $ strs'+ unless (length strs > 0) $ error "no structures given!"+ let l = length $ head strs+ unless (all ((l==) . length) strs) $ error "structures of different size detected"+ let dp = mkDesignProblem veclen strs (if sequenceConstraints then scs else [])+ let defOpt old new = let oldS = scoreSequence optfun turner dp old+ newS = scoreSequence optfun turner dp new+ in do t <- exponential scale+ return $ ropt newS <= ropt oldS || t >= ropt newS - ropt oldS+ let calcScore = scoreSequence optfun turner dp+ let walk old new = do t <- exponential scale+ let sn = ropt $ score new+ let so = ropt $ score old+ return $ sn <= so || t >= sn - so+ let ini = if null initial -- start from initial sequence or generate one from the ensemble+ then mkInitial l dp+ else return $ Candidate (mkPrimary initial) (Score [] 999999)+ xs <- runWithSystemRandom . asRandIO $ (ini >>= SM.toList . unfoldStreamNew burnin number thin calcScore walk dp)+ let pna = product . map numAssignments $ assignments dp+ printf "# Size of sequence space: %d %s\n\n" pna {-(product . map numAssignments $ assignments dp)-} (show . map numAssignments $ assignments dp)+ unless (pna>0) $ error "empty sequence space, aborting!"+ mapM_ (\ys -> printf "%s %4d %8.2f\n" (concatMap show . VU.toList . candidate . head $ ys) (length ys) (ropt . score $ head ys))+ . ( if explore+ then map (:[])+ else ( sortBy (comparing (ropt . score . head))+ . groupBy ((==) `on` candidate)+ . sortBy (comparing candidate)+ )+ )+ $ xs+
+ Setup.hs view
@@ -0,0 +1,2 @@+import Distribution.Simple+main = defaultMain
+ changelog view
@@ -0,0 +1,3 @@+0.0.2.1+ * post-publication version+ * allows continuous Markovian walk for special applications