diff --git a/BioInf/RNAEval.hs b/BioInf/RNAEval.hs new file mode 100644 --- /dev/null +++ b/BioInf/RNAEval.hs @@ -0,0 +1,122 @@ + +-- | Given a sequence and a structure, evaluate the energy. +-- +-- TODO switch to 'SSTree [Energy]' type! + +module BioInf.RNAEval where + +import Text.Printf +import qualified Data.Vector.Unboxed as VU + +import Biobase.RNA +import Biobase.Structure +import Biobase.Structure.DotBracket +import Biobase.Types.Ring +import Biobase.Vienna +import Data.PrimitiveArray + +import BioInf.RNAFold.EnergyInt +import BioInf.RNAFold.Functions + + + +-- | Sum up a complete (sub-) tree. + +rnaEval :: ViennaTables -> String -> String -> Int +rnaEval vna pri' sec' = treeSum $ annotateWithEnergy vna pri sst where + sec = dotbracketToPairlist sec' + sst = toSSTree sec + pri = mkPrimary pri' + + + +-- | Evaluate the energy of a secondary structure tree with sequence. We abuse +-- the normal folding functions with a dummy table full of (one :: Energy). +-- This is probably slower than another method but quickly written. +-- +-- TODO this is basically crapfuck ;-) Should use the FoldFunctions directly +-- instead of that strange table. Should not xxxOpt either. + +annotateWithEnergy :: ViennaTables -> Primary -> SSTree () -> SSTree [Int] +annotateWithEnergy trnr pri t = f t where + -- extern part + f (SSExt l _ []) = SSExt l [one] [] + f (SSExt l _ xs) = + let + es = map ((\(i,j) -> externalLoopOpt trnr pri dummy i j) . treeIJ) xs + in + SSExt l es (map f xs) + -- hairpin + f (SSTree i j _ []) = SSTree i j [hairpinOpt trnr pri i j] [] + -- 1-loop + f (SSTree i j _ [x]) + -- stack + | i+1==k&&j-1==l + = SSTree i j [stackOpt trnr pri dummy i j] [f x] + | (di,dj) `VU.elem` tabbedInteriorLoopDistances i j + = SSTree i j [tabbedInteriorLoopOpt trnr pri dummy i j] [f x] + | di==0&&dj>1 + = SSTree i j [bulgeLOpt trnr pri dummy i j] [f x] + | di>1&&dj==0 + = SSTree i j [bulgeROpt trnr pri dummy i j] [f x] + | di==1&&dj>1 + = SSTree i j [interior1xnLOpt trnr pri dummy i j] [f x] + | di>1&&dj==1 + = SSTree i j [interior1xnROpt trnr pri dummy i j] [f x] + | ds+dl>30 + = error "not handling loops with size >30" + -- large interiorr loop + | otherwise = SSTree i j [largeInteriorLoopOpt trnr pri dummy i j] [f x] + where + (k,l) = treeIJ x + di = k-i-1 + dj = j-l-1 + ds = min di dj + dl = max di dj + -- multiple loop + f (SSTree i j _ xs) = + let + cl = multibranchCloseOpt trnr pri dummy dummy i j + ls = map ((\(k,l) -> multibranchIJLoopOpt trnr pri dummy k l) . treeIJ) xs + in + SSTree i j (cl:ls) (map f xs) + + dummy = fromAssocs (0,0) (n,n) one [] + n = snd $ bounds pri + + + +-- | convert an annotated tree into strings that explain each score. +-- +-- TODO this is a stupid name + +explainTree :: Primary -> SSTree [Int] -> [String] +explainTree inp sst = f sst where + -- | exterior loop + f (SSExt _ _ []) = [""] + f (SSExt _ _ xs) = this : concatMap f xs where + eners = map (\(SSTree _ _ [e] _) -> e) xs + ener = sum eners + this = printf "%-20s %6d %s" "External loop" ener (show eners) + -- | hairpin + f (SSTree i j [e] []) = [this] where + this = printf "%-20s (%4d,%4d) %4s %6d" "Hairpin loop" (i+1) (j+1) (show $ pair inp i j) e + f (SSTree i j [e] [x@(SSTree k l _ _)]) = this : f x where + this = printf "%-20s (%4d,%4d) %4s (%4d,%4d) %4s %6d" "Interior" (i+1) (j+1) (show $ pair inp i j) (k+1) (l+1) (show $ pair inp k l) e + f (SSTree i j es xs) = concatMap f xs ++ [this] where + this = printf "%-20s (%4d,%4d) %4s %6d %6d, %s" "Multi loop" (i+1) (j+1) (show $ pair inp i j) (sum es) (head es) (show $ tail es) + + + +-- | input sequence indices + +treeIJ (SSTree i j _ _) = (i,j) + + +-- | Run a sum over the tree. (foldl (+), the tree annotations) +-- +-- TODO that should go into Biobase.Structure as a generic walk over the tree + +treeSum t = f t where + f (SSExt _ es xs) = ringProductL $ es ++ map f xs + f (SSTree _ _ es xs) = ringProductL $ es ++ map f xs diff --git a/BioInf/RNAFold.hs b/BioInf/RNAFold.hs new file mode 100644 --- /dev/null +++ b/BioInf/RNAFold.hs @@ -0,0 +1,115 @@ + +-- | ViennaRNA folding based on an algebraic ring structure. This should +-- combine the goals of few lines of codes, multiple different folding +-- functions and extensibility. +-- +-- NOTE Assume that you want '-d 3' for folding with dangles. Then you can just +-- instanciate the folding functions, replacing only those functions where the +-- folding changes based on the new dangle options. +-- +-- NOTE compile with: -fno-method-sharing + +module BioInf.RNAFold where + +import Control.Monad +import Control.Monad.ST + +import Biobase.RNA +import Biobase.Types.Ring +import Data.PrimitiveArray +import Biobase.Structure + +import BioInf.RNAFold.Functions + +import Debug.Trace.Tools +import Debug.Trace + + +-- | Folding works on unboxed values of a Ring-type for which a FoldFunctions +-- instance does exist. By default, we have this for Energy values. Again, we +-- use a class as we could be interested in probabilistic backtracking or +-- something like that. + +type ResultTables a = + ( Table a -- weak structures + , Table a -- strong structures + , Table a -- exactly one component + , Table a -- one or more components + , Table a -- complete external structures + ) + +type Pairlist = [(Int,Int)] + +class (FoldFunctions a) => Fold a where + + fold :: TurnerTables a -> Primary -> (ResultTables a) + foldST :: TurnerTables a -> Primary -> ST s (ResultTables a) + backtrack :: TurnerTables a -> Primary -> (ResultTables a) -> a -> [(Secondary,a)] + + -- | We have a default instance for folding based on Rings + + fold trnr inp = runST $ foldST trnr inp + {-# INLINE fold #-} + + foldST trnr inp = do + let n = snd $ bounds inp + (weakM,weak) <- mkTable n + (strongM,strong) <- mkTable n + (externM,extern) <- mkTableWith one n + (mbr1M,mbr1) <- mkTable n + (mbrM,mbr) <- mkTable n + forM_ [n,n-1..0] $ \i -> forM_ [i,i+1..n] $ \j -> do + let pIJ = pair inp i j + when (pIJ/=vpNP&&i+30&&j do + let extUP = {-# SCC "extUP" #-} if i Int -> a -> [Pairlist] + wea i j d = let bestE = weak `unsafeIndex` (i,j) in + [ [(i,j)] + | i+3 do + putStrLn "" + forM [0..n] $ \j -> do + if j>=i + then do + let v = arr `unsafeIndex` (i,j) + if isZero v + then printf "%5s" "_i_" + else printf "%5i" (unEnergy $ arr `unsafeIndex` (i,j)) + else do + putStr " " + putStrLn "" + return () +-} diff --git a/BioInf/RNAFold/EnergyInt.hs b/BioInf/RNAFold/EnergyInt.hs new file mode 100644 --- /dev/null +++ b/BioInf/RNAFold/EnergyInt.hs @@ -0,0 +1,235 @@ +{-# LANGUAGE StandaloneDeriving #-} + +-- | Temporary hackery until all base libraries understand newtype Energy. And +-- yes, for testing too. + +module BioInf.RNAFold.EnergyInt + ( FoldFunctions (..) + , Fold (..) + ) where + +import Biobase.Types.Ring +import Biobase.RNA +import Biobase.Constants +import Biobase.Structure.DotBracket +import Biobase.Structure + +import Data.PrimitiveArray + +import BioInf.RNAFold +import BioInf.RNAFold.Functions + +-- for testing only +{- +import Biobase.Vienna.Default +import Debug.Trace.Tools +import Data.List.Split +import Text.Printf +import Control.Monad +import Biobase.Turner.Tables +-} + + +instance Ring Int where + (.+.) = min + (.*.) = (+) + neg = negate + one = 0 + zero = eInf + isZero x = x>eMax + n .^. k = n * k + (.^^.) = error "write me" + {-# INLINE (.+.) #-} + {-# INLINE (.*.) #-} + {-# INLINE neg #-} + {-# INLINE one #-} + {-# INLINE zero #-} + {-# INLINE isZero #-} + {-# INLINE (.^.) #-} + +instance FoldFunctions Int where + calcTermAU tAU p = if p/=vpCG && p/=vpGC then tAU else 0 + calcNinio maxNno nno l = min maxNno (nno * l) + calcLargeLoop l = floor $ 108.856 * log (fromIntegral l / 30) + {-# INLINE calcTermAU #-} + {-# INLINE calcNinio #-} + {-# INLINE calcLargeLoop #-} + +-- TODO detach backtrack so that all instances that use this kind of +-- backtracking can immediately use it! + +instance Fold Int where + backtrack trnr inp (weak,strong,mbr1,mbr,extern) delta = filter ((<=0) . snd) $ map f $ ext 0 n delta where + f (xs,z) = (Secondary (n+1) xs,optE+delta-z) + n = snd $ bounds inp + optE = extern!(0,n) + newD d here next = d - (next - here) + -- + -- All exterior loop decompositions + -- + ext i j d = let ehere = extern!(i,j) in + [ (x,z) -- shorter ext + | i=0 + , (x,z) <- ext (i+1) j d' + ] ++ + [ (x,z) -- loop at (i,j) + | i=0 + , (x,z) <- str i j d' + ] ++ + [ (x++y,z) + | i=0 + , (x,z') <- str i k d' + , (y,z) <- ext (k+1) j z' ++ [([],z') | z'>=0 && extern!(k+1,j)==0] + ] + -- + -- A strong stem on top of strong of weak + -- + str i j d = let ehere = strong!(i,j) in + [ ((i,j):x,z) + | i=0 + , (x,z) <- str (i+1) (j-1) d' + ] ++ + [ ((i,j):x,z) + | i=0 + , (x,z) <- wea (i+1) (j-1) d' + ] + wea i j d = let ehere = weak!(i,j) in + -- + -- A hairpin closes at (i,j) + -- + [ ([(i,j)],d') + | i=0 + ] ++ + -- + -- interior loops + -- + [ ((i,j):x,z) + | i=0 + , (x,z) <- str k l d' + ] ++ + -- + -- multibranch loops closed at (i,j) + -- + [ ((i,j):x++y,z) + | i=0 + , (x,z') <- mul (i+1) k d' + , (y,z) <- mul1 (k+1) (j-1) z' -- z' is what 'mul' left us + ] + mul i j d = let ehere = mbr!(i,j) in + -- + -- unpaired nucleotide on the J side + -- + [ (x,z) + | i=0 + , (x,z) <- mul k l d' + ] ++ + -- + -- a helix (k,j) + -- + [ (x,z) + | i=0 + , (x,z) <- str k j d' + ] ++ + -- + -- add a helix to an existing structure + -- + [ (x++y,z) + | i=0 + , (x,z') <- mul i k d' + , (y,z) <- str (k+1) j z' + ] + mul1 i j d = let ehere = mbr1!(i,j) in + -- + -- Simply the strong part in a multibranch loop + -- + [ (x,z) + | i=0 + , (x,z) <- str i j d' + ] ++ + -- + -- unpaired nucleotide on the J side + -- + [ (x,z) + | i=0 + , (x,z) <- mul1 k l d' + ] + +{- +test inp' k = + let + (_,n) = bounds inp + bts = backtrack trnr inp tbls k + inp = mkPrimary inp' + trnr = fst turner2004GH + tbls@(weak,strong,mbr1,mbr,extern) = fold trnr inp + optE = extern ! (0,n) + f x + | x > 999 = " x" + | x < -999 = "-999" + | otherwise = printf "%4d" x + g t = do + let ls = splitEvery (n+1) $ map f $ toList t + putStr " " + mapM_ (printf "%4d") [0 :: Int .. (length $ head ls) -1] + putStrLn "" + zipWithM_ (\k xs -> printf "%4d" k >> mapM_ putStr xs >> putStrLn"") [0 :: Int ..] ls + in do + print "weak" + g weak + print "strong" + g strong + print "mbr L" + g mbr + print "mbr1 R" + g mbr1 + print "extern" + g extern + print optE + putStrLn inp' + mapM_ (\(s,e) -> (putStr $ dotbracket s) >> (putStrLn $ " " ++ show e)) bts +-} diff --git a/BioInf/RNAFold/Functions.hs b/BioInf/RNAFold/Functions.hs new file mode 100644 --- /dev/null +++ b/BioInf/RNAFold/Functions.hs @@ -0,0 +1,575 @@ +{-# LANGUAGE PatternGuards #-} +{-# LANGUAGE BangPatterns #-} +{-# LANGUAGE RecordWildCards #-} + +-- | These functions are implementations of RNA secondary structure folding as +-- described in "Bompfuenewere et al., 2006, Variations on RNA folding and +-- alignment" +-- +-- We have all the facilities needed for folding with the RNA parameter of +-- Turner 2004 http://rna.urmc.rochester.edu/NNDB/turner04/ but consider only +-- "double dangles" which correspond to the ViennaRNA package option "-d2". +-- They are a bit easier to implement and are what is used for partition +-- function calculations. In addition, it seems unlikely to see a statiscally +-- relevant improvement in predication with "-d1" or "-d3". +-- +-- All functions work on an algebraic ring structure. This should make it +-- easier to implement certain functionality without having to rewrite all the +-- functions given here. Try deriving a new 'Ring' instance first and see if it +-- /just works/. +-- +-- These functions do quite well, performancewise. GHC-HEAD with "-Odph" and +-- "-fllvm" takes 14.4s, while the highly optimized viennaRNA package (the yet +-- unpublished 2.0 version) takes about 1-2s on a sequence of length 1000. +-- +-- NOTE For GHC <= 6.12.3 you should copy the default instances into your +-- instance BLA, otherwise the resulting code will be slow. Or you could just +-- wait for the new GHC to arrive! The new one produces good code without such +-- stuff. +-- +-- TODO single nucleotide bulges: +-- http://rna.urmc.rochester.edu/NNDB/turner04/bulge.html , check what Vienna +-- 2.0 does! + +module BioInf.RNAFold.Functions + ( FoldFunctions (..) + , Table + , TurnerTables + , ringSumL + , pair + , riap + , ringProductL + , tabbedInteriorLoopDistances + ) where + +import qualified Data.Vector.Unboxed as VU +import Control.Exception (assert) +import Data.List (foldl') +import qualified Data.Map as M + +import Biobase.RNA +import Biobase.Turner.Tables +import Biobase.Types.Ring +import Biobase.Vienna +import Data.PrimitiveArray +import Data.Primitive.Types + +import Debug.Trace.Tools + +type Cell = (Int,Int) +type Table a = PrimArray Cell a +type TurnerTables a = Turner2004 ViennaPair Nucleotide a + + + +-- | The folding functions. It could happen that we need different folding +-- functions with the same type, hence the class-based approach. The default +-- instance uses the usual ring methods. + +class (Show a, Ring a, VU.Unbox a, Prim a) => FoldFunctions a where + + stackOpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + stackIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + hairpinOpt :: TurnerTables a -> Primary -> Int -> Int -> a + hairpinIdx :: TurnerTables a -> Primary -> Int -> Int -> [a] + + largeInteriorLoopOpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + largeInteriorLoopIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + tabbedInteriorLoopOpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + tabbedInteriorLoopIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + bulgeLOpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + bulgeLIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + bulgeROpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + bulgeRIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + interior1xnLOpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + interior1xnLIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + interior1xnROpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + interior1xnRIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + multibranchIJLoopOpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + multibranchIJLoopIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + multibranchUnpairedJOpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + multibranchUnpairedJIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + multibranchKJHelixOpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + multibranchKJHelixIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Int,a)] + + multibranchAddKJHelixOpt :: TurnerTables a -> Primary -> Table a -> Table a -> Int -> Int -> a + multibranchAddKJHelixIdx :: TurnerTables a -> Primary -> Table a -> Table a -> Int -> Int -> [(Int,a)] + + multibranchCloseOpt :: TurnerTables a -> Primary -> Table a -> Table a -> Int -> Int -> a + multibranchCloseIdx :: TurnerTables a -> Primary -> Table a -> Table a -> Int -> Int -> [(Int,a)] + + externalLoopOpt :: TurnerTables a -> Primary -> Table a -> Int -> Int -> a + externalLoopIdx :: TurnerTables a -> Primary -> Table a -> Int -> Int -> [(Cell,a)] + + externalAddLoopOpt :: TurnerTables a -> Primary -> Table a -> Table a -> Int -> Int -> a + externalAddLoopIdx :: TurnerTables a -> Primary -> Table a -> Table a -> Int -> Int -> [(Int,a)] -- return only 'k' index + + -- | Calculate the ninio asymmetric malus. Can not be written using ring + -- functions alone as a 'min' or 'max' functions is required. + + calcNinio :: a -> a -> Int -> a + + -- | Applies a terminal AU/GU penalty, where required. + -- + -- TODO shouldn't this be just: if CG||GC then one else termAU? + + calcTermAU :: a -> ViennaPair -> a -- ^ Apply terminal AU penalty + + -- | large hairpin loops >30 require special calculations that involve + -- 'floor', rounding and other stuff that can not be handled by the Ring + -- class alone + + calcLargeLoop :: Int -> a + + -- NOTE Copy these functions into your own instance. In most cases, your are + -- now done and get optimized loops. Each function that you do not copy uses + -- the version here. This can lead to less efficient code. + -- + -- NOTE Fixed in GHC 6.13. The default instances should yield superb code! + + stackOpt trnr inp tbl i j = + VU.foldl' (.+.) zero $ stackBase trnr inp tbl i j + hairpinOpt trnr inp i j = + VU.foldl' (.+.) zero $ hairpinBase trnr inp i j + largeInteriorLoopOpt trnr inp strong i j = + VU.foldl' (.+.) zero $ largeInteriorLoopBase trnr inp strong i j + tabbedInteriorLoopOpt trnr inp strong i j = + VU.foldl' (.+.) zero $ tabbedInteriorLoopBase trnr inp strong i j + bulgeLOpt trnr inp strong i j = + VU.foldl' (.+.) zero $ bulgeLBase trnr inp strong i j + bulgeROpt trnr inp strong i j = + VU.foldl' (.+.) zero $ bulgeRBase trnr inp strong i j + interior1xnLOpt trnr inp strong i j = + VU.foldl' (.+.) zero $ interior1xnLBase trnr inp strong i j + interior1xnROpt trnr inp strong i j = + VU.foldl' (.+.) zero $ interior1xnRBase trnr inp strong i j + multibranchIJLoopOpt trnr inp strong i j = + VU.foldl' (.+.) zero $ multibranchIJLoopBase trnr inp strong i j + multibranchUnpairedJOpt trnr inp mtable i j = + VU.foldl' (.+.) zero $ multibranchUnpairedJBase trnr inp mtable i j + multibranchKJHelixOpt trnr inp strong i j = + VU.foldl' (.+.) zero $ multibranchKJHelixBase trnr inp strong i j + multibranchAddKJHelixOpt trnr inp table strong i j = + VU.foldl' (.+.) zero $ multibranchAddKJHelixBase trnr inp table strong i j + multibranchCloseOpt trnr inp m m1 i j = + VU.foldl' (.+.) zero $ multibranchCloseBase trnr inp m m1 i j + externalLoopOpt trnr inp strong i j = + VU.foldl' (.+.) zero $ externalLoopBase trnr inp strong i j + externalAddLoopOpt trnr inp strong extern i j = + VU.foldl' (.+.) zero $ externalAddLoopBase trnr inp strong extern i j + + -- NOTE copy and instanciate these functions if you have to work with many + -- candidate sequences. Otherwise you probably do not need the speed-up from + -- these functions. This stuff is for backtracking mostly as you get lists + -- of indices with attached scores. + -- + -- NOTE With GHC 6.13 we should get optimized code anyways! + + stackIdx trnr inp tbl i j = + [((i+1,j-1),stackOpt trnr inp tbl i j)] + hairpinIdx trnr inp i j = + VU.toList $ hairpinBase trnr inp i j + largeInteriorLoopIdx trnr inp strong i j = + VU.toList $ VU.zip (interiorLoopIndices i j) (largeInteriorLoopBase trnr inp strong i j) + tabbedInteriorLoopIdx trnr inp strong i j = + VU.toList $ VU.zip (tabbedInteriorLoopIndices i j) $ tabbedInteriorLoopBase trnr inp strong i j + bulgeLIdx trnr inp strong i j = + VU.toList $ VU.zip (VU.map (\k -> (i+1+k,j-1)) . uncurry VU.enumFromN $ bulgeLimit i j) $ bulgeLBase trnr inp strong i j + bulgeRIdx trnr inp strong i j = + VU.toList $ VU.zip (VU.map (\k -> (i+1,j-1-k)) . uncurry VU.enumFromN $ bulgeLimit i j) $ bulgeRBase trnr inp strong i j + interior1xnLIdx trnr inp strong i j = + VU.toList $ VU.zip (VU.map (\k -> (i+1+k,j-2)) $ uncurry VU.enumFromN $ iloop1xnLimit i j) $ interior1xnLBase trnr inp strong i j + interior1xnRIdx trnr inp strong i j = + VU.toList $ VU.zip (VU.map (\k -> (i+2,j-1-k)) $ uncurry VU.enumFromN $ iloop1xnLimit i j) $ interior1xnRBase trnr inp strong i j + multibranchIJLoopIdx trnr inp strong i j = + VU.toList $ VU.zip (VU.singleton (i,j)) $ multibranchIJLoopBase trnr inp strong i j + multibranchUnpairedJIdx trnr inp mtable i j = + VU.toList $ VU.zip (VU.singleton (i,j-1)) $ multibranchUnpairedJBase trnr inp mtable i j + multibranchKJHelixIdx trnr inp strong i j = + VU.toList $ VU.zip (uncurry VU.enumFromN $ multibranchKJHelixLimit i j) $ multibranchKJHelixBase trnr inp strong i j + multibranchCloseIdx trnr inp m m1 i j = -- TODO this is wrong! + VU.toList $ VU.zip (uncurry VU.enumFromN $ multibranchCloseLimit i j) $ multibranchCloseBase trnr inp m m1 i j + multibranchAddKJHelixIdx trnr inp table strong i j = + VU.toList $ VU.zip (uncurry VU.enumFromN $ multibranchAddKJHelixLimit i j) $ multibranchAddKJHelixBase trnr inp table strong i j + externalLoopIdx trnr inp strong i j = + VU.toList $ VU.singleton ((i,j), externalLoopOpt trnr inp strong i j) + externalAddLoopIdx trnr inp strong extern i j = + VU.toList $ VU.zip (uncurry VU.enumFromN $ externalAddLoopLimit i j) $ externalAddLoopBase trnr inp strong extern i j + + + +-- * We provide a default instance working on rings. + +-- | Simple hairpin loops. If (i,j) pairs then, first, try to do a lookup of +-- the exact sequence of the hairpin in a tabulated list. If this fails then, +-- second, try length 3 hairpins and so on. + +hairpinBase :: (FoldFunctions a) => TurnerTables a -> Primary -> Int -> Int -> VU.Vector a +hairpinBase Turner2004{..} inp i j = VU.singleton go where + go + | pIJ==vpNP || l<3 = zero + | l<=6, Just v <- s `M.lookup` hairpinLookup = v + | l==3 = (hairpinL ! l) -- .*. tAU -- apparantly not anymore according to NNDB + | l>=31 = (hairpinL ! 30) .*. (hairpinMM ! (pIJ,bI,bJ)) .*. (calcLargeLoop l) + | otherwise = {-traceVal (show (i,j,pIJ,bI,bJ,hairpinL!l,tAU,hairpinMM!(pIJ,bI,bJ))) $ -} (hairpinL ! l) .*. (hairpinMM ! (pIJ,bI,bJ)) + l = j-i-1 + s = assert (i>=0 && checkBounds inp j) $ [inp ! k | k <- [i..j-1]] + bI = inp ! (i+1) + bJ = inp ! (j-1) + pIJ = pair inp i j + tAU = calcTermAU termAU pIJ +{-# INLINE hairpinBase #-} + +-- | Extend a stem by another pair. + +stackBase :: (FoldFunctions a) => TurnerTables a -> Primary -> Table a -> Int -> Int -> VU.Vector a +stackBase Turner2004{..} inp tbl i j = VU.singleton $ go (i+1,j-1) where + pIJ = pair inp i j + go (k,l) + | pIJ==vpNP || pKL==vpNP || isZero tE + = zero + | otherwise + = tE .*. ( stack ! (pIJ,pKL)) + where + pKL = riap inp k l + tE = tbl ! (k,l) +{-# INLINE stackBase #-} + +-- | These are special cases of interior loops. Short iloops, such as 1x2 loops +-- are completely tabulated. Look each one up here. +-- +-- TODO needs 1-bulges as a special case + +tabbedInteriorLoopBase :: (Show a, FoldFunctions a) => TurnerTables a -> Primary -> Table a -> Int -> Int -> VU.Vector a +tabbedInteriorLoopBase Turner2004{..} inp strong i j = res where + res = VU.map (\(k,l) -> (strong ! (k,l)) .*. (ftabbed (k-i-1,j-l-1) (k,l))) ili + ili = tabbedInteriorLoopIndices i j + ftabbed (di,dj) (k,l) + | ds==0 && dl==1 = bulgeL!1 .*. stack!(pIJ,pKL) -- no termAU, since the helical stack continues (nndb) + | ds==1 && dl==1 = iloop1x1 ! (pIJ,pKL,bI,bJ) + | di==1 && dj==2 = iloop1x2 ! (pIJ,pKL,bI,bL,bJ) + | di==2 && dj==1 = iloop1x2 ! (pIJ,pKL,bJ,bI,bK) + | ds==2 && dl==2 = iloop2x2 ! (pIJ,pKL,bI,bK,bL,bJ) + | ds==2 && dl==3 = iloop2x3MM!(pIJ,bI,bJ) .*. iloop2x3MM ! (pKL,bL,bK) .*. iloopL ! 5 .*. ninio + where + pKL = riap inp k l + bK = inp ! (k-1) + bL = inp ! (l+1) + ds = min di dj + dl = max di dj + pIJ = pair inp i j + bI = inp ! (i+1) + bJ = inp ! (j-1) +{-# INLINE tabbedInteriorLoopBase #-} + +-- | A large number of iloops up to a total maximum loop size of 30 have to be +-- checked. There are about 300 cases for j-i>>30. In addition, this loop does +-- not like fusion very much and does many different lookups. +-- +-- TODO Any performance increase here should yield substantial improvements for +-- the overall performance of folding algorithms. +-- +-- TODO performance improvement: Split mismatch calculation into its own table +-- in the caller. Callee gets an additional argument. +-- +-- TODO didjs needs to go back into a *Limit function. + +largeInteriorLoopBase :: (FoldFunctions a) => TurnerTables a -> Primary -> Table a -> Int -> Int -> VU.Vector a +largeInteriorLoopBase Turner2004{..} inp strong i j = res where + res = VU.map (\(di,dj) -> + ijmm .*. + (strong ! (i+di,j-dj)) .*. + (iloopL ! (di+dj-2)) .*. -- -2 because di,dj is total IL length +2 + (iloopMM ! (riap inp (i+di) (j-dj), inp ! (i+di-1), inp ! (j-dj+1))) .*. + calcNinio maxNinio ninio (abs $ di-dj) + ) didjs + -- NOTE NO FUSION! :-( + -- TODO check this! + didjs = interiorLoopDistances i j + {- + didjs = traceVal (show (i,j)) $ VU.unfoldr (\(di,dj) -> + if di>maxc + then Nothing + else if di+dj>=nexc + then Just ((di,dj),(di+1,3 )) + else Just ((di,dj),(di ,dj+1)) + ) (3,5) -} + -- constant + {- + maxc = min 27 (j-i-16) + nexc = min 30 (j-i-13) + -} + ijmm = iloopMM ! (pIJ,bI,bJ) + pIJ = pair inp i j + bI = inp ! (i+1) + bJ = inp ! (j-1) +{-# INLINE largeInteriorLoopBase #-} + +-- | A bulge on the left side of the inner closing pair. 1-bulges are treated +-- as tabulated interior loops. +-- +-- (..((...))) +-- 01234567890 + +bulgeLBase :: (FoldFunctions a) => TurnerTables a -> Primary -> Table a -> Int -> Int -> VU.Vector a +bulgeLBase Turner2004{..} inp strong i j = res where + res = VU.map (\k -> + strong ! (i+1+k,j-1) .*. + bulgeL ! k .*. + calcTermAU termAU (riap inp (i+1+k) (j-1)) .*. + tAUij + ) . uncurry VU.enumFromN $ bulgeLimit i j + tAUij = calcTermAU termAU $ pair inp i j +{-# INLINE bulgeLBase #-} + +-- | A bulge on the right side of the inner closing pair. Mirroring bulgeLBase +-- +-- ((~)...) + +bulgeRBase :: (FoldFunctions a) => TurnerTables a -> Primary -> Table a -> Int -> Int -> VU.Vector a +bulgeRBase Turner2004{..} inp strong i j = res where + res = VU.map (\k -> + strong ! (i+1,j-1-k) .*. + bulgeL ! k .*. + calcTermAU termAU (riap inp (i+1) (j-1-k)) .*. + tAUij + ) . uncurry VU.enumFromN $ bulgeLimit i j + tAUij = calcTermAU termAU $ pair inp i j +{-# INLINE bulgeRBase #-} + +-- | 1xn iloops work a bit like bulges. They are more complicated because we +-- have to consider 'ninio' values and terminal mismatches. +-- +-- TODO how big an improvement would 'iloopL1xn' be with integrated 'ninio' +-- values? +-- +-- (...(~).) + +interior1xnLBase Turner2004{..} inp strong i j = res where + res = VU.map (\k -> + strong ! (i+1+k,j-2) .*. + iloopL ! (k+1) .*. + iloop1xnMM ! (riap inp (i+1+k) (j-2), inp ! (i+k), inp ! (j-1)) .*. + calcNinio maxNinio ninio (k-1) .*. + pIJmm + ) . uncurry VU.enumFromN $ iloop1xnLimit i j + pIJmm = iloop1xnMM ! (pair inp i j, inp ! (i+1), inp ! (j-1)) +{-# INLINE interior1xnLBase #-} + +-- | A mirror to the above. +-- +-- (.(~)...) + +interior1xnRBase Turner2004{..} inp strong i j = res where + res = VU.map (\k -> + strong ! (i+2,j-1-k) .*. + iloopL ! (k+1) .*. + iloop1xnMM ! (riap inp (i+2) (j-1-k), inp ! (j-k), inp ! (i+1)) .*. + calcNinio maxNinio ninio (k-1) .*. + pIJmm + ) . uncurry VU.enumFromN $ iloop1xnLimit i j + pIJmm = iloop1xnMM ! (pair inp i j, inp ! (i+1), inp ! (j-1)) +{-# INLINE interior1xnRBase #-} + +-- | Close a multibranch loop by trying to combine one element of 'm' with one +-- of 'm1'. +-- +-- <[[...]][[...]]> +-- 0123456789012345 +-- 1 + +multibranchCloseBase :: (FoldFunctions a) => TurnerTables a -> Primary -> Table a -> Table a -> Int -> Int -> VU.Vector a +multibranchCloseBase Turner2004{..} inp m m1 i j = res where + res = VU.map (\k -> + m ! (i+1,k) .*. + m1 ! (k+1,j-1) .*. + ijmm .*. + mbcl + ) . uncurry VU.enumFromN $ multibranchCloseLimit i j + ijmm = multiMM ! (pIJ,bJ,bI) + mbcl = multiOffset .*. multiHelix + pIJ = riap inp i j + bI = inp ! (i+1) + bJ = inp ! (j-1) +{-# INLINE multibranchCloseBase #-} + +-- | Adds a multibranch loop at exactly (i,j). + +multibranchIJLoopBase Turner2004{..} inp strong i j = res where + res = VU.singleton $ strong ! (i,j) .*. mbrhlx .*. mbrmm + mbrhlx = multiHelix + mbrmm = multiMM ! (pIJ,bI,bJ) -- TODO correct orientation? + pIJ = pair inp i j + bI = inp ! (i-1) + bJ = inp ! (j+1) +{-# INLINE multibranchIJLoopBase #-} + +-- | Trivial function that adds a single unpaired nucleotide within a +-- multibranch loop. + +multibranchUnpairedJBase Turner2004{..} inp mtable i j = res where + res = VU.singleton $ mtable ! (i,j-1) .*. mbrup + mbrup = multiNuc +{-# INLINE multibranchUnpairedJBase #-} + +-- | Adds a multibranch loop at (k,j), with k-i unpaired nucleotides to the +-- left of 'k'. + +multibranchKJHelixBase :: (FoldFunctions a) => TurnerTables a -> Primary -> Table a -> Int -> Int -> VU.Vector a +multibranchKJHelixBase Turner2004{..} inp strong i j = res where + res = VU.map (\k -> + multiNuc .^. (k-i) .*. + strong ! (k,j) .*. + multiHelix .*. + multiMM ! (pair inp k j, inp ! (k-1), inp ! (j+1)) + ) . uncurry VU.enumFromN $ multibranchKJHelixLimit i j +{-# INLINE multibranchKJHelixBase #-} + +-- | + +multibranchAddKJHelixBase Turner2004{..} inp table strong i j = res where + res = VU.map (\k -> + table ! (i,k) .*. + strong ! (k+1,j) .*. + multiMM ! (pair inp (k+1) j, inp ! k, inp ! (j+1)) + ) . uncurry VU.enumFromN $ multibranchAddKJHelixLimit i j +{-# INLINE multibranchAddKJHelixBase #-} + +-- | [[...]] +-- 0123456 + +externalLoopBase Turner2004{..} inp strong i j = res where + res = VU.singleton $ strong ! (i,j) .*. mm .*. tAU + n = snd $ bounds inp + pIJ = pair inp i j + bI = inp ! (i-1) + bJ = inp ! (j+1) + tAU = calcTermAU termAU pIJ + mm + | i>0&&j0 = dangle5 ! (pIJ,bI) + | j TurnerTables a -> Primary -> Table a -> Table a -> Int -> Int -> VU.Vector a +externalAddLoopBase trnr@Turner2004{..} inp strong extern i j = res where + res = VU.map (\k -> + externalLoopOpt trnr inp strong i k .*. + extern ! (k+1,j) + ) . uncurry VU.enumFromN $ externalAddLoopLimit i j +{-# INLINE externalAddLoopBase #-} + + + +-- * Helper Functions. + +-- TODO We definitely need to check that this works! + +pair :: Primary -> Int -> Int -> ViennaPair +pair inp i j + = assert (checkBounds inp i && checkBounds inp j) + $ toPair (inp `unsafeIndex` i) (inp `unsafeIndex` j) +{-# INLINE pair #-} + +riap inp i j + = assert (i>=0 && j>=0 && checkBounds inp i && checkBounds inp j) + $ toPair (inp ! j) (inp ! i) +{-# INLINE riap #-} + +ringSum :: (Ring a, VU.Unbox a) => VU.Vector a -> a +ringSum v = VU.foldl' (.+.) zero v +{- INLINE ringSum #-} + +ringSumL :: (Ring a, VU.Unbox a) => [a] -> a +ringSumL v = foldl' (.+.) zero v +{-# INLINE ringSumL #-} + +ringProduct :: (Ring a, VU.Unbox a) => VU.Vector a -> a +ringProduct v = VU.foldl' (.*.) one v +{-# INLINE ringProduct #-} + +ringProductL :: (Ring a, VU.Unbox a) => [a] -> a +ringProductL v = foldl' (.*.) one v + +-- | Explicit index generator for interior loops. Does not create indices for: +-- - bulges 0 k +-- - 1xn loops 1 k +-- - 2x3 loops 2 3, 3 2 +-- - tabulated 1 1, 1 2, 2 1, 2 2 + +interiorLoopDistances i j = + VU.concatMap ( + \d -> VU.map (\d' -> (d',d-d')) -- written as a tuple + $ VU.enumFromN 3 (d-5)) -- for each distance, all possible left/right combinations + $ VU.enumFromN 8 (min 23 (j-i-13)) -- diagonal distance or number of unpaired nucleotides -2. +{-# INLINE interiorLoopDistances #-} + +-- WTF ?! the function below is 10.000x slower than the function above! + +interiorLoopIndices :: Int -> Int -> VU.Vector (Int,Int) +interiorLoopIndices !i !j = VU.map (\(k,l) -> (i+k,j-l)) $ interiorLoopDistances i j +{-# INLINE interiorLoopIndices #-} + +-- +-- TODO filter 'ili' to accept only indices that are not too close. Does + +tabbedInteriorLoopDistances :: Int -> Int -> VU.Vector (Int,Int) +tabbedInteriorLoopDistances i j + | j-i>=8 = VU.fromList [(0,1),(1,0),(1,1),(1,2),(2,1),(2,2),(2,3),(3,2)] + | otherwise = VU.empty +{-# INLINE tabbedInteriorLoopDistances #-} + +-- | Yes, therer is the (+1,+1) and yes, this is inconsistent with the other function + +tabbedInteriorLoopIndices i j = VU.map (\(di,dj) -> (i+di+1,j-dj-1)) $ tabbedInteriorLoopDistances i j +{-# INLINE tabbedInteriorLoopIndices #-} + +-- * All limits depending on (i,j) should be here. + +-- | Bulge limitations + +bulgeLimit :: Int -> Int -> (Int,Int) +bulgeLimit i j = (2,min 29 $ j-i-9) +{-# INLINE bulgeLimit #-} + +-- | 1xn iloop limits + +iloop1xnLimit :: Int -> Int -> (Int,Int) +iloop1xnLimit i j = (3,min 26 $ j-i-10) +{-# INLINE iloop1xnLimit #-} + +-- | closing of a multibranch loop + +multibranchCloseLimit :: Int -> Int -> (Int,Int) +multibranchCloseLimit i j = (i+1,j-i-2) -- (i+7, j-i-14) +{-# INLINE multibranchCloseLimit #-} + +-- | add mb helix + +multibranchAddKJHelixLimit :: Int -> Int -> (Int,Int) +multibranchAddKJHelixLimit i j = (i+1,j-i-1) +{-# INLINE multibranchAddKJHelixLimit #-} + +-- | mb helix + +multibranchKJHelixLimit :: Int -> Int -> (Int,Int) +multibranchKJHelixLimit i j = (i,j-i) +{-# INLINE multibranchKJHelixLimit #-} + +-- | add external loop + +externalAddLoopLimit :: Int -> Int -> (Int,Int) +externalAddLoopLimit i j = (i+5,j-i-5) +{-# INLINE externalAddLoopLimit #-} diff --git a/LICENSE b/LICENSE new file mode 100644 --- /dev/null +++ b/LICENSE @@ -0,0 +1,675 @@ + GNU GENERAL PUBLIC LICENSE + Version 3, 29 June 2007 + + Copyright (C) 2007 Free Software Foundation, Inc. + 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. 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If your program is a subroutine library, you +may consider it more useful to permit linking proprietary applications with +the library. If this is what you want to do, use the GNU Lesser General +Public License instead of this License. But first, please read +. + diff --git a/RNAFold.cabal b/RNAFold.cabal new file mode 100644 --- /dev/null +++ b/RNAFold.cabal @@ -0,0 +1,64 @@ +name: RNAFold +version: 0.0.2.1 +author: Christian Hoener zu Siederdissen (Haskell), Ivo L. Hofacker et al (ViennaRNA) +maintainer: choener@tbi.univie.ac.at +copyright: Christian Hoener zu Siederdissen, 2010 +category: Bioinformatics +synopsis: RNA secondary structure prediction +license: GPL-3 +license-file: LICENSE +build-type: Simple +stability: experimental +cabal-version: >= 1.4.0 +description: + Provides the folding functions as used in the ViennaRNA + package. Here, they are in Haskell form to be used by Haskell + programs. + . + - This is a release aimed at testing Data.Vector + - Expect major performance issues with GHC < 6.13! + +library + build-depends: + base >=4 && <5, + containers, + vector >=0.7, + primitive >=0.3, + + Biobase >=0.0.2, + BiobaseTurner >=0.0.2, + BiobaseVienna >=0.0.2, + BiobaseTypes >=0.0.2, + HsTools >=0.0.1.1, + PrimitiveArray >=0.0.2 && <0.0.3 + + exposed-modules: + BioInf.RNAFold, + BioInf.RNAFold.Energy, + BioInf.RNAFold.EnergyInt, + BioInf.RNAEval, + BioInf.RNAFold.Functions + + if impl(ghc > 6.13) + ghc-options: + -Odph + -fllvm + -fforce-recomp + -funbox-strict-fields + -fllvm + -optlo-O3 + -optlc-O3 + -fdicts-cheap + -fspec-constr + -funbox-strict-fields + -funfolding-use-threshold=100 + -funfolding-creation-threshold=100 + else + ghc-options:-Odph + +-- -fno-method-sharing -- performance does not improve! +-- -fdicts-cheap +-- -fspec-constr +-- -funbox-strict-fields +-- -funfolding-use-threshold=100 +-- -funfolding-creation-threshold=100 diff --git a/Setup.hs b/Setup.hs new file mode 100644 --- /dev/null +++ b/Setup.hs @@ -0,0 +1,2 @@ +import Distribution.Simple +main = defaultMain