diff --git a/app/mergeMotifs.hs b/app/mergeMotifs.hs
new file mode 100644
--- /dev/null
+++ b/app/mergeMotifs.hs
@@ -0,0 +1,153 @@
+{-# LANGUAGE OverloadedStrings #-}
+
+import           AI.Clustering.Hierarchical hiding (drawDendrogram)
+import           Control.Monad              (forM)
+import qualified Data.ByteString.Char8      as B
+import           Data.Default.Class
+import           Data.List
+import           Data.List.Split            (splitOn)
+import           Data.Ord
+{-
+import           Diagrams.Backend.Cairo
+import           Diagrams.Plots.Dendrogram
+import           Diagrams.Prelude           (dims2D, strutX, (|||))
+-}
+import           Options.Applicative
+import           System.IO
+import           Text.Printf
+
+import           Bio.Data.Fasta
+import           Bio.Motif
+import           Bio.Motif.Alignment
+import           Bio.Motif.Merge
+import           Bio.Seq                    (toBS)
+import           Bio.Utils.Functions
+
+data Options = Options
+    { input    :: FilePath
+    , output   :: FilePath
+    , prefix   :: String
+    , thres    :: Double
+    , mode     :: String
+    , svg      :: Maybe FilePath
+    , dumpDist :: Bool
+    , gap      :: Double
+    } deriving (Show)
+
+parser :: Parser Options
+parser = Options
+     <$> argument str (metavar "INPUT")
+     <*> strOption
+           ( long "output"
+          <> short 'o'
+          <> value "merged_output.meme"
+          <> metavar "OUTPUT" )
+     <*> strOption
+           ( long "prefix"
+          <> short 'p'
+          <> value "merged"
+          <> metavar "PREFIX"
+          <> help "PREFIX that being add to the name of the merged motif" )
+     <*> option auto
+           ( long "thres"
+          <> short 't'
+          <> value 0.2
+          <> metavar "THRESHOLD"
+          <> help "two motifs that have distance belowing threshold would be merged, default is 0.2" )
+     <*> strOption
+           ( long "mode"
+          <> short 'm'
+          <> value "iter"
+          <> metavar "MODE"
+          <> help "merging algorithm, could be iter or tree, default is iter" )
+     <*> (optional . strOption)
+           ( long "svg"
+          <> metavar "SVG"
+          <> help "draw merging tree in svg format, only available in tree mode" )
+     <*> switch
+           ( long "dump-dist"
+          <> help "output pairwise distances of original motifs without performing any merging" )
+     <*> option auto
+           ( long "gap"
+          <> short 'g'
+          <> value 0.15
+          <> metavar "GAP_PENALTY"
+          <> help "gap penalty" )
+
+-- | Return pairwise distances
+pairDistance :: [Motif] -> [(B.ByteString, B.ByteString, Double)]
+pairDistance ms = map (\(a,b) -> (_name a, _name b, fst $ alignment (_pwm a) (_pwm b))) $ comb ms
+
+treeMerge :: Double -> String -> [Motif] -> Double -> ([Motif], Dendrogram Motif)
+treeMerge th pre ms gap = (zipWith f [0::Int ..] $ map merge $ tree `cutAt` th, tree)
+  where
+    f i (suffix, pwm) = Motif ((B.pack $ pre ++ "_" ++ show i ++ "_" ++ show (toIUPAC pwm))
+                                 `B.append` "("
+                                 `B.append` suffix
+                                 `B.append` ")" ) pwm
+    merge tr = ( B.intercalate "+" $ map _name $ flatten tr
+               , dilute $ mergeTreeWeighted align tr)
+    tree = buildTree align ms
+    align = alignmentBy jsd $ quadPenal gap
+{-# INLINE treeMerge #-}
+
+getSuffix :: String -> String
+getSuffix = last . splitOn "."
+
+defaultMain :: Options -> IO ()
+defaultMain (Options inFl outFl pre th m svg dump gap) = do
+    let readMotif = case getSuffix inFl of
+                        "fasta" -> readFasta'
+                        _ -> readMEME
+        writeMotif = case getSuffix outFl of
+                        "fasta" -> writeFasta
+                        _ -> \fl x -> writeMEME fl x def
+    motifs <- readMotif inFl
+
+    if dump
+        then
+            mapM_ (\(a,b,c) -> B.putStrLn $ B.intercalate "\t" [a, b, B.pack $ show c]) $ pairDistance motifs
+        else do
+            let motifNumber = length motifs
+
+            hPutStrLn stderr $ printf "Merging Mode: %s" m
+            hPutStrLn stderr $ printf "Read %d motifs" motifNumber
+
+            motifs' <- case m of
+                "tree" -> do
+                    let (newMotifs, tree) = treeMerge th pre motifs gap
+                        fn x = B.unpack (_name x) ++ ": " ++ B.unpack (toBS $ toIUPAC $ _pwm x)
+
+                    case svg of
+                        Just fl -> do
+                            {-
+                            let w = 80
+                                h = 5 * fromIntegral motifNumber
+                            renderCairo fl (dims2D (10*w) (10*h)) $ drawDendrogram w h th tree fn ||| strutX 40
+                            -}
+                            return newMotifs
+                        _ -> return newMotifs
+                "iter" -> do
+                    let rs = iterativeMerge (alignmentBy jsd (quadPenal gap)) th motifs
+                    forM rs $ \(nm, pwm, ws) -> do
+                        let pwm' = dilute (pwm, ws)
+                        return $ Motif (B.intercalate "+" nm) pwm
+                 -- _ -> error "Unkown mode!"
+
+            hPutStrLn stderr $ printf "Write %d motifs" (length motifs')
+
+            writeMotif outFl motifs'
+{-# INLINE defaultMain #-}
+
+comb :: [a] -> [(a,a)]
+comb (y:ys) = zip (repeat y) ys ++ comb ys
+comb _ = []
+{-# INLINE comb #-}
+
+main :: IO ()
+main = execParser opts >>= defaultMain
+  where
+    opts = info (helper <*> parser)
+            ( fullDesc
+           <> header (printf "Merge similar PWMs, version %s" v))
+    v = "0.2.0" :: String
diff --git a/app/mkindex.hs b/app/mkindex.hs
new file mode 100644
--- /dev/null
+++ b/app/mkindex.hs
@@ -0,0 +1,11 @@
+module Main where
+
+import Bio.Seq.IO (mkIndex)
+import Shelly
+import qualified Data.Text as T
+import System.Environment
+
+main :: IO ()
+main = do [inDir, outF] <- getArgs
+          fls <- shelly . lsT . fromText . T.pack $ inDir
+          mkIndex (map T.unpack fls) outF
diff --git a/app/viewSeq.hs b/app/viewSeq.hs
new file mode 100644
--- /dev/null
+++ b/app/viewSeq.hs
@@ -0,0 +1,15 @@
+module Main where
+
+import qualified Data.ByteString.Char8 as B
+import Bio.Seq
+import Bio.Seq.IO
+import System.Environment
+
+main :: IO ()
+main = do
+    [fl, chr, start, end] <- getArgs
+    g <- pack fl
+    s <- getSeqs g [(B.pack chr, read start, read end)] :: IO [Either String (DNA IUPAC)]
+    case head s of
+        Left err -> error err
+        Right x -> B.putStrLn . toBS $ x
diff --git a/bioinformatics-toolkit.cabal b/bioinformatics-toolkit.cabal
--- a/bioinformatics-toolkit.cabal
+++ b/bioinformatics-toolkit.cabal
@@ -2,7 +2,7 @@
 -- further documentation, see http://haskell.org/cabal/users-guide/
 
 name:                bioinformatics-toolkit
-version:             0.1.1
+version:             0.2.0
 synopsis:            A collection of bioinformatics tools
 description:         A collection of bioinformatics tools
 license:             MIT
@@ -13,7 +13,7 @@
 category:            Bio
 build-type:          Simple
 extra-source-files:  README.md
-cabal-version:       >=1.10
+cabal-version:       >=1.18
 data-files:
     data/*.fasta
 
@@ -26,13 +26,14 @@
     Bio.ChIPSeq.FragLen
     Bio.Data.Bam
     Bio.Data.Bed
-    Bio.Data.BigWig
+--    Bio.Data.BigWig
     Bio.Data.Fasta
     Bio.GO
     Bio.GO.Parser
     Bio.GO.GREAT
     Bio.Motif
     Bio.Motif.Alignment
+    Bio.Motif.Merge
     Bio.Motif.Search
     Bio.RealWorld.BioGRID
     Bio.RealWorld.ENCODE
@@ -49,19 +50,19 @@
   -- other-modules:
   -- other-extensions:
   build-depends:
-      base >=4.0 && <5.0
+      base >=4.8 && <5.0
     , aeson
     , aeson-pretty
-    , bbi
+--    , bbi
     , binary
     , bytestring >=0.10
     , bytestring-lexing >=0.5
+    , clustering
     , colour
-    , conduit
+    , conduit-combinators
     , containers >=0.5
     , data-default-class
     , double-conversion
-    , clustering
     , http-conduit
     , hexpat
     , matrices >=0.4.3
@@ -78,51 +79,51 @@
     , vector
     , vector-algorithms
     , word8
-    , IntervalMap >=0.3
+    , IntervalMap >=0.5.0.0
 
   default-language:    Haskell2010
 
 executable mkindex
-  hs-source-dirs:   exe
+  hs-source-dirs:   app
   main-is: mkindex.hs
   build-depends:
-      base >=4.6 && <5.0
+      base >=4.8 && <5.0
     , bioinformatics-toolkit
     , shelly
     , text
   default-language:    Haskell2010
 
 executable viewSeq
-  hs-source-dirs:   exe
+  hs-source-dirs:   app
   main-is: viewSeq.hs
   build-depends:
-      base >=4.6 && <5.0
+      base >=4.8 && <5.0
     , bioinformatics-toolkit
     , bytestring
   default-language:    Haskell2010
 
---executable mergeMotifs
---  hs-source-dirs:   exe
---  main-is: mergeMotifs.hs
---  build-depends:
---      base >=4.6 && <5.0
---    , bioinformatics-toolkit
---    , bytestring
---    , clustering
---    , data-default-class
---    , split
---    , optparse-applicative
+executable mergeMotifs
+  hs-source-dirs:   app
+  main-is: mergeMotifs.hs
+  build-depends:
+      base >=4.6 && <5.0
+    , bioinformatics-toolkit
+    , bytestring
+    , clustering
+    , data-default-class
+    , split
+    , optparse-applicative
 --    , haskell-plot >=0.2.0.0
 --    , diagrams-cairo >=1.3
 --    , diagrams-lib >=1.3
---  default-language:    Haskell2010
+  default-language:    Haskell2010
 
 benchmark bench
   type: exitcode-stdio-1.0
   main-is: benchmarks/bench.hs
   default-language:    Haskell2010
   build-depends:
-      base >=4.6 && <5.0
+      base >=4.8 && <5.0
     , bioinformatics-toolkit
     , random
     , criterion
@@ -139,6 +140,7 @@
   main-is: test.hs
   other-modules:
       Tests.Bed
+    , Tests.Bam
     , Tests.ChIPSeq
     , Tests.Motif
     , Tests.Seq
@@ -155,6 +157,7 @@
     , tasty-hunit
     , bioinformatics-toolkit
     , conduit
+    , conduit-combinators
     , unordered-containers
     , mtl
 
diff --git a/data/1.fasta b/data/1.fasta
new file mode 100644
--- /dev/null
+++ b/data/1.fasta
@@ -0,0 +1,30 @@
+MEME version 4
+
+ALPHABET= ACGT
+
+strands: + -
+
+Background letter frequencies
+A 0.25 C 0.25 G 0.25 T 0.25
+
+MOTIF tree0.2_0_GGAKATWATMTC
+letter-probability matrix: alength= 4 w= 12 nsites= 1 E= 0
+ 0.001 0.001 0.997 0.001
+ 0.001 0.003 0.995 0.001
+ 0.997 0.001 0.001 0.001
+ 0.001 0.001 0.474 0.524
+ 0.997 0.001 0.001 0.001
+ 0.997 0.001 0.001 0.001
+ 0.25 0.25 0.25 0.25
+ 0.25 0.25 0.25 0.25
+
+MOTIF tree0.2_1_CTCCCTAAAATG
+letter-probability matrix: alength= 4 w= 12 nsites= 1 E= 0
+ 0.25 0.25 0.25 0.25
+ 0.25 0.25 0.25 0.25
+ 0.001 0.001 0.997 0.001
+ 0.001 0.003 0.995 0.001
+ 0.997 0.001 0.001 0.001
+ 0.001 0.001 0.474 0.524
+ 0.997 0.001 0.001 0.001
+ 0.997 0.001 0.001 0.001
diff --git a/data/motifs.fasta b/data/motifs.fasta
deleted file mode 100644
--- a/data/motifs.fasta
+++ /dev/null
@@ -1,1000 +0,0 @@
->H3k27me3_1
-0.606774 0.016294 0.13288 0.244052
-0.036584 0.220797 0.734391 0.008228
-0.007188 0.022713 0.970099 0
-0.880368 0.00655 0 0.113082
-0.022933 0.370323 0.588998 0.017746
-0.03691 0.064294 0.898796 0
-0.036733 0.847295 0.05167 0.064303
-0.035226 0.936624 0.009752 0.018398
-0.038192 0 0.961808 0
-0.86875 0.034126 0 0.097123
-
->H3k27me3_2
-0.027569 0.836023 0.098072 0.038336
-0.066084 0.796257 0.084066 0.053593
-0.053722 0.101794 0.788767 0.055717
-0.027115 0.851343 0.096392 0.02515
-0.057722 0.783978 0.10818 0.05012
-0.036805 0.14198 0.733304 0.087911
-0.015704 0.891019 0.070288 0.022988
-0.053043 0.784949 0.107395 0.054612
-0.050031 0.135567 0.737444 0.076958
-
->H3k27me3_3
-0.057438 0.817772 0.062863 0.061926
-0.106073 0.731281 0.120311 0.042334
-0.030535 0.018387 0.88613 0.064948
-0.030741 0.879362 0.049584 0.040314
-0.015252 0.788258 0.137458 0.059032
-0.10851 0.817518 0.033884 0.040088
-0.036468 0.01862 0.816303 0.128608
-0.009933 0.730805 0.207425 0.051837
-0.03466 0.800567 0.091489 0.073284
-
->H3k27me3_4
-0.282 0.275 0.302 0.141
-0.278 0.207 0.301 0.215
-0.646 0.04 0.091 0.223
-0.053 0.707 0.062 0.178
-0.09 0.09 0.693 0.127
-0.224 0.462 0.078 0.236
-0.178 0.053 0.57 0.199
-0.128 0.646 0.086 0.14
-0.04 0.186 0.608 0.166
-0.165 0.16 0.535 0.14
-0.228 0.24 0.279 0.253
-0.242 0.293 0.287 0.179
-
->H3k27me3_5
-0 0 0.951071 0.048929
-0 0 0 1
-0.627359 0.095216 0.049576 0.227849
-0 0.024042 0.580115 0.395842
-0.028143 0.971857 0 0
-0 0.014661 0 0.985339
-0.005613 0.019322 0.975064 0
-
->H3k27me3_6
-0.057628 0.768463 0.028808 0.145102
-0.004678 0.995322 0 0
-0.84383 0.054519 0.070009 0.031642
-0.013305 0.045173 0.836304 0.105218
-0.380657 0.550477 0.068865 0
-0.020839 0.91739 0.061771 0
-0.112091 0.040031 0.815495 0.032383
-0 0.682259 0.274559 0.043182
-0 0.058162 0.941838 0
-
->H3k27me3_7
-0.065186 0.381721 0.450664 0.102429
-0.177422 0.633336 0.1695 0.019743
-0.022156 0.928003 0.020696 0.029145
-0.00933 0.028055 0.914386 0.048229
-0.851568 0.036666 0.030642 0.081124
-0.195895 0.028873 0.743155 0.032077
-0.030455 0.668012 0.089362 0.212171
-0.05471 0.033974 0.90287 0.008447
-0 0.97092 0.018842 0.010238
-0.00204 0.035057 0.82321 0.139693
-0.189764 0.229928 0.536579 0.043729
-
->H3k27me3_8
-0.221868 0.141908 0 0.636224
-0.20352 0.751002 0.020317 0.025161
-0.201842 0.316531 0.384956 0.096671
-0.048677 0.037684 0.872111 0.041527
-0.165474 0.038256 0.665057 0.131213
-0.072201 0.842767 0.019817 0.065215
-0.146093 0.028365 0.825541 0
-0.058821 0.802287 0.041842 0.09705
-0.144684 0.067184 0.750231 0.037901
-0.08984 0.805021 0.040715 0.064423
-0.839481 0.054112 0.059255 0.047152
-0 0.934819 0.03832 0.026862
-
->H3k27me3_9
-0.167882 0.520832 0.275958 0.035328
-0.186393 0.813607 0 0
-0.314604 0 0.670072 0.015324
-0 0.926258 0.069624 0.004118
-0 0.920505 0.079495 0
-0 0.770725 0.040069 0.189206
-0.009384 0.020025 0.970591 0
-0.861156 0.05519 0 0.083654
-0 0.035565 0.964435 0
-
->H3k27me3_10
-0 0 1 0
-0.887436 0.050346 0.010708 0.05151
-0.045451 0.004784 0.935866 0.013899
-0.026369 0.089881 0.88375 0
-0.983318 0.016682 0 0
-0 0.25089 0 0.74911
-0 0.675374 0.324626 0
-0 0 0.932479 0.067521
-0 0.932663 0 0.067337
-
->H3k27me3_11
-0.224457 0.725389 0.036157 0.013997
-0.046447 0 0.953553 0
-0.063569 0.918074 0.016276 0.002081
-0.812151 0 0.15863 0.029219
-0 0.842258 0 0.157742
-0.022002 0.020292 0.957706 0
-0.081601 0.82946 0.049243 0.039696
-0.044825 0.029444 0.819662 0.10607
-0 0.64916 0.03712 0.31372
-
->H3k27me3_12
-0.001305 0.985088 0.006533 0.007073
-0.030098 0.137468 0.031795 0.800639
-0.000641 0.947329 0.050635 0.001395
-0.708868 0.138382 0.048309 0.104441
-0.01663 0.177837 0.764505 0.041027
-0.019051 0.285605 0.03219 0.663153
-0.018078 0.053027 0.222331 0.706565
-0.009817 0.183174 0.02938 0.77763
-0.003817 0.963035 0.008029 0.025119
-0.008196 0.944821 0.003097 0.043885
-0.190656 0.284665 0.035054 0.489625
-0.007074 0.235282 0.708158 0.049486
-
->H3k27me3_13
-0.201553 0.786786 0.011662 0
-0.056087 0.822486 0.109843 0.011584
-0.025109 0.017029 0.957862 0
-0.048154 0.648583 0.029026 0.274237
-0 0.034838 0.955107 0.010055
-0.887569 0 0 0.112431
-0.00911 0.869571 0.116133 0.005186
-0.224225 0.524249 0.027113 0.224412
-0.100124 0.825883 0.056214 0.017778
-
->H3k27me3_14
-0.041 0.778533 0.042471 0.137996
-0.123524 0.756722 0.072554 0.0472
-0.000288 0.917455 0.082257 0
-0.775207 0.042638 0.03771 0.144445
-0.006508 0.054321 0.897 0.042171
-0.070115 0.848451 0.062052 0.019382
-0.013144 0.870986 0.107971 0.007899
-0.147341 0.025824 0.057405 0.76943
-0.008468 0.74943 0.196232 0.04587
-0.078526 0.383205 0.380263 0.158006
-0.210026 0.546259 0.16247 0.081245
-0.13618 0.285236 0.265129 0.313454
-
->H3k27me3_15
-0 0.923859 0.049081 0.027059
-0.030773 0.054177 0.89204 0.02301
-0.03561 0.710155 0 0.254236
-0.028979 0.845767 0.059673 0.06558
-0.01451 0.083137 0.902353 0
-0.016964 0.039033 0.495903 0.448099
-0.153442 0 0.821859 0.024698
-0.003027 0.016753 0.895212 0.085008
-0.827733 0.10104 0.033935 0.037292
-
->H3k27me3_16
-0.102 0.672 0.131 0.095
-0.093 0.096 0.679 0.132
-0.077 0.744 0.095 0.084
-0.097 0.13 0.118 0.655
-0.061 0.728 0.117 0.094
-0.097 0.696 0.095 0.112
-0.096 0.117 0.694 0.093
-0.111 0.091 0.713 0.085
-0.109 0.087 0.725 0.079
-0.113 0.091 0.694 0.102
-
->H3k27me3_17
-0.001 0.898 0.1 0.001
-0.001 0.001 0.997 0.001
-0.219 0.001 0.543 0.237
-0.164 0.001 0.674 0.161
-0.098 0.001 0.9 0.001
-0.116 0.001 0.882 0.001
-0.001 0.097 0.901 0.001
-0.001 0.001 0.997 0.001
-
->H3k27me3_18
-0.030606 0.828389 0.056442 0.084563
-0.111882 0.773152 0.089181 0.025784
-0.094575 0.059243 0.746942 0.09924
-0 0.954034 0.025967 0.019999
-0.043145 0.011024 0.74285 0.202981
-0.042381 0.028283 0.791169 0.138166
-0.05721 0.033757 0.878238 0.030795
-0.727749 0.098964 0 0.173287
-0.125497 0.038022 0.795772 0.040709
-
->H3k27me3_19
-0.102 0.084 0.712 0.102
-0.104 0.675 0.115 0.106
-0.095 0.097 0.705 0.103
-0.107 0.111 0.672 0.11
-0.105 0.09 0.102 0.703
-0.089 0.105 0.111 0.695
-0.11 0.108 0.105 0.677
-0.711 0.088 0.105 0.096
-0.713 0.108 0.107 0.072
-0.738 0.082 0.094 0.086
-
->H3k27me3_20
-0.051681 0.823102 0.058038 0.06718
-0.04667 0.806892 0.04487 0.101568
-0.086563 0.079983 0.716515 0.116939
-0.003699 0.809887 0.142735 0.04368
-0.038984 0.031869 0.817261 0.111886
-0.049845 0.892505 0.051869 0.005781
-0.11927 0.072643 0.0486 0.759487
-0.010058 0.048014 0.901099 0.040829
-0.064414 0.721648 0.116811 0.097128
-
->H3k27me3_21
-0.012404 0.145428 0.788559 0.05361
-0 0.987277 0 0.012723
-0.020786 0.03082 0.877875 0.070519
-0.004679 0.016532 0.812235 0.166554
-0.052582 0.039503 0.671561 0.236354
-0.163953 0.656069 0.01867 0.161309
-0.059608 0.148713 0.084866 0.706813
-0 0.985746 0.010521 0.003733
-0 0.859543 0.092123 0.048335
-
->H3k27me3_22
-0 0 0 1
-0.012876 0 0.980217 0.006906
-0.03792 0.004296 0.957784 0
-0.053699 0 0.946301 0
-0.94609 0.013517 0 0.040393
-0.128065 0.022685 0.84925 0
-0.111168 0.053925 0.043403 0.791504
-0.473428 0.497362 0.019718 0.009492
-
->H3k27me3_23
-0.035442 0.762288 0.041676 0.160594
-0.109849 0.043451 0.732698 0.114002
-0.077134 0.893037 0.008684 0.021145
-0.185442 0.038754 0.747105 0.028699
-0.06961 0.026831 0.817424 0.086134
-0.019668 0.030807 0.911916 0.037608
-0.097454 0.082235 0.705757 0.114554
-0.8089 0.044458 0.086125 0.060517
-0.13045 0.857966 0.011584 0
-
->H3k27me3_24
-0.037785 0.189216 0 0.772999
-0 1 0 0
-0 1 0 0
-0.036078 0 0.886905 0.077017
-0 0.124555 0.83069 0.044755
-0.015533 0 0.984467 0
-0.121058 0 0.067534 0.811408
-0 0.058872 0.879147 0.06198
-0.009905 0.87634 0 0.113755
-
->H3k27me3_25
-0.761215 0.084224 0 0.154562
-0 0.095532 0.904468 0
-0.091023 0.047337 0.83473 0.02691
-0.136245 0.016155 0.726058 0.121543
-0.02227 0.026057 0.859822 0.091851
-0.206104 0.269121 0.521486 0.003288
-0.029464 0.841482 0.031084 0.097971
-0.026948 0 0.952093 0.020958
-0.016535 0.907432 0.049712 0.026321
-
->H3k27me3_26
-0.049624 0.873643 0.028015 0.048718
-0.252582 0.665923 0.025361 0.056133
-0.045616 0.891054 0.018 0.04533
-0.030306 0.009068 0.941617 0.019009
-0.008131 0.031025 0.950739 0.010106
-0.849258 0.045227 0.042674 0.062842
-0.03959 0.891805 0.053673 0.014932
-0.323839 0.048021 0.609607 0.018533
-0.006592 0.972602 0.005527 0.015279
-
->H3k27me3_27
-0.088867 0.8221 0.044076 0.044957
-0.042556 0.797011 0.143696 0.016737
-0.009207 0.88788 0.087999 0.014914
-0.781947 0.038703 0.126388 0.052963
-0.012945 0.030843 0.855373 0.100839
-0.034445 0.812728 0.144246 0.008581
-0.131431 0.047159 0.066305 0.755105
-0.00705 0.819166 0.161102 0.012682
-0.094177 0.720151 0.081899 0.103773
-0.184854 0.39469 0.329478 0.090978
-0.058616 0.370292 0.535453 0.035639
-0.006249 0.262678 0.726294 0.004778
-
->H3k27me3_28
-0.237059 0.085644 0 0.677297
-0.036429 0 0.74756 0.216011
-0 0.685895 0 0.314105
-0 0.990671 0.009329 0
-0.822357 0.086003 0.09164 0
-0 0.938432 0.061568 0
-0 0.557102 0 0.442898
-0 0.961506 0.038494 0
-0.916383 0 0.083617 0
-
->H3k36me3_1
-0.412511 0.030259 0.427783 0.129446
-0.916679 0.062226 0.01331 0.007785
-0.004271 0.008974 0.001146 0.985609
-0.00015 0.88472 0.003421 0.111709
-0.642004 0.002774 0.3484 0.006822
-0 0.983702 0 0.016298
-0.002246 0.232527 0.025492 0.739734
-0.001817 0.047181 0.00822 0.942782
-0.018288 0.012159 0.969052 0.000501
-0.972232 0.005142 0.012633 0.009994
-
->H3k36me3_2
-0.003553 0.962184 0.021214 0.013049
-0.010587 0.007471 0.007149 0.974793
-0.056903 0.002065 0.940403 0.00063
-0.029341 0.127911 0.012368 0.83038
-0.785189 0.080043 0.121928 0.01284
-0.714592 0.118011 0.145336 0.022061
-0.004274 0.118391 0.008479 0.868856
-0.008939 0.958376 0.01189 0.020794
-0.008619 0.934744 0.005097 0.05154
-0.164029 0.677445 0.093925 0.064601
-
->H3k36me3_3
-0.06728 0.003463 0.928563 0.000695
-0.042745 0.00829 0.002542 0.946423
-0.7652 0.083152 0.151537 0.000111
-0.752591 0.056491 0.174836 0.016082
-0.037203 0.041632 0.061134 0.860031
-0.009265 0.953082 0.018104 0.019549
-0.012137 0.928617 0.003188 0.056058
-0 0.953697 0.002099 0.044204
-0.988637 0.00156 0.008536 0.001267
-
->H3k36me3_4
-0.002921 0.975182 0.019283 0.002614
-0.389395 0.000673 0.019729 0.590203
-0.009176 0.003798 0.9865 0.000525
-0.0083 0.017494 0.966122 0.008083
-0.860109 0.077394 0.019347 0.04315
-0.024896 0.006935 0.96517 0.002999
-0.02811 0.022893 0.022859 0.926139
-0.031456 0.018898 0.528436 0.42121
-0.023575 0.914853 0.018795 0.042778
-0.456293 0 0.543707 0
-
->H3k36me3_5
-0.040974 0.015834 0.806165 0.137026
-0.000482 0.951344 0.005066 0.043108
-0.003276 0.952792 0.001466 0.042467
-0.015066 0.000847 0.008931 0.975156
-0.001057 0.962622 0.011316 0.025005
-0.008398 0.962897 0.007132 0.021573
-0.012183 0.890617 0.008478 0.088722
-0.732122 0.079602 0.16567 0.022606
-0.720023 0.13387 0.126859 0.019248
-
->H3k36me3_6
-0.000676 0.978498 0.018077 0.002749
-0.007447 0.021657 0.001438 0.969458
-0.02526 0.005255 0.963432 0.006053
-0.07272 0.003095 0.908564 0.015622
-0.024316 0.245887 0.724174 0.005622
-0.023618 0.808526 0.050988 0.116868
-0.780085 0.03254 0.176005 0.01137
-0.838104 0.073281 0.055882 0.032733
-0.018699 0.895298 0.064705 0.021298
-0.882149 0.01584 0.017592 0.084419
-
->H3k36me3_7
-0.932231 0.007543 0.057018 0.003208
-0.033304 0.038088 0.898609 0.029999
-0.020811 0.019055 0.953415 0.00672
-0.972527 0.020669 0.004139 0.002664
-0.020958 0.000775 0.978098 0.000169
-0.720805 0.014303 0.264037 0.000855
-0.974348 0.006919 0.010349 0.008383
-0.03354 0.013051 0.120669 0.832741
-0.006406 0.879915 0.00736 0.10632
-0.309651 0.049391 0.629367 0.01159
-0.038361 0.93892 0 0.022719
-0 0.004613 0.003955 0.991433
-
->H3k36me3_8
-0.008194 0.049311 0.015898 0.926597
-0.090861 0.564763 0.035339 0.309037
-0.178644 0.025419 0.794867 0.001069
-0.952999 0.030655 0.002213 0.014134
-0.006241 0.038922 0.951929 0.002908
-0.870211 0.060451 0.062974 0.006364
-0.01117 0.937917 0.005864 0.045049
-0.124574 0.853348 0.009747 0.012331
-0.925735 0.044778 0.020247 0.00924
-
->H3k36me3_9
-0.904352 0.033657 0.020888 0.041103
-0.025522 0.316953 0.654973 0.002552
-0.60872 0.051391 0.110131 0.229758
-0.02877 0.868779 0.089199 0.013253
-0.011526 0.964667 0.011639 0.012168
-0.933367 0.006451 0.006633 0.053549
-0.008692 0.020278 0.96526 0.00577
-0.008984 0.884634 0.094607 0.011775
-0.018634 0.916658 0.007392 0.057316
-0.172494 0.135223 0.23282 0.459462
-
->H3k36me3_10
-0.919685 0.012377 0.043492 0.024446
-0.07339 0.006966 0.901569 0.018075
-0.02117 0.041673 0.927641 0.009516
-0.039129 0.872396 0.042334 0.046141
-0.106186 0.120244 0.071998 0.701573
-0.038702 0.053091 0.907428 0.00078
-0.686984 0.061773 0.191688 0.059555
-0.212205 0.012475 0.759124 0.016196
-0.052953 0.044408 0.887356 0.015283
-
->H3k36me3_11
-0.919696 0.003455 0.049962 0.026887
-0.694257 0.264183 0.018576 0.022983
-0.009563 0.960945 0.002416 0.027076
-0.024854 0.004572 0.001935 0.968639
-0.01113 0.925409 0.014847 0.048614
-0.000416 0.958359 0.033243 0.007983
-0.046887 0.036202 0.008047 0.908863
-0.025582 0.00419 0.968692 0.001536
-0.813344 0.020974 0.142688 0.022994
-
->H3k36me3_12
-0.000105 0.991402 0.007214 0.001279
-0.00254 0.001259 0.000272 0.995929
-0.001064 0.992408 0.004293 0.002235
-0 0.010284 0.002637 0.987079
-0.949042 0.024663 0.017051 0.009244
-0.006653 0.987799 0.000557 0.00499
-0.230691 0.031043 0.008711 0.729555
-0.944702 0.008495 0.037851 0.008953
-0.90633 0.089644 0.001487 0.002539
-0.854696 0.130088 0.009795 0.005422
-
->H3k36me3_13
-0.00307 0.670061 0.000684 0.326185
-0.248509 0.001502 0.728177 0.021812
-0 0.985736 0 0.014264
-0 0 0.050282 0.949718
-0.000754 0.003429 0.011552 0.984265
-0.019913 0 0.979321 0.000766
-0.989083 0.004283 0.004944 0.00169
-0.992549 0.000812 0.005428 0.001212
-0 0.989639 0 0.010361
-0.004247 0.932986 0.048163 0.014604
-
->H3k36me3_14
-0.81174 0.019665 0.140907 0.027687
-0.080253 0.047986 0.097927 0.773834
-0.019734 0.914965 0.03224 0.033061
-0.045194 0.878126 0.026402 0.050277
-0.008454 0.956647 0.005975 0.028924
-0.928903 0.015369 0.02804 0.027687
-0.031443 0.073964 0.883553 0.01104
-0.006821 0.844347 0.128921 0.019911
-0.685602 0.075362 0.010203 0.228833
-0.162236 0.589332 0.228093 0.020339
-
->H3k36me3_15
-0.882402 0.033396 0.068885 0.015316
-0.830804 0.119149 0.04082 0.009227
-0.831424 0.037807 0.111478 0.019291
-0.048734 0.195949 0.754178 0.001138
-0.035274 0.016171 0.019563 0.928992
-0.037379 0.136887 0.820595 0.005138
-0.01301 0.923482 0.038584 0.024925
-0.046365 0.003483 0.001277 0.948875
-0.031845 0.001009 0.959658 0.007488
-
->H3k36me3_16
-0.22142 0.661973 0.052298 0.064309
-0.065963 0.723622 0.168499 0.041916
-0.672261 0.085026 0.135066 0.107646
-0.047246 0.166603 0.767594 0.018557
-0.016197 0.846993 0.012173 0.124637
-0.058715 0.772271 0.146818 0.022196
-0.062856 0.034337 0.136185 0.766622
-0.079586 0.143703 0.67515 0.101561
-0.047924 0.130594 0.775836 0.045647
-
->H3k36me3_17
-0.05465 0.033561 0.893461 0.018328
-0.084497 0.018699 0.88612 0.010684
-0.006624 0.016727 0.958797 0.017852
-0.007727 0.018333 0.002741 0.971199
-0.02039 0.170582 0.042949 0.76608
-0.003044 0.009809 0.00288 0.984266
-0.000433 0.920931 0.000922 0.077714
-0.673304 0.014996 0.159279 0.152421
-0.001107 0.990042 0.004468 0.004383
-0.019357 0.577936 0.006314 0.396393
-
->H3k36me3_18
-0 0.973926 0.007321 0.018753
-0.950074 0.005704 0.007072 0.03715
-0.010533 0.040159 0.928987 0.020321
-0.028786 0.880034 0.034524 0.056655
-0.017522 0.033617 0.016692 0.932169
-0.796171 0.092793 0.062744 0.048293
-0.069759 0.915717 0.001579 0.012946
-0.064312 0.01818 0.006552 0.910956
-0.013023 0.635436 0.094048 0.257493
-0.506109 0.152271 0.317617 0.024004
-
->H3k36me3_19
-0.009099 0.768966 0.174896 0.04704
-0.005736 0.949914 0.009358 0.034992
-0.008481 0.699832 0.004802 0.286885
-0.637203 0.048626 0.304202 0.00997
-0.700166 0.085486 0.129955 0.084392
-0.005993 0 0.994007 0
-0.022416 0.026348 0.030887 0.920349
-0.899538 0.006936 0.040875 0.052651
-0.034571 0.027553 0.922674 0.015202
-0.012281 0.974302 0.003413 0.010005
-
->H3k36me3_20
-0 0.954634 0.020821 0.024545
-0.959916 0.010502 0.01948 0.010102
-0 0.964407 0.004213 0.031381
-0.006762 0.006861 0.034083 0.952295
-0.001316 0.022362 0.188212 0.78811
-0.004588 0.039112 0.052845 0.903455
-0.097028 0.008342 0.887728 0.006902
-0.035378 0.005466 0.920855 0.038301
-0.062433 0.039808 0.892798 0.004961
-
->H3k36me3_21
-0.859214 0.02391 0.093131 0.023745
-0.011283 0.67469 0.030872 0.283154
-0.222336 0.011084 0.646888 0.119693
-0.018063 0.914944 0.018984 0.048009
-0.005282 0.966931 0.012938 0.01485
-0.018928 0.00973 0.005204 0.966138
-0.042841 0.025086 0.931121 0.000953
-0.078391 0.025731 0.053763 0.842115
-0.868978 0.057046 0.069564 0.004412
-
->H3k36me3_22
-0.60841 0.005091 0.2906 0.095899
-0.003456 0.99488 0.001023 0.00064
-0.004149 0.698563 0.081454 0.215835
-0.873008 0.0357 0.090623 0.00067
-0.138171 0.03005 0.009922 0.821856
-0.001478 0.068544 0.92731 0.002668
-0.025352 0 0.005404 0.969244
-0.16004 0.005446 0.031354 0.803159
-0.002049 0.037332 0.957441 0.003178
-
->H3k36me3_23
-0.016215 0.899832 0.033387 0.050566
-0.894176 0.061417 0.013931 0.030477
-0.000727 0.981877 0.014869 0.002526
-0.093005 0.057132 0.09865 0.751213
-0.026234 0.644096 0.256871 0.072798
-0.007867 0.906725 0.066711 0.018698
-0.755779 0.044818 0.031628 0.167774
-0.11542 0.054551 0.724506 0.105524
-0.014303 0.901416 0.055745 0.028536
-
->H3k36me3_24
-0.101078 0.638138 0.230415 0.03037
-0.04837 0.189042 0.164568 0.598021
-0.003459 0.929466 0.046241 0.020833
-0.909886 0.040184 0.017452 0.032478
-0 0.985452 0.010825 0.003723
-0.02308 0.035562 0.017328 0.924031
-0.026869 0.195428 0.681141 0.096562
-0.013393 0.791357 0.110883 0.084367
-0.852359 0.066776 0.030189 0.050677
-
->H3k36me3_25
-1 0 0 0
-0.997517 0 0.001911 0.000572
-0.989396 0.010604 0 0
-0.997988 0 0.002012 0
-0 0.004599 0.009508 0.985893
-0.002489 0.022044 0.007222 0.968244
-1 0 0 0
-0 0 1 0
-
->H3k36me3_26
-0 0.050941 0.9481 0.000958
-0.917975 0.004396 0.04399 0.033638
-0.080107 0.01739 0.009995 0.892508
-0.003122 0.910747 0.071006 0.015124
-0.856541 0.004123 0.092481 0.046855
-0 0.954192 0.021677 0.024131
-0.324062 0.003366 0.672572 0
-0.007931 0.891422 0.022519 0.078128
-0.019644 0.947779 0.008891 0.023686
-0.801951 0.055033 0.13526 0.007756
-0.064093 0.803326 0.002803 0.129778
-
->H3k36me3_27
-0.977359 0.010318 0.003964 0.008359
-0.003647 0.0648 0.922837 0.008716
-0.02984 0.134662 0.678923 0.156574
-0.057661 0.09916 0.035379 0.8078
-0.068183 0.827109 0.101843 0.002865
-0.944543 0.002283 0.03896 0.014213
-0.2072 0.0287 0.760046 0.004054
-0.072374 0.025213 0.887926 0.014487
-0.871529 0.014581 0.070648 0.043242
-
->H3k36me3_28
-0.001057 0.012283 0.98666 0
-0.080845 0.003927 0.914187 0.001042
-0.053964 0.89972 0.009015 0.037301
-0.584604 0.017961 0.397435 0
-0.000917 0.011319 0.987138 0.000625
-0.968632 0.013738 0.008291 0.009339
-0.006691 0 0.111601 0.881708
-0.001018 0.961972 0.025565 0.011445
-0.944747 0 0.055253 0
-
->H3k36me3_29
-0.919554 0.010718 0.050146 0.019582
-0.026146 0.922507 0.035952 0.015394
-0.038863 0.669532 0.038846 0.252759
-0.089452 0.798815 0.071686 0.040047
-0.003881 0.209842 0.009636 0.776641
-0.163106 0.038113 0.792181 0.0066
-0.008861 0.069439 0.010575 0.911125
-0.008895 0.891756 0.073583 0.025765
-0.042975 0.048174 0.02657 0.882281
-
->H3k36me3_30
-0.005893 0.014907 0.9792 0
-0.70184 0.008031 0 0.290129
-0.045003 0.012658 0.940072 0.002267
-0.015291 0.001339 0.983371 0
-0.023043 0.009685 0.004654 0.962617
-0.001328 0.011501 0.584003 0.403169
-0.009777 0.004999 0.978982 0.006243
-0.014365 0.929085 0.045343 0.011207
-0.965775 0.006529 0.009204 0.018492
-0 0.480552 0.457615 0.061833
-
->H3k36me3_31
-0.00587 0.212446 0.771873 0.009811
-0.013448 0.024481 0 0.962071
-0.018008 0.085861 0.223536 0.672595
-0.001198 0.066174 0.029182 0.903447
-0 0.928497 0.015111 0.056392
-0.685426 0.032575 0.123895 0.158104
-0.00504 0.949661 0.010899 0.0344
-0.000889 0.93481 0.004957 0.059345
-0.938088 0.016945 0.018351 0.026615
-0.002431 0.058992 0.241834 0.696743
-
->H3k36me3_32
-0.027825 0.835602 0.030067 0.106506
-0.147398 0.016565 0.015743 0.820294
-0.01865 0.017184 0.96346 0.000705
-0.811514 0.017567 0.103109 0.06781
-0.058709 0.010857 0.923336 0.007097
-0.22332 0.067862 0.702356 0.006463
-0.077166 0.812135 0.020988 0.08971
-0.794925 0.063402 0.106321 0.035352
-0.076781 0.017228 0.896096 0.009896
-
->H3k36me3_33
-0.28239 0.00308 0.66605 0.04848
-0.006395 0.980825 0.005253 0.007527
-0.943723 0.019739 0.007425 0.029113
-0.023457 0.026908 0.949635 0
-0.024511 0.045941 0.040224 0.889324
-0.087171 0.001414 0.90956 0.001856
-0.032953 0.086727 0.858562 0.021758
-0.043944 0.756823 0.004067 0.195166
-0.530697 0.017996 0.373231 0.078076
-
->H3k36me3_34
-1 0 0 0
-0.899924 0.012201 0.077813 0.010061
-0.983382 0.003567 0.010553 0.002498
-0.054735 0.942875 0.00239 0
-0.020183 0.708769 0.085405 0.185643
-0.010158 0.836989 0.004265 0.148587
-0.015848 0.933207 0.000393 0.050552
-0.834088 0.002349 0.160635 0.002928
-0 0.130753 0.006978 0.862269
-
->H3k36me3_35
-0.010712 0.847385 0.035623 0.10628
-0.003611 0.856391 0.005876 0.134122
-0.705357 0.008514 0.215873 0.070257
-0 0.076906 0.003708 0.919386
-0.010812 0.940153 0.010889 0.038146
-0.019558 0.011158 0.009881 0.959402
-0 0.912582 0.069699 0.017719
-0.205869 0.167232 0.034953 0.591946
-0.809279 0.042703 0.116952 0.031065
-
->H3k36me3_36
-0.774845 0.020892 0.188444 0.015819
-0.046869 0.046224 0.892087 0.014819
-0.038936 0.093175 0.711246 0.156643
-0.024784 0.926375 0.019708 0.029133
-0.845001 0.013071 0.106818 0.03511
-0.02403 0.044879 0.742407 0.188685
-0.021144 0.070082 0.903262 0.005513
-0.789184 0.064255 0.013028 0.133533
-0.057027 0.015332 0.894381 0.03326
-
->H3k36me3_37
-0.892006 0.050529 0.004518 0.052947
-0.929454 0.004419 0.02214 0.043986
-0.026154 0.889842 0.073229 0.010774
-0.916297 0.001224 0.062965 0.019515
-0.006583 0.293303 0.153373 0.546741
-0.794208 0.068959 0.115636 0.021197
-0.002683 0.179151 0.809093 0.009073
-0.053853 0.165226 0.049169 0.731753
-0.025423 0.002331 0.961049 0.011197
-
->H3k36me3_38
-0.611015 0.381214 0.004009 0.003763
-0.952794 0.025639 0.009368 0.012199
-0.153521 0.82543 0.012908 0.008141
-0.069069 0.848914 0.062295 0.019722
-0.021454 0.009984 0.010235 0.958328
-0.003052 0.943686 0.009798 0.043464
-0.015209 0.766826 0.152517 0.065448
-0.029932 0.046145 0.858404 0.065519
-0.006437 0.773855 0.007769 0.21194
-
->H3k36me3_39
-0 0.997159 0.001235 0.001606
-0.070598 0.018906 0 0.910496
-0.080071 0.670981 0.016896 0.232052
-0.847996 0.086118 0.004285 0.061601
-0.941722 0 0.058278 0
-0.945067 0 0.054022 0.000911
-0.947439 0.042437 0.006122 0.004001
-0.950897 0.042896 0.004833 0.001374
-0.972425 0.027575 0 0
-0.808207 0.189053 0.00274 0
-
->H3k36me3_40
-0 0.488302 0 0.511698
-0.326084 0.045974 0.555576 0.072367
-0 0.902679 0.003992 0.093329
-0.048088 0.945195 0.002591 0.004127
-0 0.948647 0.00164 0.049713
-0.930135 0.00143 0.056366 0.012069
-0 0.014649 0.981362 0.003989
-0.006494 0.989833 0.003673 0
-0 0.104576 0.001271 0.894152
-0.96452 0.0203 0.015181 0
-
->H3k36me3_41
-0.001894 0.950087 0.025304 0.022715
-0.921449 0.018594 0.03558 0.024377
-0.005648 0.941668 0.008425 0.044259
-0.00218 0.914476 0.023949 0.059394
-0.846917 0.039877 0.093493 0.019713
-0.02074 0.313675 0.06233 0.603255
-0.090929 0.028919 0.87049 0.009662
-0.020382 0.76811 0.015853 0.195655
-0.003603 0.882984 0.0047 0.108713
-0.11662 0.479464 0.102319 0.301596
-
->H3k36me3_42
-0.810977 0.004871 0.159193 0.024959
-0.011096 0.955056 0.019831 0.014016
-0.015746 0.961809 0.005249 0.017197
-0.076484 0.013566 0.007299 0.902651
-0 0.989289 0.010711 0
-0.886521 0.031408 0.079126 0.002945
-0.255718 0.06 0.597657 0.086624
-0.097263 0.042865 0.77098 0.088892
-0.026254 0.006217 0.021618 0.945911
-
->H3k36me3_43
-0.006143 0.003397 0.963095 0.027365
-0.064462 0.848995 0 0.086543
-0.274996 0.004109 0.202708 0.518186
-0.00106 0.965502 0.015939 0.017499
-0.834139 0.036895 0.126006 0.00296
-0.01903 0.222489 0.011339 0.747143
-0.196842 0.013587 0.781826 0.007745
-0.001173 0.95275 0.011071 0.035006
-0.006254 0.985028 0.004546 0.004172
-
->H3k36me3_44
-0.10144 0.56942 0.095451 0.233689
-0.11475 0.008777 0.699136 0.177337
-0.009882 0.005122 0.015821 0.969174
-0.013055 0.004043 0.972658 0.010244
-0.88118 0.040719 0.010247 0.067853
-0.063349 0.016347 0.798433 0.121871
-0.016712 0.94582 0.019492 0.017976
-0.009032 0.91158 0.004368 0.07502
-0.850769 0.129613 0.005472 0.014146
-
->H3k36me3_45
-0.025097 0.879699 0.024053 0.071151
-0.108123 0.03167 0.04076 0.819447
-0.01298 0.878373 0.090374 0.018274
-0.027724 0.038849 0.007367 0.92606
-0.013234 0.007289 0.965278 0.014199
-0.021564 0.046201 0.01581 0.916424
-0.042964 0.639999 0.120265 0.196773
-0.595976 0.200519 0.160376 0.043129
-0.008453 0.940496 0.012248 0.038804
-0.061462 0.542457 0.137743 0.258339
-
->H3k36me3_46
-0.114206 0.108627 0.775148 0.00202
-0.040201 0.849107 0.075996 0.034697
-0.891444 0.020683 0.048754 0.039119
-0.053378 0.047139 0.897656 0.001827
-0.091474 0.040686 0.866214 0.001626
-0.674014 0.107546 0.008192 0.210248
-0.166723 0.022014 0.806289 0.004974
-0.067126 0.021483 0.904298 0.007093
-0.804812 0.136065 0.020322 0.0388
-
->H3k36me3_47
-0.024889 0.105094 0.767292 0.102726
-0.912153 0.006795 0.081053 0
-0.013073 0.009563 0.940711 0.036653
-0.010903 0.935927 0.05317 0
-0 0.159601 0.006981 0.833418
-0.293496 0.120075 0.586429 0
-0.007238 0.023724 0.002171 0.966867
-0 0.021055 0.971398 0.007547
-0.589138 0.04026 0.035987 0.334615
-0.006491 0.013307 0 0.980203
-
->H3k36me3_48
-0.934702 0 0.062228 0.00307
-0.003373 0.970668 0.001714 0.024245
-0.356315 0.39856 0.245125 0
-0 0.003698 0 0.996302
-0.000898 0.003489 0.995613 0
-0.003142 0.029837 0.937759 0.029262
-0.014567 0.971985 0.007442 0.006006
-0.147584 0.026321 0.163884 0.66221
-0.655472 0.018438 0.083972 0.242118
-
->H3k36me3_49
-0.759851 0.087607 0.048312 0.10423
-0.024825 0.934356 0.030984 0.009836
-0.003299 0.980731 0.010745 0.005226
-0.842888 0.080928 0.066673 0.009511
-0.00237 0.978292 0.008187 0.011152
-0.85562 0.068684 0.020269 0.055427
-0.038686 0.766025 0.064353 0.130936
-0.136724 0.652591 0.163121 0.047564
-0.020079 0.82756 0.106334 0.046027
-0.339958 0.044072 0.449717 0.166253
-0.002456 0.023074 0.87749 0.096979
-0.003583 0.779471 0.203144 0.013801
-
->H3k36me3_50
-0.128161 0.129664 0.713792 0.028383
-0.004565 0.9862 0.001003 0.008232
-0.798998 0.081084 0.042152 0.077766
-0.004875 0.778633 0.205189 0.011303
-0.019553 0.939324 0.020115 0.021008
-0.868394 0.018873 0.066862 0.045871
-0.003594 0.874075 0.063006 0.059324
-0.008774 0.86022 0.035407 0.095598
-0.811466 0.007365 0.141121 0.040049
-
->H3k36me3_51
-0.737976 0.018171 0.130776 0.113077
-0.011037 0.085834 0.898712 0.004417
-0.028514 0.031026 0.073368 0.867093
-0.011541 0.027051 0.951167 0.010241
-0.842861 0.009248 0.085301 0.06259
-0.027145 0.063794 0.689289 0.219772
-0.020781 0.880483 0.088308 0.010428
-0.12984 0.012688 0.024012 0.83346
-0 0.012803 0.971691 0.015507
-
->H3k36me3_52
-0.015139 0.34128 0.00703 0.636552
-0.705418 0.180077 0.07348 0.041025
-0 0.978434 0.014328 0.007238
-0.176047 0.203605 0.000578 0.619769
-0.003157 0.895704 0.097982 0.003157
-0.879347 0.005983 0.037696 0.076973
-0.054011 0.024876 0.919087 0.002026
-0.082555 0.068701 0.827464 0.02128
-0.782412 0.02585 0.008528 0.18321
-
->H3k36me3_53
-0.101 0.587 0.141 0.171
-0.073 0.1 0.678 0.149
-0.348 0.2 0.102 0.35
-0.178 0.476 0.055 0.291
-0.042 0.226 0.705 0.027
-0.85 0.034 0.065 0.051
-0.025 0.65 0.115 0.21
-0.184 0.081 0.705 0.03
-
->H3k36me3_54
-0.135136 0.697312 0.074937 0.092615
-0 0.947702 0.044472 0.007827
-0.029985 0.931444 0.029358 0.009212
-0.628134 0.001826 0.01032 0.359719
-0 0.938682 0.030387 0.030932
-0.078092 0.814343 0.022242 0.085322
-0.014109 0.045762 0.005665 0.934464
-0 0.943892 0.056108 0
-0.010588 0.148248 0.784909 0.056254
-0.320235 0.016901 0.521988 0.140877
-
->H3k36me3_55
-0.706908 0.042083 0.075769 0.17524
-0.013156 0.001979 0.950923 0.033942
-0.00974 0.851683 0.135991 0.002586
-0.035698 0.955895 0.008407 0
-0.726227 0.007418 0.245694 0.020661
-0 0.067194 0.922738 0.010068
-0.081936 0.063635 0.834154 0.020275
-0.014378 0.785319 0.011176 0.189127
-0.944722 0.01517 0.010148 0.02996
-
->H3k36me3_56
-0.923371 0.040613 0.035004 0.001011
-0.834497 0.090343 0.04551 0.029651
-0.007527 0.030823 0.959929 0.001721
-0.125878 0 0.870903 0.003219
-0.007889 0.832338 0 0.159773
-0.025808 0.084089 0.857356 0.032747
-0.029025 0.001524 0.962293 0.007158
-0.014345 0.238691 0.738412 0.008552
-0.018055 0.714245 0.101775 0.165925
-
->H3k4me1_1
-0.021 0.018 0.002 0.959
-0.041 0.136 0.015 0.808
-0.245 0.001 0.014 0.74
-0.243 0.078 0.666 0.013
-0.142 0.835 0.002 0.021
-0.878 0.04 0.001 0.081
-0.256 0.026 0.021 0.697
-0.34 0.116 0.217 0.327
-0.452 0.062 0.114 0.373
-0.085 0.464 0.321 0.13
-0.863 0.072 0.002 0.063
-0.805 0.071 0.091 0.033
-
->H3k4me1_2
-0.126221 0.096725 0.652362 0.124692
-0.157713 0.76706 0.074905 0.000322
-0.123264 0.011594 0.004509 0.860634
-0.006538 0.043494 0.947226 0.002742
-0.850792 0.026025 0.048173 0.07501
-0.029324 0.225233 0.739268 0.006175
-0.048641 0.103353 0.059443 0.788562
-0.091813 0.767385 0.096649 0.044154
-0.823017 0.070473 0.006845 0.099666
-
->H3k4me1_3
-0.142656 0.046092 0.628207 0.183044
-0.077532 0.721399 0.068271 0.132798
-0.862808 0.039974 0.036854 0.060365
-0.01964 0.009924 0.018916 0.95152
-0.053006 0 0.025394 0.9216
-0.033778 0.023827 0.012824 0.929571
-0.123322 0.106461 0.047877 0.72234
-0.764536 0.032298 0.029472 0.173695
-0.754843 0.118183 0.056065 0.070909
diff --git a/data/universal_motifs.fasta b/data/universal_motifs.fasta
new file mode 100644
--- /dev/null
+++ b/data/universal_motifs.fasta
@@ -0,0 +1,6260 @@
+>tree0.2_0_GGAKATWATMTC
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+
+>tree0.2_1_CTCCCTAAAATG
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+
+>tree0.2_2_TGCCTWAACYGA
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+
+>tree0.2_3_NAAACTTAAGTN
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+0.117 0.184 0.333 0.366
+
+>tree0.2_4_GAAACTKCTTTGT
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+
+>tree0.2_5_CGGACWCTCTTT
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+0.001 0.12 0.788 0.091
+0.001 0.001 0.861 0.137
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+0.137 0.803 0.001 0.059
+0.375 0.001 0.001 0.623
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+
+>tree0.2_6_AAAASAGTGTTTC
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+0.971 0.02475 0.00175 0.0025
+0.989875 0.001375 0.007375 0.001375
+0.0022500000000000003 0.38225 0.6145 0.001
+0.9915 0.004125 0.001 0.003375
+0.0023750000000000004 0.233875 0.7621249999999999 0.001625
+0.013875000000000002 0.001 0.00175 0.983375
+0.00175 0.0795 0.917 0.00175
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+0.001125 0.001 0.001 0.996875
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+0.007000000000000001 0.7665 0.0125 0.214
+
+>tree0.2_7_CRAAAASAGTGT
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+0.6105 0.038 0.3505 0.001
+0.85432825 0.07225 0.00174725 0.07167449999999999
+0.91697175 0.07722175 0.00194375 0.00386275
+0.98480975 0.008608000000000001 0.005832250000000001 0.00075
+0.8295174999999999 0.01547925 0.07183750000000001 0.08316575000000001
+0.0171595 0.634059 0.3449695 0.003812
+0.79377575 0.1401455 0.03825 0.0278285
+0.00075 0.023721 0.974779 0.00075
+0.00075 0.003666 0.0173815 0.97820275
+0.0005 0.0005 0.9985 0.0005
+0.002 0.081 0.142 0.775
+
+>tree0.2_8_GTGGTTGAAGTC
+0.039 0.001 0.959 0.001
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+
+>tree0.2_9_CTCTTGCATCAG
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+
+>tree0.2_10_GCTGCTGAAAGC
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+0.001 0.924 0.074 0.001
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+
+>tree0.2_11_ACSGGCTTAAAA
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+0.001 0.902 0.001 0.096
+0.063 0.373 0.518 0.046
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+
+>tree0.2_12_RGGCGCTTTAAA
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+0.001 0.001 0.9605 0.0375
+0.001 0.8400000000000001 0.001 0.158
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+0.707 0.1795 0.038 0.0755
+
+>tree0.2_13_GGAGCTGTAGAC
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+0.00325 0.001 0.855 0.14075
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diff --git a/exe/mkindex.hs b/exe/mkindex.hs
deleted file mode 100644
--- a/exe/mkindex.hs
+++ /dev/null
@@ -1,11 +0,0 @@
-module Main where
-
-import Bio.Seq.IO (mkIndex)
-import Shelly
-import qualified Data.Text as T
-import System.Environment
-
-main :: IO ()
-main = do [inDir, outF] <- getArgs
-          fls <- shelly . lsT . fromText . T.pack $ inDir
-          mkIndex (map T.unpack fls) outF
diff --git a/exe/viewSeq.hs b/exe/viewSeq.hs
deleted file mode 100644
--- a/exe/viewSeq.hs
+++ /dev/null
@@ -1,15 +0,0 @@
-module Main where
-
-import qualified Data.ByteString.Char8 as B
-import Bio.Seq
-import Bio.Seq.IO
-import System.Environment
-
-main :: IO ()
-main = do
-    [fl, chr, start, end] <- getArgs
-    g <- pack fl
-    s <- getSeqs g [(B.pack chr, read start, read end)] :: IO [Either String (DNA IUPAC)]
-    case head s of
-        Left err -> error err
-        Right x -> B.putStrLn . toBS $ x
diff --git a/src/Bio/ChIPSeq.hs b/src/Bio/ChIPSeq.hs
--- a/src/Bio/ChIPSeq.hs
+++ b/src/Bio/ChIPSeq.hs
@@ -2,12 +2,12 @@
 {-# LANGUAGE OverloadedStrings #-}
 {-# LANGUAGE BangPatterns #-}
 module Bio.ChIPSeq
-    ( rpkmBed
+    ( monoColonalize
+    , rpkmBed
     , rpkmSortedBed
-    , monoColonalize
-    , profiling
-    , profilingCoverage
+    , rpkmBinBed
     , rpkmBam
+    , rpgcBinBed
     , tagCountDistr
     , peakCluster
     ) where
@@ -16,9 +16,7 @@
 import qualified Bio.SamTools.BamIndex as BI
 import Control.Monad (liftM, forM_, forM)
 import Control.Monad.Primitive (PrimMonad)
-import Control.Monad.Trans.Class (lift)
-import Data.Conduit
-import qualified Data.Conduit.List as CL
+import Conduit
 import Data.Function (on)
 import qualified Data.Foldable as F
 import qualified Data.HashMap.Strict as M
@@ -79,7 +77,7 @@
               => Sorted (V.Vector b) -> Sink BED m (v Double)
 rpkmSortedBed (Sorted regions) = do
     vec <- lift $ GM.replicate l 0
-    n <- CL.foldM (count vec) (0 :: Int)
+    n <- foldMC (count vec) (0 :: Int)
     let factor = fromIntegral n / 1e9
     lift $ liftM (G.imap (\i x -> x / factor / (fromIntegral . size) (regions V.! i)))
          $ G.unsafeFreeze vec
@@ -89,7 +87,7 @@
             p | _strand tag == Just True = chromStart tag
               | _strand tag == Just False = chromEnd tag - 1
               | otherwise = error "Unkown strand"
-            xs = concat . snd . unzip $
+            xs = concat $ IM.elems $
                 IM.containing (M.lookupDefault IM.empty chr intervalMap) p
         addOne v xs
         return $ succ nTags
@@ -102,11 +100,11 @@
 
 -- | divide each region into consecutive bins, and count tags for each bin. The
 -- total number of tags is also returned
-profiling :: (PrimMonad m, G.Vector v Int, BEDLike b)
-          => Int   -- ^ bin size
-          -> [b]   -- ^ regions
-          -> Sink BED m ([v Int], Int)
-profiling k beds = do
+rpkmBinBed :: (Num a, PrimMonad m, G.Vector v a, BEDLike b)
+           => Int   -- ^ bin size
+           -> [b]   -- ^ regions
+           -> Sink BED m ([v a], Int)
+rpkmBinBed k beds = do
     initRC <- lift $ forM beds $ \bed -> do
         let start = chromStart bed
             end = chromEnd bed
@@ -124,11 +122,13 @@
                 let p | strand == Just True = start
                       | strand == Just False = end - 1
                       | otherwise = error "profiling: unkown strand"
-                    overlaps = concat . snd . unzip $
+                    overlaps = concat $ IM.elems $
                         IM.containing (M.lookupDefault IM.empty chr intervalMap) p
                 lift $ forM_ overlaps $ \x -> do
                     let (v, idxFn) = vs `G.unsafeIndex` x
-                        i = idxFn p
+                        i = let i' = idxFn p
+                                l = GM.length v
+                            in if i' >= l then l - 1 else i'
                     GM.unsafeRead v i >>= GM.unsafeWrite v i . (+1)
                 sink (nTags+1) vs
 
@@ -136,15 +136,16 @@
                     return (rc, nTags)
 
     intervalMap = bedToTree (++) $ zip beds $ map return [0..]
-{-# INLINE profiling #-}
+{-# INLINE rpkmBinBed #-}
 
--- | divide each region into consecutive bins, and count tags for each bin. The
--- total number of tags is also returned
-profilingCoverage :: (PrimMonad m, G.Vector v Int, BEDLike b1, BEDLike b2)
+-- | divide each region into consecutive bins, and compute
+-- reads per genome coverage (RPGC) for each bin. The
+-- total number of tags is also returned.
+rpgcBinBed :: (Num a, PrimMonad m, G.Vector v a, BEDLike b1, BEDLike b2)
           => Int   -- ^ bin size
           -> [b1]   -- ^ regions
-          -> Sink b2 m ([v Int], Int)
-profilingCoverage k beds = do
+          -> Sink b2 m ([v a], Int)
+rpgcBinBed k beds = do
     initRC <- lift $ forM beds $ \bed -> do
         let start = chromStart bed
             end = chromEnd bed
@@ -162,12 +163,15 @@
                 let chr = chrom bed
                     start = chromStart bed
                     end = chromEnd bed
-                    overlaps = concat . snd . unzip $ IM.intersecting
+                    overlaps = concat $ IM.elems $ IM.intersecting
                         (M.lookupDefault IM.empty chr intervalMap) $ IM.IntervalCO start end
                 lift $ forM_ overlaps $ \x -> do
                     let (v, idxFn) = vs `G.unsafeIndex` x
-                        lo = idxFn start
-                        hi = idxFn end
+                        lo = let i = idxFn start
+                             in if i < 0 then 0 else i
+                        hi = let i = idxFn end
+                                 l = GM.length v
+                             in if i >= l then l - 1 else i
                     forM_ [lo..hi] $ \i ->
                         GM.unsafeRead v i >>= GM.unsafeWrite v i . (+1)
                 sink (nTags+1) vs
@@ -176,14 +180,14 @@
                     return (rc, nTags)
 
     intervalMap = bedToTree (++) $ zip beds $ map return [0..]
-{-# INLINE profilingCoverage #-}
+{-# INLINE rpgcBinBed #-}
 
 
 -- | calculate RPKM using BAM file (*.bam) and its index file (*.bam.bai), using
 -- constant space
 rpkmBam :: BEDLike b => FilePath -> Conduit b IO Double
 rpkmBam fl = do
-    nTags <- lift $ readBam fl $$ CL.foldM (\acc bam -> return $
+    nTags <- lift $ readBam fl $$ foldMC (\acc bam -> return $
                                   if isUnmap bam then acc else acc + 1) 0.0
     handle <- lift $ BI.open fl
     conduit nTags handle
@@ -198,7 +202,7 @@
                            rc <- lift $ viewBam h (chr, s, e) $$ readCount s e
                            yield $ rc * 1e9 / n / fromIntegral (e-s)
                            conduit n h
-    readCount l u = CL.foldM f 0.0
+    readCount l u = foldMC f 0.0
       where
         f acc bam = do let p1 = fromIntegral . fromJust . position $ bam
                            rl = fromIntegral . fromJust . queryLength $ bam
@@ -237,7 +241,7 @@
             -> Int   -- ^ radius
             -> Int   -- ^ cutoff
             -> Source m BED
-peakCluster peaks r th = mergeBedWith mergeFn peaks' $= CL.filter g
+peakCluster peaks r th = mergeBedWith mergeFn peaks' $= filterC g
   where
     peaks' = map f peaks
     f b = let chr = chrom b
diff --git a/src/Bio/Data/Bam.hs b/src/Bio/Data/Bam.hs
--- a/src/Bio/Data/Bam.hs
+++ b/src/Bio/Data/Bam.hs
@@ -21,8 +21,7 @@
 import Bio.SamTools.BamIndex
 import Control.Monad.Trans.Class (lift)
 import qualified Data.ByteString.Char8 as B
-import Data.Conduit (Source, Conduit, yield)
-import qualified Data.Conduit.List as CL
+import Conduit (Source, Conduit, yield, concatMapC)
 import Data.Maybe (fromJust)
 import Bio.Data.Bed
 
@@ -37,7 +36,7 @@
 {-# INLINE readBam #-}
 
 bamToBed :: Monad m => Conduit Bam1 m BED
-bamToBed = CL.mapMaybe f
+bamToBed = concatMapC f
   where
     f bam =case targetName bam of
         Just chr ->
@@ -52,7 +51,7 @@
 viewBam :: IdxHandle -> (B.ByteString, Int, Int) -> Source IO Bam1
 viewBam handle (chr, s, e) = case lookupTarget (idxHeader handle) chr of
     Nothing -> return ()
-    Just chrId -> do 
+    Just chrId -> do
         q <- lift $ query handle chrId (fromIntegral s,fromIntegral e)
         go q
   where
diff --git a/src/Bio/Data/Bed.hs b/src/Bio/Data/Bed.hs
--- a/src/Bio/Data/Bed.hs
+++ b/src/Bio/Data/Bed.hs
@@ -46,8 +46,7 @@
 import Control.Arrow ((***))
 import Control.Monad.State.Strict
 import qualified Data.ByteString.Char8 as B
-import Data.Conduit
-import qualified Data.Conduit.List as CL
+import Conduit
 import Data.Default.Class (Default(..))
 import Data.Function (on)
 import qualified Data.Foldable as F
@@ -98,7 +97,7 @@
 
     -- | non-streaming version
     hReadBed' :: MonadIO m => Handle -> m [b]
-    hReadBed' h = hReadBed h $$ CL.consume
+    hReadBed' h = hReadBed h $$ sinkList
     {-# INLINE hReadBed' #-}
 
     readBed :: MonadIO m => FilePath -> Source m b
@@ -109,7 +108,7 @@
 
     -- | non-streaming version
     readBed' :: MonadIO m => FilePath -> m [b]
-    readBed' fl = readBed fl $$ CL.consume
+    readBed' fl = readBed fl $$ sinkList
     {-# INLINE readBed' #-}
 
     hWriteBed :: MonadIO m => Handle -> Sink b m ()
@@ -121,7 +120,7 @@
     {-# INLINE hWriteBed #-}
 
     hWriteBed' :: MonadIO m => Handle -> [b] -> m ()
-    hWriteBed' handle beds = CL.sourceList beds $$ hWriteBed handle
+    hWriteBed' handle beds = yieldMany beds $$ hWriteBed handle
     {-# INLINE hWriteBed' #-}
 
     writeBed :: MonadIO m => FilePath -> Sink b m ()
@@ -131,7 +130,7 @@
     {-# INLINE writeBed #-}
 
     writeBed' :: MonadIO m => FilePath -> [b] -> m ()
-    writeBed' fl beds = CL.sourceList beds $$ writeBed fl
+    writeBed' fl beds = yieldMany beds $$ writeBed fl
     {-# INLINE writeBed' #-}
 
     {-# MINIMAL asBed, fromLine, toLine, chrom, chromStart, chromEnd #-}
@@ -238,7 +237,7 @@
 -- | return records in A that are overlapped with records in B
 intersectSortedBed :: (BEDLike b1, BEDLike b2)
                    => [b1] -> Sorted (V.Vector b2) -> [b1]
-intersectSortedBed a (Sorted b) = filter (not . null . f) a
+intersectSortedBed a (Sorted b) = filter (not . IM.null . f) a
   where
     f bed = let chr = chrom bed
                 interval = IM.IntervalCO (chromStart bed) $ chromEnd bed
@@ -263,7 +262,7 @@
   where
     f bed = let chr = chrom bed
                 interval = IM.IntervalCO (chromStart bed) $ chromEnd bed
-            in (bed, fn $ map snd $ IM.intersecting (M.lookupDefault IM.empty chr tree) interval)
+            in (bed, fn $ IM.elems $ IM.intersecting (M.lookupDefault IM.empty chr tree) interval)
     tree = sortedBedToTree const . Sorted . V.toList . V.zip b $ b
 {-# INLINE intersectSortedBedWith #-}
 
@@ -407,7 +406,7 @@
 {-# INLINE fetchSeq #-}
 
 fetchSeq' :: (BioSeq DNA a, MonadIO m) => Genome -> [BED] -> m [Either String (DNA a)]
-fetchSeq' g beds = CL.sourceList beds $= fetchSeq g $$ CL.consume
+fetchSeq' g beds = yieldMany beds $= fetchSeq g $$ sinkList
 {-# INLINE fetchSeq' #-}
 
 -- * BED3 format
diff --git a/src/Bio/Data/BigWig.hs b/src/Bio/Data/BigWig.hs
deleted file mode 100644
--- a/src/Bio/Data/BigWig.hs
+++ /dev/null
@@ -1,32 +0,0 @@
-module Bio.Data.BigWig
-    ( module Data.BBI.BigWig
-    , accumScores
-    , normalizedScores
-    ) where
-
-import Data.BBI.BigWig
-import Data.Conduit
-import qualified Data.Conduit.List as CL
-import Bio.Data.Bed
-
--- | for each BED region, return total scores of all wig records overlapped with it
-accumScores :: BEDLike b => BWFile -> Conduit b IO Double
-accumScores bwF = CL.mapM (helper bwF)
-{-# INLINE accumScores #-}
-
--- | for each BED region, return normalized scores (divided by the length) of
--- all wig records overlapped with it
-normalizedScores :: BEDLike b => BWFile -> Conduit b IO Double
-normalizedScores bwF = CL.mapM $ \bed -> do
-    x <- helper bwF bed
-    return $ x / (fromIntegral . size) bed
-{-# INLINE normalizedScores #-}
-
-helper :: BEDLike b => BWFile -> b -> IO Double
-helper bwF bed = queryBWFile bwF (chr, start, end) $$ CL.fold f 0.0
-  where
-    f acc (_, s, e, v) = acc + fromIntegral (e - s) * v
-    chr = chrom bed
-    start = chromStart bed
-    end = chromEnd bed
-{-# INLINE helper #-}
diff --git a/src/Bio/Data/Fasta.hs b/src/Bio/Data/Fasta.hs
--- a/src/Bio/Data/Fasta.hs
+++ b/src/Bio/Data/Fasta.hs
@@ -22,8 +22,7 @@
 import Bio.Seq
 import Control.Monad.State.Lazy
 import qualified Data.ByteString.Char8 as B
-import Data.Conduit
-import qualified Data.Conduit.List as CL
+import Conduit
 import System.IO
 
 class FastaLike f where
@@ -37,7 +36,7 @@
 
     -- | non-stream version, read whole file in memory
     readFasta' :: FilePath -> IO [f]
-    readFasta' fl = readFasta fl $$ CL.consume
+    readFasta' fl = readFasta fl $$ sinkList
 --    writeFasta :: FilePath -> [f] -> IO ()
     {-# MINIMAL fromFastaRecord #-}
 
@@ -54,7 +53,7 @@
                     loop [] handle
   where
     loop :: [B.ByteString] -> Handle -> Source IO (B.ByteString, [B.ByteString])
-    loop acc h = do 
+    loop acc h = do
         eof <- liftIO $ hIsEOF h
         if eof then liftIO (hClose h) >> output acc else do
             l <- liftIO $ B.hGetLine h
diff --git a/src/Bio/GO.hs b/src/Bio/GO.hs
--- a/src/Bio/GO.hs
+++ b/src/Bio/GO.hs
@@ -9,7 +9,6 @@
 import qualified Data.Text as T
 import Data.Text.Encoding (decodeUtf8)
 import qualified Data.ByteString.Char8 as B
-import Data.Foldable (foldl')
 import qualified Data.HashMap.Strict as M
 import Data.Maybe
 
diff --git a/src/Bio/GO/GREAT.hs b/src/Bio/GO/GREAT.hs
--- a/src/Bio/GO/GREAT.hs
+++ b/src/Bio/GO/GREAT.hs
@@ -7,7 +7,7 @@
 
 import Control.Monad.Primitive
 import qualified Data.ByteString.Char8 as B
-import Data.Conduit
+import Conduit
 import Data.Default.Class
 import qualified Data.HashMap.Strict as M
 import qualified Data.IntervalMap as IM
@@ -41,12 +41,14 @@
 getRegulatoryDomains (BasalPlusExtension up dw ext) gs =
     bedToTree undefined $ flip map basal $ \(BED3 chr s e, go) ->
         let intervals = fromJust . M.lookup chr $ basalTree
-            s' = case IM.intersecting intervals (IM.OpenInterval (s - ext)  s) of
-                [] -> s - ext
-                x -> min s (maximum $ map (upperBound . fst) x)
-            e' = case IM.intersecting intervals (IM.OpenInterval e (e + ext)) of
-                [] -> e + ext
-                x -> max e (minimum $ map (lowerBound . fst) x)
+            s' = let im = IM.intersecting intervals $ IM.OpenInterval (s-ext) s
+                 in if IM.null im
+                     then s - ext
+                     else min s $ maximum $ map upperBound $ IM.keys im
+            e' = let im = IM.intersecting intervals $ IM.OpenInterval e (e+ext)
+                 in if IM.null im
+                     then e + ext
+                     else max e $ minimum $ map lowerBound $ IM.keys im
         in (BED3 chr s' e', go)
   where
     basalTree = bedToTree (error "encounter redundant regions") basal
@@ -69,7 +71,7 @@
                 let chr = chrom bed
                     s = chromStart bed
                     e = chromEnd bed
-                    terms = nub' . concatMap snd . IM.intersecting
+                    terms = nub' . concat . IM.elems . IM.intersecting
                         (M.lookupDefault IM.empty chr tree) $ IM.IntervalCO s e
                 go (n+1) $ foldl (\acc t -> M.insertWith (+) t 1 acc) termCount terms
             _ -> return (n, termCount)
diff --git a/src/Bio/GO/Parser.hs b/src/Bio/GO/Parser.hs
--- a/src/Bio/GO/Parser.hs
+++ b/src/Bio/GO/Parser.hs
@@ -5,7 +5,6 @@
     ) where
 
 import Control.Arrow ((&&&))
-import Control.Applicative ((<$>))
 import qualified Data.ByteString.Lazy.Char8 as L
 import qualified Data.HashMap.Strict as M
 import Data.Maybe
diff --git a/src/Bio/Motif.hs b/src/Bio/Motif.hs
--- a/src/Bio/Motif.hs
+++ b/src/Bio/Motif.hs
@@ -14,7 +14,7 @@
     , scores'
     , score
     , optimalScore
-    , CDF
+    , CDF(..)
     , cdf
     , cdf'
     , scoreCDF
@@ -35,7 +35,7 @@
 import Control.Arrow ((&&&))
 import Control.Monad.State.Lazy
 import qualified Data.ByteString.Char8 as B
-import Data.Conduit
+import Conduit
 import Data.Double.Conversion.ByteString (toShortest)
 import Data.Default.Class
 import Data.List (sortBy, foldl')
@@ -224,7 +224,7 @@
 pValueToScore :: Double -> Bkgd -> PWM -> Double
 pValueToScore p bg pwm = cdf' (scoreCDF bg pwm) $ 1 - p
 
-newtype CDF = CDF (V.Vector (Double, Double))
+newtype CDF = CDF (V.Vector (Double, Double)) deriving (Read, Show)
 
 -- P(X <= x)
 cdf :: CDF -> Double -> Double
diff --git a/src/Bio/Motif/Alignment.hs b/src/Bio/Motif/Alignment.hs
--- a/src/Bio/Motif/Alignment.hs
+++ b/src/Bio/Motif/Alignment.hs
@@ -1,21 +1,18 @@
 {-# LANGUAGE Rank2Types #-}
+{-# LANGUAGE OverloadedStrings #-}
 {-# LANGUAGE FlexibleContexts #-}
 {-# LANGUAGE BangPatterns #-}
-
 module Bio.Motif.Alignment
     ( alignment
     , alignmentBy
     , linPenal
     , quadPenal
     , cubePenal
-    , mergePWM
-    , buildTree
-    , progressiveMerging
+    , expPenal
+    , AlignFn
     ) where
 
-import AI.Clustering.Hierarchical
 import qualified Data.Vector.Generic as G
-import qualified Data.Vector as V
 import qualified Data.Vector.Unboxed as U
 import qualified Data.Matrix.Unboxed as M
 
@@ -25,32 +22,41 @@
 -- | penalty function takes the gaps number as input, return penalty value
 type PenalFn = Int -> Double
 
-type DistanceFn = (G.Vector v Double, G.Vector v (Double, Double)) => v Double -> v Double -> Double
+type DistanceFn = forall v. (G.Vector v Double, G.Vector v (Double, Double))
+               => v Double -> v Double -> Double
 
-alignment :: PWM -> PWM -> (Double, (PWM, PWM, Int))
-alignment = alignmentBy jsd quadPenal
+type AlignFn = PWM
+            -> PWM
+            -> (Double, (Bool, Int))  -- ^ (distance, (on same direction,
+                                      -- position w.r.t. the first pwm))
 
+alignment :: AlignFn
+alignment = alignmentBy jsd $ quadPenal 0.15
+
 -- | linear penalty
-linPenal :: PenalFn
-linPenal n = fromIntegral n * 0.3
+linPenal :: Double -> PenalFn
+linPenal x n = fromIntegral n * x
 
 -- | quadratic penalty
-quadPenal :: PenalFn
-quadPenal n = fromIntegral (n ^ (2 :: Int)) * 0.15
+quadPenal :: Double -> PenalFn
+quadPenal x n = fromIntegral (n ^ (2 :: Int)) * x
 
 -- | cubic penalty
-cubePenal :: PenalFn
-cubePenal n = fromIntegral (n ^ (3 :: Int)) * 0.01
+cubePenal :: Double -> PenalFn
+cubePenal x n = fromIntegral (n ^ (3 :: Int)) * x
 
 -- | exponentail penalty
-expPenal :: PenalFn
-expPenal n = fromIntegral (2^n :: Int) * 0.01
+expPenal :: Double -> PenalFn
+expPenal x n = fromIntegral (2^n :: Int) * x
 
 -- internal gaps are not allowed, larger score means larger distance, so the smaller the better
-alignmentBy :: DistanceFn -> PenalFn -> PWM -> PWM -> (Double, (PWM, PWM, Int))
+alignmentBy :: DistanceFn  -- ^ compute the distance between two aligned pwms
+            -> PenalFn     -- ^ gap penalty
+            -> AlignFn
 alignmentBy fn pFn m1 m2
-    | fst forwardAlign <= fst reverseAlign = (fst forwardAlign, (m1, m2, snd forwardAlign))
-    | otherwise = (fst reverseAlign, (m1, m2', snd reverseAlign))
+    | fst forwardAlign <= fst reverseAlign =
+        (fst forwardAlign, (True, snd forwardAlign))
+    | otherwise = (fst reverseAlign, (False, snd reverseAlign))
   where
     forwardAlign | d1 < d2 = (d1,i1)
                  | otherwise = (d2,-i2)
@@ -94,26 +100,3 @@
     n1 = length s1
     n2 = length s2
 {-# INLINE alignmentBy #-}
-
-mergePWM :: (PWM, PWM, Int) -> PWM
-mergePWM (m1, m2, i) | i >= 0 = PWM Nothing (M.fromRows $ take i s1 ++ zipWith f (drop i s1) s2 ++ drop (n1 - i) s2)
-                     | otherwise = PWM Nothing (M.fromRows $ take (-i) s2 ++ zipWith f (drop (-i) s2) s1 ++ drop (n2 + i) s1)
-  where
-    f = G.zipWith (\x y -> (x+y)/2)
-    s1 = M.toRows . _mat $ m1
-    s2 = M.toRows . _mat $ m2
-    n1 = length s1
-    n2 = length s2
-
-progressiveMerging :: Dendrogram Motif -> PWM
-progressiveMerging t = case t of
-    Branch _ _ left right -> f (progressiveMerging left) $ progressiveMerging right
-    Leaf a -> _pwm a
-  where
-    f a b = mergePWM $! snd $ alignment a b
-
--- | build a guide tree from a set of motifs
-buildTree :: [Motif] -> Dendrogram Motif
-buildTree motifs = hclust Average (V.fromList motifs) δ
-  where
-    δ (Motif _ x) (Motif _ y) = fst $ alignment x y
diff --git a/src/Bio/Motif/Merge.hs b/src/Bio/Motif/Merge.hs
new file mode 100644
--- /dev/null
+++ b/src/Bio/Motif/Merge.hs
@@ -0,0 +1,185 @@
+{-# LANGUAGE OverloadedStrings #-}
+{-# LANGUAGE FlexibleContexts #-}
+module Bio.Motif.Merge
+    ( mergePWM
+    , mergePWMWeighted
+    , dilute
+    , trim
+    , mergeTree
+    , mergeTreeWeighted
+    , iterativeMerge
+    , buildTree
+    )where
+
+import           AI.Clustering.Hierarchical    hiding (size)
+import Control.Arrow (first)
+import           Control.Monad                 (forM_, when)
+import           Control.Monad.ST              (runST, ST)
+import qualified Data.ByteString.Char8         as B
+import           Data.List                     (dropWhileEnd)
+import qualified Data.Matrix.Symmetric.Mutable as MSU
+import qualified Data.Matrix.Unboxed           as MU
+import           Data.Maybe
+import qualified Data.Vector                   as V
+import qualified Data.Vector.Mutable           as VM
+import qualified Data.Vector.Unboxed           as U
+
+import           Bio.Motif
+import           Bio.Motif.Alignment
+import           Bio.Utils.Functions           (kld)
+
+mergePWM :: (PWM, PWM, Int) -> PWM
+mergePWM (m1, m2, shift) | shift >= 0 = merge shift (_mat m1) $ _mat m2
+                         | otherwise = merge (-shift) (_mat m2) $ _mat m1
+  where
+    merge s a b = PWM Nothing $ MU.fromRows $ loop 0
+      where
+        n1 = MU.rows a
+        n2 = MU.rows b
+        loop i | i' < 0 || (i < n1 && i' >= n2) = MU.takeRow a i : loop (i+1)
+               | i < n1 && i' < n2 = f (MU.takeRow a i) (MU.takeRow b i') : loop (i+1)
+               | i >= n1 && i' < n2 = MU.takeRow b i' : loop (i+1)
+               | otherwise = []
+          where
+            i' = i - s
+            f = U.zipWith (\x y -> (x+y)/2)
+
+mergePWMWeighted :: (PWM, [Int])  -- ^ pwm and weights at each position
+                 -> (PWM, [Int])
+                 -> Int                  -- ^ shift
+                 -> (PWM, [Int])
+mergePWMWeighted m1 m2 shift
+    | shift >= 0 = merge shift (first _mat m1) $ first _mat m2
+    | otherwise = merge (-shift) (first _mat m2) $ first _mat m1
+
+  where
+    merge s (p1,w1) (p2,w2) = first (PWM Nothing . MU.fromRows) $ unzip $ loop 0
+      where
+        a = V.fromList $ zip (MU.toRows p1) w1
+        b = V.fromList $ zip (MU.toRows p2) w2
+        n1 = V.length a
+        n2 = V.length b
+        loop i | i' < 0 || (i < n1 && i' >= n2) = a V.! i : loop (i+1)
+               | i < n1 && i' < n2 = f (a V.! i) (b V.! i') : loop (i+1)
+               | i >= n1 && i' < n2 = b V.! i' : loop (i+1)
+               | otherwise = []
+          where
+            i' = i - s
+            f (xs, wx) (ys, wy) = (U.zipWith (\x y ->
+                (fromIntegral wx * x + fromIntegral wy * y) /
+                fromIntegral (wx + wy)) xs ys, wx + wy)
+
+-- | dilute positions in a PWM that are associated with low weights
+dilute :: (PWM, [Int]) -> PWM
+dilute (pwm, ws) = PWM Nothing $ MU.fromRows $ zipWith f ws $ MU.toRows $ _mat pwm
+  where
+    f w r | w < n = let d = fromIntegral $ n - w
+                    in U.map (\x -> (fromIntegral w * x + 0.25 * d) / fromIntegral n) r
+          | otherwise = r
+    n = maximum ws
+{-# INLINE dilute #-}
+
+trim :: Bkgd -> Double -> PWM -> PWM
+trim (BG (a,c,g,t)) cutoff pwm = PWM Nothing $ MU.fromRows $ dropWhileEnd f $
+    dropWhile f rs
+  where
+    f x = kld x bg < cutoff
+    rs = MU.toRows $ _mat pwm
+    bg = U.fromList [a,c,g,t]
+{-# INLINE trim #-}
+
+mergeTree :: AlignFn -> Dendrogram Motif -> PWM
+mergeTree align t = case t of
+    Branch _ _ left right -> f (mergeTree align left) $ mergeTree align right
+    Leaf a -> _pwm a
+  where
+    f a b | isSame = mergePWM (a, b, i)
+          | otherwise = mergePWM (a, rcPWM b, i)
+      where (_, (isSame, i)) = align a b
+
+mergeTreeWeighted :: AlignFn -> Dendrogram Motif -> (PWM, [Int])
+mergeTreeWeighted align t = case t of
+    Branch _ _ left right -> f (mergeTreeWeighted align left) $
+        mergeTreeWeighted align right
+    Leaf a -> (_pwm a, replicate (size $ _pwm a) 1)
+  where
+    f (a,w1) (b,w2)
+        | isSame = mergePWMWeighted (a,w1) (b,w2) i
+        | otherwise = mergePWMWeighted (a,w1) (rcPWM b, reverse w2) i
+      where (_, (isSame, i)) = align a b
+{-# INLINE mergeTreeWeighted #-}
+
+iterativeMerge :: AlignFn
+               -> Double    -- cutoff
+               -> [Motif]   -- ^ Motifs to be merged. Motifs must have unique name.
+               -> [([B.ByteString], PWM, [Int])]
+iterativeMerge align th motifs = runST $ do
+    motifs' <- V.unsafeThaw $ V.fromList $ flip map motifs $ \x ->
+        Just ([_name x], _pwm x, replicate (size $ _pwm x) 1)
+
+    let n = VM.length motifs'
+        iter mat = do
+            -- retrieve the minimum value
+            ((i, j), (d, (isSame, pos))) <- loop ((-1,-1), (1/0, undefined)) 0 1
+            if d < th
+                then do
+                    Just (nm1, pwm1, w1) <- VM.unsafeRead motifs' i
+                    Just (nm2, pwm2, w2) <- VM.unsafeRead motifs' j
+                    let merged = (nm1 ++ nm2, pwm', w')
+                        (pwm',w') | isSame = mergePWMWeighted (pwm1, w1) (pwm2, w2) pos
+                                  | otherwise = mergePWMWeighted (pwm1, w1)
+                                              (rcPWM $ pwm2, reverse w2) pos
+
+                    -- update
+                    forM_ [0..n-1] $ \i' -> MSU.unsafeWrite mat (i',j) Nothing
+                    VM.unsafeWrite motifs' i $ Just merged
+                    VM.unsafeWrite motifs' j Nothing
+                    forM_ [0..n-1] $ \j' -> when (i /= j') $ do
+                        x <- VM.unsafeRead motifs' j'
+                        case x of
+                            Just (_, pwm2',_) -> do
+                                let ali | i < j' = Just $ align pwm' pwm2'
+                                        | otherwise = Just $ align pwm2' pwm'
+                                MSU.unsafeWrite mat (i,j') ali
+                            _ -> return ()
+                    iter mat
+                else return ()
+          where
+            loop ((i_min, j_min), d_min) i j
+                | i >= n = return ((i_min, j_min), d_min)
+                | j >= n = loop ((i_min, j_min), d_min) (i+1) (i+2)
+                | otherwise = do
+                    x <- MSU.unsafeRead mat (i,j)
+                    case x of
+                        Just d -> if fst d < fst d_min
+                            then loop ((i,j), d) i (j+1)
+                            else loop ((i_min, j_min), d_min) i (j+1)
+                        _ -> loop ((i_min, j_min), d_min) i (j+1)
+
+    -- initialization
+    mat <- MSU.replicate (n,n) Nothing :: ST s (MSU.SymMMatrix VM.MVector s (Maybe (Double, (Bool, Int))))
+    forM_ [0..n-1] $ \i -> forM_ [i+1 .. n-1] $ \j -> do
+        Just (_, pwm1, _) <- VM.unsafeRead motifs' i
+        Just (_, pwm2, _) <- VM.unsafeRead motifs' j
+        MSU.unsafeWrite mat (i,j) $ Just $ align pwm1 pwm2
+
+    iter mat
+    results <- V.unsafeFreeze motifs'
+    return $ V.toList $ V.map fromJust $ V.filter isJust results
+{-# INLINE iterativeMerge #-}
+
+-- | build a guide tree from a set of motifs
+buildTree :: AlignFn -> [Motif] -> Dendrogram Motif
+buildTree align motifs = hclust Average (V.fromList motifs) δ
+  where
+    δ (Motif _ x) (Motif _ y) = fst $ align x y
+
+cutTreeBy :: Double   -- ^ start
+          -> Double   -- ^ step
+          -> ([Dendrogram a] -> Bool) -> Dendrogram a -> [Dendrogram a]
+cutTreeBy start step fn tree = go start
+  where
+    go x | fn clusters = clusters
+         | x - step > 0 = go $ x - step
+         | otherwise = clusters
+      where clusters = cutAt tree x
diff --git a/src/Bio/Motif/Search.hs b/src/Bio/Motif/Search.hs
--- a/src/Bio/Motif/Search.hs
+++ b/src/Bio/Motif/Search.hs
@@ -1,50 +1,74 @@
-{-# LANGUAGE BangPatterns #-}
+{-# LANGUAGE BangPatterns     #-}
+{-# LANGUAGE FlexibleContexts #-}
 
 module Bio.Motif.Search
     ( findTFBS
     , findTFBS'
     , findTFBSSlow
     , maxMatchSc
-    , MotifCompo(..)
-    , spacingConstraint
+    , SpaceDistribution(..)
+    , spaceConstraint
+    , spaceConstraintHelper
     ) where
 
-import Bio.Seq (DNA, toBS)
-import qualified Bio.Seq as Seq (length)
-import Bio.Motif
-import Control.Parallel.Strategies (parMap, rdeepseq)
-import Data.Conduit
-import qualified Data.HashSet as S
-import Data.List (foldl', intercalate)
-import Data.Ord (comparing)
-import qualified Data.ByteString.Char8 as B
-import qualified Data.Vector.Unboxed as U
-import qualified Data.Matrix.Unboxed as M
+import           Conduit                     (Source, await, mapC, sinkVector,
+                                              yield, ($$), (=$=))
+import           Control.Arrow               ((***))
+import           Control.Monad.ST            (runST)
+import           Control.Parallel.Strategies (parMap, rdeepseq)
+import qualified Data.ByteString.Char8       as B
+import           Data.Function               (on)
+import qualified Data.HashMap.Strict         as HM
+import qualified Data.HashSet                as S
+import           Data.List                   (nubBy)
+import qualified Data.Matrix.Unboxed         as M
+import           Data.Ord                    (comparing)
+import qualified Data.Vector.Unboxed         as U
 
+import           Bio.Motif                   (Bkgd (..), Motif (..), PWM (..),
+                                              pValueToScore, rcPWM, scores',
+                                              size)
+import           Bio.Seq                     (DNA, toBS)
+import qualified Bio.Seq                     as Seq (length)
+
 -- | given a user defined threshold, look for TF binding sites on a DNA
 -- sequence, using look ahead search. This function doesn't search for binding
 -- sites on the reverse strand
-findTFBS :: Monad m => Bkgd -> PWM -> DNA a -> Double -> Source m Int
-findTFBS bg pwm dna thres = loop 0
+findTFBS :: Monad m
+         => Bkgd
+         -> PWM
+         -> DNA a
+         -> Double
+         -> Bool    -- ^ whether to skip ambiguous sequences. Recommend: True
+                    -- in most cases
+         -> Source m Int
+findTFBS bg pwm dna thres skip = loop 0
   where
     loop !i | i >= l - n + 1 = return ()
-            | otherwise = do let (d, _) = lookAheadSearch bg pwm sigma dna i thres
+            | otherwise = do let (d, _) = searchFn bg pwm sigma dna i thres
                              if d == n - 1
                                 then yield i >> loop (i+1)
                                 else loop (i+1)
     sigma = optimalScoresSuffix bg pwm
     l = Seq.length dna
     n = size pwm
+    searchFn | skip = lookAheadSearch'
+             | otherwise = lookAheadSearch
 {-# INLINE findTFBS #-}
 
 -- | a parallel version of findTFBS
-findTFBS' :: Bkgd -> PWM -> DNA a -> Double -> [Int]
-findTFBS' bg pwm dna th = concat $ parMap rdeepseq f [0,step..l-n+1]
+findTFBS' :: Bkgd
+          -> PWM
+          -> DNA a
+          -> Double
+          -> Bool
+          -> [Int]
+findTFBS' bg pwm dna th skip = concat $ parMap rdeepseq f [0,step..l-n+1]
   where
     f x = loop x
       where
         loop i | i >= x+step || i >= l-n+1 = []
-               | otherwise = let d = fst $ lookAheadSearch bg pwm sigma dna i th
+               | otherwise = let d = fst $ searchFn bg pwm sigma dna i th
                              in if d == n-1
                                    then i : loop (i+1)
                                    else loop (i+1)
@@ -52,11 +76,13 @@
     l = Seq.length dna
     n = size pwm
     step = 500000
+    searchFn | skip = lookAheadSearch'
+             | otherwise = lookAheadSearch
 {-# INLINE findTFBS' #-}
 
 -- | use naive search
 findTFBSSlow :: Monad m => Bkgd -> PWM -> DNA a -> Double -> Source m Int
-findTFBSSlow bg pwm dna thres = scores' bg pwm dna $=
+findTFBSSlow bg pwm dna thres = scores' bg pwm dna =$=
                                        loop 0
   where
     loop i = do v <- await
@@ -137,59 +163,112 @@
     n = size pwm
 {-# INLINE lookAheadSearch #-}
 
+-- | this version skip sequences contain ambiguous bases, like "N"
+lookAheadSearch' :: Bkgd              -- ^ background nucleotide distribution
+                 -> PWM               -- ^ pwm
+                 -> U.Vector Double   -- ^ best possible match score of suffixes
+                 -> DNA a             -- ^ DNA sequence
+                 -> Int               -- ^ starting location on the DNA
+                 -> Double            -- ^ threshold
+                 -> (Int, Double)     -- ^ (d, sc_d), the largest d such that sc_d > th_d
+lookAheadSearch' (BG (a, c, g, t)) pwm sigma dna start thres = loop (0, -1) 0
+  where
+    loop (!acc, !th_d) !d
+      | acc < th_d = (d-2, acc)
+      | otherwise = if d >= n
+                       then (d-1, acc)
+                       else loop (acc + sc, thres - sigma U.! d) (d+1)
+      where
+        sc = case toBS dna `B.index` (start + d) of
+              'A' -> log $! matchA / a
+              'C' -> log $! matchC / c
+              'G' -> log $! matchG / g
+              'T' -> log $! matchT / t
+              _ -> -1 / 0
+        matchA = addSome $ M.unsafeIndex (_mat pwm) (d,0)
+        matchC = addSome $ M.unsafeIndex (_mat pwm) (d,1)
+        matchG = addSome $ M.unsafeIndex (_mat pwm) (d,2)
+        matchT = addSome $ M.unsafeIndex (_mat pwm) (d,3)
+        addSome !x | x == 0 = pseudoCount
+                   | otherwise = x
+        pseudoCount = 0.0001
+    n = size pwm
+{-# INLINE lookAheadSearch' #-}
+
+{-
 data MotifCompo = MotifCompo
-    { _motif1 :: Motif
-    , _motif2 :: Motif
+    { _motif1        :: Motif
+    , _motif2        :: Motif
     , _sameDirection :: Bool
-    , _spacing :: Int
-    , _score :: Double
+    , _spacing       :: Int
+    , _score         :: Double
     }
 
 instance Show MotifCompo where
     show (MotifCompo m1 m2 isSame sp sc) = intercalate "\t"
         [B.unpack $ _name m1, B.unpack $ _name m2, show isSame, show sp, show sc]
+        -}
 
+data SpaceDistribution = SpaceDistribution
+    { _motif1   :: Motif
+    , _nSites1  :: (Int, Int)
+    , _motif2   :: Motif
+    , _nSites2  :: (Int, Int)
+    , _same     :: [(Int, Int)]
+    , _opposite :: [(Int, Int)]
+    } deriving (Show, Read)
+
 -- | search for spacing constraint between two TFs
-spacingConstraint :: Motif   -- ^ motif 1
-                  -> Motif   -- ^ motif 2
-                  -> Bkgd    -- ^ backgroud nucleotide distribution
-                  -> Double  -- ^ p-Value for motif finding
-                  -> Int     -- ^ half window size
-                  -> Int     -- ^ max distance to search
-                  -> DNA a -> [MotifCompo]
-spacingConstraint m1@(Motif _ pwm1) m2@(Motif _ pwm2) bg th w k dna = same ++ oppose
+spaceConstraint :: [(Motif, Motif)]   -- ^ motifs, names must be unique
+                -> Bkgd    -- ^ backgroud nucleotide distribution
+                -> Double  -- ^ p-Value for motif finding
+                -> Int     -- ^ half window size, typical 5
+                -> Int     -- ^ max distance to search, typical 300
+                -> DNA a -> [SpaceDistribution]
+spaceConstraint pairs bg th w k dna = flip map pairs $ \(a, b) ->
+    let (m1, site1) = HM.lookupDefault undefined (_name a) sites
+        (m2, site2) = HM.lookupDefault undefined (_name b) sites
+        (same, opposite) = spaceConstraintHelper site1 site2 w k
+    in SpaceDistribution m1 ((U.length *** U.length) site1) m2
+        ((U.length *** U.length) site2) same opposite
   where
-    rs = let rs' = [-k, -k+2*w+1 .. 0]
-         in rs' ++ map (*(-1)) (reverse rs')
-    -- on the same orientation
-    same = zipWith f rs $ zipWith (+) nFF nRR
-      where
-        nFF = map (nOverlap forward1 forward2 w) rs
-        nRR = map (nOverlap reverse1 reverse2 w) $ reverse rs
-        f r c = MotifCompo m1 m2 True r $ fromIntegral c / n
-    oppose = zipWith f rs $ zipWith (+) nFR nRF
+    motifs = nubBy ((==) `on` _name) $ concatMap (\(a,b) -> [a,b]) pairs
+    findSites (Motif _ pwm) = (fwd, rev)
       where
-        nFR = map (nOverlap forward1 reverse2 w) rs
-        nRF = map (nOverlap reverse1 forward2 w) $ reverse rs
-        f r c = MotifCompo m1 m2 False r $ fromIntegral c / n
-    forward1 = findTFBS' bg pwm1 dna th1
-    forward2 = S.fromList $ findTFBS' bg pwm2 dna th2
-    reverse1 = map (+ (s1 - 1)) $ findTFBS' bg (rcPWM pwm1) dna th1'
-    reverse2 = S.fromList $ map (+ (s2 - 1)) $ findTFBS' bg (rcPWM pwm2) dna th2'
-    th1 = pValueToScore th bg pwm1
-    th1' = pValueToScore th bg $ rcPWM pwm1
-    th2 = pValueToScore th bg pwm2
-    th2' = pValueToScore th bg $ rcPWM pwm2
-    s1 = size pwm1
-    s2 = size pwm2
-    n = sqrt $ fromIntegral $ (length forward1 + length reverse1) * (S.size forward2 + S.size reverse2)
+        fwd = runST $ findTFBS bg pwm dna cutoff True $$ sinkVector
+        rev = runST $ findTFBS bg pwm' dna cutoff' True =$=
+              mapC (+ (size pwm - 1)) $$ sinkVector
+        cutoff = pValueToScore th bg pwm
+        cutoff' = pValueToScore th bg pwm'
+        pwm' = rcPWM pwm
+    sites = HM.fromList $ map (\m -> (_name m, (m, findSites m))) motifs
+{-# INLINE spaceConstraint #-}
 
-    nOverlap :: [Int] -> S.HashSet Int -> Int -> Int -> Int
-    nOverlap xs ys w' i = foldl' f 0 xs
+spaceConstraintHelper :: (U.Vector Int, U.Vector Int)
+                      -> (U.Vector Int, U.Vector Int)
+                      -> Int
+                      -> Int
+                      -> ([(Int, Int)], [(Int, Int)])
+spaceConstraintHelper (fw1, rv1) (fw2, rv2) w k = (same, oppose)
+  where
+    rs = let rs' = [-k, -k+2*w+1 .. 0]
+         in rs' ++ map (*(-1)) (reverse rs')
+    fw2' = S.fromList $ U.toList fw2
+    rv2' = S.fromList $ U.toList rv2
+    nOverlap :: U.Vector Int -> S.HashSet Int -> Int -> Int -> Int
+    nOverlap xs ys w' i = U.foldl' f 0 xs
       where
         f acc x | any (`S.member` ys) [x + i - w' .. x + i + w'] = acc + 1
                 | otherwise = acc
-{-# INLINE spacingConstraint #-}
+    same = zip rs $ zipWith (+) nFF nRR
+      where
+        nFF = map (nOverlap fw1 fw2' w) rs
+        nRR = map (nOverlap rv1 rv2' w) $ reverse rs
+    oppose = zip rs $ zipWith (+) nFR nRF
+      where
+        nFR = map (nOverlap fw1 rv2' w) rs
+        nRF = map (nOverlap rv1 fw2' w) $ reverse rs
+{-# INLINE spaceConstraintHelper #-}
 
 {-
 computePValue :: Double -> [Int] -> [(Int, Double)]
diff --git a/src/Bio/RealWorld/BioGRID.hs b/src/Bio/RealWorld/BioGRID.hs
--- a/src/Bio/RealWorld/BioGRID.hs
+++ b/src/Bio/RealWorld/BioGRID.hs
@@ -82,7 +82,8 @@
     let request = initReq { method = "GET"
                           , requestHeaders = [("Content-type", "text/plain")]
                           }
-    r <- withManager $ \manager -> httpLbs request manager
+    manager <- newManager tlsManagerSettings
+    r <- httpLbs request manager
     return $ map parseAsTab2 $ BL.lines $ responseBody r
   where
     url = base ++ "/interactions/?searchNames=ture&includeInteractors=false"
diff --git a/src/Bio/RealWorld/ENCODE.hs b/src/Bio/RealWorld/ENCODE.hs
--- a/src/Bio/RealWorld/ENCODE.hs
+++ b/src/Bio/RealWorld/ENCODE.hs
@@ -39,7 +39,6 @@
     , showResult
     ) where
 
-import Control.Applicative ((<$>))
 import Data.Aeson
 import Data.Aeson.Types
 import Data.Aeson.Encode.Pretty (encodePretty)
@@ -47,12 +46,10 @@
 import qualified Data.ByteString.Lazy.Char8 as B
 import qualified Data.ByteString.Char8 as BS
 import qualified Data.Sequence as S
-import qualified Data.Foldable as F
 import qualified Data.Text as T
 import qualified Data.Vector as V
 import Network.HTTP.Conduit
 import Data.Default.Class
-import Data.Monoid
 
 import Bio.RealWorld.ID
 
@@ -66,9 +63,9 @@
     show (KeyWords x y) = f x ++ g y
       where
         f x' | S.null x' = ""
-             | otherwise = "searchTerm=" ++ F.foldr1 (\a b -> b ++ ('+':a)) x' ++ "&"
+             | otherwise = "searchTerm=" ++ foldr1 (\a b -> b ++ ('+':a)) x' ++ "&"
         g y' | S.null y' = ""
-             | otherwise =  F.foldr1 (\a b -> b ++ ('&':a)) y'
+             | otherwise =  foldr1 (\a b -> b ++ ('&':a)) y'
 
 instance Monoid KeyWords where
     mempty = KeyWords S.empty S.empty
@@ -80,14 +77,15 @@
 -- | general search using keywords and a set of constraints. Example:
 -- search ["chip", "sp1"] ["type=experiment"]
 search :: KeyWords -> IO (Either String [Value])
-search kw = do 
+search kw = do
     initReq <- parseUrl url
-    let request = initReq { method = "GET" 
+    let request = initReq { method = "GET"
                           , requestHeaders = [("accept", "application/json")]
                           }
-    r <- withManager $ \manager -> httpLbs request manager
+    manager <- newManager tlsManagerSettings
+    r <- httpLbs request manager
     return $ (eitherDecode . responseBody) r >>=
-                parseEither (withObject "ENCODE_JSON" (.: "@graph"))
+        parseEither (withObject "ENCODE_JSON" (.: "@graph"))
   where
     url = base ++ "search/?" ++ show kw
 
@@ -119,10 +117,11 @@
 openUrl :: String -> String -> IO B.ByteString
 openUrl url datatype = do
     initReq <- parseUrl url
-    let request = initReq { method = "GET" 
+    let request = initReq { method = "GET"
                           , requestHeaders = [("accept", BS.pack datatype)]
                           }
-    r <- withManager $ \manager -> httpLbs request manager
+    manager <- newManager tlsManagerSettings
+    r <- httpLbs request manager
     return $ responseBody r
 
 jsonFromUrl :: String -> IO (Either String Value)
@@ -148,6 +147,6 @@
 as :: FromJSON a => Value -> a
 as = getResult . fromJSON
   where
-    getResult (Error e) = error e 
+    getResult (Error e) = error e
     getResult (Success x) = x
 {-# INLINE as #-}
diff --git a/src/Bio/RealWorld/Ensembl.hs b/src/Bio/RealWorld/Ensembl.hs
--- a/src/Bio/RealWorld/Ensembl.hs
+++ b/src/Bio/RealWorld/Ensembl.hs
@@ -28,11 +28,12 @@
 lookupHelp :: [EnsemblID] -> IO (Either String Object)
 lookupHelp xs = do
     initReq <- parseUrl url
-    let request = initReq { method = "POST" 
+    let request = initReq { method = "POST"
                           , requestHeaders = [("Content-type", "application/json")]
                           , requestBody = body
                           }
-    r <- withManager $ \manager -> httpLbs request manager
+    manager <- newManager tlsManagerSettings
+    r <- httpLbs request manager
     return . eitherDecode . responseBody $ r
   where
     url = base ++ "/lookup/id/"
diff --git a/src/Bio/RealWorld/UCSC.hs b/src/Bio/RealWorld/UCSC.hs
--- a/src/Bio/RealWorld/UCSC.hs
+++ b/src/Bio/RealWorld/UCSC.hs
@@ -21,10 +21,8 @@
     , readUCSCGenes'
     ) where
 
-import Control.Monad.IO.Class (liftIO)
 import qualified Data.ByteString.Char8 as B
-import Data.Conduit
-import qualified Data.Conduit.List as CL
+import Conduit
 import qualified Data.Vector.Unboxed as U
 import System.IO
 
@@ -69,7 +67,7 @@
 {-# INLINE readUCSCGenes #-}
 
 readUCSCGenes' :: FilePath -> IO [UCSCGene]
-readUCSCGenes' fl = readUCSCGenes fl $$ CL.consume
+readUCSCGenes' fl = readUCSCGenes fl $$ sinkList
 {-# INLINE readUCSCGenes' #-}
 
 readGeneFromLine :: B.ByteString -> UCSCGene
diff --git a/src/Bio/Seq.hs b/src/Bio/Seq.hs
--- a/src/Bio/Seq.hs
+++ b/src/Bio/Seq.hs
@@ -1,8 +1,8 @@
 {-# LANGUAGE MultiParamTypeClasses #-}
 {-# LANGUAGE BangPatterns #-}
 {-# LANGUAGE FlexibleContexts #-}
-module Bio.Seq 
-    ( 
+module Bio.Seq
+    (
     -- * Alphabet
       Basic
     , IUPAC
@@ -24,7 +24,6 @@
 import qualified Data.HashMap.Strict as M
 import qualified Data.HashSet as S
 import Data.Char8 (toUpper)
-import Data.Monoid (Monoid(..))
 
 -- | Alphabet defined by http://www.chem.qmul.ac.uk/iupac/
 -- | Standard unambiguous alphabet
@@ -77,7 +76,7 @@
 
 class BioSeq' s => BioSeq s a where
     alphabet :: s a -> S.HashSet Char
-    fromBS :: B.ByteString -> s a 
+    fromBS :: B.ByteString -> s a
 
 instance BioSeq DNA Basic where
     alphabet _ = S.fromList "ACGT"
diff --git a/src/Bio/Seq/IO.hs b/src/Bio/Seq/IO.hs
--- a/src/Bio/Seq/IO.hs
+++ b/src/Bio/Seq/IO.hs
@@ -16,7 +16,6 @@
 
 import Bio.Seq
 import Bio.Utils.Misc (readInt)
-import Control.Applicative ((<$>))
 import qualified Data.ByteString.Char8 as B
 import qualified Data.HashMap.Lazy as M
 import Data.List.Split
diff --git a/src/Bio/Utils/Functions.hs b/src/Bio/Utils/Functions.hs
--- a/src/Bio/Utils/Functions.hs
+++ b/src/Bio/Utils/Functions.hs
@@ -18,6 +18,7 @@
     , ihs'
     , scale
     , filterFDR
+    , slideAverage
     , hyperquick
     , kld
     , jsd
@@ -32,7 +33,7 @@
 import qualified Data.Vector as V
 import qualified Data.Vector.Generic as G
 import qualified Data.Vector.Unboxed as U
-import Statistics.Sample (meanVarianceUnb)
+import Statistics.Sample (meanVarianceUnb, mean)
 import Statistics.Function (sortBy)
 
 -- | inverse hyperbolic sine transformation
@@ -55,7 +56,10 @@
 {-# INLINE scale #-}
 
 -- | given the p-values, filter data by controling FDR
-filterFDR :: G.Vector v (a, Double) => Double -> v (a, Double) -> v (a, Double)
+filterFDR :: G.Vector v (a, Double)
+          => Double  -- ^ desired FDR value
+          -> v (a, Double)  -- ^ input data and pvalues
+          -> v (a, Double)
 filterFDR α xs = go n . sortBy (comparing snd) $ xs
   where
     go rank v | rank <= 0 = G.empty
@@ -64,6 +68,19 @@
     n = G.length xs
 {-# INLINE filterFDR #-}
 
+-- | Compute the sliding average for each entry in a vector
+slideAverage :: (Fractional a, G.Vector v a)
+             => Int              -- ^ size of HALF sliding window, 2 means a total
+                                 -- window size is 5
+             -> v a
+             -> v a
+slideAverage k xs = G.generate n $ \i -> go xs (max 0 (i-k)) (min (n-1) (i+k))
+  where
+    go v i j = let l = j - i + 1
+               in G.foldl' (+) 0 (G.unsafeSlice i l v) / fromIntegral l
+    n = G.length xs
+{-# INLINE slideAverage #-}
+
 hyperquick :: Int -> Int -> Int -> Int -> Double
 hyperquick x m _n _N = loop (m-2) s s (2*e)
   where
@@ -82,28 +99,9 @@
                           ( 1 - fromIntegral (_n-1-x) / fromIntegral (_N-1-m) )
     e = 1e-20
 
-{-
-hyperquick' :: Int -> Int -> Int -> Int -> Double
-hyperquick' x m _n _N = loop (m-2) s s (2*e)
-  where
-    loop !k !ak !bk !epsk
-        | k < _N - (_n-x) - 1 && epsk > e =
-            let ck = ak / bk
-                k' = k + 1
-                jjm = invJm _n x _N k'
-                bk' = bk * jjm + 1
-                ak' = ak * jjm
-                espk' = fromIntegral (_N - (_n - x) - 1 - k') * (ck - ak' / bk')
-            in loop k' ak' bk' espk'
-        | otherwise = 1 - (ak / bk - epsk / 2)
-    s = foldl' (\s' k -> 1 + s' * invJm _n x _N k) 1.0 [x..m-2]
-    invJm _n x _N m = ( 1 - fromIntegral x / fromIntegral (m+1) ) /
-                          ( 1 - fromIntegral (_n-1-x) / fromIntegral (_N-1-m) )
-    e = 1e-200
-    -}
 
 -- | compute the Kullback-Leibler divergence between two valid (not check) probability distributions.
--- kl(X,Y) = \sum_i P(x_i) log_2(P(x_i)\/P(y_i)). 
+-- kl(X,Y) = \sum_i P(x_i) log_2(P(x_i)\/P(y_i)).
 kld :: (G.Vector v Double, G.Vector v (Double, Double)) => v Double -> v Double -> Double
 kld xs ys | G.length xs /= G.length ys = error "Incompitable dimensions"
           | otherwise = G.foldl' f 0 . G.zip xs $ ys
diff --git a/src/Bio/Utils/Overlap.hs b/src/Bio/Utils/Overlap.hs
--- a/src/Bio/Utils/Overlap.hs
+++ b/src/Bio/Utils/Overlap.hs
@@ -13,9 +13,7 @@
 import Data.Function
 import Bio.Data.Bed
 import Control.Monad
-import Data.Conduit
-import qualified Data.Conduit.List as CL
-import Control.Monad.Trans.Class (lift)
+import Conduit
 
 -- | convert lines of a BED file into a data structure - A hashmap of which the
 -- | chromosomes, and values are interval maps.
@@ -45,7 +43,7 @@
                 intervals = case set of
                     Just iMap -> IM.intersecting iMap.toInterval $ b
                     _ -> []
-            forM_ intervals (\interval -> do 
+            forM_ intervals (\interval -> do
                 let i = snd interval
                     nucl = overlap b . fst $ interval
                 VM.write v i . (+nucl) =<< VM.read v i
@@ -56,7 +54,7 @@
     featMap = toMap.map (\x -> (x^.chrom, (x^.chromStart, x^.chromEnd))) $ bin
     featWidth = V.fromList.map (\x -> x^.chromEnd - x^.chromStart) $ bin
     n = length bin
-    overlap (l, u) (IM.ClosedInterval l' u') 
+    overlap (l, u) (IM.ClosedInterval l' u')
         | l' >= l = if u' <= u then u'-l'+1 else u-l'+1
         | otherwise = if u' <= u then u'-l+1 else u-l+1
     overlap _ _ = 0
@@ -71,16 +69,16 @@
     sink :: Sink BED IO (V.Vector Int)
     sink = do
         v <- lift $ VM.replicate (n+1) 0
-        CL.mapM_ $ \t -> do
+        mapM_C $ \t -> do
                 let set = M.lookup (_chrom t) featMap
                     s = _chromStart t
                     e = _chromEnd t
                     b = (s, e)
                     l = e - s + 1
                     intervals = case set of
-                        Just iMap -> IM.intersecting iMap.toInterval $ b
+                        Just iMap -> IM.toList . IM.intersecting iMap . toInterval $ b
                         _ -> []
-                forM_ intervals (\interval -> do 
+                forM_ intervals (\interval -> do
                     let i = snd interval
                         nucl = overlap b . fst $ interval
                     VM.write v i . (+nucl) =<< VM.read v i
@@ -91,13 +89,13 @@
     featMap = toMap.map (\x -> (_chrom x, (_chromStart x, _chromEnd x))) $ bin
     featWidth = V.fromList.map (\x -> _chromEnd x - _chromStart x) $ bin
     n = length bin
-    overlap (l, u) (IM.ClosedInterval l' u') 
+    overlap (l, u) (IM.ClosedInterval l' u')
         | l' >= l = if u' <= u then u'-l'+1 else u-l'+1
         | otherwise = if u' <= u then u'-l+1 else u-l+1
     overlap _ _ = 0
     normalize a b = fromIntegral a / fromIntegral b
 
-overlapFragment, overlapNucl :: 
+overlapFragment, overlapNucl ::
                   [(Int, Int)] -- ^ Ascending order list
                 -> [(Int, Int)] -- ^ tags in any order
                 -> V.Vector Int
@@ -107,7 +105,7 @@
         iMap = IM.fromAscList $ zip (map toInterval xs) [0..]
         go ts' v = do
             forM_ ts' (\x -> do
-                let indices = snd.unzip.IM.intersecting iMap.toInterval $ x
+                let indices = IM.elems . IM.intersecting iMap . toInterval $ x
                 forM_ indices (\i -> VM.write v i . (+1) =<< VM.read v i)
                 )
             return v
@@ -118,15 +116,15 @@
         iMap = IM.fromAscList $ zip (map toInterval xs) [0..]
         go ts' v = do
             forM_ ts' (\x -> do
-                let intervals = IM.intersecting iMap.toInterval $ x
-                forM_ intervals (\interval -> do 
+                let intervals = IM.toList . IM.intersecting iMap . toInterval $ x
+                forM_ intervals (\interval -> do
                     let i = snd interval
                         nucl = overlap x . fst $ interval
                     VM.write v i . (+nucl) =<< VM.read v i
                     )
                 )
             return v
-        overlap (l, u) (IM.ClosedInterval l' u') 
+        overlap (l, u) (IM.ClosedInterval l' u')
             | l' >= l = if u' <= u then u'-l'+1 else u-l'+1
             | otherwise = if u' <= u then u'-l+1 else u-l+1
         overlap _ _ = 0
diff --git a/tests/Tests/Bam.hs b/tests/Tests/Bam.hs
new file mode 100644
--- /dev/null
+++ b/tests/Tests/Bam.hs
@@ -0,0 +1,21 @@
+{-# LANGUAGE OverloadedStrings #-}
+
+module Tests.Bam (tests) where
+
+import Bio.Data.Bed
+import Bio.Data.Bam
+import Conduit
+import Test.Tasty
+import Test.Tasty.HUnit
+import qualified Data.Vector as V
+
+tests :: TestTree
+tests = testGroup "Test: Bio.Data.Bam"
+    [ testCase "bamToBed" bamToBedTest
+    ]
+
+bamToBedTest :: Assertion
+bamToBedTest = do
+    bed <- readBed' "tests/data/example.bed"
+    bed' <- readBam "tests/data/example.bam" =$= bamToBed $$ sinkList
+    bed @=? bed'
diff --git a/tests/test.hs b/tests/test.hs
--- a/tests/test.hs
+++ b/tests/test.hs
@@ -1,4 +1,5 @@
 import qualified Tests.Bed as Bed
+import qualified Tests.Bam as Bam
 import qualified Tests.Motif as Motif
 import qualified Tests.ChIPSeq as ChIPSeq
 import qualified Tests.Seq as Seq
@@ -7,6 +8,7 @@
 main :: IO ()
 main = defaultMain $ testGroup "Main"
     [ Bed.tests
+    , Bam.tests
     , Seq.tests
     , ChIPSeq.tests
     , Motif.tests
