Safe Haskell  None 

Language  Haskell2010 
Pileup, similar to Samtools
Pileup turns a sorted sequence of reads into a sequence of "piles", one for each site where a genetic variant might be called. We will scan each read's CIGAR line and MD field in concert with the sequence and effective quality. Effective quality is the lowest available quality score of QUAL, MAPQ, and BQ. For aDNA calling, a base is represented as four probabilities, derived from a position dependent damage model.
Synopsis
 data PrimChunks
 = Seek !Int PrimBase
  Indel [Nucleotides] [DamagedBase] PrimBase
  EndOfRead
 data PrimBase = Base {
 _pb_wait :: !Int
 _pb_base :: !DamagedBase
 _pb_mapq :: !Qual
 _pb_chunks :: PrimChunks
 type PosPrimChunks = (Refseq, Int, Bool, PrimChunks)
 data DamagedBase = DB {
 db_call :: !Nucleotide
 db_qual :: !Qual
 db_dmg_tk :: !DmgToken
 db_dmg_pos :: !Int
 db_ref :: !Nucleotides
 newtype DmgToken = DmgToken {
 fromDmgToken :: Int
 decompose :: DmgToken > BamRaw > [PosPrimChunks]
 data CallStats = CallStats {
 read_depth :: !Int
 reads_mapq0 :: !Int
 sum_mapq :: !Int
 sum_mapq_squared :: !Int
 newtype V_Nuc = V_Nuc (Vector Nucleotide)
 newtype V_Nucs = V_Nucs (Vector Nucleotides)
 data IndelVariant = IndelVariant {
 deleted_bases :: !V_Nucs
 inserted_bases :: !V_Nuc
 type BasePile = [DamagedBase]
 type IndelPile = [(Qual, ([Nucleotides], [DamagedBase]))]
 data Pile' a b = Pile {
 p_refseq :: !Refseq
 p_pos :: !Int
 p_snp_stat :: !CallStats
 p_snp_pile :: a
 p_indel_stat :: !CallStats
 p_indel_pile :: b
 type Pile = Pile' (BasePile, BasePile) (IndelPile, IndelPile)
 pileup :: Enumeratee [PosPrimChunks] [Pile] IO b
 newtype PileM m a = PileM {}
 type PileF m r = Refseq > Int > ([PrimBase], [PrimBase]) > (Heap, Heap) > (Stream [Pile] > Iteratee [Pile] m r) > Stream [PosPrimChunks] > Iteratee [PosPrimChunks] m (Iteratee [Pile] m r)
 get_refseq :: PileM m Refseq
 get_pos :: PileM m Int
 upd_pos :: (Int > Int) > PileM m ()
 yieldPile :: CallStats > BasePile > BasePile > CallStats > IndelPile > IndelPile > PileM m ()
 pileup' :: PileM m ()
 pileup'' :: PileM m ()
 p'feed_input :: PileM m ()
 p'check_waiting :: PileM m ()
 p'scan_active :: PileM m ((CallStats, BasePile), (CallStats, BasePile), (CallStats, IndelPile), (CallStats, IndelPile))
 data Heap
 unionH :: Heap > Heap > Heap
 getMinKeyH :: Heap > Maybe Int
 viewMinH :: Heap > Maybe (Int, PrimBase, Heap)
Documentation
data PrimChunks Source #
The primitive pieces for genotype calling: A position, a base represented as four likelihoods, an inserted sequence, and the length of a deleted sequence. The logic is that we look at a base followed by some indel, and all those indels are combined into a single insertion and a single deletion.
Seek !Int PrimBase  skip to position (at start or after N operation) 
Indel [Nucleotides] [DamagedBase] PrimBase  observed deletion and insertion between two bases 
EndOfRead  nothing anymore 
Instances
Show PrimChunks Source #  
showsPrec :: Int > PrimChunks > ShowS # show :: PrimChunks > String # showList :: [PrimChunks] > ShowS # 
Base  more chunks 

type PosPrimChunks = (Refseq, Int, Bool, PrimChunks) Source #
data DamagedBase Source #
Represents our knowledge about a certain base, which consists of the base itself (A,C,G,T, encoded as 0..3; no Ns), the quality score (anything that isn't A,C,G,T becomes A with quality 0), and a substitution matrix representing postmortem but presequencing substitutions.
Unfortunately, none of this can be rolled into something more simple, because damage and sequencing error behave so differently.
Damage information is polymorphic. We might run with a simple version (a matrix) for calling, but we need more (a matrix and a mutable matrix, I think) for estimation.
DB  reference base from MD field 

Instances
Show DamagedBase Source #  
showsPrec :: Int > DamagedBase > ShowS # show :: DamagedBase > String # showList :: [DamagedBase] > ShowS # 
decompose :: DmgToken > BamRaw > [PosPrimChunks] Source #
Decomposes a BAM record into chunks suitable for piling up. We pick apart the CIGAR and MD fields, and combine them with sequence and quality as appropriate. Clipped bases are removed/skipped as needed. We also apply a substitution matrix to each base, which must be supplied along with the read.
Statistics about a genotype call. Probably only useful for fitlering (so not very useful), but we keep them because it's easy to track them.
CallStats  

Instances
Eq CallStats Source #  
Show CallStats Source #  
Generic CallStats Source #  
Semigroup CallStats Source #  
Monoid CallStats Source #  
type Rep CallStats Source #  
type Rep CallStats = D1 (MetaData "CallStats" "Bio.Bam.Pileup" "biohazard1.0.3BRJ7LTjY7czK9dQ2OiWm8P" False) (C1 (MetaCons "CallStats" PrefixI True) ((S1 (MetaSel (Just "read_depth") SourceUnpack SourceStrict DecidedStrict) (Rec0 Int) :*: S1 (MetaSel (Just "reads_mapq0") SourceUnpack SourceStrict DecidedStrict) (Rec0 Int)) :*: (S1 (MetaSel (Just "sum_mapq") SourceUnpack SourceStrict DecidedStrict) (Rec0 Int) :*: S1 (MetaSel (Just "sum_mapq_squared") SourceUnpack SourceStrict DecidedStrict) (Rec0 Int)))) 
data IndelVariant Source #
Instances
type BasePile = [DamagedBase] Source #
Map quality and a list of encountered bases, with damage information and reference base if known.
type IndelPile = [(Qual, ([Nucleotides], [DamagedBase]))] Source #
Map quality and a list of encountered indel variants. The deletion has the reference sequence, if known, an insertion has the inserted sequence with damage information.
Running pileup results in a series of piles. A Pile
has the
basic statistics of a VarCall
, but no likelihood values and a
pristine list of variants instead of a proper call. We emit one pile
with two BasePile
s (one for each strand) and one IndelPile
(the
one immediately following) at a time.
Pile  

type Pile = Pile' (BasePile, BasePile) (IndelPile, IndelPile) Source #
Raw pile. Bases and indels are piled separately on forward and backward strands.
pileup :: Enumeratee [PosPrimChunks] [Pile] IO b Source #
The pileup enumeratee takes BamRaw
s, decomposes them, interleaves
the pieces appropriately, and generates Pile
s. The output will
contain at most one BasePile
and one IndelPile
for each position,
piles are sorted by position.
This top level driver receives BamRaw
s. Unaligned reads and
duplicates are skipped (but not those merely failing quality checks).
Processing stops when the first read with invalid br_rname
is
encountered or a t end of file.
The pileup logic keeps a current coordinate (just two integers) and
two running queues: one of active PrimBase
s that contribute to
current genotype calling and on of waiting PrimBase
s that will
contribute at a later point.
Oppan continuation passing style! Not only is the CPS version of the
state monad (we have five distinct pieces of state) somewhat faster,
we also need CPS to interact with the mechanisms of Iteratee
. It
makes implementing yield
, peek
, and bump
straight forward.
type PileF m r = Refseq > Int > ([PrimBase], [PrimBase]) > (Heap, Heap) > (Stream [Pile] > Iteratee [Pile] m r) > Stream [PosPrimChunks] > Iteratee [PosPrimChunks] m (Iteratee [Pile] m r) Source #
The things we drag along in PileM
. Notes:
* The active queue is a simple stack. We add at the front when we
encounter reads, which reverses them. When traversing it, we traverse
reads backwards, but since we accumulate the BasePile
, it gets reversed
back. The new active queue, however, is no longer reversed (as it should
be). So after the traversal, we reverse it again. (Yes, it is harder to
understand than using a proper deque type, but it is cheaper.
There may not be much point in the reversing, though.)
get_refseq :: PileM m Refseq Source #
yieldPile :: CallStats > BasePile > BasePile > CallStats > IndelPile > IndelPile > PileM m () Source #
Sends one piece of output downstream. You are not expected to
understand how this works, but inlining eneeCheckIfDone
plugged an
annoying memory leak.
pileup' :: PileM m () Source #
The actual pileup algorithm. If active contains something, continue here. Else find the coordinate to continue from, which is the minimum of the next waiting coordinate and the next coordinate in input; if found, continue there, else we're all done.
p'feed_input :: PileM m () Source #
Feeds input as long as it starts at the current position
p'check_waiting :: PileM m () Source #
Checks waiting queue. If there is anything waiting for the current position, moves it to active queue.
p'scan_active :: PileM m ((CallStats, BasePile), (CallStats, BasePile), (CallStats, IndelPile), (CallStats, IndelPile)) Source #