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map_genome.pl
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map_genome.pl
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#!/usr/bin/env perl
use strict;
use warnings;
use Carp;
use English;
use Getopt::Long;
use Pod::Usage;
use Data::Dumper;
use Memoize;
use DBD::SQLite;
use List::Util qw/min max/;
$OUTPUT_AUTOFLUSH = 1;
memoize "mirror";
memoize "phase";
memoize "consistent";
memoize "linked";
memoize "calc_LR";
memoize "separate_intercross";
my $sex = "ABBABABBBBAABBBBBBBAAAAABABAAABBBBABABABBBABBABABBAAAAAABABBAABBAABAB";
# Chroms only used for graphics and output! Patterns are inferred correctly without them
my %chromosomes = (
"ABBBBBBABABAABAAAABBBBBAABABBABABAABAAABABBBABBABBABBAABBABBAABBAABBB" => "1",
"ABBBABABBAABBBBBBABBAABBBBBBABBBABBABABAABBAAABBABBABBAAAAAAAABBAABAB" => "2",
"ABABABAABAABBBBBBABBBAABBBBAABAABAABAABAAAAABAABBAAAAAAAABBBBABBABBBA" => "3",
"ABBABBBBBABBABAAAAABAABBBBBBAAAAABABBAABABABAABABBAABABBAAABBBAABBABB" => "4",
"AABABBABBBABABABBBBABBBBBAABBABABAABABBABAAAAABBBAAABBAABBBBABBBBBABA" => "5",
"AABABBBBBABBAABABAABAABABABAAAAABAAAABAABBBBAABAABBBBAAABABAABAAAABAB" => "6",
"AABBAABBABBBAAABBBBBBBBABAAABBAAABAAAAAAABBAAABAAAABAABBBBABABABAABBB" => "7",
"AABBABBAABBBAAABAABABAAAAABBABBAAAABBABAABABABBBAABAABAAABABAAAAAAAAB" => "8",
"AABBBABBABAABBABBABBBAABABBBABBABAAAAAABABABAAAAABBBBBAABBABBAABABBAA" => "9",
"BAHHBABHBBBHABBAABBABHBABAABABABAHBABAAAABAABAAAAAAAABHBBHBBHAABHBAAA" => "10",
"ABAABBBABBAABAABBAAAAAABABBAABAAAAABBAAAAAAABABBABAAABBABAAAABABABBAB" => "11",
"AAABBAABBBBABBBABABABBABBAAAAABAAABBABAABBBABAABAAABAAABBBBBBAABBBBAA" => "12",
"ABAABBBBAAAABABAABBBAAAAAABBBBBBBBAAAAABAAABABABBBABABAABAAABBAABBBAA" => "13",
"AAABAHHBABHBAHHABBHHBBHAAAABBABBAHBBAAHBAAHBAHBBBHBAABHABBHBBBAABHAHB" => "14",
"ABBBBBABBAAAABBBBBBABBABBBAAABAABBABAAAAAAAABBABAABABBABBAAAAABAABBAA" => "15",
"ABBAABBABBBABBBBBBAAAABABBAAABBBBAABABAABBAAABAAABBBBBBBBBABBBAAABABB" => "16",
"ABBBAABAABBABAABABABABBAABAABBABBAABBAAAABAAABBBAAAABAABBBAAABBBAABAB" => "17",
"ABAAAABAAAABAABAAAAABAABBAABABBAABAABBAABBBAAAABBAABABBBABBABBBAAABBB" => "18",
"ABBAABBAABBBAABBBBBAAABBBBAABBBAABAABBBABABBAAABAABBAABBAAAAAABBAABAA" => "19",
"ABBBABAAABBBBABAABBBBAABBABBABBABBABBBBBBBBBAAABBAAAABBBBBBBABBBBAAAA" => "20",
"ABBABABBBBAABBBBBBBAAAAABABAAABBBBABABABBBABBABABBAAAAAABABBAABBAABAB" => "21",
);
my %args;
$args{input} = "";
$args{error} = "";
$args{output} = "test";
$args{verbose} = "";
my $options_okay = GetOptions(
'input=s' => \$args{input},
'error=s' => \$args{error},
'output=s' => \$args{output},
'verbose' => \$args{verbose}
);
my $metadata = { verbose => $args{verbose} };
print STDERR "INFER MARKERS\n";
my ( $blocklist, $linkage_groups, $marker_blocks ) = infer_markers( $args{input}, $args{error}, $metadata );
print STDERR "MAKING LINKAGE MAPS\n";
my $genome = make_linkage_maps( $blocklist, $args{output}, $linkage_groups, $marker_blocks );
output_marker_blocks( $genome, $marker_blocks, $args{output} );
print STDERR "Done\n";
exit;
## INFER MARKERS
sub infer_markers {
my ( $input, $error, $metadata ) = @_;
print STDERR "Loading blocks...\n";
my $blocklist = load_blocks( $input, $error, $metadata );
my $valid_patterns = validate_blocks( $blocklist, $metadata );
correct_maternal_patterns( $blocklist, $valid_patterns, $metadata );
fill_valid_patterns( $blocklist, $valid_patterns, $metadata );
complete_maternal_patterns( $blocklist, $valid_patterns, $metadata );
# collapse( $blocklist, $metadata );
print STDERR "Writing clean blocks...\n";
output_blocks( $input, $blocklist );
exit;
my ( $linkage_groups, $marker_blocks ) = build_linkage_groups( $blocklist, $metadata );
( $blocklist, $linkage_groups, $marker_blocks );
}
sub load_blocks {
my ( $input, $error, $metadata ) = @_;
my $blocklist = [];
my $header;
my $types;
my %error;
if ( $error ne '' ) {
print STDERR "Loading error corrections...\n";
open my $errorfile, "<", $error or croak "Can't open error file $error! $OS_ERROR\n";
while ( my $errorline = <$errorfile> ) {
chomp $errorline;
my ( $error, $corrected, @other ) = split /\t/, $errorline;
$error{$error} = $corrected;
}
close $errorfile;
}
print STDERR "Load blocks from database...\n" if $metadata->{verbose};
my @inputfiles = split ',', $input;
for my $inputfile (@inputfiles) {
my $dbh = DBI->connect( "dbi:SQLite:dbname=$inputfile", "", "" );
( $header, $types ) = get_header_types($dbh);
my $sth = $dbh->prepare("SELECT * FROM blocks ORDER BY scaffold, start");
my $fileblocklist = $dbh->selectall_arrayref( $sth, { Slice => {} } );
push @{$blocklist}, @{$fileblocklist};
$sth->finish;
$dbh->disconnect;
}
print STDERR "Phasing and correcting blocks...\n" if $metadata->{verbose};
# Make empty pattern by checking first Maternal pattern (could be any pattern)
my $empty;
my $samplenum;
for my $block ( @{$blocklist} ) {
if ( $block->{Maternal} ne "" ) {
$samplenum = length $block->{Maternal};
$empty = ' ' x $samplenum;
last;
}
}
for my $block ( @{$blocklist} ) {
$block->{validity} = 'i m p ';
for my $type ( keys %{$block} ) {
if ( $block->{$type} eq "" ) {
$block->{$type} = $empty;
next;
}
if ( defined $error{ $block->{$type} } ) {
$block->{$type} = $error{ $block->{$type} };
}
if ( defined $error{ mirror( $block->{$type} ) } ) {
$block->{$type} = $error{ mirror( $block->{$type} ) };
}
# Phase and record presence of type patterns
if ( defined $types->{$type} ) {
$block->{$type} = phase( $block->{$type} );
my $typekey = substr $type, 0, 1;
my $lctk = lc $typekey;
$block->{validity} =~ s/$lctk /$typekey / if $block->{$type} ne $empty;
}
}
}
$metadata->{header} = $header;
$metadata->{samples} = $samplenum;
$metadata->{types} = $types;
$metadata->{empty} = $empty;
get_block_stats( "After loading blocks", $blocklist, $metadata );
$blocklist;
}
sub validate_blocks {
my ( $blocklist, $metadata ) = @_;
my $empty = $metadata->{empty};
my %valid_patterns;
$valid_patterns{'Maternal'}{$sex}{'Paternal'} = undef;
$valid_patterns{'Maternal'}{$sex}{'IntercrossHom'} = undef;
for my $block ( @{$blocklist} ) {
infer_intercross( $block, $empty );
validate_parental( $block, $empty );
store_valid_patterns( $block, \%valid_patterns );
}
get_block_stats( "After validating blocks", $blocklist, $metadata );
\%valid_patterns;
}
sub infer_intercross {
my ( $block, $empty ) = @_;
if ( $block->{'IntercrossHet'} ne $empty ) {
if ( $block->{'IntercrossHom'} ne $empty ) {
if ( intercross_in_phase( $block->{'IntercrossHet'}, $block->{'IntercrossHom'} ) ) {
my $intercross =
merge_coupled_intercross( $block->{'IntercrossHet'}, $block->{'IntercrossHom'} );
if ( $intercross =~ /-/ ) {
$block->{'validity'} =~ s/I /Ie/;
}
else {
$block->{'validity'} =~ s/I /IE/;
$block->{'IntercrossHet'} = $empty;
}
}
else {
my ( $i1, $i2 ) = merge_repulsion_intercross( $block->{'IntercrossHet'}, $block->{'IntercrossHom'} );
my $iv = $i1 =~ /-/ ? 'Id' : 'ID';
$block->{'validity'} =~ s/I /$iv/;
}
}
else {
$block->{'IntercrossHom'} = $block->{'IntercrossHet'};
$block->{'IntercrossHet'} = $empty;
$block->{'validity'} =~ s/I /Is/;
}
}
elsif ( $block->{'IntercrossHom'} ne $empty ) {
$block->{'validity'} =~ s/I /Is/;
}
else {
# No Intercross patterns, do nothing
}
return;
}
sub validate_parental {
my ( $block, $empty ) = @_;
return if $block->{'Maternal'} eq $empty and $block->{'Paternal'} eq $empty;
if ( $block->{'validity'} =~ /^I[EDs]/ ) {
my $intercross = $block->{'IntercrossHom'};
if ( $block->{'Maternal'} ne $empty and $block->{'Paternal'} ne $empty ) {
if ( $intercross ne create_intercross( $block->{'Maternal'}, $block->{'Paternal'} )
and $intercross ne create_intercross( $block->{'Maternal'}, mirror( $block->{'Paternal'} ) )
and $intercross ne create_intercross( mirror( $block->{'Maternal'} ), $block->{'Paternal'} )
and $intercross ne create_intercross( mirror( $block->{'Maternal'} ), mirror( $block->{'Paternal'} ) ) )
{
$block->{'validity'} =~ s/I(.) /I$1b/;
}
else {
$block->{'validity'} =~ s/I(.) /I$1B/;
}
}
check_parent_consistent( $block, $intercross, 'Maternal' )
if $block->{'Maternal'} ne $empty;
check_parent_consistent( $block, $intercross, 'Paternal' )
if $block->{'Paternal'} ne $empty;
}
}
sub check_parent_consistent {
my ( $block, $intercross, $parent ) = @_;
my $pch = substr $parent, 0, 1;
if ( consistent( $intercross, $block->{$parent} )
or consistent( $intercross, mirror( $block->{$parent} ) ) )
{
$block->{'validity'} =~ s/$pch /$pch=/;
}
else {
$block->{'validity'} =~ s/$pch /$pch-/;
}
}
sub store_valid_patterns {
my ( $block, $valid_patterns ) = @_;
if ( $block->{'validity'} =~ /I[EDs]BM=P=/ ) {
$valid_patterns->{'Maternal'}{ $block->{'Maternal'} }{'Paternal'}{ $block->{'Paternal'} }++;
$valid_patterns->{'Maternal'}{ $block->{'Maternal'} }{'IntercrossHom'}{ $block->{'IntercrossHom'} }++;
$valid_patterns->{'Paternal'}{ $block->{'Paternal'} }{'Maternal'}{ $block->{'Maternal'} }++;
$valid_patterns->{'Paternal'}{ $block->{'Paternal'} }{'IntercrossHom'}{ $block->{'IntercrossHom'} }++;
$valid_patterns->{'IntercrossHom'}{ $block->{'IntercrossHom'} }{'Maternal'}{ $block->{'Maternal'} }++;
$valid_patterns->{'IntercrossHom'}{ $block->{'IntercrossHom'} }{'Paternal'}{ $block->{'Paternal'} }++;
$block->{'validity'} =~ s/[EDs=]/V/g;
$block->{'validity'} =~ s/I../ /;
$block->{'validity'} =~ s/ $/V/;
}
}
sub correct_maternal_patterns {
my ( $blocklist, $valid_patterns, $metadata ) = @_;
my $empty = $metadata->{empty};
my @maternal =
sort {
keys %{ $valid_patterns->{'Maternal'}{$b}{'Paternal'} } <=>
keys %{ $valid_patterns->{'Maternal'}{$a}{'Paternal'} }
}
keys %{ $valid_patterns->{'Maternal'} };
my %merge;
my %delete;
for my $i ( 0 .. $#maternal ) {
my $mi = $maternal[$i];
next if !defined $valid_patterns->{'Maternal'}{$mi};
for my $j ( $i + 1 .. $#maternal ) {
my $mj = $maternal[$j];
next if !defined $valid_patterns->{'Maternal'}{$mj};
if ( linked( $mi, $mj ) ) {
$merge{$mj} = $mi;
for my $type ( 'Paternal', 'IntercrossHom' ) {
for my $pattern ( keys %{ $valid_patterns->{'Maternal'}{$mj}{$type} } ) {
# If this pattern only occurs at the erroneous Maternal print, delete it
if ( keys %{ $valid_patterns->{$type}{$pattern}{'Maternal'} } == 1 ) {
$delete{$pattern}++;
for my $type2 ( 'Paternal', 'IntercrossHom' ) {
next if $type eq $type2;
for my $pattern2 ( keys %{ $valid_patterns->{$type}{$pattern}{$type2} } ) {
delete $valid_patterns->{$type2}{$pattern2}{$type}{$pattern};
}
}
delete $valid_patterns->{$type}{$pattern};
}
else {
# If the pattern occurs at a real print too, replace the wrong Maternal print
# with the real print
delete $valid_patterns->{$type}{$pattern}{'Maternal'}{$mj};
$valid_patterns->{'Maternal'}{$mi}{$type}{$pattern}++;
$valid_patterns->{$type}{$pattern}{'Maternal'}{$mi}++;
}
}
}
delete $valid_patterns->{'Maternal'}{$mj};
}
}
}
for my $block ( @{$blocklist} ) {
next if $block->{'Maternal'} eq $empty;
if ( defined $delete{ $block->{'IntercrossHom'} } ) {
$block->{'IntercrossHom'} = $empty;
$block->{'validity'} =~ s/I../i /;
}
elsif ( defined $delete{ $block->{'Paternal'} } ) {
$block->{'Paternal'} = $empty;
$block->{'validity'} =~ s/P./p /;
}
if ( defined $valid_patterns->{'Maternal'}{ $block->{'Maternal'} } ) {
$block->{'validity'} =~ s/M./MV/;
}
elsif ( defined $merge{ $block->{'Maternal'} } ) {
$block->{'Maternal'} = $merge{ $block->{'Maternal'} };
$block->{'validity'} =~ s/M./MV/;
}
else {
# If a maternal pattern in a non-valid block contains an error, find the real maternal pattern
for my $valid_maternal ( keys %{ $valid_patterns->{'Maternal'} } ) {
if ( linked( $valid_maternal, $block->{'Maternal'} ) ) {
$block->{'Maternal'} = $valid_maternal;
$block->{'validity'} =~ s/M./MV/;
last;
}
}
}
}
get_block_stats( "After correcting maternal patterns", $blocklist, $metadata );
return;
}
sub fill_valid_patterns {
my ( $blocklist, $valid_patterns, $metadata ) = @_;
my $empty = $metadata->{empty};
my $block_count;
print STDERR "Blocks to process:";
print STDERR scalar @{$blocklist};
print STDERR "\n";
for my $block ( @{$blocklist} ) {
$block_count++;
print STDERR "." if ( $block_count % 1000 == 0 );
print STDERR "$block_count\n" if ( $block_count % 10000 == 0 );
next if $block->{'validity'} =~ /V$/; # Skip already valid blocks
next
if $block->{'IntercrossHom'} eq $empty
and $block->{'Paternal'} eq $empty; # Cannot fill from Maternal alone
fill_parents_from_intercross( $block, $valid_patterns, $empty );
check_existing_valid_patterns( $block, $valid_patterns, $empty );
}
print STDERR "\n";
get_block_stats( "After filling valid patterns", $blocklist, $metadata );
}
sub fill_parents_from_intercross {
my ( $block, $valid_patterns, $empty ) = @_;
return if $block->{'IntercrossHom'} eq $empty or $block->{'Maternal'} ne $empty;
my $intercross = match_maternal_candidates_to_intercross( $block, $valid_patterns, $empty );
return if $intercross eq '';
# Fill empty Paternal pattern given Maternal pattern and Intercross pattern
if ( $block->{'Maternal'} ne $empty and $block->{'Paternal'} eq $empty ) {
my $paternal_candidate = separate_intercross( $block->{'Maternal'}, $block->{$intercross} );
$block->{'Paternal'} = $paternal_candidate;
if ( defined $valid_patterns->{'Paternal'}{$paternal_candidate} ) {
$block->{'validity'} =~ s/p /PV/;
}
else {
$block->{'validity'} =~ s/p /Pc/;
}
}
return;
}
sub match_maternal_candidates_to_intercross {
my ( $block, $valid_patterns, $empty ) = @_;
my @intercross_types =
$block->{'validity'} =~ /^I[Dde]/ ? ( 'IntercrossHom', 'IntercrossHet' ) : ('IntercrossHom');
for my $candidate ( keys %{ $valid_patterns->{'Maternal'} } ) {
for my $intercross_type (@intercross_types) {
next if $block->{$intercross_type} eq $empty;
my $status = '';
if ( consistent( $candidate, $block->{$intercross_type} )
or consistent( mirror($candidate), $block->{$intercross_type} ) )
{
$status = 'c';
}
elsif (linked( $candidate, $block->{$intercross_type} )
or linked( mirror($candidate), $block->{$intercross_type} ) )
{
$status = 'l';
}
next if $status eq '';
$block->{'Maternal'} = $candidate;
$block->{'validity'} =~ s/M./MV/i;
$block->{'validity'} =~ s/I(.)./I$1$status/;
return $intercross_type;
}
}
return '';
}
sub check_existing_valid_patterns {
my ( $block, $valid_patterns, $empty ) = @_;
# Find valid types in this block
my %valid_types;
for my $type ( 'IntercrossHom', 'Maternal', 'Paternal' ) {
if ( defined $valid_patterns->{$type}{ $block->{$type} } ) {
my $pch = substr $type, 0, 1;
$block->{'validity'} =~ s/${pch}./${pch}V/;
$valid_types{$type}++;
}
}
# Check valid patterns are consistent with each other
for my $i ( keys %valid_types ) {
for my $j ( keys %valid_types ) {
next if $i eq $j;
if ( !defined $valid_patterns->{$i}{ $block->{$i} }{$j}{ $block->{$j} }
or !defined $valid_patterns->{$j}{ $block->{$j} }{$i}{ $block->{$i} } )
{
map { my $pch = substr $_, 0, 1; $block->{'validity'} =~ s/${pch}V/${pch}X/; } ( $i, $j );
}
}
}
return if $block->{'validity'} =~ /X/;
# Fill empty Paternal and Intercross patterns with matching valid patterns
for my $valid_type ( keys %valid_types ) {
next if $valid_type eq 'Maternal';
for my $type ( 'Maternal', 'Paternal', 'IntercrossHom' ) {
next if $type eq $valid_type;
my $pch = substr $type, 0, 1;
next if $block->{validity} =~ /${pch}V/;
$block->{$type} =
( keys %{ $valid_patterns->{$valid_type}{ $block->{$valid_type} }{$type} } )[0];
$block->{'validity'} =~ s/${pch}./${pch}V/i;
}
}
$block->{'validity'} = " MVPVV" if $block->{'validity'} =~ /MVPV/;
return 0;
}
sub complete_maternal_patterns {
my ( $blocklist, $valid_patterns, $metadata ) = @_;
infer_intercross_maternal( $blocklist, $valid_patterns );
fill_remaining_maternal_patterns( $blocklist, $valid_patterns, $metadata );
}
sub infer_intercross_maternal {
my ( $blocklist, $valid_patterns ) = @_;
my %maternal_candidates;
my %intercross_blocks;
for my $b ( 0 .. $#{$blocklist} ) {
my $block = $blocklist->[$b];
if ( $block->{'validity'} =~ /IE m p / ) {
push @{ $maternal_candidates{ $block->{'IntercrossHom'} }{patterns} }, $block->{'IntercrossHom'};
$maternal_candidates{ $block->{'IntercrossHom'} }{length} += $block->{'length'};
push @{ $intercross_blocks{ $block->{'IntercrossHom'} } }, $b;
}
}
my $merged = merge_maternal_candidates( \%maternal_candidates );
# Update maternal patterns for inferred intercross chromosomes
for my $m ( keys %{$merged} ) {
$valid_patterns->{'Maternal'}{$m}{'Paternal'} = undef;
$valid_patterns->{'Maternal'}{$m}{'IntercrossHom'} = undef;
for my $i ( @{ $merged->{$m}{patterns} } ) {
my $pattern = $i->{original};
for my $b ( @{ $intercross_blocks{$pattern} } ) {
$blocklist->[$b]{'Maternal'} = $m;
$blocklist->[$b]{'Paternal'} = separate_intercross( $m, $pattern );
$blocklist->[$b]{'validity'} =~ s/I(.).M.P./I$1cMVPc/i;
}
}
}
get_block_stats( "After inferring intercross maternals", $blocklist, $metadata );
return;
}
sub merge_maternal_candidates {
my ($candidates) = @_;
my @candidates = sort { $candidates->{$b}{length} <=> $candidates->{$a}{length} }
keys %{$candidates};
my $longest_candidate = shift @candidates;
my %merged = (
$longest_candidate => {
patterns => [
{
pattern => $longest_candidate,
original => $longest_candidate,
length => $candidates->{$longest_candidate}{length}
}
],
length => $candidates->{$longest_candidate}{length}
}
);
for my $c (@candidates) {
my $patterns = @{ $candidates->{$c}{patterns} };
my $update_pattern = $c;
my $out_c = $c;
my @merged = sort { $merged{$b}{length} <=> $merged{$a}{length} } keys %merged;
for my $m (@merged) {
my $new_pattern = "";
if ( int_hamming( $c, $m ) <= 6 ) {
$new_pattern =
get_intercross_consensus( $c, $candidates->{$c}{length}, $merged{$m}{patterns} );
}
if ( int_hamming( mirror($c), $m ) <= 6 ) {
$new_pattern = get_intercross_consensus( mirror($c), $candidates->{$c}{length}, $merged{$m}{patterns} );
$out_c = mirror($c);
}
# Update merged pattern
if ( $new_pattern ne "" ) {
$update_pattern = $new_pattern;
if ( $m ne $update_pattern ) {
push @{ $merged{$update_pattern}{patterns} }, @{ $merged{$m}{patterns} };
$merged{$update_pattern}{length} +=
$merged{$m}{length};
delete $merged{$m};
}
last;
}
}
# Add candidate to merged patterns
push @{ $merged{$update_pattern}{patterns} },
{ original => $c, pattern => $out_c, length => $candidates->{$c}{length} };
$merged{$update_pattern}{length} += $candidates->{$c}{length};
$patterns = @{ $merged{$update_pattern}{patterns} };
}
\%merged;
}
sub get_intercross_consensus {
my ( $c, $c_length, $merged ) = @_;
my $cM = { pattern => $c, length => $c_length };
my @consensus_calls;
for my $m ( $cM, @{$merged} ) {
my @m = split //, $m->{pattern};
for my $i ( 0 .. $#m ) {
$consensus_calls[$i]{ $m[$i] } += $m->{length};
}
}
my $consensus = "";
for my $con (@consensus_calls) {
if ( keys %{$con} == 1 ) {
$consensus .= ( keys %{$con} )[0];
}
else {
map { $con->{$_} = 0 if !defined $con->{$_} } ( 'A', 'B', 'H' );
my $max = ( $con->{'A'} > $con->{'B'} ) ? 'A' : 'B';
$consensus .= ( $con->{$max} > ( $con->{'H'} * 0.1 ) ) ? $max : 'H';
}
}
$consensus;
}
sub fill_remaining_maternal_patterns {
my ( $blocklist, $valid_patterns, $metadata ) = @_;
my ( $paternal, $orphans ) = assign_remaining_maternal_to_intercross( $blocklist, $valid_patterns );
assign_orphans( $paternal, $orphans, $blocklist );
get_block_stats( "After filling remaining maternals", $blocklist, $metadata );
}
sub assign_remaining_maternal_to_intercross {
my ( $blocklist, $valid_patterns ) = @_;
my %paternal;
my %orphans;
for my $b ( 0 .. $#{$blocklist} ) {
my $block = $blocklist->[$b];
my $new_print;
if ( $block->{'validity'} =~ /I.l/ ) {
for my $print ( keys %{ $valid_patterns->{'Maternal'} } ) {
$new_print = $print
if consistent( $print, $block->{'IntercrossHom'} )
or consistent( mirror($print), $block->{'IntercrossHom'} );
}
}
if ( $block->{'validity'} =~ /I. m p / ) {
my $max_lod = 0;
for my $print ( keys %{ $valid_patterns->{'Maternal'} } ) {
$new_print = $print
if consistent( $print, $block->{'IntercrossHom'} )
or consistent( mirror($print), $block->{'IntercrossHom'} );
last if defined $new_print;
my $lod = linked( $print, $block->{'IntercrossHom'} )
or linked( mirror($print), $block->{'IntercrossHom'} );
if ( $lod > $max_lod ) {
$max_lod = $lod;
$new_print = $print;
}
}
}
if ( defined $new_print ) {
$block->{'Maternal'} = $new_print;
$block->{'Paternal'} = separate_intercross( $new_print, $block->{'IntercrossHom'} );
$block->{'validity'} =~ s/I(.)(.+)/I$1cMVPc /;
}
if ( $block->{'validity'} =~ /MVP[Vc ]/ ) {
$paternal{ $block->{'Paternal'} }{ $block->{'Maternal'} } += $block->{'length'};
}
if ( $block->{'validity'} =~ /m P/ ) {
if ( defined $paternal{ $block->{'Paternal'} }
or defined $paternal{ mirror( $block->{'Paternal'} ) } )
{
$block->{'Maternal'} =
defined $paternal{ $block->{'Paternal'} }
? ( keys %{ $paternal{ $block->{'Paternal'} } } )[0]
: ( keys %{ $paternal{ mirror( $block->{'Paternal'} ) } } )[0];
$block->{'validity'} =~ s/m P./MVPc/i;
}
else {
$orphans{ $block->{'Paternal'} }{length} += $block->{'length'};
push @{ $orphans{ $block->{'Paternal'} }{blocks} }, $b;
}
}
}
( \%paternal, \%orphans );
}
sub assign_orphans {
my ( $paternal, $orphans, $blocklist ) = @_;
print "Paternal only patterns to assign: " . scalar keys( %{$orphans} ) . "\n";
my $count = 0;
for my $orphan ( sort { $orphans->{$b}{length} <=> $orphans->{$a}{length} } keys %{$orphans} ) {
$count++;
print "." if $count % 10 == 0;
print "$count\n" if $count % 100 == 0;
my %maternal_candidates;
if ( defined $paternal->{$orphan}
or defined $paternal->{ mirror($orphan) } )
{
my $maternal =
defined $paternal->{$orphan}
? ( keys %{ $paternal->{$orphan} } )[0]
: ( keys %{ $paternal->{ mirror($orphan) } } )[0];
$maternal_candidates{$maternal}++;
}
else {
for my $paternal_candidate ( keys %{$paternal} ) {
next if $paternal_candidate eq $orphan;
my $lod = linked( $paternal_candidate, $orphan );
if ( $lod == 0 ) {
$lod = linked( mirror($paternal_candidate), $orphan );
$paternal_candidate = mirror($paternal_candidate) if $lod > 0;
}
next if $lod == 0;
for my $maternal ( keys %{ $paternal->{$paternal_candidate} } ) {
$maternal_candidates{$maternal} += $lod;
}
}
}
next if keys %maternal_candidates == 0;
my $maternal = ( sort { $maternal_candidates{$b} <=> $maternal_candidates{$a} } keys %maternal_candidates )[0];
$paternal->{$orphan}{$maternal} += $orphans->{$orphan}{length};
for my $b ( @{ $orphans->{$orphan}{blocks} } ) {
my $block = $blocklist->[$b];
$block->{'Maternal'} = $maternal;
$block->{'validity'} =~ s/m P./MVPc/i;
}
}
}
sub collapse {
my ( $blocklist, $metadata ) = @_;
my $i = 0;
my $j = 1;
while ( $j <= $#{$blocklist} ) {
my $same = 1;
$same = 0
if ( $blocklist->[$i]{'scaffold'} ne $blocklist->[$j]{'scaffold'} );
map {
if ( $blocklist->[$i]{$_} ne $blocklist->[$j]{$_} ) {
my $phase_j = phase( $blocklist->[$j]{$_} );
if ( $blocklist->[$i]{$_} eq $phase_j ) {
$blocklist->[$j]{$_} = $phase_j;
}
else {
$same = 0;
}
}
} keys %{ $metadata->{types} };
if ($same) {
$blocklist->[$i]{'end'} = $blocklist->[$j]{'end'};
$blocklist->[$i]{'length'} = $blocklist->[$i]{'length'} + $blocklist->[$j]{'length'};
splice( @{$blocklist}, $j, 1 );
}
else {
$i = $j;
$j++;
}
}
update_block_stats( "After collapse", $blocklist, $metadata );
return;
}
sub build_linkage_groups {
my ( $blocklist, $metadata ) = @_;
my %linkage_groups;
my %marker_blocks;
for my $block ( @{$blocklist} ) {
# next if $block->{'validity'} !~ /V$/;
next if $block->{validity} !~ /MVP[Vc]/;
my $maternal = $block->{Maternal};
my $paternal = $block->{Paternal};
next if ( $maternal eq $metadata->{empty} or $paternal eq $metadata->{empty} );
$linkage_groups{$maternal}{$paternal}{length} += $block->{length};
$linkage_groups{$maternal}{$paternal}{blocks}++;
$linkage_groups{$maternal}{$paternal}{lookup} = $paternal;
$marker_blocks{$paternal}{ $block->{scaffold} }{ $block->{start} } =
$block->{end};
}
( \%linkage_groups, \%marker_blocks );
}
sub int_hamming {
# Calculate hamming distance between intercross and paternal pattern
my ( $int, $pat ) = @_;
my $hamming = 0;
my @i = split //, $int;
my @p = split //, $pat;
for my $b ( 0 .. $#i ) {
next if $i[$b] eq 'H' or $i[$b] eq '-' or $p[$b] eq 'H' or $p[$b] eq '-';
$hamming++ if $i[$b] ne $p[$b];
}
$hamming;
}
sub int_match {
# Check for complete match between intercross and other pattern,
# ignoring missing bases in intercross pattern
my ( $intercross, $pattern ) = @_;
my @i = split //, $intercross;
my @p = split //, $pattern;
my $match = 1;
for my $a ( 0 .. $#i ) {
next if $i[$a] =~ /[H\-]/ or $p[$a] =~ /[H\-]/;
if ( $i[$a] ne $p[$a] ) { $match = 0; last; }
}
$match;
}
sub output_blocks {
my $input = shift;
my $blocklist = shift;
my $inputfile = ( split ',', $input )[0];
my $dbh = DBI->connect( "dbi:SQLite:dbname=$inputfile", "", "", { AutoCommit => 0 } );
my $sth = $dbh->prepare("DROP TABLE IF EXISTS cleanblocks");
$sth->execute;
$dbh->commit;
my ( $header, $types ) = get_header_types($dbh);
splice @{$header}, 4, 0, 'validity';
my $columns = $#{$header};
my $statement =
"CREATE TABLE cleanblocks (scaffold text, start integer, end integer, length integer, validity text";
map { $statement .= ", \"$_\" text" } @{$header}[ 5 .. $columns ];
$statement .= ")";
$sth = $dbh->prepare($statement);
$sth->execute;
$dbh->commit;
$statement = "INSERT INTO cleanblocks VALUES (?,?,?,?,?";
map { $statement .= ",?" } @{$header}[ 5 .. $columns ];
$statement .= ")";
my $insert_handle = $dbh->prepare_cached($statement);
for my $block ( @{$blocklist} ) {
my @values = map { $block->{$_} } @{$header};
$insert_handle->execute(@values);
}
$dbh->commit;
$dbh->disconnect;
return;
}
## MAKE LINKAGE MAPS
sub make_linkage_maps {
my ( $blocklist, $output, $linkage_groups, $marker_block ) = @_;
my %genome;
for my $chromosome_print ( keys %{$linkage_groups} ) {
my $chromosome = $chromosomes{$chromosome_print} // '-';
printf STDERR
"Building map for print $chromosome_print chromosome %3s with %4d paternal markers",
$chromosome, scalar keys %{ $linkage_groups->{$chromosome_print} };
clean_print( $linkage_groups, $chromosome_print );
if ( !defined $linkage_groups->{$chromosome_print} ) {
print STDERR "\tReject\n";
next;
}
$genome{$chromosome_print} =
make_linkage_map( $chromosome_print, $linkage_groups->{$chromosome_print}, $output );
}
\%genome;
}
sub clean_print {
my ( $linkage_groups, $chromosome_print ) = @_;
# Delete paternal patterns less than 1kb long or occurring in only 1 or 2 blocks
for my $marker ( keys %{ $linkage_groups->{$chromosome_print} } ) {
$linkage_groups->{$chromosome_print}{$marker}{output} = $marker;
# delete $linkage_groups->{$chromosome_print}{$marker}
# if ( $linkage_groups->{$chromosome_print}{$marker}{length} < 1000
# and $linkage_groups->{$chromosome_print}{$marker}{blocks} <= 2 );
}
if ( keys %{ $linkage_groups->{$chromosome_print} } == 0 ) {
delete $linkage_groups->{$chromosome_print};
}
}
sub make_linkage_map {
my ( $chromosome_print, $markers, $output ) = @_;
# Make map for this maternal pattern
my $marker_id = run_mstmap( $chromosome_print, $markers, $output );
my $map = load_map( $output, $chromosome_print );
my $chromosome_lgs = keys %{$map};
print STDERR "\tBuilt $chromosome_lgs linkage groups";
# If more than one linkage map returned for this chromosome,
# attempt to rephase markers and remake the map
my $phased_markers;
if ( $chromosome_lgs == 2 ) {
phase_linkage_groups( $map, $markers, $marker_id );
$marker_id = run_mstmap( $chromosome_print, $markers, $output );
$map = load_map( $output, $chromosome_print );
my $chromosome_lgs = keys %{$map};
print STDERR "\tAfter phasing, $chromosome_lgs linkage groups";
}
# smooth_markers( $map, $markers, $marker_id );
# $marker_id = run_mstmap( $chromosome_print, $markers, $output );
# $map = load_map( $output, $chromosome_print );
my $map_markers = write_map_markers( $map, $markers, $marker_id, $output, $chromosome_print );
print STDERR "\n";
$map_markers;
}
sub run_mstmap {
my ( $chromosome_print, $markers, $output ) = @_;
my $mstmap_input = write_mstmap_header( $output, $chromosome_print, $markers );
my $id = 1;
my %marker_id;
for my $marker ( keys %{$markers} ) {
$marker_id{$id} = $marker;
$markers->{$marker}{output} = check_mirror( $markers->{$marker}{output}, $markers );
$id = write_marker( $id, $markers->{$marker}, $mstmap_input );
}
close $mstmap_input;
system(
"MSTMap.exe $output.$chromosome_print.mstmap.input $output.$chromosome_print.mstmap.map > $output.$chromosome_print.mstmap.log"
);
\%marker_id;
}
sub write_mstmap_header {
my ( $output, $chromosome_print, $markers ) = @_;
my %mst_header = (
population_type => "RIL2",
population_name => "HeliconiusWGS",
distance_function => "kosambi",
cut_off_p_value => "0.000001",